Corkins ASPEN Ped Curriculum 2010

The A.S.P.E.N.
Pediatric Nutrition Support

Core Curriculum
EDITOR-IN-CHIEF
Mark R. Corkins, MD, CNSP, SPR, FAAP
Associate Professor
Indiana University School of Medicine, Riley Hospital for Children
Indianapolis, IN
SECTION EDITORS
Jane Balint, MD
Director, Intestinal Support Service
Pediatric Gastroenterology, Hepatology and Nutrition
Nationwide Children’s Hospital
Columbus, OH
Elizabeth Bobo, MS, RD, LDN, CNSD

Clinical Dietitian, Gastroenterology and Nutrition
Nemours Children’s Clinic
Jacksonville, FL
Steve Plogsted, PharmD, BCNSP

Clinical Pharmacy Specialist
Nutrition Support Pharmacist
Nationwide Children’s Hospital
Columbus, OH
Jane Anne Yaworski, MSN, RN

Clinical Nurse Specialist/Nutrition Support Service/Intestinal Care Center
Children’s Hospital of Pittsburgh
Pittsburgh, PA
MANAGING EDITOR
Nina D. Seebeck
AMERICAN SOCIETY FOR PARENTERAL AND ENTERAL NUTRITION

The American Society for Parenteral and Enteral Nutrition (A.S.P.E.N.) is a scientific society whose members are health care professionals—physi-
cians, dietitians, nurses, pharmacists, other allied health professionals, and researchers—dedicated to assuring that every patient receives optimal
nutrition care.
A.S.P.E.N.’s mission is to serve as a preeminent, interdisciplinary, nutrition society dedicated to patient-centered clinical practice worldwide through
advocacy, education, and research in specialized nutrition support.
NOTE: This publication is designed to provide accurate authoritative information in regard to the subject matter covered. It is sold with the under-
standing that the publisher is not engaged in rendering medical or other professional advice. Trademarked commercial product names are used only
for education purposes and do not constitute endorsement by A.S.P.E.N.
This publication does not constitute medical or professional advice, and should not be taken as such. To the extent the information published herein
may be used to assist in the care of patients, this is the result of the sole professional judgment of the attending health professional whose judgment is
the primary component of quality medical care. The information presented herein is not a substitute for the exercise of such judgment by the health
professional.
All rights reserved. No part of this may be used or reproduced in any manner whatsoever without written permission from A.S.P.E.N. For informa-
tion write: American Society for Parenteral and Enteral Nutrition (A.S.P.E.N.), 8630 Fenton Street, Suite 412, Silver Spring, MD 20910-3805; (301)
587-6315, www.nutritioncare.org, email: aspen@nutr.org.
Copyright © 2010. American Society for Parenteral and Enteral Nutrition.
ISBN: 978-1-889622-14-9
Printed in the United States of America.

Contents
Contributors. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . v 7. Water-Soluble Essential Micronutrients. . . . . . . . . . . . . . 56

Winston Koo, MBBS, FACN, CNS
Reviewers. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . xi
Judith Christie, RN, MSN
Foreword . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . xv May Saba, PharmD, BCNSP
Mirjana Lulic-Botica, BSc, BCPS
Preface . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . xvii Letitia Warren, RD, CSP
Acknowledgments & Dedication. . . . . . . . . . . . . . . . . . . . . . . xix 8. Fat-Soluble Vitamins . . . . . . . . . . . . . . . . . . . . . . . . . . . . 74
May Saba, PharmD, BCNSP
PART I Mirjana Lulic-Botica, BSc, BCPS
INTRODUCTORY AND BASIC PHYSIOLOGY Judith Christie, RN, MSN
1. Mechanics of Nutrient Intake. . . . . . . . . . . . . . . . . . . . . . . 3 9. Fluids and Electrolytes. . . . . . . . . . . . . . . . . . . . . . . . . . . 87
Mark R. Corkins, MD, CNSP, SPR, FAAP Gerald L. Schmidt, PharmD, BCNSP
Carol G. McKown, DDS, MS
Anna M. Dusick, MD
2. Gross Digestion Principles: Gastric Grinding PART II
and Gastrointestinal Motility. . . . . . . . . . . . . . . . . . . . . . 11 AGE-SPECIFIC NUTRITION FOR GROWTH
Jane P. Balint, MD AND DEVELOPMENT
3. Carbohydrates: Changes with Development. . . . . . . . . . . 17 10. Nutrition and Early Development. . . . . . . . . . . . . . . . . 105
Seema Mehta, MD Russell J. Merritt, MD, PhD, FAAP
Robert J. Shulman, MD Barbara Marriage, PhD, RD
Ricardo Rueda, MD, PhD
4. Fats. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 22
Peggy R. Borum, PhD 11. Human Milk . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 120
Jacqueline J. Wessel, RD, CNSD
5. Protein Digestion, Absorption, and Metabolism. . . . . . . . 31
Richard A. Helms, PharmD 12. Infant Formulas and Complementary Feeding. . . . . . . 129
Emma M. Tillman, PharmD Kelly Green-Corkins, MS, RD, CNSD
Anup J. Patel, MD Timothy Sentongo, MD
John A. Kerner, MD
13. Growth Assessment and Monitoring . . . . . . . . . . . . . . 143
6. Minerals. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 45 Timothy Sentongo, MD
14. Obesity and Metabolic Disorders. . . . . . . . . . . . . . . . . 149
Michelle Battista, BS, PhD Candidate
Robert Murray, MD
Letitia Warren, RD, CSP
15. Lipid Disorders. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 162
Shirley Huang, MD
Melanie Katrinak, RD, CSP, LDN
iii
iv CONTENTS
16. Use of Fad and Popular Diets. . . . . . . . . . . . . . . . . . . . 169 30. Oncology, Hematopoietic Transplant,
Catherine Christie, PhD, RD and Survivorship. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 349
Julia A. Watkins, PhD, MPH Nancy Sacks, MS, RD, LDN
Judith C. Rodriguez, PhD, RD Elizabeth Wallace, RD, CNSC, LDN
Seema Desai, MS, RD, LDN, CNSD
17. Sports Nutrition . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 178
Vinod K Prasad, MD, MRCP (London)
Jackie Buell, PhD, RD, LD, ATC, LAT
David Henry, MS, BCOP
Diane L. Habash, PhD, RD, LD
Virginia Guzikowski, MSN, CRNP
Liesje Nieman Carney, RD, CNSD, LDN
Beth Bogucki Wright, MS, RD, CSP, LDN
PART III Susan Rheingold, MD
DISEASE STATES AND NUTRITION
31. Trauma and Burns . . . . . . . . . . . . . . . . . . . . . . . . . . . . 378
18. Developmental Delay . . . . . . . . . . . . . . . . . . . . . . . . . . 191 Arlet G. Kurkchubasche, MD
Kathleen J. Motil, MD, PhD
32. Surgery. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 387
19. Eating Disorders . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 204 Arlet G. Kurkchubasche, MD
Christina Fitzgerald, MS, RD, LDN
Betsy Hjelmgren, MS, RD, LDN, CSP
20. Food Allergies. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 213 PART IV
Mary Beth Feuling, MS, RD, CD, CNSD NUTRITION CARE OF THE PEDIATRIC PATIENT
Michael B. Levy, MD
33. Assessment of Nutrition Status by Age
Praveen S. Goday, MBBS, CNSP
and Determining Nutrient Needs. . . . . . . . . . . . . . . . . 409
21. Diabetes Mellitus and Other Endocrine Disorders. . . . 226 Liesje Nieman Carney, RD, CNSD, LDN
Diane Olson, RD, CNSD, CSP, LD Jennifer Blair, MA, RD, CSP, LDN
W. Frederick Schwenk II, MD
34. Parenteral and Enteral Nutrition Support:
22. Inborn Errors of Metabolism . . . . . . . . . . . . . . . . . . . . 232 Determining the Best Way to Feed. . . . . . . . . . . . . . . . 433
Bridget Reineking, MS, RD, CD Liesje Nieman Carney, RD, CNSD, LDN
Sandra van Calcar, PhD, RD, CD Andrea Nepa, MS, RD, CSP, LDN
Sherri Shubin Cohen, MD, MPH
23. Cardiac Disease. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 247 Amy Dean, MPH, RD, LDN
Anupama Chawla, MD, CNSP, DCH (UK) Colleen Yanni, MS, RD, LDN
Janice Antino, RD, MS, CNSD, CSP Goldie Markowitz, MSN, CRNP
Mindy Freudenberg, RD, MS, CNSD
35. Implementation of the Plan. . . . . . . . . . . . . . . . . . . . . 448
24. Renal Disease. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 256 Beth Lyman, RN, MSN
Christina L. Nelms, MS, RD, CSP, CNSC, LD Jennifer M. Colombo, MD
Marisa Juarez, MPH, RD, LD Jodi L. Gamis, OTR
Bradley A. Warady, MD
36. Evaluation and Monitoring of Pediatric Patients
25. Gastrointestinal Disease. . . . . . . . . . . . . . . . . . . . . . . 283 Receiving Specialized Nutrition Support . . . . . . . . . . . 460
Donald George, MD Elaina Szeszycki, PharmD, BCNSP
Elizabeth Bobo, MS, RD, LDN, CNSD Wendy Cruse, MMSc, RD, CNSD
26. Hepatic Disease. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 302 Michelle Strup, PharmD
Samuel A. Kocoshis, MD 37. Ethical Issues in the Provision of Nutrition . . . . . . . . . 477
Renee A. Wieman, RD, CSP, LD, CNSD Patrick M. Jones, MD, MA
27. Intestinal Failure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 311 Brian Carter, MD
Robert H. Squires, Jr., MD
28. Pulmonary Disorders . . . . . . . . . . . . . . . . . . . . . . . . . . 323 Test Your Knowledge Answers. . . . . . . . . . . . . . . . . . . . . . . . 487
Allison Mallowe, RD, LDN
Suzanne Michel, MPH, RD, LDN
Maria Mascarenhas, MBBS
Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 495
29. Organ Transplantation. . . . . . . . . . . . . . . . . . . . . . . . . 337
Anita Nucci, PhD, RD, LD
Sharon Strohm, MBA, RD, LDN
Neelam Katyal, MS, RD, LDN
Beth Lytle, RD, LDN
Contributors
Janice Antino, RD, MS, CNSD, CSP Brian S. Carter, MD

Certified Specialist in Pediatric Nutrition, Registered Dietitian Professor of Pediatrics
Stony Brook University Hospital Vanderbilt University Medical Center
Stony Brook, NY Nashville, TN
Jane P. Balint, MD Anupama Chawla, MD, CNSP, DCH (UK)

Director, Intestinal Support Service Director of Pediatric Gastroenterology and Nutrition
Pediatric Gastroenterology, Hepatology and Nutrition Stony Brook University Hospital
Nationwide Children’s Hospital Stony Brook, NY
Columbus, OH
Catherine Christie, PhD, RD
Michelle Battista, BS, PhD Candidate Chair, Department of Nutrition and Dietetics
The Ohio State University University of North Florida
OSUN Interdisciplinary PhD Program Jacksonville, FL
Columbus, OH
Jennifer Blair, MA, RD, CSP, LDN Children’s Hospital of Michigan
Clinical Dietitian III Detroit, MI
The Children’s Hospital of Philadelphia
Philadelphia, PA Sherri Shubin Cohen, MD, MPH
Medical Director, Pediatric Feeding and Swallowing Center
Elizabeth Bobo, MS, RD, LDN, CNSD The Children’s Hospital of Philadelphia
Clinical Dietitian, Gastroenterology and Nutrition Philadelphia, PA
Nemours Children’s Clinic
Jacksonville, FL Jennifer M. Colombo, MD
Pediatric Gastroenterology Fellow
Peggy R. Borum, PhD Children’s Mercy Hospital
Professor of Human Nutrition Kansas City, MO
University of Florida
Gainesville, FL Mark R. Corkins, MD, CNSP, SPR, FAAP
Associate Professor
Jackie Buell, PhD, RD, LD, ATC, LAT Indiana University School of Medicine,
Director of Sports Nutrition, Department of Human Nutrition Riley Hospital for Children
College of Education and Human Ecology Indianapolis, IN
Ohio State University
Columbus, OH
v
vi CONTRIBUTORS
Wendy Cruse, MMSc, RD, CNSD Kelly Green-Corkins, MS, RD, CNSD
Pediatric Dietitian Clinical Dietitian Specialist
Indianapolis, IN Clarian Home Care
Indianapolis, IN
Amy Dean, MPH, RD, LDN
Clinical Dietitian Virginia Guzikowski, MSN, CRNP
The Children’s Hospital of Philadelphia Nurse Practitioner
Philadelphia, PA Division of Oncology
Seema Desai, MS, RD, LDN, CNSD Philadelphia, PA
Clinical Dietitian
Duke University Medical Center Diane L. Habash, PhD, RD, LD
Durham, NC Bionutrition Clinical Research Manager
General Clinical Research Center
Anna M. Dusick, MD Ohio State University
Associate Professor of Clinical Pediatrics Columbus, OH
Indianapolis University School of Medicine
Riley Hospital for Children Richard A. Helms, PharmD
Indianapolis, IN Department of Clinical Pharmacy
The University of Tennessee Health Science Center
Mary Beth Feuling, MS, RD, CD, CNSD Memphis, TN
Clinical Dietitian Specialist
Children’s Hospital of Wisconsin David W. Henry, MS, BCOP
Milwaukee, WI Associate Professor, Pharmacy Practice
University of Kansas Medical Center
Christina Fitzgerald, MS, RD, LDN Kansas City, KS
Owner/President
Nourished, Nutrition and Wellness Services Betsy Hjelmgren, MS, RD, LD, CSP
Chicago, IL Founder, Feed to Succeed
Chicago, IL
Mindy Freudenberg, RD, MS, CNSD
Certified Nutrition Support Dietitian, Registered Dietitian Shirley Huang, MD
Stony Brook University Hospital Medical Director, Healthy Weight Program
Stony Brook, NY Attending Physician, Division of GI, Hepatology and Nutrition
Jodi L. Gamis, OTR Philadelphia, PA
Occupational Therapist
Children’s Mercy Hospital Patrick M. Jones, MD, MA
Kansas City, Missouri Clinical Fellow (Neonatology)
Vanderbilt Children’s Hospital
Donald E. George, MD Nashville, TN
Division Chief Gastroenterology
Nemours Childrens Clinic Marisa Juarez, MPH, RD, LD
Jacksonville, FL Pediatric Renal Dietitian
Texas Children’s Hospital
Praveen S. Goday, MBBS, CNSP Houston, TX
Associate Professor
Pediatric Gastroenterology, Hepatology and Nutrition Melanie Katrinak, RD, CSP, LDN
Medical College of Wisconsin Clinical Nutritionist
Milwaukee, WI The Children’s Hospital of Philadelphia
Philadelphia, PA
CONTRIBUTORS vii
Neelam Katyal, MS, RD, LDN Allison Mallowe, RD, LDN

Clinical Dietitian Clinical Dietitian – Pediatric
Children’s Hospital of Pittsburgh The Children’s Hospital of Philadelphia
Pittsburgh, PA 15213 Philadelphia, PA
John A. Kerner, MD Goldie Markowitz, MSN, CRNP

Pediatric Gastroenterology, Hepatology and Nutrition Pediatric Nurse Practitioner
Stanford University The Children’s Hospital of Philadelphia
Palo Alto, CA Philadelphia, PA
Samuel A. Kocoshis, MD Barbara Marriage, PhD, RD

Professor of Pediatrics Senior Research Scientist
University of Cincinnati College of Medicine Abbott Nutrition
Director, Nutrition and Small Bowel Transplantation Columbus, OH
Cincinnati Children’s Hospital Medical Center
Cincinnati, OH Maria Mascarenhas, MBBS
Section Chief, Nutrition, Division of Gastroenterology
Winston Koo, MBBS, FACN, CNS and Nutrition
Clinical Director, NICU The Children’s Hospital of Philadelphia
Hutzel Women’s Hospital Associate Professor of Pediatrics
Professor of Pediatrics University of Pennsylvania School of Medicine
Children’s Hospital of Michigan Philadelphia, PA
Carman and Ann Adams Department of Pediatrics
Wayne State University Carol G. McKown, DDS, MS
Detroit, MI Owner/President
Carol G. McKown, M.S., D.D.S., P.C
Arlet G. Kurkchubasche, MD Volunteer Faculty, Riley Hospital Pediatric Dentistry Dept.
Associate Professor of Surgery and Pediatrics Carmel, IN
Alpert Medical School
Brown University Seema Mehta, MD
Providence, RI Department of Pediatric Gastroenterology,
Hepatology, and Nutrition
Michael B. Levy, MD Baylor College of Medicine
Associate Professor Texas Children’s Hospital
Allergy-Immunology Houston, TX
Medical College of Wisconsin
Milwaukee, WI Russell J. Merritt, MD, PhD, FAAP
Director of Medical Affairs
Mirjana Lulic-Botica, BSc, BCPS Abbott Nutrition
Hutzel Women’s Hospital Columbus, OH
Detroit, MI Medical Director, Nutrition Support & Intestinal Rehabilitation
Childrens Hospital of Los Angeles
Beth Lyman, RN, MSN Keck School of Medicine
Senior Program Coordinator for the Nutrition Support Team University of Southern California
Children’s Mercy Hospital Los Angeles, CA
Kansas City, MO
Suzanne Michel, MPH, RD, LDN
Beth Lytle, RD, LDN Clinical Dietitian, Pediatric Cystic Fibrosis Center
Clinical Dietitian The Children’s Hospital of Philadelphia
Children’s Hospital of Pittsburgh Philadelphia, PA
Pittsburgh, PA
viii CONTRIBUTORS
Kathleen J. Motil, MD, PhD Susan R. Rheingold, MD

Associate Professor of Pediatrics Assistant Professor of Pediatrics
USDA/ARS Children’s Nutrition Research Center Division of Oncology
Baylor College of Medicine The Children’s Hospital of Philadelphia
Houston, TX Philadelphia, PA
Robert Murray, MD Judith C. Rodriguez, PhD, RD

Nationwide Children’s Hospital Professor
Center for Healthy Weight and Nutrition University of North Florida
Columbus, OH Jacksonville, FL
Christina L. Nelms, MS, RD, CSP, CNSC, LD Ricardo Rueda, MD, PhD
Clinical Nutrition Specialist, Pediatric Renal Dietitian Associate Director Discovery Technology
Children’s Mercy Hospitals and Clinics Abbott Nutrition
Kansas City, KS Granada, Spain
Andrea Nepa, MS, RD, CSP, LDN May Saba, PharmD, BCNSP
The Children’s Hospital of Philadelphia Children’s Hospital of Michigan
Philadelphia, PA Department of Pharmacy Practice
Detroit, MI
Clinical Dietitian IV, Publication Specialist Nancy Sacks, MS, RD, LDN
The Children’s Hospital of Philadelphia Clinical Dietitian/Research Coordinator
Philadelphia, PA Division of Oncology
Anita Nucci, PhD, RD, LD Philadelphia, PA
Assistant Professor
Georgia State University Gerald L. Schmidt, PharmD, BCNSP
Division of Nutrition Nutrition Specialist
Atlanta, GA Shands Jacksonville
Jacksonville, FL
Diane L. Olson, RD, CNSD, CSP, LD Clinical Associate Professor
Assistant Professor of Pediatrics University of Florida College of Pharmacy
Mayo Clinic College of Medicine Gainesville, FL
Rochester, MN
W. Frederick Schwenk II, MD
Anup J. Patel, MD Professor of Pediatrics
Pediatric Gastroenterology, Hepatology and Nutrition Mayo Clinic College of Medicine
Stanford University Rochester, MN
Palo Alto, CA
Timothy Sentongo, MD
Vinod K. Prasad, MD, MRCP (London) Assistant Professor
Attending Physician University of Chicago
Pediatric Bone Marrow and Stem Cell Transplant Service Chicago, IL
Duke University Medical Center
Durham, NC Robert J. Shulman, MD
Professor of Pediatrics
Bridget Reineking, MS, RD, CD Baylor College of Medicine
Clinical Dietitian Specialist Texas Children’s Hospital Foundation Chair
Children’s Hospital of Wisconsin – Milwaukee in Pediatric Gastroenterology
Milwaukee, WI Texas Children’s Hospital
Children’s Nutrition Research Center
Houston, TX
CONTRIBUTORS ix
Robert H. Squires, Jr., MD Letitia Warren, RD, CSP

Clinical Director, Pediatric Gastroenterology Children’s Hospital of Michigan
Children’s Hospital of Pittsburgh Detroit, MI
Pittsburgh, PA
Julia A. Watkins, PhD, MPH
Sharon Strohm, MBA, RD, LDN Associate Professor
Dietitian Coordinator Department of Nutrition and Dietetics
Children’s Hospital of Pittsburgh University of North Florida
Pittsburgh, PA Jacksonville, FL
Michelle Strup, PharmD Jacqueline J. Wessel, RD, CNSD

Home Infusion Pharmacist Neonatal Nutritionist
Clarian Home Care Cincinnati Children’s Hospital
Indianapolis, IN Cincinnati, OH
Elaina Szeszycki, PharmD, BCNSP Renee A. Wieman, RD, CSP, LD, CNSD
Clinical Pharmacist – Nutrition Support and Pediatric Registered Dietician II
Gastroenterology Liver and Intestinal Transplantation Services and
Riley Hospital for Children Comprehensive Nutrition Center
Indianapolis, IN Cincinnati Children’s Hospital Medical Center
Cincinnati, OH
Emma M. Tillman, PharmD
Fellow, Department of Clinical Pharmacy Beth Bogucki Wright, MS, RD, CSP, LDN
The University of Tennessee Health Science Center Clinical Dietician IV, Technology Specialist
Memphis, TN Clinical Nutrition Development
Sandy van Calcar, PhD, RD, CD Philadelphia, PA
Metabolic Dietitian
Biochemical Genetics Program Colleen Yanni, MS, RD, LDN
University of Wisconsin – Madison Clinical Dietitian & Education Coordinator (Outpatient)
Madison, WI The Children’s Hospital of Philadelphia
Philadelphia, PA
Elizabeth Wallace, RD, CNSC, LDN
Clinical Dietitian
Philadelphia, PA
University of Missouri-Kansas City School of Medicine
Associate Chairman, Department of Pediatrics
Chief, Section of Pediatric Nephrology
Director, Dialysis and Transplantation
The Children’s Mercy Hospital
Kansas City, MO
Reviewers
Judith M. Bailer, BS, RD, LDN Katherine H. Chessman, PharmD, FCCP, BCPS, BCNSP
Clinical Dietitian II Professor, Clinical Pharmacy and Outcome Sciences;
Children’s Hospital of Philadelphia Clinical Pharmacy Specialist, Pediatrics/Pediatric Surgery
Philadelphia, PA South Carolina College of Pharmacy
Medical University of South Carolina Campus
Jane P. Balint, MD Medical University of South Carolina Children’s Hospital
Director, Intestinal Support Service Charleston, SC
Pediatric Gastroenterology, Hepatology and Nutrition
Nationwide Children’s Hospital Michael L. Christensen, PharmD
Columbus, OH Stevens Professor, Pharmacy Director
Department of Clinical Pharmacy
Laura E. Beerman, RD, CNSD University of Tennessee Health Science Center and
Regional Home Nutrition Support Dietitian Le Bonheur Children’s Medical Center
Walgreens-Optioncare Home IV Infusion Company Memphis, TN
Omaha, NE
Conrad R. Cole, MD, MPH, MSc
Jatinder Bhatia, MD Assistant Professor
Professor and Chief, Section of Neonatology Division of Gastroenterology, Hepatology and Nutrition
Medical College of Georgia Department of Pediatrics
Augusta, GA Emory University School of Medicine
Atlanta, GA
Susan Carlson, MMSc, RD, CSP, LD
Neonatal Dietitian Mark R. Corkins, MD, CNSP, SPR, FAAP
University of Iowa Childrens Hospital at Associate Professor
The University of Iowa Hospitals and Clinics Indiana University School of Medicine
Iowa City, IA Riley Hospital for Children
Indianapolis, IN
Pamela Charney, PhD, RD
Lecturer, Nutrition Sciences and Kimberly Cover, MS, RD, CSSD, LDN
Affiliate Associate Professor, Pharmacy Sports Nutrition Therapist/Clinical Specialist
University of Washington The Sports Medicine and Performance Center
Seattle, WA of the Children’s Hospital of Philadelphia
King of Prussia, PA
xi
xii REVIEWERS
Wendy Cruse, MMSc, RD, CNSD Kelly Green-Corkins, MS, RD, CNSD
Pediatric Dietitian Clinical Dietitian Specialist
Indianapolis, IN Clarian Home Care
Indianapolis, IN
Douglas Drenckpohl, MS, RD, CNSC, LDN
Advanced Practice Dietitian-Neonatal Kathleen M. Gura, BS, PharmD, BCNSP
Children’s Hospital of Illinois at Clinical Pharmacy Specialist GI/Nutrition
OSF Saint Francis Medical Center Associate Professor Pharmacy Practice
Peoria, IL Children’s Hospital Boston
Massachusetts College of Pharmacy and Health Sciences
Jeanne Ann Farrell, MS, RD, CNSC, LD/N Boston, MA
Clinical Dietitian
All Children’s Hospital Geraldine Hennies, RN III
St. Petersburg, FL Nutrition Support Nurse, Case Manager
Dianne Frazier, PhD, MPH, RD Cincinnati, OH
University of North Carolina Simon Horslen, MB ChB FRCPCH
Department of Pediatrics, Division of Genetics and Metabolism Professor of Pediatrics, Medical Director,
Chapel Hill, NC Liver & Intestine Transplantation
University of Washington and Seattle Children’s Hospital
Praveen S. Goday, MBBS, CNSP Seattle, WA
Associate Professor
Pediatric Gastroenterology, Hepatology and Nutrition Shirley Huang, MD
Medical College of Wisconsin Medical Director, Healthy Weight Program
Milwaukee, WI Attending Physician, Division of GI, Hepatology and Nutrition
David E. Goldstein, MD Philadelphia, PA
Professor Emeritus
University of Missouri Health Sciences Center Susanna Y. Huh, MD, MPH
Columbia, MO Instructor in Pediatrics
Harvard Medical School, Children’s Hospital Boston
Susan Goode, MS, RD, MD Boston, MA
Assistant Professor of Pediatrics
Tufts University School of Medicine Khursheed Jeejeebhoy, MBBS, PhD, FRCPC
Attending Physician Emeritus Professor of Medicine
Pediatric Gastroenterology & Nutrition University of Toronto and St. Michael’s Hospital
Baystate Children’s Hospital Toronto Ontario Canada
Springfield, MA
Doron D. Kahana, MD, FAAP
Barbara Goodin, MS, RD Assistant Clinical Professor
Pediatric Nutrition Specialist in Cystic Fibrosis, Pediatric Gastroenterology & Nutrition
Inborn Errors of Metabolism and Diabetes Harbor-UCLA Medical Center
University of Virginia Health System Torrance, CA
Department of Pediatrics/Div of Genetics
Metabolic Diseases Program Ajay Kaul, MBBS, MD
Charlottesville, VA Director, Impedance/Motility Disorders Program
Lori Grant, MEd, RD, CSP, LD Cincinnati, OH
Pediatric Dietitian
The University of Texas Health Science Center at San Antonio
San Antonio, TX
REVIEWERS xiii
Craig Lawrence Kien, MD, PhD Carrie McFarland, RD, CNSD

The Mary Kay Davignon Green and Gold Professor, Pediatric and Neonatal Clinical Dietitian
Depts. of Pediatrics and Medicine UCSF Medical Center
The University of Vermont College of Medicine San Francisco, CA
Burlington, VT
Clare McLaughlin, RD, CNSD, CSP
Angela Kirkwood, RN, BSN, IBCLC, RLC Pediatric Dietitian
Nurse Feeding Specialist and Clarian Health Inc.
Board Certified Lactation Consultant Indianapolis, IN
Children’s Hospital of Pittsburgh of UPMC
Clinical Nutrition Department Catherine M. McDonald, PhD, RD, CNSD
Pittsburgh, PA Clinical Dietitian
Primary Children’s Medical Center
Ronald E. Kleinman, MD Salt Lake City, UT
Physician in Chief, Massachusetts General Hospital for Children
Chair, Department of Pediatrics Kate Micucci, MS, RD, LD
Chief, Pediatric Gastrointestinal and Nutrition Unit Dietitian Specialist
Massachusetts General Hospital The University of Pittsburgh Medical Center
Charles Wilder Professor of Pediatrics Boardman, OH
Harvard Medical School
Boston, MA Shideh Mofidi, MS, RD, CSP
Metabolic Dietitian and Clinical Coordinator in the Inherited
Susan Konek, MA, RD, CSP, CNSD, LDN Metabolic Disease Center
Director of Clinical Nutrition Maria Fareri Children’s Hospital
The Children’s Hospital of Philadelphia West Chester, NY
Philadelphia, PA
Linda V. Muir, MD
Carolyn Kusenda, MS, RD, CNSD, LD Dietitian, Pediatric Gastroenterologist
Neonatal Nutrition Support Specialist/Clinical Swedish Medical Center
Nutrition Manager Seattle, WA
Children’s National Medical Center
Washington, DC Anita Nucci, PhD, RD, LD
Assistant Professor
Joel Lim, MD Georgia State University
Assistant Professor of Clinical Pediatrics Atlanta, GA
Riley Hospital for Children
Indiana University Patricia O’Brien, RD
Indianapolis, IN Senior Supervising Dietitian, Pediatric
University of California at Davis Health System
Allison M. Mallowe, RD, LDN Sacramento, CA
Clinical Pediatric Dietitian
The Children’s Hospital of Philadelphia Surekha Pendyal, MSc, MEd, RD
Philadelphia, PA Assistant Professor of Pediatrics
Metabolic Nutritionist
Maria R Mascarenhas, MBBS University of North Carolina
Section Chief, Nutrition, Division of Chapel Hill, NC
Gastroenterology and Nutrition
The Children’s Hospital of Philadelphia Barbara Robinson, MPH, RD, CNSD
Associate Professor of Pediatrics Pediatric Nutrition Specialist
University of Pennsylvania School of Medicine Hasbro Children’s Hospital
Philadelphia, PA Clinical Teaching Associate
Alpert Medical School of Brown University
Providence, RI
xiv REVIEWERS
Jill Rockwell, RD, LD, CNSD Eric Sibley, MD, PhD

Children’s Medical Center Dallas Associate Professor of Pediatrics
Dallas, TX Stanford University School of Medicine
Palo Alto, CA
Carol J. Rollins, MS, RD, CNSD, PharmD, BCNSP
Coordinator, Nutrition Support Team Edwin Simpser, MD
University Medical Center Chief Medical Officer
Tucson, AZ St. Mary’s Hospital for Children
Assistant Professor of Pediatrics, NYU School of Medicine
William O. San Pablo, Jr., MD Bayside, NY
Director, Nutrition Support and
Inflammatory Bowel Disease Program Jonathan M. Spergel, MD, PhD
Assistant Professor of Pediatrics Chief, Allergy Section
Children’s Mercy Hospital and Clinics, Associate Professor of Pediatrics
UMKC School of Medicine Director, Center for Pediatric Eosinophilic Disorders
Kansas City, MO Division of Allergy and Immunology
Sue Schiller, RD University of Pennsylvania School of Medicine
Pediatric Clinical Dietitian III Philadelphia, PA
Inova Fairfax Hospital for Children
Falls Church, VA Nancy Spinozzi, RD, LDN
Renal Dietitian
Timothy Sentongo, MD Childrens Hospital
Assistant Professor of Pediatrics, Boston, MA
Director Pediatric Nutrition Support Service
The University of Chicago Medical Center Christina J. Valentine, MD, MS, RD
Chicago, IL Medical Director, Neonatal Nutrition and Lactation
Section of Neonatology, The Ohio State University and
Robert J. Shulman, MD Nationwide Children’s Hospital
Professor of Pediatrics Columbus, OH
Baylor College of Medicine
Texas Children’s Hospital Foundation Chair Wendy Wittenbrook, MA, RD, CSP, LD
in Pediatric Gastroenterology Clinical Dietitian
Texas Children’s Hospital Texas Scottish Rite Hospital for Children
Children’s Nutrition Research Center Dallas, TX
Houston, TX
Foreword
I am very pleased to be asked to write the foreward to The to know. Dr. Corkins, his co-authors, and all of us who have
A.S.P.E.N. Pediatric Nutrition Support Core Curriculum— lived and contributed to the evolution of pediatric nutrition
an outgrowth of the pediatric section concept which Russ science believe that a well-organized and disciplined core
Merritt, MD, PhD, Bill Byrne, MD, Walter Faubion, RN, curriculum for pediatric caregivers is greatly needed.
and I started in the early 1980s. We recognized early on the A wide range of specialty fields require a working knowl-
importance of programmatic recognition within A.S.P.E.N. edge of pediatric nutrition and form our target audience:
of the special needs of infants and children, and the advan- dietetics, nursing, pharmacy, medicine, gastroenterology,
tages of continuing the multidisciplinary approach to surgery, and pediatrics. In addition to the expected compre-
pediatric nutrition which has been the hallmark of the hensive treatment of the basics of developmental physiology
success of the A.S.P.E.N. model. The evolution of the art and of the digestive process and the nutrition requirements
science of pediatric nutrition support is well demonstrated of various organ systems, chapters include Obesity and
in the postgraduate courses, seminars, workshops, round Metabolic Disorders, Use of Fad and Popular Diets, Sports
tables, and paper/poster presentations that have punctu- Nutrition, Implementation of the Plan, and Ethical Issues in
ated our annual clinical congresses. the Provision of Nutrition. Each chapter contains evidence-
The Pediatric Nutrition Support Core Curriculum is a based background information emphasizing core science,
well-earned and anticipated culmination of the multidis- intended for the professional who already possesses a basic
ciplinary approach developed and refined over the years. It understanding of the principles of food biochemistry, and
has been shaped by A.S.P.E.N.’s Standards of Practice, Clin- nutrition in wellness and disease. The layout of each chapter
ical Guidelines, and Interdisciplinary Nutritional Support includes a table of contents, learning objectives, and a
Competencies. In addition, it is designed to serve as: (1) a concluding set of self-assessment questions to test the read-
companion resource to the A.S.P.E.N. Nutrition Support er’s understanding of the subject matter.
Practice Manual, and the A.S.P.E.N. Nutrition Support Core It is my hope that this book will provide an effective
Curriculum: A Case-Based Approach—the Adult Patient; (2) learning experience and referenced resource for all health
an educational resource for those preparing for the special- professionals caring for infants and children, leading to
ization certification examination in nutrition support; (3) a improved patient care.
valuable clinical resource for the generalist: and (4) an inter-
disciplinary document that recognizes both the common
body of knowledge and the unique skills that each member John R. Wesley, MD, FACS, FAAP
of the multidisciplinary team possesses. Currently, there are Adjunct Professor of Surgery
general guidelines that allude to the importance of nutrition Pediatric Surgery
for infants and children and the need for training in pedi- Children’s Memorial Medical Center
atric nutrition. However, there is no defined curriculum Feinberg School of Medicine
that states explicitly what a pediatric caregiver is required Northwestern University
xv
Preface
The A.S.P.E.N. Pediatric Nutrition Support Core Curriculum

is the result of a question. One of the pediatric residency
directors asked me several years ago if A.S.P.E.N. had a
curriculum for teaching the residents about nutrition. They
had been looking for a way to teach the residents nutrition
and found nothing. I sadly told her no. It turned out that in
the pediatric section I was not the only person who saw the
need for a pediatric core curriculum.
This curriculum is designed to start with the basic
nutrition physiology then progress through the principles
for nutrition in disease states. It ends with the nuts and
bolts for daily care. Each chapter begins with an outline of
the important contents of that chapter and then ends with
“test your knowledge” questions. These are designed to
help you find out if you learned the important concepts of
the chapter. What this curriculum doesn’t have is in-depth
coverage of neonatal nutrition, although some of this is
covered in the context of the physiology of development.
It is also not exhaustive in its coverage of nutrition in the
various disease states. This is designed to be the pediatric
“core” curriculum; to be a disease-specific specialist will
require study beyond this “starting point.” The desire here
is to create a firm foundation of pediatric nutrition that
anyone can build on any way they wish.
Mark R. Corkins
Editor-in-Chief
xvii
Acknowledgments & Dedication
I have to thank Michelle Spangenburg and Nina Seebeck

for keeping everything on track to pull this book together.
I also must thank my Associate Editors—Jane Balint, Eliz-
abeth Bobo, Steve Plogsted, and Jane Anne Yaworski—for
their input and help with the legwork that goes into pulling
lots of authors and reviewers together and helping with
ideas to improve the curriculum. Finally, I wish to thank
Amy Cevario and Pattie Covert at Clayton Design Group.
I have to dedicate this book to the best pediatric
learning experience ever, my children and my personal
dietitian, best friend, and wife, Kelly.
Mark R. Corkins
Editor-in-Chief
xix
PART I
INTRODUCTORY AND
BASIC PHYSIOLOGY
1. Mechanics of Nutrient Intake. . . . . . . . . . . . . . . . . . . . 3

Mark R. Corkins, MD, CNSP, SPR, FAAP
Carol G. McKown, DDS, MS
Anna M. Dusick, MD
2. Gross Digestion Principles: Gastric Grinding
and Gastrointestinal Motility. . . . . . . . . . . . . . . . . . . 11
Jane P. Balint, MD
3. Carbohydrates: Changes with Development. . . . . . . . 17
Seema Mehta, MD
Robert J. Shulman, MD
4. Fats. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 22
Peggy R. Borum, PhD
5. Protein Digestion, Absorption, and Metabolism. . . . . 31
Richard A. Helms, PharmD
Emma M. Tillman, PharmD
Anup J. Patel, MD
John A. Kerner, MD
6. Minerals. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 45
7. Water-Soluble Essential Micronutrients. . . . . . . . . . . 56
8. Fat-Soluble Vitamins . . . . . . . . . . . . . . . . . . . . . . . . . 74
9. Fluids and Electrolytes. . . . . . . . . . . . . . . . . . . . . . . . 87
Gerald L. Schmidt, PharmD, BCNSP
1
Mechanics of Nutrient Intake
Mark R. Corkins, MD, CNSP, SPR, FAAP, Carol G. McKown, DDS, MS, and Anna M. Dusick, MD
CONTENTS Learning Objectives

Background. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 1. Understand how societal and behavioral influences
Appetite . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 guide food consumption.
2. Identify the psychological, mechanical, biochemical, and
Mastication/Dentition. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4
hormonal inputs that determine appetite and intake.
Feeding Development. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5
3. Describe the developmental stages in deglutition
Swallowing
Feeding Skills in the First Year and corresponding changes in appropriate feedings
Feeding Skills in the Second Year in children.
Dysphagia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8
Feeding Teams . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8
Background
This is a curriculum for nutrition in the pediatric age group.
Thus, by necessity, it focuses on the biological and physi-
ological needs of pediatric patients. Unlike other areas of
medicine directed by genetic programming, a great deal of
emotions and memories are associated with nutrition right
from the start. The original source of nutrition is food, yet
food is so much more than nutrition. It is symbolic, from
the stalk of wheat in the A.S.P.E.N. logo to the traditional
birthday cake. Marion Winkler, in her 2007 A.S.P.E.N.
presidential address, related the story of the foods her
mother requested when dying from cancer. Winkler real-
ized that it was about more than just food, stating “It was
always about the nostalgic stories that surrounded the food,
the memories, the social aspects, and the companionship of
the sharing of meals.”1
Appetite
When we begin to explore the desire to eat, we realize that
appetite has a cultural aspect.2 Part of this derives from the
environment; certain foods are more available in different
geographic regions, and one culture’s delicacy may be unac-
ceptable in another. Children’s memories and associations
will thus influence their intake. 3 Also, human beings will
3
4 THE A.S.P.E.N. PEDIATRIC NUTRITION SUPPORT CORE CURRICULUM
eat some foods just because they taste good. The reward of the anticipated meal.12 The rest of the responses from the
taste stimulates feeding even in the absence of a true energy stomach and small intestine tend to decrease appetite.9
deficit.4 Once beyond the cephalic phase, appetite level is
There are critical periods of infant development that modified by inputs from the enteric nervous system (ie,
hinge upon exposures to new tastes and textures. Genetic from chemical and stretch receptors in the GI tract) and
input affects the sense of taste itself, including the strength hormonal and metabolic signals.9 During the gastric phase
of response to sweet, salty, bitter, and sour. 5 Studies show the brain receives signals concerning the volume of food
that breastfed infants have greater willingness to try ingested and data about its nutrient content.9 Endocrine
new tastes2,6; this is believed to be from their exposure cells in the stomach produce ghrelin that stimulates appe-
to various flavors in breast milk. Early exposure to tastes tite4; ghrelin levels are high when the stomach is empty
determines taste and food preferences before the child and fall after eating.4,10 Emptying of the stomach also influ-
develops neophobia. 2 Neophobia is the developmental stage ences the neural control of appetite with gastric distention
between 18 months to 2 years of age when children resist signaling via the vagus nerve to decrease appetite.10
trying new foods. 2,5 The more a child is exposed to a taste, The intestinal phase is communicated by a variety of
the more likely it is to be accepted as a preferred taste. 5,6 signaling peptides that are released into the circulation.
Studies indicate that it may take 5 to 10 exposures before These peptides act to decrease appetite and are released in
a food becomes an accepted taste. 6 Also, there appears to proportion to the amount of various nutrients ingested.4
be a critical period for beginning solid foods, due to their These include peptide YY, glucagon-like peptide 1, oxynto-
texture, which is before 10 months of age. Northstone et al modulin, cholecystokinin, and pancreatic polypeptide.4 A
reported on long-term feeding problems related to accep- variety of other peptides may influence appetite but these
tance of the taste and texture of foods.7 Feeding difficulties await confirmatory studies.
in children identified by 9,360 parents were found to occur The hypothalamus integrates all of these signals to
more often in those children whose parents delayed initi- regulate appetite. The heightened appetite drive that occurs
ating solid foods until after 10 months of age.7 in pediatric patients that increases the caloric intake for
Biological preferences are also altered by modeling growth is not well understood. This drive may derive from
that children see when observing their parents and peers.2,5 programming within the hypothalamus itself or from
Eating with others influences the feeding behaviors and the signals indicating increased nutrient needs due to growth.
food preferences that children ultimately develop.6
Appetite control is centered in the hypothalamus of the Mastication/Dentition
brain and integrates information from multiple sources.4,8 An important part of digestion is the initial homogenization
The general level of appetite is influenced by the amount of food that takes place in the mouth. Mastication, or the act
of the hormone, leptin, produced by the body’s adipose of chewing, depends on the teeth to make foods a uniform
tissue.4,9 The liver also sends appetite-influencing signals consistency. Human beings are born toothless, which neces-
to the brain, primarily through the energy products fat and sitates a reliance on liquid feedings. The muscles used in
glucose and the level of adenosine triphosphate (ATP) in mastication are the temporalis, the masseter, and the medial
the liver cells.8 The insulin level produced by the pancreas and lateral pterygoids. The trigeminal nerve is the primary
in response to serum glucose levels influences the general nerve involved in mastication. The act of chewing involves
appetite level as well.4,8 Leptin and insulin suppress inhibi- two sets of teeth, the anterior teeth (incisors and canines)
tion, or drive the appetite, via the hypothalamus.10 and the posterior teeth (premolars and molars). The anatomy
The first stage in appetite is the cephalic phase, which of the incisors and canines with their single cusps and their
is a biological response to feeding cues. This concept was anterior position in the mouth allow them to tear food. The
first presented by Ivan Pavlov. Pavlov demonstrated that anatomy of the premolars and molars with multiple cusps
he could condition dogs to salivate at the ringing of a bell and their posterior position in the mouth allow them to
by developing an association with feedings.11 A variety of grind and chew food, preparing it for swallowing.13
studies have shown that visual, olfactory, gustatory, tactile, The primary dentition, or development and eruption of
and auditory inputs stimulate processes in the salivary teeth, consists of 20 teeth, all of which begin development
glands, gastrointestinal (GI) tract, pancreas, and cardio- between 13 to 20 weeks in utero. Teething, the act of tooth
vascular and renal systems.12 These responses are quick eruption, may cause infants malaise, with increased drooling
and prepare the body for the digestion and absorption of plus stomach or bowel changes, but it is not associated with
© 2010 A.S.P.E.N. www.nutritioncare.org

MECHANICS OF NUTRIENT INTAKE 5
fevers. The mandibular central incisors are the first teeth Feeding Development
to erupt between ages 6 to 10 months. The next teeth to
erupt are the maxillary central incisors between ages 8 to 12 Swallowing
months. Over the next 2 years the other primary teeth come The process of swallowing is divided into 3 distinct
in as shown in Table 1-1. physiological phases. These phases are the oral phase, the
pharyngeal phase, and the esophageal phase. Each phase
Table 1-1 Primary Teeth by Age of Eruption depends on the correct anatomy and neurophysiology of
Primary Teeth Age of Eruption the muscles for feeding and appropriate ventilation.
Mandibular central incisors 6–10 mo The oral phase consists of the preparatory stage and the
Maxillary central incisors 8–12 mo movement of food being propelled to the back of the mouth.
Maxillary lateral incisors 9–13 mo Infants take most liquids into the mouth already on the
Mandibular lateral incisors 10–16 mo back third of the tongue; this changes as they develop more
Maxillary first molars 13–19 mo skill in the front of the mouth (tongue, jaw, and lips), and
Mandibular first molars 14–18 mo develop teeth. Purees and solids are propelled to the back of
Maxillary canines 16–22 mo the mouth by the tongue. (Later in infant development the
Mandibular canines 17–23 mo
lips are used for assisting with eating during the oral phase.
Second molars 2–3 y
Skills such as taking purees off a spoon or drinking through
The primary dentition stays intact until ages 5 to 7 years a straw will occur in the last half of the first year.)
when the permanent dentition begins to erupt. As the root The pharyngeal phase consists of the liquid or food
end of the permanent tooth develops in the bone, it causes coming to the back of the mouth, the pharynx, and reflex-
the crown of the tooth to emerge, which resorbs the root of ively being swallowed. The soft palate and uvula lift so that
the primary tooth leaving only the crown. The crown of the liquid or food will not pass into the nasopharynx. The larynx
primary tooth is then shed, allowing the permanent tooth closes by muscle contractions and the downward movement
to erupt. The mandibular central incisors and mandibular of the epiglottis. Respiration ceases briefly (deglutition
and maxillary first molars are the first permanent teeth to apnea) and, after the food has started its descent, expiration
erupt between ages 6 and 7 years. Their hard tissue forma- then inspiration will occur. In the infant, the swallow can
tion begins shortly after birth. The subsequent progression occur at any part of the respiratory cycle and it is variable.15
of permanent tooth acquisition is shown in Table 1-2. The upper esophageal sphincter relaxes so that the food
can enter the esophagus in the beginning of the esophageal
Table 1-2 Permanent Teeth by Age of Eruption phase. The cricopharyngeus muscle relaxes at the upper
Permanent Teeth Age of Eruption end of the esophagus and food travels to the stomach by
Mandibular central incisors 6–7 y peristalsis. Successful swallowing depends on all of these
Mandibular first molars 6–7 y structures, muscles, and neurological and respiratory
Maxillary first molars 6–7 y systems working in coordinated millisecond timing.16,17
Maxillary central incisors 7–8 y Anatomical or physiological abnormalities with these
Mandibular lateral incisors 7–8 y systems will affect feeding effectiveness and efficiency.
Maxillary lateral incisors 8–9 y
Mandibular canines 9–10 y Feeding Skills in the First Year
Maxillary premolars 10–11 y
The typical newborn is ready to feed shortly after birth.
Mandibular premolars 10–12 y
The reflexive root allows the infant to open the mouth,
Maxillary second premolars 10–12 y
turn toward the food source, latch, and begin to suck. The
Mandibular second premolars 11–12 y
Maxillary canines 11–12 y
newborn will suck, swallow, and breathe in a rhythmic
sequence. This pattern is established with the help of the
The permanent third molars, or wisdom teeth, are the most early reflexes and behaviors that are developed in utero
common missing teeth and normally erupt between ages 17 and improves by the third day of life.18 The rooting reflex
and 21 years.14 is among the most important and is activated by a light
touch on or near the infant’s mouth. Once latched onto the
nipple, the infant’s tongue and jaw work together to stroke
the nipple and express milk.19 The infant will feed in a burst-

pause pattern that is usually quite regular, with the bursts with small single bite-size pieces for the infant to move
being suck-swallow-and-breathe cycles and the pauses around in the mouth and eventually swallow. There is less
being brief and regular rest periods. Bursts of 8 sucks or rhythm to this feeding as compared to nutritive sucking.
more are seen in the typical newborn. 20 Sensing changes in The movements are volitional and no longer directed by
the nipple, the infant can vary the suck pressure quite easily reflex. Early reflexes are fading between 4 to 8 months and
to control the flow of milk. During early infancy, the infant volitional patterns of oromotor skills are the norm. 26 By 9
will increase the rate of expression per minute with age. months of age, with the development of the fine motor skills
Studies have varied on the changes in the volume of expres- of reach, grasp, and release, self-feeding is established. Now
sion; however, it ranges from 0.26 to 0.4 mL per suck. 21,22 the infant is skillful at watching others, communicating
In a typical newborn, one suck-swallow-breathe cycle interests in foods and eating. Cup and straw drinking begin
including all 3 phases lasts approximately 1 second. 21 As the as the infant is guided by a parent. The infant will not gum
infant’s oromotor skills develop, the increase in control and the cup, but opens his or her mouth to accept liquids from
efficiency of intake allows the older infant to take more milk the cup that is guided by the parent. At this age, both breast-
in less time. feeding and bottle feeding begin to diminish as the infant
Pacifier sucking differs from feeding. In pacifier sucking takes in a greater proportion of liquids by cup and solids by
(non-nutritive sucking), the suck rate is twice as fast as nutri- spoon or hand.24
tive sucking.20 Only the oral phase is seen in non-nutritive
sucking. The swallow-and-breathe phases of feeding are not Problems in Infant Feeding Skills
coordinated. This is why many non-feeding infants can non- Infant feeding difficulties can be broadly related to prob-
nutritively suck but have difficulty when liquid is introduced lems with anatomy, neurodevelopment, or respiration.
by a nipple. Anatomical abnormalities of the head and neck are typi-
Readiness for transitioning to spoon feeding has been cally congenital and may affect the muscles of feeding as
debated, and recommendations have changed over the well as the physiological timing and efficiency of feeding,
years. Brain growth and neural pathway maturation support and lead to poor efficiency of intake. In the extreme,
development of a larger variety of oromotor movements. The dysphagia (or swallowing dysfunction) can be seen. Clas-
tongue no longer moves in a forward-backward patterned sically, cranial nerve abnormalities cause dysphagia, and it
response. The infant’s tongue is able to stay in the mouth, not is being recognized earlier along with the subtle effects of
thrust out, and move side to side in response to stimulation, muscle tone and posture on feeding. Neurodevelopmental
such as mouthing his or her fingers or hand. The infant no problems, such as an infant with muscle tone abnormalities,
longer has a single oral response of suck-swallow-breathe, or persistence of early reflexes, or abnormal oral reflexes, can
bursts of sucking without swallowing as in pacifier sucking. also lead to dysphagia.27 Infants with hypotonia (as may
At 5 to 6 months of age an infant typically has some sitting be seen in infants with Down syndrome) may have signifi-
balance and wants to feed in an upright position. The infant cant oromotor dysfunction, dysphagia, and aspiration.28
can anticipate the food and will open his or her mouth for Even infants with normal development can have difficulty
the spoon. The lips will close on the spoon to pull the food feeding if they have abnormal respirations or gastroesopha-
off.23 The food is moved all around in the mouth, not strictly geal reflux. They may tire easily and self-limit their intake,
kept over the center of the tongue for propulsion back for or they may have difficulty with the suck-swallow-breathe
swallowing. The tongue and the jaw no longer work only as sequence and self-limit due to aspiration, which is passage
a single unit. The gag is diminished to allow for non-liquids of liquid or solids into the airway during swallowing.29
and will continue to be modulated as the experience with Premature infants frequently have feeding difficulties
textures continues.24 because of either, or both, respiratory problems and neurode-
When infants begin to pick up objects, at age 6 to 7 velopmental problems. Early birth does not allow for the
months, they naturally put them into their mouths. As the typical developmental sequence of oral skills. Poor growth,
tongue can move in multiple directions and mouth objects, of especially the youngest gestational age infants, may not
the parent introduces meltable solids and foods with greater allow for maturation of neural pathways. Many premature
texture (lumps) for the infant to handle. In late infancy, the infants have difficulty with “newborn” skills when they are
infant begins to “munch” or use an up-down motion of the at a “term-adjusted age” and may have significant feeding
jaw to begin mastication of foods. This chewing increases problems. Premature infants with bronchopulmonary
in efficiency with age.25 Soft solid foods are then provided dysplasia have been seen to have abnormal development of

suck patterns. 30 Some infants, who had significant limita- period, chewing improves and changes from the up-down
tions in oral feeding attempts due to a high level of illness munching motion to the rotary chewing that allows the
or respiratory disorders, can display aversion to attempts at toddler to grind meat fibers by age 3 years. The toddler will
oral feeding. In others, a persistent rapid breathing rate can increase chewing efficiency to 5 years of age. 33 Through trial
interfere with establishing an efficient feeding rhythm. and error, carefully, the parents will supply the toddler with
Evaluation of the infant who is not feeding appropri- small bites of their own foods and expand the toddler’s diet.
ately can be performed by a physician, nurse, occupational Meltable solids will be exchanged for non-meltable solids
therapist, or speech therapist trained in, and experienced that require biting off and chewing as the parent sees the
with, infant feeding. The evaluation will include a medical child is ready for the single bite. Gradually, the diet will
history, developmental history, and a neurological examina- reach that of the preschooler.
tion as well as an oromotor assessment including feeding or The toddler may initially allow the parent to assist with
feeding attempt. A multidisciplinary approach is required. providing bites, but this will diminish and, by 18 months, the
Pediatric specialists in gastroenterology, neurology, reha- child will insist on exclusive self-feeding. The use of utensils
bilitation, development, and others may be needed. The can start as early as 15 months, but is generally not perfected
evaluation, under the direction of a physician, may include until much later. Initially, sticky foods will be given to help
radiological testing such as a feeding study, esophagram, or with self-spoon feeding; later the child will learn to spear
studies for reflux or gastric emptying. Neurological studies with a fork as well, particularly soft foods. Eating with his
of the central nervous system may be needed for the diag- or her fingers to assist the utensil feeding will continue until
nosis of neurodevelopmental abnormalities. Studies of the preschool age. Also, the child can now drink indepen-
respiratory function and sufficiency of ventilation may be dently from an open cup.24
needed to provide optimal respiratory support for feeding. Behavior during mealtimes can be challenging as the
It is important to determine the safety of feeding and toddler will seek to exert control over this environment
ensure that the infant is not aspirating as a result of the as well. How the parents model and reinforce appropriate
underlying problems. 31 behavior to diminish unwanted behavior can affect not only
Sometimes, despite extensive evaluations, the etiology eating but also sleeping habits and play interactions. Routine
of the feeding difficulties is never discovered. There is also a meals and snacks that are eaten with the child are the best
belief that in some situations the initiating organic cause has times to teach a child appropriate mealtime behavior. As the
resolved but the resulting behavior has become established. toddler’s ability to understand language increases, the parents
Once the cause and extent of poor feeding is understood, need to demonstrate and explain appropriate behavior at
a treatment plan can be undertaken to work on oral feed- mealtimes. Praise for sitting and eating with the family is
ings, and/or to provide supplemental feedings for the safety necessary, as well as repetitive teaching of appropriate behav-
and growth of the infant. Supplemental feedings can consist iors. Watching the toddler’s cues is important, as throwing or
of nasogastric feedings or feedings into the jejunum. Such playing with food may signal that the child is full. As with all
treatment plans should be drafted with the parents and a behaviors, routine and consistency will teach both the easy as
team of medical and therapy providers. well as the difficult feeder.
Feeding Skills in the Second Year Problems with the Toddler Feeder
Toddlers typically need to expand their acceptance of foods Problems that affected an infant’s feeding may still be
and master self-feeding, including biting and chewing. This present when that child reaches toddlerhood. Medical
is a tall order as they are also developing independence and problems of anatomical anomalies, neurodevelopmental
have the ability to make choices and affect their environ- problems, or cardio-respiratory concerns require ongoing
ment. The majority of toddlers (from 1 to 3 years of age) medical and therapeutic intervention. However, those
enter this stage eating “table foods.” They have success- toddlers who had normal feeding skills in their first year
fully transitioned to some of the foods their families eat may have new behaviors affecting feedings, or have aver-
by their first birthday. 32 Due to their immature oromotor sion to advancing on to a variety of flavors and textures. In
skills, toddlers need their foods diced, chopped, or cut into one population study, parents described 20% of toddlers as
small bite-sized pieces. This continues until their ability to having feeding problems. 34 At times a sentinel event can be
bite a single mouthful of food becomes skillful. Only then recalled (“he had his tonsils out and couldn’t eat”); other
can a parent rely on the toddler not to choke. During this times, subtle problems with advancing textures in infancy

were present and not well recognized. Still other problems The real-time images are observed by the therapist or other
include the toddler with behavioral problems that are now personnel performing the study, and are further reviewed
more evident at this age, such as short attention span, oppo- by a radiologist. When a child aspirates, the feeding plan
sitionality, or slow learning. Sometimes the organic process is modified to avoid liquids or textures that the child is not
that caused a feeding problem will resolve but the inappro- able to eat safely. Further neurological diagnosis as to the
priate feeding behavior persists. cause of dysphagia should be investigated by the physician.
Evaluating new feeding problems in the toddler begins Therapeutic interventions can include:
with a thorough feeding history of who, what, when, where, • physical, occupational, and speech therapy to advance
how, and how much the child is fed. Often through this skills;
history, the initial therapeutic interventions can be deter- • modifications of liquids or foods offered;
mined. Review of the anthropometric measures since birth • adaptation of cups and utensils for feeding;
will identify growth failure, and a physical examination will • positioning assistance to provide a flexed and upright
determine the need for additional cardiac, respiratory, or GI position for feeding;
evaluation. The neurological and developmental examina- • dietitian adaptation of the diet to meet caloric, nutri-
tion can determine the need for feeding studies, or further tion, and volume goals;
psychological or developmental evaluation. • nutrition support through gastrostomy feedings;
Most therapeutic plans include a mealtime routine and • diagnosis and treatment of gastroesophageal reflux;
appropriate modeling of eating behavior by parents and • medications to normalize tone and posture; and
caregivers. Choosing a nutritious variety of foods to serve • repeated feeding studies.
at meals and as snacks will expand the feeding experience The goals of therapy will be to normalize tone and
of the toddler and decrease pickiness. 35–37 It is important posture, particularly around head control and seating for
to ascertain the toddler’s baseline abilities with oromotor feeding. Other goals will be to foster feeding development
function, fine motor development, and cognitive function in the typical sequence as determined by the child’s level
to determine the level at which to begin. Identification of of function and the safety of the feeding. For example, an
the problem(s) as well as the parents’ goals for feeding will infant who has had brain damage from meningitis may be
direct the therapist’s plans, dietary plans, and home inter- seen to have dysphagia. Methods that lead to relaxation
vention. In toddlers with weight loss, worsening feeding may need to be used on the infant to decrease hypertonicity
problems, or significant family stress, referral to a feeding and foster normal positioning. This infant may require a
team can be helpful. The toddler with feeding problems may feeder seat for good positioning, and may need to be offered
need such a team approach, including a psychologist, occu- purees only, because liquids are aspirated. This infant may
pational and speech therapists, and dietitian, to provide need dietary assistance with increased caloric density to
behavioral plans, therapy, and dietary advice. decrease the volume of intake needed by tube feeding; or he
may need to have small and frequent feedings if intolerant
Dysphagia of large gastrostomy feeding volumes. Once again, a team
Neuromotor impairment in swallowing can also be termed approach is needed in the feeding care of the infant or child
dysphagia. In the infant and young child, feeding proceeds in who has dysphagia. 38
the developmental sequence mentioned, and abnormalities
in feeding abilities need to be evaluated for a neurological Feeding Teams
cause. This diagnosis is made by history, a neurological Pediatric institutions that form feeding teams draw from
examination by a physician, and a feeding observation. the professional expertise at their organizations. With that
Feeding studies, in which the infant or child is fed using the in mind, each team will determine the problems they feel
observation of video fluoroscopy, can identify neuromotor are appropriate in their setting and for their population. The
problems of pharyngeal pooling, nasopharyngeal reflux, or usual team members include:
laryngeal aspiration. During a swallow/feeding study, the • child and parents;
infant or child is fed liquids, purees, or solids laced with • a physician, who may be a developmental pediatrician,
barium so that the ingested substance is visible under video gastroenterologist, general pediatrician, or a pediatric
fluoroscopy. At some institutions, feeding studies can be physiatrist;
done with pulse oximetry to see the effect of respiratory • a coordinator, who may be in social work, psychology,
effort or deglutition apnea on the total saturation of oxygen. or nursing;

• a child psychologist; Test Your Knowledge Questions

• a speech and/or occupational therapist; 1. Appetite is suppressed by:
• a dietitian; and A. Sensory stimulus before eating
• a social worker. B. Ghrelin release by the stomach
For the feeding team to be successful, the parents must C. Intestinal release of glucagon-like peptide 1
clearly identify their goals and be willing to make changes, D. Low leptin levels
and to work with the team members. Each professional 2. An abnormal swallow contains:
must also be willing to work with team members and to A. Lift of the soft palate and uvula
support the parents and patient during the process. Setting B. Continued respirations
clear goals with the team and reviewing those goals is an C. Closure of the epiglottis
important part of a feeding team program. D. Opening of the upper esophageal sphincter
For example, “Abby” is a young toddler who has 3. Chewing that allows the intake of higher texture foods
aversiveness to eating because of severe respiratory prob- requires:
lems caused by prematurity. Her respiratory status has A. Rotary chewing
significantly improved and she needs only occasional bron- B. Forward-backward patterning
chodilators. She is gastrostomy fed and is very sensitive to C. Suck-swallow-and breathe cycles
the rate of feedings. Her mother has cut back on her feed- D. Up-down motion of the jaw
ings so Abby is also failing to thrive. There are many goals
for the team members, and progress may vary in these goals. See p. 487 for answers.
The family hopes to shorten feeding times and increase
Abby’s oral feedings so she can eventually stop gastrostomy References
feedings. These are appropriate goals for the child and the 1. Winkler MF. American Society for Parenteral and Enteral
team members; however, these are long-term goals and the Nutrition presidential address: food for thought: it’s more
than nutrition. J Parenter Enteral Nutr. 2007;31(4):334–340.
progress is incremental and variable. The parents, with the 2. Harris G. Development of taste and food preferences in
team’s help, determine the daily schedule for feeding, and children. Curr Opin Clin Nutr Metab Care. 2008;11(3):
continue in the routine of feedings. The physician and dieti- 315–319.
tian may work on a short-term goal of improving Abby’s 3. Lupton D. Food, The Body and the Self. Thousand Oaks, CA:
weight gain while trying to shorten her feeding times. The Sage Publications; 1996.
4. Druce M, Bloom SR. The regulation of appetite. Arch Dis
therapists may start by improving her ability to stay at the
Child. 2006;91:183–187.
table at mealtime and touch food for short time periods. 5. Scaglioni S, Salvioni M, Galimberti C. Influence of parental
The dietitian and therapists may use a “chaining” technique attitudes in the development of children eating behaviour. Br J
to select foods that are similar to foods Abby likes so as to Nutr. 2008;99(Suppl 1):S22–S25.
slowly broaden her food choices. At each follow-up visit 6. Birch LL, Fisher JO. Development of eating behaviors
with the team, the goals are reassessed and the plan of care is among children and adolescents. Pediatrics. 1998;101(3)
(Suppl):539–549.
revised based on the child’s progress. 39 Referral to a feeding 7. Northstone K, Emmett P, Nethersole F. The effect of
team is generally made by the child’s primary care provider age of introduction to lumpy solids on foods eaten and
and reviewed by the coordinator for appropriateness to the reported difficulties at 6 and 15 months. J Hum Nutr Dietet.
team. 2001;14(1):43–54.
8. Erlanson-Albertsson C. Appetite regulation and energy
balance. Acta Paediatr. 2005;94(6)(Suppl):40–41.
9. Blundell JE. The control of appetite: Basic concepts
and practical implications. Schweiz Med Wochenschr.
1999;129(5):182–188.
10. Inui A, Asakawa A, Bowers CY, Mantovani G, Laviano A,
Meguid MM, et al. Ghrelin, appetite, and gastric motility: the
emerging role of the stomach as an endocrine organ. FASEB J.
2004;18:439–456.
11. Pavlov IP. The centrifugal (efferent) nerves to the gastric
glands and the pancreas. In: Thompson WH, ed. The Work
of the Digestive Glands. Philadelphia, PA: Charles Griffin and
Co; 1910:48–59.

12. Mattes RD. Physiologic responses to sensory stimula- 27. Arvedson JC. Dysphagia in pediatric patients with neurologic
tion by food: nutritional implications. J Am Diet Assoc. damage. Semin Neurol. 1996;16(4):371–385.
1997;97(4):406–413. 28. Frazier JB, Friedman B. Swallow function in children with
13. McDonald RE, Avery DR, Dean JA. Dentistry for the Child and Down syndrome: A retrospective study. Dev Med Child Neurol.
Adolescent. 8th ed. St. Louis, MO: Mosby; 2004:176–178. 1996;38(8):695–703.
14. Kronfeld R, Schour I. Chronology of the human dentition. J 29. Mercado-Deane MG, Burton EM, Harlow SA, et al. Swal-
Am Dent Assoc. 1939;26:18–32. lowing dysfunction in infants less than 1 year of age. Pediatr
15. Kelly BN, Huckabee ML, Jones RD, Frampton CMA. The Radiol. 2001;31(6):423–428.
first year of human life: Coordinating respiration and nutri- 30. Gewolb IH, Bosma JF, Taciak VL, Vice FL. Abnormal devel-
tive swallowing. Dysphagia. 2007; 22(1):37–43. opmental patterns of suck and swallow rhythms during
16. Bosma JF. Development of feeding. Clin Nutr. 1986;5(5): feeding in preterm infants with bronchopulmonary dysplasia.
210–218. Dev Med Child Neurol. 2001;43(7):454–459.
17. Derkay SD, Schechter GL. Anatomy and physiology of 31. Arvedson J, Rogers B, Buck G, Smart P, Msall M. Silent aspi-
pediatric swallowing disorders. Otolaryngol Clin North Am. ration prominent in children with dysphagia. Inter J Pediatr
1998;31(3):397–404. Otorhinolaryngol. 1994;28(2–3):173–181.
18. Weber F, Wollridge MW, Baum JD. An ultrasonographic study 32. Briefel RR, Reidy K, Karwe V, Jankowski L, Hendricks
of the organisation of sucking and swallowing by newborn K. Toddlers’ transition to table foods: Impact on nutrient
infants. Dev Med Child Neurol. 1986;28(1)19–24. intakes and food patterns. J Am Diet Assoc. 2004;104(1)(Suppl
19. Tamura Y, Horikawa Y, Yoshida S. Co-ordination of tongue 1):S38–44.
movements and peri-oral muscle activities during nutritive 33. Gisel EG. Chewing cycles in 2- to 8-year-old normal children:
sucking. Dev Med Child Neurol. 1996;38(6):503–510. A developmental profile. Am J Occup Ther. 1988;41(1):40–46.
20. Wolff PH. The serial organization of sucking in the young 34. Wright CM, Parkinson KN, Shipton D, Drewett RF.
infant. Pediatrics. 1968;42(6):943–956. How do toddler eating problems relate to their eating
21. Qureshi MA, Vice FL, Taciak VL, Bosma JF, Gewolb IH. behavior, food preferences, and growth? Pediatrics.
Changes in rhythmic suckle feeding patterns in term infants 2007;120(4):e1069–e1075.
in the first month of life. Dev Med Child Neurol. 2002;44(1): 35. Gidding SS, Dennison BA, Birch LL, Daniels SR. Dietary
34–39. recommendations for children and adolescents: A guide for
22. McGowan JS, Marsh RR, Fowler SM, Levy SE, Stallings VA. practitioners. Pediatrics. 2006;17(2)544–559.
Developmental patterns of normal nutritive sucking in infants. 36. Satter E. How to Get Your Kid to Eat: But Not Too Much.
Dev Med Child Neurol. 1991;33(10):891–897. Boulder, CO: Bull Publishing Co; 1987.
23. Ayano R, Tamura F, Ohtsuka Y, Mukai Y. The development 37. Jana L, Shu J. Food Fights: Winning the Nutritional Challenges of
of normal feeding and swallowing: Showa University study of Parenthood Armed with Insight, Humor, and a Bottle of Ketchup.
the feeding function. Int J Orofacial Myology. 2000;26:24–32. Washington, DC: American Academy of Pediatrics; 2008.
24. Gesell A, Ilg FL. Feeding Behavior in Infants. A Pediatric 38. Dusick AM. Investigation and management of dysphagia.
Approach to the Mental Hygiene of Early Life. Philadelphia, PA: Semin Pediatr Neurol. 2003;10(4):255–264.
J.B. Lippincott Co; 1937. 39. Fraker C, Fishbein M, Cox S, Walbert L. Food Chaining: The
25. Gisel EG. Effect of food texture on the development of chewing Proven 6-Step Plan to Stop Picky Eating, Solve Feeding Prob-
of children between six months and two years of age. Dev Med lems, and Expand Your Child’s Diet. New York, NY: Marlowe
Child Neurol. 1991;33(1):69–79. & Co; 2007.
26. Sheppard JJ, Mysak ED. Ontogeny of infantile oral refluxes
and emerging chewing. Child Dev. 1984;55(3):831–843.

2
Gross Digestion Principles: Gastric
Grinding and Gastrointestinal Motility
Jane P. Balint, MD

Background . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11 1. Describe the normal response of the stomach to
Gastric Motility. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .12 nutrient intake.
2. Explain the different motor patterns of the small intes-
Small Bowel Motility . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12
tine in the fasting and fed states.
Effect of Intake on Motor Activity. . . . . . . . . . . . . . . . . . . . 13 3. Predict the response of the intestinal tract to different
Consistency
Nutrient Content types of nutrients.
Caloric Density 4. Develop management strategies for altered gastrointes-
Osmolarity tinal motility.
Altered Patterns of Motility and Potential Interventions . 13
Delayed Gastric Emptying Background
Dumping Gastrointestinal (GI) motility is necessary for the movement
Slow Intestinal Transit of nutrients from the stomach through the intestinal tract as
Rapid Intestinal Transit
well as for the breakdown and mixing of these nutrients with
digestive enzymes, which in turn allows for digestion and
absorption. An elementary understanding of these processes
is helpful in planning and managing nutrition support.
The motor activity of the GI tract is regulated by the
enteric nervous system (ENS), which consists of two nerve
plexuses. The myenteric plexus (Auerbach’s plexus) lies
between the outer longitudinal muscle layer and the inner
circular muscle layer. This plexus is key to the motility of the
GI tract, including regulation of the normal motor patterns
seen in the GI tract described below. The submucosal plexus
(Meissner’s plexus), found between the muscularis mucosa
and the circular muscle layer, affects absorption, secretion,
and blood flow. While the ENS can act independently, it
receives input from the parasympathetic nervous system
(primarily the vagus nerve), the sympathetic nervous
system, and sensory nerves in the intestine, as well as from
mast cells, paracrine signals, and endocrine signals. In addi-
tion, the ENS has multiple neurotransmitters for signaling,
including acetylcholine, norepinephrine, serotonin,
11
vasoactive intestinal peptide, nitric oxide, somatostatin, The preterm infant has an immature pattern of GI
and tachykinins.1–4 motility affecting both gastric emptying and small bowel
Integral to the functioning of the GI tract are the inter- motility, which impacts feeding. The normal electrical ac-
stitial cells of Cajal (ICC). There are two types: those around tivity of the stomach, with a slow wave frequency of 3 cycles
the myenteric plexus that generate and propagate electrical per minute, does not develop until 32 weeks gestation and
slow waves (pacemakers), and those between neural fibers does not become the dominant pattern until 35 weeks ges-
and smooth muscle cells providing communication between tation. This results in slower gastric emptying in these more
the two. The ICC help to coordinate peristaltic movement premature infants in comparison to the term infant.4,12,13
of the GI tract. 5,6 Slow waves have variable frequency in
different parts of the GI tract. In the stomach, the slow-wave Small Bowel Motility
rhythm is 3 cycles per minute. In the proximal small bowel Motor activity of the small intestine serves a number of
the rhythm is 11 to 12 cycles per minute, decreasing to 7 to important functions, including mixing chyme with intes-
9 cycles per minute in the distal ileum. Slow waves do not tinal secretions for further digestion, enhancing contact
generate contractions but dictate the frequency at which between enteric contents and the mucosa for absorption,
they can occur.4,7 moving ingested contents distally, and clearing the intes-
tinal tract by powerful contractions that propagate in an
Gastric Motility aboral direction.14
The gastric fundus, which is the uppermost portion of the In the fasting state, or interdigestive period, there are 3
stomach, acts as a reservoir for ingested food. It is in the phases of the migrating motor complex (MMC). Phase I is a
antrum and body of the stomach where food is ground into quiescent phase. In phase II there are intermittent, irregular
small particles prior to passage into the small intestine. With contractions. Phase III is characterized by strong, propa-
swallowing at the onset of a feeding or meal, vagally mediated gating contractions that begin almost simultaneously in the
relaxation of the fundus occurs. As food enters the stomach, stomach and duodenum and travel through the small bowel.
there is further relaxation of the proximal stomach to provide This phase III of the MMC provides the housekeeping func-
a reservoir for nutrients. This receptive relaxation/gastric tion of intestinal motility, sweeping material through the
accommodation allows for an initial increase in the volume small bowel. It occurs at irregular intervals, ranging from
of the stomach without an increase in pressure. However, 18 to 145 minutes with an average occurrence of every 80
ultimately the pressure will increase, leading to a tonic minutes, and lasts from 2 to 14 minutes.1,4,14–16
contraction that then pushes the gastric contents toward In the fed state, there is a combination of mixing and
the antrum. With this there is the start of regular phasic propulsion of intestinal contents. In general, there are
contractions at 3 cycles per minute that both mix and grind random bursts of activity, primarily resulting in mixing.
(triturate) the gastric contents. During the churning process, When a contraction occurs, intestinal contents move. If the
the food bolus is first pushed toward the antrum where some contraction in one region of the small intestine occurs in a
grinding takes place. Distention of the antrum results in coordinated manner with proximal and distal bowel, then
fundic relaxation and in turn retropulsion of contents back to the intestinal contents will be propelled downstream. If
the body of the stomach. Grinding is important for creating the contraction is not coordinated with activity of adjacent
small particles, less than 1 to 2 mm in size, that will pass into areas, then the intestinal contents moves both retrograde
the duodenum through the pylorus. Mixing with gastric and antegrade in the intestine, resulting in mixing. 3,15
acid and pepsin begins the chemical digestion of food. This As noted above, the premature infant has not developed
initial phase of mixing and grinding is the lag phase in gastric a normal pattern of intestinal motility. The fasting pattern of
emptying that occurs after ingestion of nutrients.1,4,8–11 premature infants is characterized by short bursts of activity
Once the ingested nutrients are appropriately mixed called clusters that do not progress aborally as a mature
and solid material is ground into small particles, antral phase III MMC does. The nature of these clusters is different
contractions accompanied by pyloric relaxation allow small depending upon the gestational age. The length of a cluster
aliquots of this chyme to empty into the duodenum. This increases with gestational age from less than 90 seconds
begins the second or linear gastric emptying phase. The time in the 27- to 28-week gestation infant to 5 to 6 minutes at
for gastric emptying is variable, and depends upon a variety 36 weeks gestation. At the same time the frequency with
of factors as discussed below, but is generally complete by 4 which the clusters occur decreases. The fed pattern also
hours.1,4,7,8,10,11 differs in the premature infant with most demonstrating

GROSS DIGESTION PRINCIPLES: GASTRIC GRINDING AND GASTROINTESTINAL MOTILITY 13
an abrupt cessation of intestinal contractions after a bolus Caloric Density

feeding. Not surprisingly, intestinal transit is slower in the Increased calorie content of the ingested food or liquid will
preterm infant. There is some evidence that feeding prema- result in slower emptying from the stomach.21,30 It has also
ture infants, even small amounts, can promote maturation been demonstrated that a higher calorie content meal will
of intestinal motility.12,17–19 result in a longer fed pattern in the small bowel leading to a
longer transit time through the small intestine. 31
Effect of Intake on Motor Activity
Gastric emptying can be affected by a variety of charac- Osmolarity
teristics of the ingested material as well as the rapidity of Finally, solutions that have a higher osmolarity will empty
transit through the GI tract. With this, the time for gastric more slowly from the stomach than those that are lower in
emptying can vary from 1 to 4 hours. The effect of nutrient osmolarity.27
composition on motor activity has been more clearly delin- While each of these factors individually can influence
eated for the stomach than the small bowel. gastric emptying in the older infant, child, and adult, the
same has not been found to be true in premature infants.
Consistency In one study of 25 to 30 weeks gestation infants, it was
Liquids will empty from the stomach more quickly than demonstrated that altering osmolality, caloric density, or
solids. In turn, clear liquids will empty more rapidly than the volume of the feeding separately did not change gastric
full liquids, with non-nutritive liquids emptying the fastest, emptying. However, when the volume of the feeding was
leaving the stomach in about 20 minutes.11,20 The viscosity increased in combination with decreasing the osmolality,
of the feeds will also affect the speed of gastric emptying, gastric emptying was more rapid. 32 Additionally, across age
with lower viscosity material emptying more rapidly. Thus groups in clinical practice, these factors can clearly overlap
both soluble and insoluble fibers mixed with the feedings as nutrient content is closely tied to caloric density. For
will slow emptying.21,22 In addition to delaying gastric example, a meal or formula higher in fat will likely be higher
emptying, soluble fibers can prolong transit through the GI in calories.
tract by prolonging the duration of the fed pattern of small
bowel motor activity.22 Altered Patterns of Motility
and Potential Interventions
Nutrient Content Disordered motility in any part of the GI tract can impact
The response to the type of nutrient ingested is complex. feeding tolerance.
There are both hormonal and neural responses to food that
regulate motor activity of the stomach and small intestine. Delayed Gastric Emptying
These are interrelated in that neural activity can affect As noted above, slower gastric emptying occurs in the prema-
the release of some GI hormones. Once chyme starts to ture infant and may impair feeding advancement. Premature
pass through the pylorus, there is feedback via vagal affer- infants who require tube feedings due to immature suck
ents from receptors in the duodenum that regulate gastric and swallow may benefit from a slower intermittent infu-
emptying. These receptors include those that detect fat, sion over as long as 2 hours, rather than a 15-minute bolus,
amino acids, glucose, pH, and osmolarity.23 A component as this slower infusion has been demonstrated to result both
of the response is mediated by release of gastrin, cholecys- in improved gastric emptying and a more mature duodenal
tokinin, pancreatic polypeptide, glucagon-like peptide 1, motor pattern. 33,34 In the older infant or child, delayed
and peptide YY.4,24,25 It has been demonstrated that carbo- emptying may occur during or following a viral illness,
hydrates will empty from the stomach before proteins, with associated with a significant systemic illness, as well as after
fats emptying the most slowly.4,26,27 Fats reaching the distal surgery, resulting in fullness, bloating, decreased appetite,
ileum inhibit both gastric emptying and small intestinal and emesis. 35 Management strategies depend on the degree
motility, a mechanism known as the ileal brake.28 Complex of the problem and how the child was being fed prior to the
carbohydrates that reach the distal small intestine can onset of the problem. If the child was eating a regular diet,
also stimulate the ileal brake.1 In addition to the actual smaller more frequent meals that are lower in fat, in fiber,
nutrient content, the pH will affect gastric emptying as well and in caloric density may empty better from the stomach. 36
with more acidic material emptying more slowly from the As liquids empty more readily than solids, increasing the
stomach.29 liquid content of the meal may help. If the child is unable to

tolerate any solids, a trial of liquid nutritional supplements bowel. There are some data to indicate that amoxicillin-
is warranted. If the child was tube fed prior to the onset of clavulonic acid may promote small bowel motility.42 In
the delayed gastric emptying, then adjusting the formula or more severe cases, octreotide may be beneficial. This soma-
the manner of delivery may be necessary. The osmolarity, tostatin analogue has a wide range of effects on the GI tract,
caloric content, fat content, and fiber content of the formula including induction of phase III MMC when given in small
should be evaluated and a determination made as to whether doses subcutaneously.43
a change is possible, as the higher each of these are, the
slower emptying will be even under normal circumstances. Rapid Intestinal Transit
Drip feedings, rather than bolus feedings, may need to be Rapid intestinal transit may occur following a systemic
considered. There are few pharmacologic options available illness or due to surgery on the GI tract. This can result in
currently. Erythromycin, which acts as a motilin receptor malabsorption of nutrients and diarrhea. Feeding strategies
agonist, can accelerate gastric emptying. 37 If the problem is will be discussed in detail in later chapters, including those
severe enough, continuous transpyloric or jejunal feedings on GI disease and intestinal failure. However, one approach
may be necessary, at least temporarily. that may be beneficial, regardless of the feeding selected
or route of delivery, is the addition of soluble fiber such
Dumping as pectin or guar gum to the feeding as these will prolong
Very rapid gastric emptying, or dumping, is relatively intestinal transit time.22,44 Various drugs can be used in an
uncommon in pediatrics. 35 It can occur as a result of surgery, effort to slow transit through the small bowel. Loperamide,
particularly involving the pylorus, or with damage to the a peripherally acting opioid analogue, inhibits both small
vagal nerve such as during a fundoplication or cardiac bowel and colonic motility. Anticholinergic agents, such as
surgery. Symptoms include nausea, abdominal distention, hyoscyamine, can also help to slow intestinal transit.
cramping, diarrhea, and vasomotor changes associated with While it is important to consider the impact of gastric
swings in glucose. Some management strategies are the oppo- and intestinal motility on feeding, this is only one of many
site of those suggested for use in delayed emptying. One can factors that must be taken into account as will be discussed
try to take advantage of normal physiology by increasing the in subsequent chapters.
fat and protein content of the diet and increasing the fiber
content of the diet, including the addition of pectin and guar Test Your Knowledge Questions
gum.36 Rather than mixing liquids with the meal, liquids 1. Gastric emptying can be slowed by all of the following
should be taken separately from solids. On the other hand, except:
some of the same strategies recommended for treatment of A. Soluble fibers
delayed gastric emptying may also be helpful in too rapid B. Fats
emptying, specifically smaller more frequent meals as well C. Liquids
as continuous drip or post-pyloric feedings. Pharmacologic D. Protein
therapeutic options are limited. Acarbose, an alpha-glucosi- 2. In the fed state, small bowel motor activity is charac-
dase inhibitor, has been used to treat dumping syndrome terized by:
as it delays the hydrolysis of carbohydrates with resultant A. A quiescent phase
delayed absorption of glucose38,39 Octreotide, an analogue of B. Random bursts of activity
somatostatin, can be beneficial as one of its specific actions is C. Intermittent, irregular contractions
to delay gastric emptying.40,41 D. Strong, propagating contractions
3. Which of the following is true for the premature
Slow Intestinal Transit infant?
Slow intestinal transit may occur following surgery (post- A. Bolus feeds will promote normal small bowel motor
operative ileus), following a viral illness or other systemic activity.
illness, as a side effect of many drugs, or as part of a signifi- B. Transit through the small bowel is shorter than in the
cant motility disorder, the most extreme being chronic older infant.
intestinal pseudoobstruction. There is no clear evidence or C. Gastric emptying is more rapid than in the older
consensus opinion upon which to make recommendations infant.
in terms of nutrition interventions that may be beneficial D. Feeding can promote the development of intestinal
in these circumstances. Currently, there are also a paucity motility.
of drugs available to help promote motility of the small See p. 487 for answers.

GROSS DIGESTION PRINCIPLES: GASTRIC GRINDING AND GASTROINTESTINAL MOTILITY 15
17. Berseth CL Effect of early feeding on maturation of the

References preterm infant’s small intestine. J Pediatr. 1992;120:947–953.
1. Camilleri M. Integrated upper gastrointestinal response to
18. Commare CE, Tappenden KA. Development of the infant
food intake. Gastroenterology. 2006;131:640–658.
intestine: implications for nutrition support. Nutr Clin Pract.
2. Costa M, Brookes SJH, Hennig GW. Anatomy and physi-
2007;22:159–173.
ology of the enteric nervous system. Gut. 2000;47(Suppl IV):
19. McClure RJ, Newell SJ. Randomised controlled trial of
iv15–iv19.
trophic feeding and gut motility. Arch Dis Child Fetal Neonatal
3. Leger G. Basic physiology of motility, absorption and secre-
Ed. 1999;80:F54–F58.
tion. In: Langnas AN, Goulet O, Quigley EMM, Tappenden
20. Collins PJ, Houghton LA, Read NW, et al. Role of the proximal
KA, eds. Intestinal Failure: Diagnosis, Management and Trans-
and distal stomach in a mixed solid and liquid meal emptying.
plantation. Malden, MA: Blackwell Publishing; 2008:20–32.
Gut. 1991;32:615–619.
4. Saps M, Di Lorenzo C. Gastric motility: normal motility and
21. Marciani L, Gowland PA, Spiller RC, et al. Effect of meal
development of the gastric neuroenteric system. In: Kleinman
viscosity and nutrients on satiety, intragastric dilution, and
RE, Sanderson IR, Goulet O, Sherman PM, Mieli-Vergani
emptying assessed by MRI. Am J Physiol Gastrointest Liver
G, Shneider BL, eds. Walker’s Pediatric Gastrointestinal
Physiol. 2001;280:G1227–G1233.
Disease. Vol 1. 5th ed. Hamilton, Ontario: BC Decker, Inc;
22. Schönfeld J, Evans DF, Wingate DL. Effect of viscous fiber
2008:187–193.
(guar) on postprandial motor activity in human small bowel.
5. Rolle U, Piaseczna-Piotrowska A, Puri P. Interstitial cells of
Dig Dis Sci. 1997;42:1613–1617.
Cajal in the normal gut and in intestinal motility disorders of
23. Schwartz GJ, Moran TH. Duodenal nutrient exposure elicits
childhood. Pediatr Surg Int. 2007;23:1139–1152.
nutrient-specific gut motility and vagal afferent signals
6. Sanders KM, Koh SD, Ward SM. Interstitial cells of Cajal as
in rat. Am J Physiol Regulatory Integrative Comp Physiol.
pacemakers in the gastrointestinal tract. Annu Rev Physiol.
1998;274:R1236–R1242.
2006;68:307–343.
24. MacIntosh CG, Andrews JM, Jones KL, et al. Effects of age
7. Altaf MA, Sood MR. The nervous system and gastrointestinal
on concentrations of plasma cholecystokinin, glucagon-like
function. Dev Disabil Res Rev. 2008;14:87–95.
peptide 1, and peptide YY and their relation to appetite and
8. Cuomo R, Sarnelli G. Food intake and gastrointestinal
pyloric motility. Am J Clin Nutr. 1999;69:999–1006.
motility. A complex interplay. Nutr Metab Cardiovasc Dis.
25. Feinle C, O’Donovan D, Doran S, et al. Effects of fat digestion
2004;14:173–179.
on appetite, APD motility, and gut hormones in response to
9. Hennig GW, Brookes SJH, Costa M. Excitatory and inhibitory
duodenal fat infusions in humans. Am J Physiol Gastrointest
motor reflexes in the isolated guinea-pig stomach. J Physiol.
Liver Physiol. 2003;284:G798–G807.
1997;501:197–212.
26. Houghton LA, Mangnall YF, Read NW. Effect of incorp
10. Lacy BE, Koch KL, Crowell MD. The stomach: normal func-
orating fat into a liquid test meal on the relation between
tion and clinical disorders. Manometry. In: Schuster MM,
intragastric distribution and gastric emptying in human
Crowell MD, Koch KL, eds. Schuster Atlas of Gastrointestinal
volunteers. Gut. 1990;31:1226–1229.
Motility in Health and Disease. 2nd ed. Hamilton, Ontario: BC
27. Paraskevopoulos JA, Houghton LA, Eyre-Brooke I, Johnson
Decker, Inc; 2002:135–150.
AG, and Read NW. Effect of composition of gastric contents
11. Siegel JA, Urbain J-L, Adler LP, et al. Biphasic nature of gastric
on resistance to emptying of liquids from stomach in humans.
emptying. Gut. 1988;29:85–89.
Dig Dis Sci. 1988;33:914–918.
12. Berseth CL. Assessment in intestinal motility as a guide
28. Ohtani N, Sasaki I, Naito H, Shibata C, Matsuno S. Mediators
in the feeding management of the newborn. Clin Perinatol.
for fat-induced ileal brake are different between stomach and
1999;26:1007–1015.
proximal small intestine in conscious dogs. J Gastrointest Surg.
13. Riezzo G, Indrio F, Montagna O, et al. Gastric electrical
2001;5:377–382.
activity and gastric emptying in term and preterm newborns.
29. Chaw CS, Yazaki E, Evans DF. The effect of pH change on the
Neurogastroenterol Motil. 2000;12:223–229.
gastric emptying of liquids measured by electrical impedance
14. Kellow JE. Small intestine: normal function and clinical
tomography and pH-sensitive radiotelemetry capsule. Int J
disorders. Manometry. In: Schuster MM, Crowell MD, Koch
Pharm. 2001;227:167–175.
KL, eds. Schuster Atlas of Gastrointestinal Motility in Health
30. Boulby P, Moore R, Gowland P, Spiller RC. Fat delays
and Disease. 2nd ed. Hamilton, Ontario: BC Decker, Inc;
emptying but increases forward and backward antral flow
2002:219–236.
as assessed by flow-sensitive magnetic resonance imaging.
15. Boccia G, Staiano A. Intestinal motility: normal motility
Neurogastroenterol Motil. 1999;11:27–36.
and development of the intestinal neuroenteric system. In:
31. Schönfeld J, Evans DF, Wingate DL. Daytime and night time
Kleinman RE, Sanderson IR, Goulet O, Sherman PM, Mieli-
motor activity of the small bowel after solid meals of different
Vergani G, Shneider BL, eds. Walker’s Pediatric Gastrointestinal
caloric value in humans. Gut. 1997;40:614–618.
Disease. Vol 1. 5th ed. Hamilton, Ontario: BC Decker, Inc;
32. Ramirez A, Wong WW, Shulman RJ. Factors regulating gastric
2008:665–674.
emptying in preterm infants. J Pediatr. 2006;149:475–479.
16. Scott SM, Knowles CH, Wang D, et al. The nocturnal jejunal
33. Baker JH, Berseth CL. Duodenal motor responses in preterm
migrating motor complex: defining normal ranges by study of
infants fed with formula with varying concentrations and
51 healthy adult volunteers and meta-analysis. Neurogastroen-
rates of infusion. Pediatr Res. 1997;42:618–622.
terol Motil. 2006;18:927–935.

34. De Ville K, Knapp E, Al-Tawil Y, Berseth CL. Slow infusion feed- 40. Lamers CB, Bijlstra AM, Harris AG. Octreotide, a
ings enhance duodenal motor responses and gastric emptying long-acting somatostatin analog, in the management of
in preterm infants. Am J Clin Nutr. 1998;68:103–108. post-operative dumping syndrome. An update. Dig Dis Sci.
35. Di Lorenzo C, Ciamarra P. Pediatric gastrointestinal motility. 1993;38:359–364.
In: Schuster MM, Crowell MD, Koch KL, eds. Schuster Atlas 41. Scarpignato C. The place of octreotide in the medical manage-
of Gastrointestinal Motility in Health and Disease. 2nd ed. ment of the dumping syndrome. Digestion. 1996;57(Suppl
Hamilton, Ontario: BC Decker, Inc; 2002:411–428. 1):114–118.
36. Karamanolis G, Tack J. Nutrition and motility disorders. Best 42. Caron F, Ducrotte P, Lerebours E, et al. Effects of amoxi-
Pract Res Clin Gastroenterol. 2006;20:485–505. cillin-clavulanate combination on the motility of the small
37. Karamanolis G, Tack J. Promotility medications — now and intestine in human beings. Antimicrob Agents Chemother.
in the future. Dig Dis. 2006;24:297–307. 1991;35:1085–1088.
38. Ng DD, Ferry RJ, Kelly A, et al. Acarbose treatment of 43. Di Lorenzo C, Lucanto C, Flores AF, Idries S, Hyman PE.
postprandial hypoglycemia in children after Nissen fundopli- Effect of octreotide on gastrointestinal motility in children
cation. J Pediatr. 2001;139:877–879. with functional gastrointestinal symptoms. J Pediatr Gastro-
39. Zung A, Zadik Z. Acarbose treatment of infant dumping enterol Nutr. 1998;27:508–512.
syndrome: extensive study of glucose dynamics and long-term 44. Finkel Y, Brown G, Smith HL, et al. The effects of a pectin-
follow-up. J Pediatr Endocrinol Metab. 2003;16:905–915. supplemented elemental diet in a boy with short bowel
syndrome. Acta Paediatr Scand. 1990;79:983–986.

3
Carbohydrates: Changes with Development
Seema Mehta, MD and Robert J. Shulman, MD
Contents Learning Objectives

Digestion. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17 1. Describe the structure and classification of carbo
Lactose hydrates.
Starch 2. Describe the process of carbohydrate digestion and
Absorption . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20 absorption.
Malabsorption . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20 3. Identify diseases related to carbohydrate malab
Metabolism. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20 sorption.
Digestion
Carbohydrates supply 50% of the body’s total energy
requirement. Dietary carbohydrates consist of sugars
and starches. Sugars include both monosaccharides (ie,
glucose, galactose, and fructose) and disaccharides (ie,
lactose, sucrose, maltose, and trehalose). Starches, also
known as storage carbohydrates, consist of large chains of
sugars linked together.1 Complex carbohydrate is another
term used for starch. It commonly refers to starch used in
formulas (ie, corn syrup solids, glucose polymers) and is a
smaller carbohydrate molecule than those found in other
food starches (ie, potato, corn). Small-chain starches,
generally 3 to 10 glucose units in length, are referred to as
oligosaccharides whereas long-chain starches are referred
to as polysaccharides.
Lactose
Lactose is the primary carbohydrate present in human
milk and most infant formulas.2 Lactose is hydrolyzed by
the enzyme lactase into the monosaccharides glucose and
galactose (Figure 3-1).
17
Figure 3-1 Digestion of Carbohydrates Figure 3-2 Age at Full Feedings versus Lactase Activity
Overall schema of complex carbohydrate digestion.5 There is a negative relationship between the time full enteral feedings are
achieved and lactase activity.2
Reprinted from Shulman RJ. Intraluminal digestion and absorption in

the small intestine. In: Gluckman PD, Heymann MA. Pediatrics and
Perinatology: The Scientific Basis. 2nd ed. New York, NY: Oxford University
Press; 1996. Reproduced by permission of Edward Arnold (Publishers) Ltd. Reprinted from Shulman RJ, Schanler RJ, Lau C, Heitkemper M, Ou CN,
Smith EO. Early feeding, feeding tolerance, and lactase activity in preterm
infants. J Pediatr. 1998;133(5):645-649 with permission from Elsevier.
Lactase, the sole enzyme responsible for the hydrolysis of
lactose, is located along the brush border of the enterocytes
lining the villi of the small intestine. The optimum pH for Figure 3-3 Lactase Development with Age and Type of Feeding
lactase activity is 6.0. Activity peaks in the jejunum and Lactase activity increases with age but the increase is greater in the early
fed group when compared with the standard group (p < 0.01).2 Lactase
progressively decreases toward the ileum. This gradient activity in the early fed group is greater than that in the standard group at
is established by 11 weeks gestation. Antenatally, lactase 10 and 28 days of age (p = 0.004) but not at 50 days of age (p > 0.5).2
activity increases until term with the greatest increase
occurring during the third trimester. At the beginning of
the third trimester, lactase activity is approximately 25%
of that at term. 3,4 Early in fetal life, some lactase activity is
demonstrable in the colon, but by 28 weeks gestation it is
undetectable. 5
In preterm infants, it has been suggested that incom-
plete digestion of lactose may be linked to the pathogenesis
of necrotizing enterocolitis (NEC), thereby resulting in
a reluctance to feed preterm infants lactose.6 The time to
reach full enteral feedings was found to be inversely related
to lactase activity (Figure 3-2).2 Offsetting the apprehension
for complications related to early feedings are the potential
benefits. It has been demonstrated that early enteral feed-
ings in preterm infants promote the development of lactase
activity (Figure 3-3). Infants fed human milk were found to
have greater lactase activity than those fed formula. Reprinted from Shulman RJ, Schanler RJ, Lau C, Heitkemper M, Ou CN,
Smith EO. Early feeding, feeding tolerance, and lactase activity in preterm
infants. J Pediatr. 1998;133(5):645-649 with permission from Elsevier.
In many individuals, lactase activity begins to decline

with advancing age. This genetically predetermined
process, also known as primary lactase deficiency or

CARBOHYDRATES: CHANGES WITH DEVELOPMENT 19
primary hypolactasia, starts between 3 to 5 years of age and Figure 3-4: Development Profile of Pancreatic and Salivary Amylase
continues into adulthood.4 The prevalence of hypolactasia There is little pancreatic amylase activity prior to birth but salivary amylase
demonstrates some activity prior to 40 weeks gestation.20
varies amongst individuals of different ethnic backgrounds
ranging from 90% amongst Asians, 80% for African-
Americans, followed by 53% for Hispanics, and 15% to
25% for non-Hispanic whites.7 In contrast to the adult-type
hypolactasia, congenital lactase deficiency, also a primary
lactase deficiency, is an extremely rare autosomal reces-
sive disorder associated with a complete absence of lactase
expression.8 Symptoms in these patients manifest at birth
with the introduction of a lactose-containing diet.
Secondary lactase deficiency results as a consequence
of mucosal injury to the small intestine. It occurs most
commonly in infants with an infectious gastroenteritis and Reprinted from McClean P, Weaver LT. Ontogeny of human pancreatic
generally resolves with the resolution of the illness.8 Many exocrine function. Arch Dis Child. 1993;68:62-65, with permission from
otherwise healthy infants may demonstrate no signs or BMJ Publishing Group Ltd.
symptoms of lactose intolerance during the course of their
illness.9 Other infants with either a poor nutrition status or Further digestion of the disaccharides and oligosaccha-
more prolonged illness may show clinical signs of lactose rides occurs at the level of enterocytes. Glucoamylase, like
intolerance and benefit from a lactose-free formula until lactase, is located in the brush border of the small intestine.
their symptoms resolve.10 It cleaves α-1,4 bonds of primarily non-branching glucose
polymers (ie, amylose) and non-reducing ends of polysac-
Starch charides (Figure 3-1). Short chains (ie, < 10 glucose units)
Formula-fed infants are exposed to a variety of other carbo- are more easily digested by glucoamylase than longer-chain
hydrates in infancy including starches. The simplest form units.14
of starch is amylose, a linear polymer of glucose molecules Glucoamylase activity is detectable by 20 weeks gesta-
linked by α-1,4 glycosidic bonds. Amylopectin, a plant tion. At the beginning of the third trimester, the activity
starch, is the major form of carbohydrate in the diet. Struc- level is about half that at 36 to 38 weeks gestation. 5 In addi-
turally it is similar to amylose, but for every 20 to 30 glucose tion, it is also present in low levels in the colon only early
units there are α-1,6 branch points.11 in fetal life. 5 Therefore, in newborn infants, glucoamylase
Digestion of starch begins with intraluminal digestion is the primary enzyme for complex carbohydrate digestion
by salivary and then pancreatic amylases. Amylase hydro- since pancreatic amylase activity is low. Young infants and
lyzes starch at the internal α-1,4 bonds (Figure 3-1). It is not older children have similar glucoamylase activity levels
active against those bonds located next to the α-1,6 bonds or which are approximately half those in adults.15
those at the reducing end of the starch molecule. Amylase Sucrase-isomaltase is a disaccharidase also found in the
cleaves amylose and amylopectin into maltotriose, maltose, brush border of the small intestine. At 20 weeks gestation,
and α-limit dextrans (Figure 3-1).12 sucrase-isomaltase activity is almost half to three-quar-
Salivary amylase, secreted by the salivary glands, is ters that of term newborns and adults. 5 Similar to lactase,
present in preterm infants. Amylase activity increases with sucrase-isomaltase activity is highest in the proximal small
gestational age, rising rapidly after birth and approaching intestine. Activity remains high over the course of an indi-
adult values by 6 months to 1 year of age. Salivary amylase vidual’s life. Sucrase-isomaltase is cleaved into sucrase and
is inactivated at pH < 4.5 In newborns, however, salivary isomaltase by pancreatic proteases. 5 Sucrase hydrolyzes
amylase tends to remain active because they have poorly sucrose into the monosaccharides glucose and fructose
acidified stomachs.13 Pancreatic amylase, secreted by the (Figure 3-1). Isomaltase cleaves the α-1,6 glycosidic bonds
pancreas, is present at low levels in preterm and full-term of amylopectin (Figure 3-1). 5 A genetic deficiency of
infants. Activity begins to increase at 4 to 6 months of age and sucrase-isomaltase known as congenital sucrase-isomaltase
reaches adult values by 1 to 2 years of age (Figure 3-4).2 deficiency is an autosomal recessive disorder. All patients
with this deficiency lack sucrase and have varying degrees
of isomaltase activity.16

Absorption breath test. Stool pH of < 5.5 is indicative of short-chain

Dietary carbohydrates are absorbed in the form of the mono- fatty acids in the stool, whereas stool-reducing substances
saccharides glucose, galactose, and fructose. Active transport present in the stool denote the presence (ie, malabsorption)
of glucose and galactose is present by 10 weeks gestation. 5 of sugars, usually glucose. A positive breath hydrogen test
The absorption rate of glucose increases through gestation reflects the passage of carbohydrate into the colon and its
and continues to increase postnatally into adulthood. Galac- fermentation but interpretation depends on the carbo-
tose absorption rate reaches adult values between 4 to 8 years hydrate. A significant rise in breath hydrogen would be
of age.8 expected after ingestion of a starch such as corn but not
Access into enterocytes occurs via carrier molecules. after sucrose. Disorders of carbohydrate absorption can
Glucose and galactose are actively transported via the be congenital or acquired (Table 3-1).12,19 Treatment varies
sodium-glucose linked transporter (SGLT1) located at the because it is dependent on the clinical entity causing carbo-
brush border. Glucose and galactose entry is coupled to the hydrate malabsorption. Treatment options include special
entry of sodium along its electrochemical gradient. This diets and formulas (eg, gluten-free diet for patients with
electrochemical gradient is maintained via the sodium-potas- celiac disease) and enzyme supplements (eg, pancreatic
sium-adenosine triphosphatase (Na+-K+ ATPase) located enzymes for patients with cystic fibrosis).12,19
at the basolateral surface. SGLT1 has binding sites for both
glucose and sodium. Two sodium molecules are absorbed Table 3-1 Disorders Associated with Carbohydrate Malabsorption
for every glucose molecule. Once both sites are occupied, the Sucrase-isomaltase deficiency
transporter translocates across the brush border membrane Glucose-galactose malabsorption
and releases the glucose and sodium into the enterocyte.11 Congenital lactase deficiency
The sodium-linked transport of glucose provides the basis Congenital trehalase deficiency
for adding glucose or starches to oral rehydration solutions. Fructose malabsorption
Passive absorption of glucose also can occur across the brush Adult-type hypolactasia
Cystic fibrosis
border.8
Shwachman-Diamond syndrome
Fructose transport across the brush border membrane
Congenital microvillus atrophy
occurs passively down its concentration gradient. The
Tufting enteropathy
fructose transporter, GLUT5, is not sodium dependent. Autoimmune enteropathy
Transport of glucose, galactose, and fructose across the Celiac disease
basolateral membrane also occurs by facilitated transport Postviral enteritis
via the sodium-independent transporter, GLUT2.11 Recently Postradiation enteritis
GLUT2 has been recognized in the brush border membrane,
and glucose transported by SGLT1 promotes the activation
of GLUT2 already in the apical membrane and rapid inser- Metabolism
tion of GLUT2 from vesicles.17 This observation explains the Glucose is the most abundant carbohydrate in humans.
enhancement of fructose absorption in the proximal intestine Dietary carbohydrates are converted into glucose and then
in the presence of equimolar amounts of glucose.17 metabolized for energy. Starting soon after birth, gluco-
neogenesis contributes 30% to 70% of the body’s glucose.
Malabsorption Glucose that is not immediately utilized is stored in the
Incomplete digestion and absorption of carbohydrates can form of glycogen (ie, a storage carbohydrate).1 Insulin is the
occur in the small intestine. The remaining mono- , di- , hormone responsible for glycogenesis (glycogen synthesis),
and oligosaccharides create an osmotic gradient that drives while glucagon is the hormone responsible for glycogenol-
water into the lumen. Upon reaching the colon, these carbo- ysis (glycogen degradation).
hydrates are fermented by colonic bacteria to short-chain
fatty acids which then are absorbed by the colon.18 If the Test Your Knowledge Questions
rate of malabsorption of carbohydrates exceeds their ability 1. Which one of the following is a polysaccharide?
to be fermented and absorbed as short-chain fatty acids, A. Lactose
osmotic diarrhea can result. B. Sucrose
Carbohydrate malabsorption can be detected by testing C. Maltose
stool pH, stool-reducing substances, and/or a hydrogen D. Amylose

CARBOHYDRATES: CHANGES WITH DEVELOPMENT 21
2. Lactose is hydrolyzed by the enzyme lactase into the 6. Kliegman RM. Neonatal necrotizing enterocolitis:
monosaccharides and . Bridging the basic science with the clinical disease. J Pediatr.
1990;117:833–835.
A. Glucose; glucose
7. Sahi T. Genetics and epidemiology of adult-type hypolactasia.
B. Galactose; glucose Scand J Gastroenterol. 1994;202(suppl):7–20.
C. Glucose; fructose 8. American Academy of Pediatrics, Committee on Nutrition.
D. Galactose; fructose Infant nutrition and the development of gastrointestinal func-
3. Which enzyme is present in the lowest amount in tion. In: Kleinman RE, ed. Pediatric Nutrition Handbook. 5th
preterm infants compared with term infants? ed. Elk Grove Village, IL: American Academy of Pediatrics;
2004:4–7.
A. Glucoamylase 9. Brown KH, Peerson JM, Fontaine O. Use of nonhuman
B. Lactase milks in the dietary management of young children with
C. Sucrase acute diarrhea: a meta-analysis of clinical trials. Pediatrics.
D. Salivary amylase 1994;93:17–27.
4. Which ethnic group has the lowest prevalence of 10. Caballero B, Solomons NW. Lactose-reduced formulas
for the treatment of persistent diarrhea. Pediatrics.
primary hypolactasia?
1990;86:645–646.
A. Asians 11. Johnson LR. Digestion and absorption. In: Johnson LR, ed.
B. African-Americans Gastrointestinal Physiology. 6th ed. St. Louis, MO: Mosby;
C. Hispanics 2001:122–127.
D. Non-Hispanic whites 12. Schmitz J. Maldigestion and malabsorption. In: Walker AW,
et al., eds. Pediatric Gastrointestinal Diseases. 4th ed. Hamilton,
Ontario: BC Decker Inc; 2004:8–20.
See p. 487 for answers. 13. Hodge C, Lebenthal E, Lee PC, Topper W. Amylase in the
saliva and in the gastric aspirates of premature infants: Its
References potential role in glucose polymer hydrolysis. Pediatr Res.
1. American Academy of Pediatrics, Committee on Nutrition. 1983;12:998–1001.
Carbohydrate and dietary fiber. In: Kleinman RE, ed. Pediatric 14. Shulman RJ, Kerzner B, Sloan HR, et al. Absorption and
Nutrition Handbook. 5th ed. Elk Grove Village, IL: American oxidation of glucose polymers of different lengths in young
Academy of Pediatrics; 2004:247–253. infants. Pediatr Res. 1986;20(8):740–743.
2. Shulman RJ, Schanler RJ, Lau C, Heitkemper M, Ou CN, 15. Lebenthal E, Lee PC. Glucoamylase and disaccharidase activ-
Smith EO. Early feeding, feeding tolerance, and lactase ities in normal subjects and in patients with mucosal injury of
activity in preterm infants. J Pediatr. 1998;133(5):645–649. the small intestine. J Pediatr. 1980;97:389–393.
3. Antonowicz I, Chang SK, Grand RJ. Development and distri- 16. Savilahti E, Launiala K, Kuitunen P. Congenital lactase
bution of lysosomal enzymes and disaccharidases in human deficiency: A clinical study on 16 patients. Arch Dis Child.
fetal intestine. Gastroenterology. 1974;67:51–58. 1983;58:246–252.
4. Raul F, Lacroix B, Aprahamian M. Longitudinal distri- 17. Kellett GL, Brot-Laroche E. Apical GLUT2: A major pathway
bution of brush border hydrolases and morphological of intestinal sugar absorption. Diabetes. 2005;54:3056–3062.
maturation in the intestine of the preterm infant. Early Hum 18. Cummings JH, Macfarlane GT. Colonic microflora: Nutrition
Dev. 1986;13:225–234. and health. Nutrition. 1997;13:476–478.
5. Shulman RJ. Intraluminal digestion and absorption in the 19. Montalto M, Santoro L, D’Onofrio F, et al. Classification of
small intestine. In: Gluckman PD, Heymann MA. Pediatrics malabsorption syndromes. Dig Dis. 2008;26(2):104–111.
and Perinatology: The Scientific Basis. 2nd ed. New York, NY: 20. McClean P, Weaver LT. Ontogeny of human pancreatic
Oxford University Press; 1996:630–637. exocrine function. Arch Dis Child. 1993;68:62–65.

4
Fats
Peggy R. Borum, PhD

Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 22 1. List the different types of fatty acids.
Different Types of Fat 2. Contrast the different fatty acid oxidation pathways.
Essential Fatty Acids 3. Relate different pathological conditions to altered fat
Different Functions of Adipose Tissue metabolism.
Importance of Dietary Fat in Infants
Digestion. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25 Introduction
Absorption . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 26 Lipids are one of three macronutrients in the diet, the other
Metabolism During Normal Physiology. . . . . . . . . . . . . . . . 26 two being carbohydrates and protein. Triglycerides (lipids
Synthesis of Fatty Acids containing 3 fatty acids) are one of the main storage forms
Beta-Oxidation of Long-Chain Fatty Acids in Mitochondria of metabolic energy in the body. Since fatty acids are highly
Beta-Oxidation of Medium-Chain Fatty Acids in Mitochondria
Steps of Beta-Oxidation
reduced hydrocarbons, they are calorically dense, providing
Beta-Oxidation of Very Long-Chain Fatty Acids in Peroxisomes more metabolic energy per gram than the other dietary
Omega-Oxidation of Fatty Acids macronutrients. This characteristic is advantageous when a
Metabolism During Pathophysiologies. . . . . . . . . . . . . . . . 27 patient has a limited stomach capacity or is fluid-restricted
Fat As Fuel for Preterm Infants and yet needs additional calories for rapid growth or due to
Lipid Emulsions Containing Fish Oils critical illness. Fat is often viewed negatively by the public
As Fuel for Parenteral Nutrition In Pediatrics as a nutrient that should be reduced in the diet. However
To Esterify or To Oxidize: That Is the Cell’s Question
the problem may not be excess fat, but rather excess calories.
Once the diet provides appropriate calories, careful atten-
tion should be given to the types of fatty acids included in
the diet.
Different Types of Fat

Fats are extraordinarily diverse in structure but they have in
common poor solubility in water. Triglycerides are the major
dietary form of lipid and, as noted above, consist of 3 fatty
acids joined by a glycerol backbone. Typical fatty acids are
carboxylic acids with hydrocarbon chains ranging from 4 to
24 carbons (Figure 4-1). The chains are often unbranched,
but can contain a variety of substituents including rings,
hydroxyl groups, and methyl groups. The chain can be
saturated (no double bonds), monounsaturated (1 double
22
FATS 23
bond), or polyunsaturated (2 or more double bonds).1 As concentration of polyunsaturated fatty acids (PUFAs)
diagrammed in Figure 4-2, fatty acids can be classified in the membrane increases membrane susceptibility to
according to degree of chain saturation as well as chain oxidation and peroxidation. Because vitamin E is a major
length. Although there is no consensus definition for the antioxidant in the membrane, an increase in dietary PUFAs
general terms of short chain (2–6 carbons), medium chain should always be accompanied by a careful evaluation of
(8–12 carbons), and long chain (14 carbons or more), the adequate vitamin E intake. Since the fatty acid composition
chain lengths of the fatty acids will contribute to both the of the membrane reflects the fatty acid composition of the
physical characteristics of the food and the metabolism of diet, careful attention to the type of fatty acid in the diet is
the fat once it enters the body via ingestion, tube feeding, warranted.2 Optimizing the dietary fatty acid profile can
or parenteral nutrition. The shorter the chain and the more alter membrane structure which in turn can possibly alter
unsaturated the chain, the lower the melting point of fat cell signaling associated with clinical symptomatology.
with the result that the fat is more likely to be liquid at room
temperature. Thus, an animal product with a significant Figure 4-2 Classification of Fatty Acids
amount of stearic acid (18 carbons, no double bonds) (Figure
4-1) is solid at room temperature, whereas a medium-chain
triglyceride oil (8–12 carbons) with a significant amount of
saturated fatty acids is liquid at room temperature. Olive oil,
with a higher percentage of monounsaturated oleic acid (18
carbons, 1 double bond), is a liquid at room temperature.1
Figure 4-1 Structural Representation of a Saturated Fatty Acid
Membrane fluidity is important in the function of many

cell types and is greatly influenced by the degree of satura-
tion of the fatty acids in the membrane phospholipids.1 A
three-dimensional view of saturated fatty acids reveals that
the hydrocarbon chains are straight and thus can be packed
very tightly in membrane phospholipids. Most physiological Essential Fatty Acids
unsaturated fatty acids have cis double bonds (ie, the chains There are two different methods to number the carbons
on the same side of the double bond). Every cis double bond of a fatty acid. The chemist usually begins the numbering
puts a “kink” into the hydrocarbon chain. The result is that with the carboxylic acid carbon. In the field of nutrition,
the trans-fatty acid (where chains are on the opposite side the numbering usually begins with the methyl carbon
of the double bond) is a straight hydrocarbon and can be or omega carbon (ω) which is at the opposite end of the
packed very tightly in membranes, reducing membrane molecule from the carboxylic acid (Figure 4-1). Using the
fluidity. Phospholipids containing unsaturated fatty acids ω system of numbering, an omega-3 (ω-3) fatty acid has its
cannot be packed as tightly, resulting in a membrane with first double bond between C3 and C4 from the ω carbon, an
increased fluidity. omega-6 (ω-6) fatty acid has its first double bond between
In the food industry, trans-fatty acids are made from C6 and C7 from the ω carbon, and an omega-9 (ω-9) fatty
unsaturated fatty acids to both change the consistency of the acid has its first double bond between C9 and C10 from
fat product to a less liquid-like product at room temperature the ω carbon. Humans cannot synthesize ω-3 or ω-6 fatty
and to increase shelf life by reducing the double bonds that acids, but many physiological processes are dependent on
make the fat product susceptible to rancidity. An increased these fatty acids and their myriad products. Therefore ω-3

24
and ω-6 fatty acids are required in the human diet and are excreted. Diets with excess calories are frequently high in
termed essential fatty acids (EFAs).1 The simplest ω-6 fatty fat because dietary fat is highly palatable and calorically
acid is linoleic acid (LA). Humans can convert LA to arachi- dense. Excess dietary energy from any of the macronutri-
donic acid (ARA). The simplest ω-3 fatty acid is α-linolenic ents is converted to fatty acids and stored as triglycerides in
acid (α-LA). Humans can convert α-LA to eicosapentaeonic adipocytes. Therefore, surplus dietary calories will increase
acid (EPA), and EPA very slowly to docosahexaenoic acid adipose depots.
(DHA). The same enzyme pool is used to metabolize LA and
α-LA to their respective longer-chain metabolites. The more Figure 4-3 The Different Functions of Fat
prevalent fatty acid is metabolized preferentially. Thus a diet
high in the ω-6 fatty acid LA will preferentially metabolize
it over the ω-3 fatty acid α-LA. ARA (20-carbon polyun-
saturated ω-6) and EPA (20-carbon polyunsaturated ω-3)
are released from membranes and further metabolized to a
cascade of eicosanoids. Although it is not quite that simple,
eicosanoids from ω-6 fatty acids generally are considered
pro-inflammatory and those from ω-3 fatty acids are consid-
ered weakly anti-inflammatory. The docosanoid products
of DHA also have anti-inflammatory actions. 3 Fatty acids
and eicosanoids can change the abundance of transcription
factors which in turn regulate gene expression. Thus, the
fatty acid composition of the diet influences the composi-
tion of the cell membranes which influences the availability
of appropriate substrate to make either pro- or anti-inflam-
matory fatty acid products. Traditionally low intake of ω-3
and ω-6 fatty acids associated with an increase in an ω-9
fatty acid known as Mead acid in plasma has been used
to diagnose EFA deficiency. A more recent method uses
red blood cells and measures two additional parameters.4
The emerging field of investigation known as lipidomics
measures all small molecular weight lipids in a sample and Adipose tissue is not simply a place for the body to store
will likely provide the nutrition community with improved fat. Adipose tissue is a complex organ with many different
methods for specific EFA evaluation. cell types containing receptors sensitive to inflammatory
With the industrialization of Western society, dietary signals. Thus, changing the size of adipose tissue has far-
intake of EFAs has changed, reflecting the trend away from reaching effects. When stimulated, adipose tissue releases
grains to more processed foods high in fat. Intake of LA more than 20 diverse molecules known as adipokines that
relative to α-LA has increased significantly. Currently the have a wide range of metabolic effects both during health
ratio of LA to α-LA in the diet is 14:1 in contrast to the 2:1 and disease. Fat deposits can be found in subcutaneous,
or 1:1 ratio that is usually recommended.2 Interestingly, intramuscular, and intrathoracic depots that differ in fatty
the change in dietary fat intake follows a similar temporal acid composition, adipokine secretion, and storage capacity.
pattern to the increase in inflammatory bowel disease inci- Macrophage content of adipose tissue can increase from
dence in the pediatric population. 5 the usual 5% to 10% to as much as 60% during obesity and
secrete an increasing amount of inflammatory cytokines.
Different Functions of Adipose Tissue Taken together, obesity can have a striking effect not only
Storage of a metabolic fuel source and structural elements on the size but also on the metabolism of the body.2
of membranes are the most generally recognized func-
tions of fats. However, a long list of other functions for fat Importance of Dietary Fat in Infants
is now recognized (Figure 4-3). Adipose tissue maintains The percent of total body weight that is adipose tissue
a balance between clearance of plasma triglycerides and dramatically increases during human gestation. Fetal white
release of fatty acids. Excess dietary energy cannot be adipose tissue increases at a rate of about 67 mg/d during

FATS 25
the last trimester, and most of that is DHA. The brain also hydrolyze triglycerides to diglycerides and free fatty acids.
grows rapidly during the last trimester and requires a large After activation by colipase, pancreatic lipase hydrolyzes
amount of DHA for the synthesis of myelin. At birth, the dietary fat to 2-monoglycerides which are poor substrates
brain of the human is at about 50% of its adult size and for continued hydrolysis.16 Gastric lipolysis is incomplete in
continues to grow rapidly until it reaches near adult size adults, being responsible for 30% or less of dietary fat lipol-
at about 2 years of age. Thus, the extremely preterm infant ysis.17 Since neonates have limited expression of pancreatic
born at 24 or 25 weeks gestation requires a large amount of enzymes needed for fat digestion in the intestine, it has
EFAs, and ω-3 fatty acids in particular, to achieve the type been assumed that gastric lipolysis has a more important
of growth usually experienced by a fetus in utero during the role in neonates.18 Supplementation of infant formula with
same period postconception.6,7 medium-chain triglycerides (MCTs) has been reported to
Regulation of gene expression by nutrients is critically have conflicting effects on intragastric lipolysis in infants
important in preterm neonates. Regulation of gene expres- (no effect versus decreased lipolysis).19 This may be related
sion by ω-3 fatty acids involves multiple complex processes to differences in the MCT concentration of the formula
including regulation of the transcription factors sterol regu- studied.20
latory element-binding proteins (SREBPs) and peroxisome The pH increases as the acidic stomach contents move
proliferator-activated receptors (PPARs) that modulate to the intestine. The free fatty acid products of gastric
many critical steps in metabolism.8,9 lipase are ionized and become oriented to the outside of
The two most abundant long-chain PUFAs in the brain the oil droplets, surrounding the oil droplet with charge
are DHA and ARA. DHA is concentrated in the prefrontal and stabilizing the emulsion. Some of the free fatty acids
cortex and in some retinal cells.10 Inadequate intake of ω-3 dissociate from the droplet and interact with the intestinal
fatty acids not only results in decreased brain DHA but also epithelium. These fatty acids are potent stimuli of chole-
increased brain ω-6 fatty acid concentration.11,12 Worldwide cystokinin (CCK) release. CCK stimulates an increase in
there are a variety of enteral products that vary in their pancreatic enzymes, relaxes the sphincter of Oddi which
supply of ω-3 fatty acids and in DHA in particular. However allows the pancreatic juice to flow into the intestinal lumen,
none of them provide the amount of EFAs that would accu- and contracts the gallbladder to provide a bolus of concen-
mulate in the fetal brain during the last trimester of gestation trated bile needed to form micelles.17 Secreted bile contains
without additional supplementation. Thus, the current diet bile salts made in the liver that emulsify the products of lipid
provided to these infants appears to be deficient in DHA. digestion. The resulting micelles transport the digested fat
Although it is not known how these infants would develop products through the aqueous intestinal lumen making
if fed to sufficiency, preterm infants fed increased amounts close contact with the brush border of the mucosal cells.
of DHA have been reported to have improved visual acuity Bile salts continue to the ileum where they are absorbed
and mental development.13,14 A recent multicenter prospec- into the enterohepatic circulation.16
tive, randomized, double-blind placebo-controlled trial Phospholipase A 2 from the pancreas cleaves the fatty
in Italy compared 580 healthy term neonates receiving acid in the 2 position of dietary phospholipids. Pancreatic
20 mg of liquid DHA to 580 healthy term infants receiving juice also contains cholesterol esterase that hydrolyzes
placebo with a focus on developmental milestones. The cholesterol esters, esters of vitamins A, D, and E, and all
infants receiving DHA were able to sit without support 3 fatty acids in triglycerides.17 Cystic fibrosis (CF) affects
1 week earlier, but there was no difference between groups many aspects of metabolism, including adequate secretion
for hands-and-knees crawling, standing alone, and walking of pancreatic enzymes for dietary fat absorption. Adminis-
alone.15 It is unclear how these data from healthy term tration of pancreatic enzyme supplements can assist with
neonates relate to preterm neonates. In infants being fed the problem. Careful monitoring is required to assure that
parenterally, the challenge to provide adequate DHA and children with CF do not develop EFA deficiency or defi-
ARA is even greater with currently available lipid emulsions ciency in fat-soluble vitamins. Breast milk lipase produced
approved for use in this population. by the mammary gland of lactating females is similar to
cholesterol esterase. Breast milk lipase also has broad speci-
Digestion ficity and may “predigest” the lipid components of breast
Because dietary lipids are hydrophobic, they must be hydro- milk and thus increase the efficiency of their uptake.17,19
lyzed and emulsified to very small micelles before they can
be absorbed by the intestine. Lingual and gastric lipases

Absorption EPA, and DHA.22,23 The optimal ratio of preformed EPA

Bile acids play an important role in solubilizing the prod- and DHA has not been established, but ratios of 1:2 to 2:1
ucts of lumenal lipolysis and facilitating their transfer to are expected to be effective.24
the absorptive epithelium. Fatty acids and monoglycerides
have enough solubility in the lumenal contents that they Beta-Oxidation of Long-Chain Fatty Acids
can diffuse to the brush border and be absorbed.16 in Mitochondria
The intestinal epithelium is the site of significant Lipoprotein lipase in the capillary endothelium releases free
metabolic activities. The absorbed 2-monoglycerides are fatty acids delivered to tissues by chylomicrons. Hormone-
re-acylated to triglycerides. Some 1-monoglycerides in the sensitive lipase mobilizes triglycerides from adipose tissue
emulsion are absorbed and hydrolyzed to fatty acids and when needed. The fatty acids are carried in the blood bound
glycerol. The glycerol released within the intestinal epithe- to albumin and delivered to the tissues to use for fuel. When
lium is reutilized for triglyceride synthesis. Long-chain fatty fatty acids are to be used for fuel, they are activated to the
acids (LCFAs) are esterified to triglycerides, secreted into fatty acyl-CoA at the outer mitochondrial membrane. Fatty
the lymphatics as chylomicrons, and enter the blood via the acyl-CoA is the correct high-energy state for beta-oxidation
thoracic duct. Free short- and medium-chain fatty acids are (β-oxidation), but the enzymes for β-oxidation are located
absorbed into the hepatic portal vein.16 within the mitochondrial matrix (Figure 4-4) and the fatty
acyl-CoA cannot cross the inner membrane of the mito-
Metabolism During Normal Physiology chondria to reach these enzymes. In order to use LCFAs for
Dietary fat can enter a diverse set of metabolic pathways metabolic energy, fatty acyl-CoA is converted to fatty acyl-
intricately controlled and coordinated to meet the needs of carnitine via carnitine palmitoyltransferase 1, transported
the body. The cell can either oxidize fatty acids for imme- across the inner mitochondrial membrane via carnitine-
diate metabolic energy or synthesize fatty acids from other acylcarnitine translocase in exchange for free carnitine,
dietary components and store them for later use. and reconverted to fatty acyl-CoA in the matrix of the
mitochondria via carnitine palmitoyltransferase 2. The end
Synthesis of Fatty Acids result is that the high-energy fatty acyl-CoA is now in the
Excess calories in the form of protein, carbohydrate, or same location as the metabolic machinery for β-oxidation.
fat cannot be eliminated from the body once ingested or Fatty acid oxidation and fatty acid synthesis do not occur at
administered and must be stored in the form of fatty acids. the same time because malonyl-CoA (an early intermediate
Six cytosolic enzymes plus an acyl carrier protein (ACP) in fatty acid synthesis) inhibits carnitine palmitoyltrans-
are needed for fatty acid synthesis from acetyl-coenzyme A ferase1 and thus prevents the fatty acyl-CoA from reaching
(acetyl-CoA). In the first step, malonyl-CoA is formed from the site of β-oxidation.1,25
acetyl-CoA which has been shuttled out of the mitochon-
dria. This reaction-forming malonyl-CoA is the regulatory Figure 4-4 Sites of Fatty Acid Oxidation
step for fatty acid synthesis. The sequence of reactions that
follows is a condensation, a reduction, a dehydration, and
a second reduction. Both reduction reactions use nicotin-
amide adenine dinucleotide phosphate (NADPH) as the
electron donor. The sequence of reactions adds 2 carbons
at a time and is repeated until a chain length of about 16
carbons is made and released from the ACP.1
As discussed in the Essential Fatty Acids section,
humans cannot synthesize LA or αLA. Although humans
have the necessary enzymes to make EPA from α-LA and
DHA from EPA, the capacity to do so is very low.21 Only
about 5% of α-LA can be converted to EPA and less than
0.5% of α-LA can be converted to DHA. There is also a low
capacity to convert LA to ARA. Thus, although only LA
and α-LA are termed EFAs, the administration of only LA
or α-LA often has only a negligible effect on plasma ARA,

FATS 27
Patients with high plasma levels of triglycerides are some- shortened fatty acyl-CoA and acetyl-CoA. When the fatty
times given heparin (assuming that it will stimulate lipolysis acyl-CoA is a medium-chain fatty acyl-CoA, the oxidation
of triglycerides) and carnitine (assuming it will stimulate sequence stops. Acetyl-CoA and the medium-chain fatty
β-oxidation of the released fatty acids). Definitive data to acyl-CoA must be transported out of the peroxisome via a
confirm these assumptions in patients on special nutrition carnitine shuttle. The medium-chain fatty acyl carnitine is
support are yet to be obtained. In addition, it should be transported into mitochondria to complete the oxidation to
remembered that supplemented heparin and carnitine each acetyl-CoA.1
have a variety of effects on the body’s metabolism.
Omega-Oxidation of Fatty Acids
Beta-Oxidation of Medium-Chain Fatty Acids Omega-oxidation of fatty acids occurs in the endoplasmic
in Mitochondria reticulum in the cytoplasm (Figure 4-4). The omega carbon
In liver cells, medium-chain fatty acids (MCFAs) are trans- is first converted to an alcohol by a cytochrome P450
ported into mitochondria (Figure 4-4) as free fatty acids mixed function oxidase which requires both oxygen and
and then activated to medium-chain fatty acyl-CoA. There- NADPH. Alcohol dehydrogenase and aldehyde dehydroge-
fore, oxidation of MCFAs is carnitine independent in the nase convert the alcohol to a carboxylic acid on the omega
liver. However, other tissues activate MCFAs to medium- carbon. Thus, the fatty acid is converted to a dicarboxylic
chain fatty acyl-CoA on the cytoplasmic side of the inner acid which can be esterified to carnitine and transported to
mitochondrial membrane and require the carnitine shuttle the mitochondrial matrix. There it can enter the β-oxidation
for β-oxidation.26,27 Thus, if dietary MCFAs are provided pathway to be shortened at both ends of the molecule at
in quantities where they are expected to be a fuel substrate the same time. Omega-oxidation of fatty acids is normally
for skeletal muscle, carnitine will be required for their a minor pathway. Dysfunctional β-oxidation in the mito-
oxidation. chondria will increase omega-oxidation.28
Steps of Beta-Oxidation Metabolism During Pathophysiologies

In mitochondria, 4 repeating reactions (dehydrogenation Many chronic pathological conditions, including type 2
requiring flavin adenine dinucleotide (FAD), hydration, diabetes, hypertension, atherosclerosis, and obesity, are
dehydrogenation requiring nicotinamide adenine dinucleo associated with altered fat metabolism. In some situations,
tide (NAD), and cleavage requiring CoA) produce a fatty inappropriate dietary fat quantity and/or composition
acyl-CoA shortened by 2 carbons and acetyl-CoA. The contribute to the observed pathology.
shortened fatty acyl-CoA reenters the sequence and the
acetyl-CoA is oxidized to carbon dioxide in the citric acid Fat As Fuel for Preterm Infants
cycle. The citric acid cycle coupled to the oxidative phos- Early introduction of lipid emulsions to preterm neonates
phorylation pathway yields metabolic energy as adenosine has not been shown to increase complications, 29 but also has
triphosphate (ATP). Oxidation of unsaturated fatty acids not been shown to improve short-term growth or prevent
requires 2 additional enzymes in the mitochondria to morbidity and mortality. 30 An emulsion with a mixture
oxidize the double bonds.1 of medium-chain and long-chain fatty acids appears to be
superior to an emulsion containing only LCFAs in terms of
Beta-Oxidation of Very Long-Chain Fatty Acids incorporation of EFAs and long-chain PUFAs into circu-
in Peroxisomes lating lipids. 31 Adequate energy intake during the first days
Peroxisomes are subcellular organelles in the cytoplasm of life is associated with improved brain function. A recent
that carry out β-oxidation in 4 repeating steps similar to study of 148 extremely low-birth-weight survivors showed
those in the mitochondria. The difference is that the first that every 42 kJ (10 kcal)/kg/d provided during the first
reaction transfers electrons directly to oxygen-producing postnatal week is associated with a 4.6 point increase in the
hydrogen peroxide. Peroxisomes oxidize very LCFAs Mental Development Index. 32
(Figure 4-4) and branched fatty acids. Fatty acids enter the
peroxisome before they are esterified to fatty acyl-CoA, Lipid Emulsions Containing Fish Oils As Fuel
so the carnitine shuttle is not needed to deliver the fatty for Parenteral Nutrition In Pediatrics
acids to the peroxisomes. The very LCFAs are shortened As discussed earlier, ω-3 fatty acids including EPA and DHA
by 2 carbons during each reaction sequence producing the (sometimes called fish oils) have several important functions

in the body both during health and disease. Twelve chil- fatty acid catabolism, resulting in a situat ion some have
dren with pediatric short bowel syndrome who developed termed “glucolipotoxicity.”23 Intake of excess carbohydrate
parenteral nutrition-associated liver disease received paren- increases cellular malonyl-CoA concentrations which
teral ω-3 fatty acids while awaiting liver transplant. They in turn inhibits carnitine palmitoyltransferase 1 activity,
showed restoration of liver function to the point that 9 of impairing β-oxidation of fatty acids. Insulin resistance is
the children were no longer considered for liver transplant. associated not only with the intake of excess calories but also
The remaining 3 children received a liver transplant with no with high intakes of saturated fat. Substituting saturated fat
complications attributable to the ω-3 emulsion. 33 In another with unsaturated fat seems to improve insulin sensitivity. 35
study, 18 infants who developed cholestasis while receiving
a parenteral emulsion high in ω-6 fatty acids were switched Figure 4-5 Path to Lipid Overload or Lipotoxicity
to an emulsion high in ω-3 fatty acids and compared to
21 historical controls who had similar symptoms and had
been maintained on the ω-6 fatty acid emulsion. Patients
receiving the ω-3 fatty acids experienced a reversal of
cholestasis 6.8 times faster when the data were adjusted for
baseline bilirubin concentration, gestational age, and diag-
nosis of necrotizing enterocolitis. The ω-3 fatty acid cohort
had had 2 deaths and no liver transplants and the historical
control cohort had 7 deaths and 2 liver transplantations. 34
Parenteral lipid emulsions containing fish oil are still
not approved for use in children or available in the United
States and Canada.
To Esterify or To Oxidize: That Is the Cell’s Question

The ability to synthesize or to oxidize fatty acids allows the
cell to store excess calories as fat and to mobilize the stored
fatty acids for metabolic fuel which is a life-saving adapta- Metabolism of dietary fat is altered in overweight patients.
tion during times of starvation. When products of digested For example, overweight patients with a fatty liver have a
macronutrients enter the cell during normal physiological higher postprandial triglyceride response and an increased
situations, the cell responds to metabolic signals indicating production of large very low-density lipoproteins after a fat
the metabolic fuel status of the cell and either uses the fuel load compared to control subjects. 36 When providing nutri-
substrates to produce needed metabolic energy or stores the tion support, it is important not only to provide appropriate
fuel substrate as fatty acids in triglycerides. If excess calories calories for the specific patient, but to carefully evaluate
are chronically delivered to the cell, however, the ability of how the patient’s current metabolic status may impact the
adipose tissue to serve as a “sink” and protect non-adipose body’s metabolism of the nutritional fat substrate provided.
tissues from fatty acid “spillover” appears to become satu-
rated. As diagrammed in Figure 4-5, the result is lipid
overload or lipotoxicity that overwhelms the abilities of both
the endoplasmic reticulum and mitochondria to maintain
cellular homeostasis and results in systemic release of both
free fatty acids and inflammatory cytokines. Accumulation
of fatty acids in skeletal muscle, heart, liver, and pancreas
is likely the underlying factor during the development of
insulin resistance, cardiomyopathy, liver steatosis, and
type 2 diabetes. During normal physiological conditions,
there is intricate coordination of the use of fatty acids for
energy and the use of glucose for energy. Likewise during
chronic intake of excess calories, excess lipids inhibit the
utilization of glucose and hyperglycemia interferes with

FATS 29
Test Your Knowledge Questions 9. Sampath H, Ntambi JM. Polyunsaturated fatty acid
regulation of genes of lipid metabolism. Annu Rev Nutr.
1. In order to maintain health and prevent a home paren-
2005;25:317–340.
teral nutrition patient from becoming overweight, the 10. Agostoni C. Role of long-chain polyunsaturated fatty acids in
optimal nutrition support prescription: the first year of life. J Pediatr Gastroenterol Nutr. 2008;47(suppl
A. Restricts fat to an absolute minimum while 2):S41–S44.
providing a generous amount of glucose. 11. Innis SM. Dietary omega 3 fatty acids and the developing
B. Provides adequate calories including a fatty acid brain. Brain Res. 2008;1237:35–43.
12. Novak EM, Dyer RA, Innis SM. High dietary omega-6 fatty
blend with appropriate chain length, chain satura- acids contribute to reduced docosahexaenoic acid in the
tion, and ratios of LA, α-LA, ARA, EPA, and DHA. developing brain and inhibit secondary neurite growth. Brain
C. Provides 80% of the calories recommended for oral Res. 2008;1237:136–145.
intake. 13. Hay WW Jr. Strategies for feeding the preterm infant. Neona-
D. Provides all the fat calories as the essential fatty tology. 2008;94(4):245–254.
14. Innis SM. Omega-3 Fatty acids and neural development to 2
acids LA and α-LA.
years of age: do we know enough for dietary recommendations?
2. The cellular site(s) for fatty acid oxidation in the body J Pediatr Gastroenterol Nutr. 2009;48 (Suppl 1):S16–S24.
is (are): 15. Agostoni C, Zuccotti GV, Radaelli G et al. Docosahexaenoic
A. Mitochondria acid supplementation and time at achievement of gross
B. Peroxisomes motor milestones in healthy infants: a randomized, prospec-
C. Cytoplasm tive, double-blind, placebo-controlled trial. Am J Clin Nutr.
2009;89(1):64–70.
D. Mitochondria, peroxisomes, and cytoplasm 16. Bender DA, Mayes PA. Nutrition, digestion, & absorption. In:
3. The essential fatty acid needs of a critically ill 24-week Murray RK, Granner DK, Rodwell VW, eds. Harper’s Illus-
neonate in the neonatal intensive-care unit requires trated Biochemistry. 27th ed. New York, NY: McGraw-Hill;
dietary: 2006.
A. LA and α-LA 17. Barrett KE. Lipid assimilation. In: Barrett KE, ed. Gastrointes-
tinal Physiology. New York, NY: McGraw-Hill; 2006.
B. α-LA and DHA
18. Hamosh M. Digestion in the newborn. Clin Perinatol.
C. LA and ARA 1996;23(2):191–209.
D. LA, α-LA, ARA, and DHA 19. Hernell O, Blackberg L. Human milk bile salt-stimulated
lipase: functional and molecular aspects. J Pediatr. 1994;125(5)
See p. 487 for answers. (pt 2):S56–S61.
20. Hamosh M, Bitman J, Liao TH, et al. Gastric lipolysis and
fat absorption in preterm infants: effect of medium-chain
References triglyceride or long-chain triglyceride-containing formulas.
1. Nelson DL, Cox MM. Lehniger Principles of Biochemistry. 5th Pediatrics. 1989;83(1):86–92.
ed. New York, NY: W.H. Freeman and Co; 2008. 21. Russo GL. Dietary n-6 and n-3 polyunsaturated fatty acids:
2. Innis SM. Dietary lipids in early development: relevance to from biochemistry to clinical implications in cardiovascular
obesity, immune and inflammatory disorders. Curr Opin prevention. Biochem Pharmacol. 2009;77(6):937–946.
Endocrinol Diabetes Obes. 2007;14(5):359–364. 22. Plourde M, Cunnane SC. Extremely limited synthesis of long
3. Fritsche K. Fatty acids as modulators of the immune response. chain polyunsaturates in adults: implications for their dietary
Annu Rev Nutr. 2006;26:45–73. essentiality and use as supplements. Appl Physiol Nutr Metab.
4. Fokkema MR, Smit EN, Martini IA, Woltil HA, Boersma ER, 2007;32(4):619–634.
Muskiet FAJ. Assessment of essential fatty acid and omega 23. Brenna JT, Salem N Jr, Sinclair AJ, Cunnane SC. alpha-Lino-
3-fatty acid status by measurement of erythrocyte 20:3ω9 lenic acid supplementation and conversion to n-3 long-chain
(Mead acid), 22:5ω6/20:4ω6 and 22:5ω6/22:6ω3. Prosta- polyunsaturated fatty acids in humans. Prostaglandins Leukot
glandins Leukot Essent Fatty Acids. 2002;67(5):345–356. Essent Fatty Acids 2009;80(2-3):85–91.
5. Innis SM, Jacobson K. Dietary lipids in early development 24. Harris WS, Mozaffarian D, Lefevre M, et al. Towards estab-
and intestinal inflammatory disease. Nutr Rev. 2007;65(12) lishing dietary reference intakes for eicosapentaenoic and
(pt 2):S188–S193. docosahexaenoic acids. J Nutr. 2009;139(4):804S–819S.
6. Marszalek JR, Lodish HF. Docosahexaenoic acid, fatty 25. Rasmussen BB, Wolfe RR. Regulation of fatty acid oxidation
acid-interacting proteins, and neuronal function: breast- in skeletal muscle. Annu Rev Nutr. 1999;19:463–484.
milk and fish are good for you. Annu Rev Cell Dev Biol. 26. Groot PHE, Hulsmann WC. The activation and oxidation of
2005;21:633–657. octanoate and palmitate by rat skeletal muscle mitochondria.
7. Heird WC, Lapillonne A. The role of essential fatty acids in Biochim Biophys Acta. 1973;316:124–135.
development. Annu Rev Nutr. 2005;25:549–571. 27. Rössle C, Carpentier YA, Richelle M, et al. Medium-chain
8. Deckelbaum RJ, Worgall TS, Seo T. n-3 fatty acids and gene triglycerides induce alterations in carnitine metabolism. Am J
expression. Am J Clin Nutr. 2006;83(6):1520S–1525S. Physiol Endocrinol Metab. 1990;258:E944–E947.

28. Croston G. BioCarta omega oxidation pathway. http://www. 33. Diamond IR, Sterescu A, Pencharz PB, Kim JH, Wales PW.
biocarta.com/pathfiles/omegaoxidationPathway.asp. 2009. Changing the paradigm: omegaven for the treatment of liver
Accessed July 1, 2009. failure in pediatric short bowel syndrome. J Pediatr Gastroen-
29. Drenckpohl D, McConnell C, Gaffney S, Niehaus M, Macwan terol Nutr. 2009;48(2):209–215.
KS. Randomized trial of very low birth weight infants receiving 34. Gura KM, Lee S, Valim C, et al. Safety and efficacy of
higher rates of infusion of intravenous fat emulsions during a fish-oil-based fat emulsion in the treatment of paren-
the first week of life. Pediatrics. 2008;122(4):743–751. teral nutrition-associated liver disease. Pediatrics.
30. Simmer K, Rao SC. Early introduction of lipids to paren- 2008;121(3):e678–e686.
terally-fed preterm infants. Cochrane Database Syst Rev. 35. Riserus U. Fatty acids and insulin sensitivity. Curr Opin Clin
2005;(2);CD005256. Nutr Metab Care. 2008;11(2):100–105.
31. Krohn K, Koletzko B. Parenteral lipid emulsions in paediat- 36. Assy N, Nassar F, Nasser G, Grosovski M. Olive oil consump-
rics. Curr Opin Clin Nutr Metab Care. 2006;9(3):319–323. tion and non-alcoholic fatty liver disease. World J Gastroenterol.
32. Stephens BE, Walden RV, Gargus RA, et al. First-week protein 2009;15(15):1809–1815.
and energy intakes are associated with 18-month devel-
opmental outcomes in extremely low birth weight infants.
Pediatrics. 2009;123(5):1337–1343.

5
Protein Digestion, Absorption,
and Metabolism
Richard A. Helms, PharmD, Emma M. Tillman, PharmD, Anup J. Patel, MD, and John A. Kerner, MD

Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 31 1. Explain how protein metabolism and physiology is
Ontogeny of the Gastrointestinal Tract profoundly affected by the ontogeny of the gastrointes-
in Relation to Protein. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 31 tinal tract.
Protein Digestion. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 32 2. Describe the roles of the liver and kidney in amino acid
metabolism.
Protein Absorption. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 33
3. Understand the functions of amino acids and proteins,
Digestion and Absorption of Whey and Casein . . . . . . . . . 34
protein requirements for age, and protein energy ratios
Amino Acids . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 35 during growth.
Conditionally Essential Amino Acids
4. Discuss protein turnover, assessment of plasma amino
Amino Acids of the Urea Cycle
Useful Classification of Amino Acids for the Clinician acids, and nitrogen balance.
Liver and Kidney: Roles in Amino Acid Metabolism. . . . . . 38
Introduction
Functions of Amino Acids and Proteins . . . . . . . . . . . . . . . 39 There is an extraordinary range of knowledge related to
Protein Requirements and protein in human nutrition. The basics of protein in adult
Protein-Energy Ratio During Growth. . . . . . . . . . . . . . . . . . 40
nutrition have been nicely reviewed in The A.S.P.E.N. Nutri-
Assessment of Protein Status
Monitoring Plasma Amino Acids tion Support Core Curriculum, and materials covered in that
publication will not be extensively revisited here.1 Because
Case Presentation and Discussion. . . . . . . . . . . . . . . . . . . 41
this chapter is restricted to protein in pediatrics, it will focus
particularly on the rapidly developing neonate and infant.
Ontogenic events relating to protein metabolism and physi-
ology render the small child as much different than the
older child and adult. This chapter will review aspects of
digestion, absorption, and metabolism of protein focusing
on these differences.
Ontogeny of the Gastrointestinal Tract

in Relation to Protein
The gastrointestinal (GI) tract has been described as the
largest endocrine organ. It produces numerous regulatory
gut peptides that are involved in GI tract development,
growth, absorption, secretion, and gut motility. They
function in classic endocrine, autocrine, paracrine, and
31
neurocrine pathways.2,3 Selected gastrointestinal regula- proteolysis and transport are relatively intact, even in the
tory peptides involved with the ontogeny of the GI tract as preterm infant.9
it relates to proteins are outlined in Table 5-1. All of these
peptides are present by the end of the first trimester in the Protein Digestion
fetus, but adult levels may not be present until term.4 These Initial protein digestion occurs in the stomach, where
peptides that function as hormones are released in response proteins are exposed to hydrochloric acid (HCl) and pepsin.
to feeding. The release of some of these hormones is limited Gastric acid produces an acidic environment in the stomach,
in the newborn compared to the adult.4,5 and denatures protein.10,11 Although protein digestive
There are significant differences in the ontogeny of activity within the GI tract has been identified as early as 16
the two main enzymes secreted by the gastric mucosa. In weeks gestation, there are relatively low amounts of gastric
the human, even though both pepsin and gastric lipase are acid secretion and consequently less protein denaturation
located at the same site (ie, in the chief cells of the gastric in both preterm and term infants. In fact, there is relatively
mucosa), the enzymes have different developmental minimal functional protein digestion in the stomach in the
patterns.6 Pepsin activity and output are much lower in first few weeks of life. It is not until about 2 years of age that
infants than adults.7,8 In contrast, gastric lipase activity and adult levels of gastric acid secretion are reached.9
output are equal in infants and adults.7,8 Chief cells secrete proenzymes (pepsinogen 1 and 2)
The ontogeny of the brush border amino-oligopep- into the stomach, which undergo auto-activation to form
tidases as well as the dipeptide and amino acid transport pepsins in the acidic milieu.12 This acidic environment is
systems parallel that of the carbohydrate enzymes. Amino- critical for pepsin function as evidenced by its inactivity
oligopeptidases are first detected immunohistochemically in the duodenum, where the pH is neutral.13 These pepsins
by 10 to 16 weeks gestation. By 28 to 30 weeks gestation, function as endopeptidases; they hydrolyze internal bonds
enzyme levels are approximately one-half of the values of the polypeptides to primarily form shorter polypep-
found in term infants. Therefore, all aspects of intestinal tides, oligopeptides, and some free amino acids.9,11 Gastrin
Table 5-1 Gastrointestinal Regulatory Peptides2

Regulatory Peptide Sources Mechanisms Actions
Epidermal Growth Factor Salivary glands Hormone – Stimulates mucosal proliferation and differentiation
Brunner glands Paracrine – Regulates gastrointestinal secretion
Paneth cells – Has cytoprotective/ulcer-healing effects
Insulin-like Growth Factor Gastrointestinal tract Hormone – Stimulates crypt cell proliferation and enterocyte differentiation
Liver Autocrine – Promotes intestinal adaptation
Paracrine
Enteroglucagon Ileum Hormone – Stimulates gut mucosal growth
Colon – Regulates gut motility
Neurotensin Ileum Hormone – Inhibits gastric emptying and acid secretion
Central nervous system Neurocrine
Vasoactive Intestinal All tissues Neurocrine – Promotes secretomotor, vasodilatation, and smooth
Polypeptide muscle relaxation
Pancreatic Polypeptide Pancreas Hormone – Inhibits pancreatic enzyme secretion and gallbladder
contraction
Motilin Proximal small intestine Hormone – Stimulates gastrointestinal motility
Peptide YY Gastrointestinal tract Hormone – Inhibits gastric acid secretion and gut motility
Central nervous system Paracrine
Neurocrine
Reprinted from Gilger MA. Normal gastrointestinal function. Table 342-1. In: McMillan JA, Feigin RD, DeAngelis C, Jones MD, eds. Oski’s Pediatrics. 4th ed.
Copyright © 2006 with permission from Lippincott Williams & Wilkins.

PROTEIN DIGESTION, ABSORPTION, AND METABOLISM 33
stimulates both gastric acid and pepsin production and secre- Figure 5-1 Pancreatic Enzyme Activation10
tion, which initiates protein digestion in the stomach.10
The protein denaturation within the stomach does not
appear to be critical because patients with a more neutral
gastric pH do not have impaired protein digestion. However,
the amino acids that are produced from protein digestion in
the stomach do assist in releasing cholecystokinin (CCK)
or pancreozymin.12 CCK has a role in protein digestion by
helping to release pancreatic digestive enzymes, stimulate
gallbladder contraction, and relax the sphincter of Oddi.11,12
In contrast, the hormone secretin promotes pancreatic
secretion of bicarbonate-rich fluid to help establish a favor- Reprinted from Wahbeh GT, Christie DL. Basic aspects of digestion and
able pH.10 absorption. In: Wyllie R, Hyams JS, eds. Pediatric Gastrointestinal and Liver
The pancreatic digestive enzymes are secreted in their Disease: Pathophysiology, Diagnosis, Management. 3rd ed.
Copyright © 2006 with permission from Elsevier.
inactive proenzyme form, similar to the secretion of pepsin
as pepsinogen in the stomach. The pancreas secretes both
endopeptidases (trypsinogen, chymotrypsinogen, and Protein Absorption
proelastase) and exopeptidases (procarboxypeptidase A Normal protein absorption involves lumenal processing,
and B) into the proximal small intestine.11 The activated absorption into the intestinal mucosa, and transport into
endo- and exopeptidases hydrolyze the proteins at peptide the circulation.12 At the brush border of enterocytes, there
bonds within the polypeptide chains to form oligopeptides are different types of peptidases, including oligopepti-
and at the carboxyl terminal to form single amino acids, dases, that further hydrolyze the partially digested proteins
respectively.9–11 into amino acids, dipeptides, and tripeptides (see Figure
Bile acids and trypsinogen together cause the release 5-2).9,10,12,16 Oligopeptidases have been detected as early as
of enterokinase, a brush border enzyme, which converts 10 to 16 weeks gestation, and they increase to nearly half of
trypsinogen into its active form trypsin. Trypsin then full-term levels by 28 to 30 weeks gestation.9
converts the remaining pancreatic peptidases into their Absorption into the enterocyte involves both sodium-
respective active forms (chymotrypsin, elastase, and dependent and -independent transport systems.9 The
carboxypeptidase A and B), and assists in forming more sodium-dependent amino acid transporters are driven
trypsin from trypsinogen (see Figure 5-1).9,10,13 Overall, the by a low intracellular sodium concentration and negative
products of lumenal protein digestion are about 70% oligo- intracellular potential resulting from the sodium-potas-
peptides and 30% free amino acids.9 sium-adenosine triphosphatase (Na+-K+ ATPase) pump.12
Enterokinase and trypsin have been detected at 26 There are many different transporters including those for
and 28 weeks gestation, respectively. Enterokinase levels at neutral, acidic, and basic amino acids with narrow substrate
time of birth are about 10% of adult levels except in those specificity, and for di- and tripeptides with a broad substrate
rare infants with congenital enterokinase deficiency.9,14 specificity (see Figure 5-3).9,10,12,16
Trypsin activity in duodenal juice of the premature infant Once the amino acids are transported into the cyto-
is slightly less than in the full-term infant but does increase plasm, there is additional processing by cytoplasmic
in response to food as it does in full-term infants. Infants peptidases, mostly dipeptidases and tripeptidases, which
have been found to have decreased trypsin activity in convert the di- and tripeptides into free amino acids.10,12,13
duodenal fluid compared to older children.15 This reduced Although most of these amino acids are transported into the
trypsin activity has been demonstrated to increase over the blood stream, it is estimated that about 10% of amino acids,
first 4 months of life, possibly resulting from their relative particularly glutamine and glutamic acid, are used directly
increased enteral protein intake.9 However, the significance by the enterocyte.10,13 This coincides with the observation
of these differences is unclear given that protein digestion that animals receiving total parenteral nutrition without
and absorption is fairly efficient even in preterm infants. It enteral feeds have developed mucosal atrophy.10
is estimated that term infants digest and absorb about 80% Some of the sodium-independent amino acid trans-
to 85% of lumenal proteins while estimates for adults range porters are located on the basolateral surface of the
from 95% to 98%.9,11 enterocyte, and function to transport amino acids into the

Figure 5-2 Overview of Protein Digestion and Absorption
Reprinted from Roy CC, Silverman A, Alagille D. Pediatric Clinical Gastroenterology. Malabsorption syndrome. p. 307. (Modified and published with
permission from Ahnen DJ. Protein digestion and assimilation. In Yamada T, et al. Textbook of Gastroenterology, Philadelphia. 1991. Lippincott.)
portal vein.9 Although a significant majority of the protein Figure 5-3 The Transport of Amino Acids
that enters the portal circulation is in the form of free amino
acids, there are small amounts of di- and tripeptides that
enter the blood stream intact through normal transport
systems.10
Studies have shown that an infant’s intestine may have
a higher capacity for absorption of macromolecules than
the adult intestine.17 Thus, among susceptible infants, for
example infants who sustain severe post-infectious villous
injury, the early introduction of specific foods of increased
antigenic potential may increase their risk of protein
sensitization.18,19
Given the broad substrate specificity for di- and tripep-
tidases at the brush border, it is not surprising that clinically Reprinted from Roy CC, Silverman A, Alagille D. Pediatric Clinical
Gastroenterology. 4th ed. Copyright © 1995 with permission from Elsevier.
significant deficiencies resulting from specific amino acid
transport abnormalities are uncommon. Two of the more
well-known inherited defects of protein absorption include Digestion and Absorption of Whey and Casein
Hartnup syndrome and cystinuria. In Hartnup syndrome, The major proteins in milk are whey and casein. Unmodi-
neutral amino acid transport is defective and patients fied cow’s milk is approximately 18% whey and 82% casein.
present with pellagra-like skin eruptions. In cystinuria When this unheated casein-predominant protein enters
(see Chapter 24), there is a defect in cystine reabsorption the acidic environment of the stomach, it forms a relatively
resulting in excessive cystine in the urine and subsequent hard curd of casein and minerals that can be difficult to
renal stone formation. In contrast, acquired defects of digest. In contrast, human milk protein is approximately
protein absorption, including exocrine pancreatic insuffi- 60% to 70% whey and 30% to 40% casein.20,21 Human milk
ciency and transient brush border enzyme deficiency from forms a very small, soft curd in acid. Some infant formula
gastroenteritis, are more common.8 companies have developed whey-predominant formulas by
combining equal amounts of demineralized whey protein

and skim milk protein to yield a formula with 60% whey Amino Acids
and 40% casein. There are literally hundreds of amino acids found in nature,
There are other important differences between these two but only 20 are considered relevant in human nutrition.
types of proteins. Whey results in a faster gastric emptying Lafayette B. Mendel (1872-1935) demonstrated for the first
time, and is overall more easily digested. In contrast, casein time that some amino acids cannot be synthesized in rats,
is less soluble and has a slower rate of digestion, which and, hence, defined them as essential amino acids required
results in an extended release of amino acids into the circu- in their diet. In an amazing series of experiments completed
lation. In human studies, casein-predominant formulas in the 1940s and 1950s, William C. Rose (1887-1985, who
result in lower zinc bioavailability than whey-predominant completed his training under Mendel) and co-investiga-
formulas, presumably because of less complete digestion of tors determined the amino acid requirements of normal
casein.22 adults.27 These experiments revealed 8 amino acids that
Other types of human whey proteins include secretory resulted in negative nitrogen balance when excluded from
IgA and lactoferrin.21 Secretory IgA attaches to the lining the diet. Upon resumption of these amino acids in adequate
of the GI tract and prevents potential pathogenic micro- amounts, there was a complete reversal of the negative
organisms from adhering.9 Lactoferrin is an iron-binding nitrogen balance. These 8 amino acids are isoleucine,
protein that limits the ability of bacteria to thrive in the leucine, valine, lysine, methionine, phenylalanine, threo-
intestines. Because this protein is biochemically similar to nine, and tryptophan (Table 5-2). Other amino acids could
transferrin, it is suggested that it may have a significant role be withheld without appreciable effect on nitrogen balance.
in iron absorption. However, in vivo studies do not defini- Studies have confirmed these findings in infants and school-
tively establish this role.23 Also, there is some evidence that age children.
suggests that lactoferrin has a role in stimulating intestinal
mucosa growth.24 These two proteins found in human milk, Table 5-2 Essential, Non-Essential, and Conditionally Essential Amino
secretory IgA and lactoferrin, and the main protease inhibi- Acids in the Human Nutrition
tors, alpha 1-antitrypsin and alpha 1-antichymotrypsin, are Essential Conditionally Essential Non-Essential
not well-digested in early infancy.24,25 In fact, it has been Histidine* Cyst(e)ine Alanine
estimated that about 10% of intact milk proteins have been Isoleucine Taurine Aspartic Acid
found in infant stools prior to 1 month of age while this
Leucine Tyrosine Asparagine
decreases to about 3% at 4 months of age.24 In vitro studies
Lysine Glutamic Acid
suggest that alpha 1-antitrypsin resists proteolysis by pepsin
and pancreatic enzymes.24,26 Alpha 1-antitrypsin has been Methionine Glutamine
found in considerable quantities in both human milk and Phenylalanine Glycine†
in the stool of infants fed human milk; therefore it should Threonine Proline†
not be used to ascertain enteric protein loss in breastfed Tryptophan Serine†
infants.26 Valine Arginine†
Overall, infant formulas traditionally contain more
Cyst(e)ine = sum of cysteine and cystine. Glycine and Serine carbon
protein than human milk due to the concern that proteins skeletons can be readily synthesized by neonates and infants, but the
found in infant formulas are less digestible. This is supported rate of transamination is low.
by the observation that formula-fed infants have higher
blood urea nitrogen (BUN) levels due to the higher exposure * Not initially identified by Rose as being an essential amino acid.
to proteins. These formulas also have a higher proportion of †
Laidlaw-Kopple classification as acquired indispensible (see Table 5-4).
whey, which should increase their digestibility. In addition,
it is important to note that heat treatment of milk proteins Amino acids are capable of existing in two isomeric
does affect their digestibility. It has been observed that forms. The L-amino acids are utilized in humans and most
protein digestibility in powdered formulas is increased in animals. The stereoselectivity is related to enzymes that
comparison to identical liquid solutions. The heat treatment only recognize and utilize the L isomer. Amino acids do
for powdered formulas is less intense than liquid formulas exist as D isomers, but only D-methionine can be converted
with a lower maximum temperature and shorter duration. to L-methionine by some animals, but not humans. For
As a result, protein digestibility is increased with less intense the rest of this chapter the authors will not identify amino
heat treatment.24 acids as the L isomer; one can assume the L isomer is being
discussed.

Conditionally Essential Amino Acids 5-4). Many investigators have shown that multiple enzymes
Investigations that followed Rose’s extraordinary work in this pathway have lower or no activity in the fetal liver,
generated questions as to whether other amino acids may or in the livers of infants of various gestational ages who
be required in the diet under certain conditions of immatu- died from non-liver-related causes. 38,39 λ-cystathionase and
rity, metabolic imbalance, organ failure, disease, and highly cystathionine β-synthase were found to be absent or to have
defined diets such as parenteral nutrition (PN). activity of less than half of the older child or adult. Zlotkin40
Histidine is now considered essential in the human demonstrated that λ-cystathionase in liver of premature and
diet. While the original exclusion studies by Rose did not term infants did not reach adult activity until 6 to 9 months
demonstrate negative nitrogen balance, Nasset was able postnatal age. This may be the reason that human milk is
to demonstrate that the hemoglobin of Rose’s subjects fell relatively rich in cysteine content. This renders cysteine as
while on histidine-free diets.28 These investigators calcu- conditionally essential in neonates and infants.
lated that the loss of hemoglobin was sufficient to supply
the subjects with 240 mg/d of histidine. Histidine stores Figure 5-4 The Transsulfuration Pathway in the Metabolism of Methionine
are particularly high in hemoglobin and in carnosine
(found in large quantities in muscle). Observations by
Kopple confirmed these findings.29,30 It is widely accepted
that histidine is the ninth essential amino acid in humans
(Table 5-2). Snyderman established histidine intake
requirements in infants of 24 mg/kg/d, which is generally
less than other essential amino acids. 31 In studies by Heird,
the histidine requirements in neonates and infants on PN
were greater than demonstrated by these earlier studies and
than predicted from older child and adult requirements
(adjusted by kilogram of weight). 32,33 The Guidelines for the
Use of Parenteral and Enteral Nutrition in Adult and Pediatric
Patients34 states that histidine is a conditionally essential
amino acid for neonates and infants up to 6 months of age.
Sulfur amino acid requirements of infants and chil-
dren have been an area of intense research. The sulfur amino
acids include methionine (defined as essential by Rose) and
cysteine and taurine (both defined as nonessential in adults
by Rose). Cysteine contains a free sulfhydryl group, and is
oxidized with another cysteine moiety to form the dimer Cysteine is gradually oxidized to the dimer cystine
cystine. After cysteine is incorporated into newly synthe- in aqueous solution at neutral pH. Therefore, for PN solu-
sized protein, the formation of cystine dimers aid in proper tions containing cysteine, cysteine is added at the time of
protein folding and stability. Cysteine is metabolized from preparation. The commonly used intravenous additive
methionine, and can replace 50% to 80% of methionine is provided as the cysteine hydrochloride salt. The pedi-
intake. Because it can reduce the intake of an essential amino atric daily requirement for cysteine has been studied by
acid, it has been classified as a conditionally essential amino Helms et al.41,42 These investigators found that a dose of
acid by Jackson. 35 Snyderman36 defined intakes of cysteine 77.4 mg/kg/d, close to that of Snyderman, appears to be
in infants at 85 mg/kg/d, similar to many of the essential required for ideal nitrogen retention, nitrogen balance, and
amino acids. Pohlandt37 discovered that the requirement for growth in infants on PN. 36 Problems of acidosis occasion-
cysteine continues in diet into infancy, perhaps to 5 months ally occur in very low birth-weight (VLBW) infants, and
of age. require the substitution of acetate for chloride in PN solu-
Most of the metabolic machinery for the metabolism tions. For every 160 mg of cysteine HCl that is infused as
of methionine and cysteine resides in liver parenchymal part of PN, 1 mmol of HCl is given to the pediatric patient.
tissue near the portal vein. The transsulfuration pathway For the preterm infant and neonate, the prescriber should
for methionine metabolism is a complex series of enzymatic consider substitution of 1 mmol of acetate for 1 mmol of
steps leading to cysteine and taurine production (Figure additional chloride given as part of cysteine HCl.

Taurine is one of the most abundant free “amino” acids kg/d in preterm infants. 36 Classic phenylketonuria (PKU),
in humans. It is not incorporated into protein in that no the absence of the enzyme phenylalanine hydroxylase,
aminoacyl tRNA synthetase recognizing taurine has been results in extreme elevations in phenylalanine concentra-
identified. Taurine is actually a sulfonic acid (rare in nature) tion, and a requirement for tyrosine in diet. PKU can lead
and does not contain a carboxyl group as do other amino to brain damage and possibly death if untreated. Tyrosine
acids. It has a host of important biological functions (Table may be conditionally essential in patients with liver disease,
5-3). It is essential in the feline diet, and its absence results and is the precursor for the neurotransmitter, dopamine.
in retinal degeneration and blindness. In children on home Tyrosine content in parenteral amino acid solutions
parenteral nutrition (HPN) with no added taurine, degen- is restricted because of poor solubility. Christensen found
erative changes in electroretinograms were observed.43 that N-acetyl-tyrosine (NAT), an aqueously soluble form
Cysteine sulfinic acid decarboxylase is key to production of of tyrosine with good stability in solution, was a reasonable
taurine from cysteine (Figure 5-4). The enzyme has much intravenous source of tyrosine in older infants.48 However,
lower overall activity in humans than in rats and cats, but its clearance and non-renal clearance was significantly
activity is even lower in human fetal liver.44 Taurine is found decreased in younger infants of lower postconceptional
in high concentrations in human milk when compared age, suggesting NAT may not be the ideal tyrosine source
to cow’s milk.45 Formulas made from cow’s milk protein in VLBW neonates. This investigative group was unable to
require taurine supplementation, and taurine deficiency normalize plasma tyrosine concentrations in most infants
may occur in synthetic formulas not containing taurine. at a dose of approximately 50 mg/kg/d. Van Goudoever
In neonates and premature infants these infants continue was able to normalize plasma tyrosine levels with NAT
to renally waste taurine even in the presence of low serum intake of 162 mg/kg/d.49
taurine.46
Amino Acids of the Urea Cycle
Table 5-3 Taurine Functions The amino acids of the urea cycle are considered nones-
Neurotransmitter sential (Figure 5-5). Snyderman50 found no evidence that
Bile acid conjugation arginine is essential in preterm infants. However, early
Brain and central nervous system development amino acid solutions with relatively lower concentrations of
Osmoregulation arginine resulted in hyperammonemia in infants receiving
Immunoregulation these formulas as part of PN. 51 Higher concentrations of
Antioxidant arginine reversed the finding of hyperammonemia. 52 Acute
Retinal physiology renal failure patients given large doses of protein with
Platelet function
little supplemental arginine also present with hyperam-
Mitochondrial function
monemia, and can be reversed with the supplementation
of arginine. 53 Treatment of urea cycle disorders generally
Taurine is added to crystalline amino acid formulas involves the supplementation of low-dose essential amino
designed for infants. Helms et al. described plasma amino acids, and arginine.
acid concentrations in preterm infants, and in long-term
home parenteral nutrition (PN) patients receiving a
pediatric-designed amino acid formula as part of their
PN.42,47 For infants, these investigators demonstrated that
concentrations of the sulfur amino acids remain within
age-related norms with the use of one of the commercially
available formulas with L-cysteine HCl supplementation.
Interestingly, even older children on home PN required
cysteine supplementation to normalize plasma taurine
concentrations.47
Tyrosine is exclusively metabolized from phenyla
lanine. Tyrosine, like cysteine for methionine, can spare
dietary requirement for phenylalanine. Snyderman demon-
strated a dietary need for tyrosine of approximately 50 mg/

Figure 5-5 Urea Cycle With Enzymes and Substrates lower concentrations in plasma in premature infants. Lipo-
protein concentrations rise rapidly after birth in response
to high dietary fat intake, while albumin and TTR increase
toward adult values in the first months to year of life. Acute
phase proteins, such as C-reactive protein (CRP), appear to
be induceable even in prematurity, and are used to monitor
inflammatory response to infection or metabolic stress.
Reduction in visceral protein occurs in preterm infants,
and response to protein and energy intake can be assessed
through monitoring changes in serum concentrations of
albumin, TTR, and RBP. 57
The production of glutathione in the liver is essential;
however, other tissues can produce the tripeptide. Gluta-
thione is an important sulfhydryl-reducing agent that
protects cells from oxygen free radicals. 58 It is synthesized
CPS = carbamyl phosphate synthetase, OTC = ornithine transcarbamylase, from glutamate, cysteine, and glycine, and studies have
ASAS = argininosuccinic acid synthetase, AS = argininosuccinase, shown cysteine is the rate-limiting substrate in glutathione
A = arginase production. It is dependent in two distinct steps on cysteine
production via the transsulfuration pathway (principally in
Useful Classification of Amino Acids for the Clinician the liver), or from dietary intake. The tripeptide also appears
Laidlaw and Kopple offer an alternative approach to the to be important in the transport of amino acids, and in the
Jacksonian35 classification of essential and nonessential synthesis of leukotrienes via the enzyme gamma-glutamyl
amino acids. 54 These 5 classifications enable the clinician transpeptidase. 59,60
to better understand the requirement of amino acids in diet The metabolism of amino acids is an important func-
(Table 5-4). tion of the liver. Several enzymes and enzyme systems, such
as the transsulfuration pathway and phenylalanine hydroxy-
Table 5-4 Modification of Amino Acid Classification in Humans54 lase, both predominantly located in the liver, are responsible
1. Totally indispensable amino acids. No metabolic precursor or for the metabolism of the essential amino acids methionine
product can be substituted. Lysine and threonine. and phenylalanine, respectively. Enzyme activity is reduced
2. Carbon-skeleton indispensable. Ketoacid analogue or in prematurity and early infancy, rendering the products
hydroxyacid analogue can be substituted. Histidine, isoleucine,
leucine, methionine, phenylalanine, tryptophan, and valine. of these enzyme systems as conditionally essential amino
3. Conditionally indispensable. Reduce requirement for acids.
indispensable, and become indispensable in the absence Approximately one-third of amino acids entering the
of precursor in diet. Tyrosine, cysteine, taurine, and possibly liver from portal blood are used for protein synthesis.61 The
orthnithine, and citrulline.
remainder may be used in energy production, or gluconeo-
4. Acquired indispensable. Become indispensable in states of
metabolic disorders, immaturity, severe stress. Cysteine, taurine, genesis, with perhaps only a third of dietary amino acids
tyrosine, arginine, citrulline, glycine, serine, and proline. entering to the peripheral blood. This explains why plasma
5. Dispensible. Alanine, glutamate, aspartate. amino acids do not fluctuate substantially in the postpran-
dial period. One group of amino acids that are released at
Liver and Kidney: Roles in Amino higher relative concentrations from the liver in the post-
Acid Metabolism prandial period are the branched-chain amino acids.62 These
The liver is important in synthesis of transport and other are leucine, isoleucine, and valine. The branched-chain
constituent and functional proteins, metabolism of amino amino acids are preferentially metabolized in the periphery
acids, gluconeogenesis, and urea formation. 55,56 Major as these amino acids and arginine stimulate insulin release
plasma proteins derived from liver, such as albumin, and muscle protein synthesis.63 All is reversed in the post-
transthyretin (TTR) (also known as prealbumin for its absorptive period. As insulin concentrations fall, the
migration pattern during electrophoresis), and retinol- muscle then provides the principal gluconeogenic substrate,
binding protein (RBP) are present at early stages of alanine, to the liver for production of glucose in the fasting
development. Most liver-derived plasma proteins are at period.

In parenterally fed neonates and infants, Heird found and may explain increased amino acid needs in these
that the branched-chain amino acid needs of infants was patients when compared to older children, or adults.65,66
increased even with their relatively lower muscle mass. 32,33
This would suggest that the shuttling of amino acids between Functions of Amino Acids and Proteins
the periphery and the small infant liver is actually higher Protein has multiple functions; it is essential for cell struc-
than in the adult. Increased requirement of amino acids and ture, maturation, remodeling, and growth. Besides being
energy for synthesis may be the likely explanation. utilized for energy, amino acids and proteins serve as precur-
The urea cycle is the principal mechanism for nitrogen sors that are essential for many biological processes.67
disposal (Figure 5-5). The catabolism of proteins, and their When protein is consumed, it is extensively broken
component amino acids, results in ammonia production. down in the GI tract to amino acids, which can then enter
The liver will hydrolyze arginine to form urea and ornithine cells or continue to circulate in plasma. Once in the cell,
under the enzymatic control of arginase. Urea then is deliv- amino acids can be combined by peptide linkages to form
ered to the kidney for excretion. In neonates and infants, small peptides (such as glutathione), they can be substrates
the quantity of amino acids that enter into urea production for protein synthesis, or they can function as individual
is small, presumably due to substantial need of amino acids amino acids in the urea cycle. Specific amino acids can act
for growth; therefore, BUN will be low.64 as substrates, regulators, transporters, and precursors to
The kidney plays a minor role in amino acid and protein neurotransmitters and hormones.67
metabolism. Ninety percent of dietary protein nitrogen is In the cell, protein can be utilized for energy or it can be
incorporated into new tissue, and therefore never requires stored. There is a continuous flux of proteins being broken
formation of urea in the liver, and excretion by the kidney. down. The carbon chain of the amino acids can be utilized
In premature infants and neonates, excretion of nitrogen is for energy, and free amino acids can be released back into the
limited for the first months of life. Tubular reabsorption of plasma to maintain plasma amino acid concentrations. 67
amino acids is reduced in premature infants and neonates, After synthesis within the cell, many proteins are
Table 5-5 Functions of Amino Acids and Protein67

Function Example
Amino acids
Substrates for protein synthesis Amino acids with a codon
Regulators of protein turnover Leucine, arginine
Regulators of enzyme activity (allosteric) Arginine and NAG synthetase, Phe and PAH activation
Precursor of signal transducer Arginine and nitric oxide
Methylation reactions Methionine
Neurotransmitters Tryptophan (serotonin); glutamate, glycine, GABA
Ion fluxes Taurine; glutamate
Precursor of physiologic molecules Arginine (creatinine); glutamine
Nitrogen transport Alanine; glutamine
Oxidation and reduction Cystine; glutathione
Precursor of conditionally indispensable amino acids Methionine (cys); phe (thy)
Gluconeogenic substrate and fuel Alanine; serine; glutamine
Proteins
Enzymatic catalysis BCKADH
Transport B-12 binding proteins; ceruloplasmin; apolipoproteins
Messenger / signals Insulin; growth hormones
Movement Kinesin; actin
Structure Collagens; elastin
Storage / sequestration Ferritin; metallothionein
Immunity Antibodies; TNF; interleukins
Growth; differentiation; gene expression EGF; IGFs; transcription factors

released into the plasma. The three major types of plasma Assessment of Protein Status
proteins are albumin, globulin, and fibrinogen. Albumin’s Besides monitoring of visceral proteins (ie, albumin, TTR)
role is to maintain osmotic pressure in the plasma. Globu- and acute phase proteins (ie, CRP), nitrogen balance can
lins are involved in enzymatic activity in the plasma, as well be a useful tool in monitoring protein repletion and deple-
as playing a vital role in natural and acquired immunity. tion in pediatric patients receiving specialized nutrition
Fibrinogen is essential for coagulation, both in blood clot- support. Nitrogen balance is an estimate of nitrogen intake
ting and repair of blood vessels.67 For specific examples of minus nitrogen excretion. In adults, urinary urea nitrogen
the functions of amino acids and protein refer to Table 5-5. (UUN in g/L × 1.2 to yield total urinary nitrogen (TUN))
multiplied by the urine volume (L/d) plus 2 to 4 g nitrogen
Protein Requirements and Protein-Energy (to reflect all other unmeasured nitrogen lost) results in
Ratio During Growth nitrogen balance. The method for collection and calculation
Protein requirements (similar to total caloric requirements) of nitrogen balance is altered in pediatric patients.
are greater for VLBW neonates and gradually decrease with Urine collections in neonates and infants are problem-
increased age.28 VLBW neonates have the highest protein atic, but not impossible. The use of urine bags with attentive
requirements, often requiring 3 to 4 g/kg/d, while term clinician support, or collection of diapers with elution of
neonates require 2 to 2.5 g/kg/d. Protein requirements all urinary and stool nitrogen, has been used successfully
in term infants are based on studies in freely breastfed in the clinical arena to assess nitrogen output in children.72
infants.68 Protein is essential for growth, and its requirement While 24-hour urine collections have been considered the
increases during periods of rapid growth and decreases with standard, there is published experience using 6-hour collec-
slowed growth. In infancy, 55% of daily protein is dedicated tion in pediatrics.73 These authors are more comfortable
for growth while 45% is for maintenance. This ratio gradu- using 24-hour urine collections to predict actual nitrogen
ally decreases and by 4 years of age only about 10% of total balance over the period of observation.
protein requirement is utilized for growth and the remaining Nitrogen balance has been reviewed nicely in the
90% is used for daily maintenance.69 Refer to Table 5-6 for Protein chapter of The A.S.P.E.N. Nutrition Support Core
age-based protein requirements. Curriculum,1 but several issues should be considered when
completing nitrogen balance studies in pediatrics. Helms
Table 5-6: Protein Requirements68 characterized nitrogen excretion in stressed pediatric
Protein (g/kg/d) intensive care unit patients and sick neonates.74 Urea as
Very Low Birth Weight 3–4 a percentage of total nitrogen output was in the range of
Preterm 2.5–3 40% to 60%, distinctly different from the 80% excretion as
Infant / neonate 2–2.5 urea assumed in adults. Because the percentage of nitrogen
Infant 1.5–2 excreted as urea is substantially different than the adult
Preschool / School age 1–1.5 patient and varies with clinical condition, it is recommended
Adolescent 0.8–1.5 that TUN be used to increase accuracy and reliability for
Many studies have demonstrated that adequate protein both children and adults.
may be more critical for nutritional status and growth than
total caloric requirements in preterm neonates and sick chil- Monitoring Plasma Amino Acids
dren.18 Protein requirements can be increased by as much as Plasma amino acids have been widely reported in pedi-
20% to 50% in critical illness, thermal injury, and catch-up atric patients. Storm75 reviewed the hypothesis regarding
growth.70 normalization of plasma amino acids, and its validation
Early initiation of protein has been shown to be benefi- as a predictive tool in understanding outcome in neonates
cial in extremely low birth-weight infants. Poindexter et al. and infants receiving PN. This led to a number of inves-
concluded that early amino acid administration was signifi- tigations suggesting normalization results in improved
cant for better growth outcomes and neurodevelopment growth, nitrogen balance, increased calcium and phos-
when evaluated at 36 weeks postmenstrual age and again at phorus intakes, and improved liver health.76–80 It is likely
18 months follow-up.71 that plasma amino acids will continue to be a benchmark
for efficacy of newly developed pediatric amino acid formu-
lations. It is unclear whether plasma amino acid assessment

will ultimately migrate to the clinical environment as a Test Your Knowledge Questions
useful tool for evaluating efficacy in the individual pediatric 1. All of the following are functions of taurine EXCEPT:
patient; this will require less expensive and more accessible A. Antioxidant
analytical technologies than those currently used in clinical B. CNS development
research. C. Nitrogen transport
D. Bile acid conjugation
Case Presentation and Discussion E. Immunoregulation
A 2-month-old female was admitted to the hospital today 2. Which of the following is an advantage of human milk
after having been seen by her primary care physician for a over bovine milk?
well baby visit. She was born at 38 weeks gestation with a A. Human milk contains IgA which is important in
birth weight of 3.4 kg. Her weight in the clinic today was host defense.
3.1 kg. The mother reports that she had to return to work B. Human milk has a decreased whey content that
2 weeks ago and transitioned her daughter from breast promotes rapid gastric emptying.
milk to an infant formula. Since then, the infant has had C. Human milk has an increased caloric density as
increased fussiness, crying, spitting up, and small specks of compared to bovine milk.
blood in the stool. The infant was admitted with a diagnosis D. Human milk prevents children from developing
of feeding intolerance and failure to thrive. The nutrition colic.
team was consulted to evaluate the infant’s nutrition needs. E. All of the above are advantages of human milk.
Question: Explain how the infant’s symptoms could 3. Protein digestion:
be associated with the change from breast milk to an infant A. Occurs mostly in the small intestine.
formula. B. Is dependent on hydrochloric acid and pepsin to
Comment: Human milk has an increased whey content denature protein.
that is more easily digestible and promotes gastric emptying. C. Has been identified as early as 16 weeks gestation,
Bovine milk is composed of beta-lactoglobulin, which is but gastric acid secretion does not reach adult levels
associated with protein allergy, feeding intolerance, and until 38 weeks gestation.
colic. D. Products include approximately 30% oligopeptides
Question: What are your recommendations for this and 70% amino acids.
infant’s nutrition? 4. Which of the following is TRUE regarding nitrogen
Comment: Since this patient has demonstrated feeding balance?
intolerance after switching from human milk to this infant A. Nitrogen balance is not an accurate way to assess
formula, it would be prudent to change her to an infant protein needs in a pediatric patient.
formula that is easier to digest. A hydrolyzed or amino acid- B. In order to estimate a nitrogen balance, you must do
based formula should be considered for this infant. a 24-hour urine collection.
Question: What is the estimated protein requirement C. Total urinary nitrogen (TUN) is a better estimate of
for this infant? urinary losses as compared to urinary urea nitrogen
Comment: Infants require approximately 2 g/kg/d of (UUN).
protein. Because this infant has lost weight from her birth D. Nitrogen balance is an estimate of nitrogen intake
weight, protein should be dosed based on the birth weight divided by nitrogen excreted.
of 3.4 kg. This corresponds to a total protein dose of approx-
imately 7 g/d. See p. 487 for answers.
Question: What is the best nethod of monitoring nutri-
tion status in this patient? References
Comment: The best method for evaluation of protein 1. Young LS, Kearns LR, Schoepfel SL. Protein. In: Gottschlich
and overall nutrition status in this patient would be daily MM, DeLegge MH, Mattox T, Mueller C, Worthington
P, eds. The A.S.P.E.N. Nutrition Support Core Curriculum:
weights. At this time there is no indication that this infant A Case-Based Approach – The Adult Patient. Silver Spring,
has higher than normal protein or caloric requirements. If MD: American Society for Parenteral and Enteral Nutrition;
the infant does not gain weight with appropriate protein 2007:71–87.
and calories, further evaluation may be necessary.

2. Gilger MA. Normal gastrointestinal function. In: McMillan 18. Motil KJ. Meeting protein needs. In: Tsang RC, Zlotkin SH,
JA, Feigin RD, DeAngelis C, Jones MD, eds. Oski’s Pediatrics. Nichols BL, Hansen JW, eds. Nutrition During Infancy: Prin-
4th ed. Philadelphia, PA: Lippincott Williams & Wilkins; ciples and Practice. 2nd ed. Cincinnati, OH: Digital Education
2006:1915–1921. Publishing, Inc; 1997:83–103.
3. Berseth CL. Overview of the development of the gastrointes- 19. Philipps AF, Sherman MP. Neonatal nutrition and gastroin-
tinal tract. UpToDate Web site. http://www.uptodate.com/ testinal function. In: Rudolph CD, Rudolph AM, Hostetter
home/index.html. October 11, 2005. Accessed December 19, MK, Lister GE, Siegel NJ, eds. Rudolph’s Pediatrics. 21st ed.
2008. New York, NY: McGraw-Hill; 2003.
4. Lucas A, Bloom SR, Aynsley-Green A. Development of gut 20. Hansen JW, Boettcher JA. Human milk substitutes. In: Tsang
hormone responses to feeding in neonates. Arch Dis Child. RC, Zlotkin SH, Nichols BL, Hansen JW, eds. Nutrition
1980;55(9):678–682. During Infancy: Principles and Practice. 2nd ed. Cincinnati,
5. Berseth CL, Nordyke CK, Valdes MG, Furlow BL, Go VL. OH: Digital Education Publishing, Inc; 1997:441–466.
Responses of gastrointestinal peptides and motor activity to 21. Schanler, RJ. Nutritional composition of human milk and
milk and water feedings in preterm and term infants. Pediatr preterm formula for the premature infant. UpToDate Web site.
Res. 1992;31(6):587–590. http://www.uptodate.com/home/index.html. September 7,
6. Moreau H, Bernadac A, Gargouri Y, Benkouka F, Laugier 2007. Accessed December 19, 2008.
R, Verger R. Immunocytolocalization of human gastric 22. Lönnerdal B, Cederblad A, Davidsson L, Sandström B.
lipase in chief cells of the fundic mucosa. Histochemistry. The effect of individual components of soy formula and
1989;91(5):419–423. cow’s milk formula on zinc bioavailability. Am J Clin Nutr.
7. Armand M, Hamosh M, Mehta NR, et al. Effect of human 1984;40(5):1064–1070.
milk or formula on gastric function and fat digestion in the 23. Brock, JH. Lactoferrin in human milk: its role in iron absorp-
premature infant. Pediatr Res. 1996;40(3):429–437. tion and protection against enteric infection in the newborn
8. Armand M, Hamosh M, DiPalma JS, et al. Dietary fat modu- infant. Arch Dis Child. 1980 Jun;55(6):417–421.
lates gastric lipase activity in healthy humans. Am J Clin Nutr. 24. Lönnerdal B. Digestibility and absorption of protein in
1995;62(1):74–80. infants. In: Räihä NC, ed. Protein Metabolism During Infancy.
9. Rudolph CD. Structure and development of the gastrointes- New York, NY: Raven Press; 1994:53–65.
tinal tract. In: Rudolph CD, Rudolph AM, Hostetter MK, 25. Lindberg T, Ohlsson K, Weström B. Protease inhibitors and
Lister GE, Siegel NJ, eds. Rudolph’s Pediatrics. 21st ed. New their relation to protease activity in human milk. Pediatr Res.
York, NY: McGraw-Hill; 2003. 1982 Jun;16(6):479–483.
10. Wahbeh GT, Christie DL. Basic aspects of digestion and 26. Davidson LA, Löonnerdal B. Fecal alpha 1-antitrypsin
absorption. In: Wyllie R, Hyams JS, eds. Pediatric Gastrointes- in breast-fed infants is derived from human milk and is
tinal and Liver Disease: Pathophysiology, Diagnosis, Management. not indicative of enteric protein loss. Acta Paediatr Scand.
3rd ed. Netherlands: Saunders Elsevier; 2006:11–23. 1990;79(2):137–141.
11. Colaizzo-Anas T. Nutrient intake, digestion, absorption, 27. Rose WC. The amino acid requirements of adult man. Nutr
and excretion. In: Gottschlich MM, DeLegge MH, Mattox Abstr Rev. 1957;27:631–647.
T, Mueller C, Worthington P, eds. The A.S.P.E.N. Nutrition 28. Nasset ES, Gatewood VH. Nitrogen balance and hemoglobin
Support Core Curriculum: A Case-based Approach – The Adult of adult rats fed amino acid diets low in L- and D-histidine. J
Patient. Silver Spring, MD: American Society for Parenteral Nutr. 1956;53:163–176.
and Enteral Nutrition; 2007:3–18. 29. Kopple JD, Swendseid ME. Evidence that histidine is an
12. Mason JB. Mechanisms of nutrient absorption and malab- essential amino acid in normal and chronically uremic man.
sorption. UpToDate Web site. http://www.uptodate.com/ J Clin Invest. 1975;55:881–891.
home/index.html. October 18, 2007. Accessed December 19, 30. Kopple JD, Swendseid ME. Effect of histidine intake on plasma
2008. and urine histidine levels, nitrogen balance and N-methylhis-
13. DeLegge MH, Ridley C. Nutrient digestion, absorption, and tidine excretion in normal and chronically uremic men. J Nutr.
excretion. In: Gottschlich, MM, Fuhrman MP, Hammond 1981;111:931–942.
KA, Holcombe BJ, Seidner DL, eds. The Science and Practice of 31. Snyderman SE, Boyer A, Roitman E, Holt LE Jr, Prose
Nutrition Support: A Case-Based Core Curriculum. Dubuque, PH. The histidine requirement of the infant. Pediatrics.
IA: Kendall/Hunt Publishing Co; 2001:1–16. 1963;31:786–801.
14. Hadorn B, Tarlow MJ, Lloyd JK, Wolff OH. Intestinal enter- 32. Heird WC, Dell RB, Helms RA, et al. Evaluation of an amino
okinase deficiency. Lancet. 1969;1(7599):812–813. acid mixture designed to maintain normal plasma amino acid
15. Johnson TR, Moore WM, Jeffries JE. Developmental Physiology. patterns in infants and children requiring parenteral nutrition.
2nd ed. Columbus, OH: Ross Laboratories; 1978:150–152. Pediatrics. 1987;80:401–408.
16. Roy CC, Silverman A, Alagille D. Pediatric Clinical Gastro- 33. Heird WC, Hay W, Helms RA, Storm MC, Kashyap S, Dell,
enterology. 4th ed. St. Louis, MO: Mosby-Year Book, Inc; RB. Pediatric parenteral amino acid mixture in low birth
1995:307–309. weight infants. Pediatrics. 1988;81(1):41–50.
17. Axelsson I, Jakobsson I, Lindberg T, Polberger S, Benedik-
tsson B, Räihä NC. Macromolecular absorption in preterm
and term infants. Acta Paediatr Scand. 1989;78(4):532–537.

34. Anonymous. Practice guidelines: protein requirements. 52. Thomas DW, Sinatra FR, Hack SL, Smith TM, Platzker ACG,
In: Guidelines for the Use of Parenteral and Enteral Nutri- Merritt RJ. Hyperammonemia in neonates receiving intrave-
tion in Adult and Pediatric Patients. J Parenter Enteral Nutr. nous nutrition. J Parenter Enteral Nutr. 1982;6:503–506.
2002;26:27SA–28SA. 53. Motil KJ, Harmon WE, Grupe WE. Complications of essen-
35. Jackson AA. Amino acids: essential and non-essential? Lancet. tial amino acid hyperalimentation in children with acute renal
1983;1:1034–1037. failure. J Parenter Enteral Nutr. 1980;4:32–35.
36. Snyderman SE. The protein and amino acid requirements of 54. Laidlaw SA, Kopple JD. Newer concepts of the indispensable
the premature infant. In: Ionxix JHP, Visser HKA, Troelstra amino acids. Am J Clin Nutr. 1987;46:593–605.
JD, eds. Metabolic Processes in the Fetus and Newborn Infant. 55. Raiha NCR, Suihkonen J. Development of urea-synthe-
Leiden: HE Stenfert Kroesse NV; 1971:128–141. sizing enzymes in human liver. Acta Pediatr Scand.
37. Pohlandt F. Cystine: a semi-essential amino acid in the 1968;57:121–124.
newborn infant. Acta Pediatr Scand. 1974;63:801–804. 56. Raiha NCR, Lindros KO. Development of some enzymes
38. Gaull G, Sturman JA, Raiha NCR. Development of mamma- involved in gluconeogenesis in human liver. Ann Med Exp
lian sulfur metabolism: absence of cystathionase in human Biol. 1969;47:146–150.
fetal tissues. Pediatr Res. 1972;6:538–547. 57. Helms RA, Dickerson RN, Ebbert ML, Christensen ML,
39. Sturman JA, Gaull G, Raiha NCR. Absence of cysta- Herrod HG. Retinol-binding protein and prealbumin: useful
thionase in human fetal liver: is cystine essential? Science. measures of protein repletion in critically ill, malnourished
1970;169:74–76. infants. J Pediatr Gastroenteral Nutr. 1986;5:586–592.
40. Zlotkin SH, Anderson GH. Sulfur balances in intravenously 58. Beutler E. Nutritional and metabolic aspects of glutathione.
fed infants: effects of cysteine supplementation. Am J Clin Annu Rev Nutr. 1989;9:287–302.
Nutr. 1982;36: 862–867. 59. Meister A. On the enzymology of amino acid transport.
41. Helms RA, Chesney RW, Storm MC. Sulfur amino acid Science. 1973;180:33–39.
metabolism in infants on parenteral nutrition. Clin Nutr. 60. Svartz J, Hallin E, Soderstorm M, Hammarstrom S. Identifi-
1995;14:381–387. cation of regions of leukotriene C4 synthase which direct the
42. Helms RA, Christensen ML, Storm MC, Chesney RW. enzyme to its nuclear envelope localization. J Cell Biochem.
Adequacy of sulfur amino acid intake in infants receiving 2006;98;1517–1527.
parenteral nutrition. Nutr Biochem. 1995;6:462–466. 61. Yamamoto H, Aikawa T, Matsutaka H, Okuda O, Ishikawa
43. Vinton NE, Ament ME, Heckenlively JR, et.al. Visual func- E. Interorganal relationships of amino acid metabolism in fed
tion in patients in patients undergoing home total parenteral rats. Am J Physiol. 1974;226;1428–1433.
nutrient. Am J Clin Nutr. 1986;43:689. 62. Munro HN. Fifth annual Jonathan E. Rhoads lecture. Meta-
44. Sturman JA, Hayes KC. The biology of taurine in nutrition bolic integration of organs in health and disease. J Parenter
and development. In: Draper HH, ed. Advances in Nutri- Enteral Nutr. 1982;6:271.
tion Research. Vol. 3. New York, NY: Plenum Publishing Co; 63. Rocha DM, Falona GR, Unger RH. Glucagon-stimu-
1980:231–299. lating activity of 20 amino acids in dogs. J Clin Invest.
45. Rassin DK, Sturman JA, Gaull GE. Taurine and other free 1972;51:2346.
amino acids in milk of man and other mammals. Early Hum 64. Raiha NCR, Kekomaki MP. Studies on the development of
Dev. 1978;2:1–13. ornithine-keto acid amino transferase activity in the liver.
46. Zelikovic I, Chesney RW, Freidman AL, Ahlfors CE. Taurine Biochem J. 1968;108:521–524.
depletion in very low birth weight infants receiving prolonged 65. Edelman CM, Wolfish NM. Dietary influence on renal matu-
total parenteral nutrition: Role of renal immaturity. J Pediatr. ration in premature infants. Pediatr Res. 1968;2:421–422.
1990;116:301–306. 66. Brodehl J, Gellissen K. Endogenous renal transport of
47. Helms RA, Storm MC, Christensen ML, Hak EB, Chesney free amino acids in infancy and childhood. Pediatrics.
RW. Cysteine supplementation results in normalization of 1968;42:395–404.
plasma taurine concentrations in children receiving home 67. Protein metabolism. In: Guyton AC, ed. Textbook of
parenteral nutrition. J Pediatr. 1999; 134:358–361. Medical Physiology. Philadelphia, PA: W.B. Saunders Co;
48. Christensen ML, Helms RA, Veal DF, Boehm KA, Storm MC. 1991:765–770.
Clearance of N-acetyl-L-tyrosine in infants receiving a pedi- 68. Wu PYK, Edwards N, Storm MC. The plasma amino
atric amino acid solution. Clin Pharm. 1993;12:606–609. acid pattern of normal term breast-fed infants. J Pediatr.
49. Van Goudoever JB, Sulkers EJ, Timmerman M, et al. Amino 1986;109:347–349.
acid solutions for premature neonates during the first week of 69. American Academy of Pediatrics, Committee on Nutrition.
life: the role of N-acety-L-cysteine and N-acetyl-L-tyrosine. J Protein. In: Kleinman RE. Pediatric Nutrition Handbook. 6th
Parenter Enteral Nutr. 1994;18:404–408. ed. Elk Grove Village, IL: American Academy of Pediatrics;
50. Snyderman SE, Boyer A, Holt LE Jr. The arginine requirement 2009:325–341.
of the infant. AMA J Dis Child. 1959;97:192–195. 70. Scrimshaw NS. Effect of infection on nutritional status. Proc
51. Heird WC, Nicholson JF, Driscoll JM Jr, Schullinger JN, Natl Sci Counc Repub China B. 1992;16:46–64.
Winters RW. Hyperammonemia resulting from intravenous
alimentation using a mixture of synthetic L-amino acids: a
preliminary report. J Pediatr. 1972;81:162–167.

71. Poindexter BB, Langer JC, Dusick AM, Ehrenkranz RA. Early 76. Helms RA, Christensen ML, Muer EC, Storm MC. Compar-
provision of parenteral amino acids in extremely low birth ison of a pediatric versus standard amino acid formulation
weight infants: relation to growth and neurodevelopmental in preterm neonates requiring parenteral nutrition. J Pediatr.
outcome. J Pediatr. 2006;148:300–305. 1987;110:466–470.
72. Boehm KA, et al. Assessing the validity of adjusted urinary 77. Beck R. Use of a pediatric parenteral amino acid mixture in a
urea nitrogen as an estimate of total urinary nitrogen population of extremely low birth weight neonates: frequency
in three pediatric populations. J Parenter Enteral Nutr. and spectrum of direct bilirubinemia. Am J Perinatol. 1990
1994;18(2):172–176. Jan;7(1):84–86.
73. Lopez et al. Estimation of nitrogen balance based on a six- 78. Forchielli ML, Gura KM, Sandler R, Lo C. Aminosyn PF
hour urine collection in infants. J Parenter Enteral Nutr. or TrophAmine: which provides more protection from
1986;10(5):517–518. cholestasis associated with total parenteral nutrition? J Pediatr
74. Helms RA, Mowatt-Larssen CA, Boehm KA, et al. Urinary Gastroenterol Nutr. 1995;21:374–382.
nitrogen constituents in the postsurgical preterm neonate 79. Pratt CA, Garcia MG, Poole RL, Kerner JA. Life-long total
receiving parenteral nutrition. J Parenter Enteral Nutr. parenteral nutrition versus intestinal transplantation in chil-
1993;17:68–72. dren with microvillus inclusion disease. J Pediatr Pharmacol
75. Strom MC, Helms RA. Normalizing plasma amino acid levels Ther. 2001;6:498–503.
in pediatric patients requiring parenteral nutrition. Nutr Clin 80. Fitzgerald KA, MacKay MW. Calcium and phosphate solu-
Pract. 2007;22:194–203. bility in neonatal parenteral nutrient solutions containing
TrophAmine. Am J Hosp Pharm. 1986 Jan;43(1):88–93.

6
Minerals
Winston Koo, MBBS, FACN, CNS, Mirjana Lulic-Botica, BSc, BCPS, May Saba, PharmD, BCNSP, and Letitia Warren, RD, CSP

Overview . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 45 1. Understand the physiological basis for the functions
Biochemistry and Physiology of and requirements for calcium, phosphorus, and
Sources magnesium.
Dietary Requirements 2. Understand the common risk factors for the develop-
Absorption and Excretion
Metabolism
ment of deficiency in these nutrients.
Deficiency States 3. Understand the common manifestations of deficiency
Excess Intake and Adverse Effects states for these nutrients.
Calcium. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 48 4. Understand the potential risks with excessive intake of
Biochemistry and Physiology these nutrients.
Sources
Absorption, Excretion, and Metabolism Overview
Deficiency States
Excess Intake and Adverse Effects
Biochemistry and Physiology
Phosphorus. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 50 Calcium (Ca) is the most abundant mineral in the body and
Sources together with phosphorus (P) forms the major inorganic
Absorption, Excretion, and Metabolism constituent of bone. Magnesium (Mg) is the fourth most
Deficiency States abundant cation and is the second most common intra-
Excess Intake and Adverse Effects cellular electrolyte in the body. The total body content of
Magnesium. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 52 Ca, P, and Mg in the skeleton is about 99%, 85%, and 60%,
Biochemistry and Physiology respectively.
Sources Less than 1% of the total body content of Ca, P, and
Absorption, Excretion, and Metabolism
Deficiency States
Mg is in the circulation. However, disturbances in serum
Excess Intake and Adverse Effects concentrations of these minerals are associated with distur-
bances of physiological function. These are manifested by
numerous clinical symptoms and signs. Acute changes in
the serum concentrations likely reflect adaptive changes and
do not reflect the state of tissue store, although chronic and
severely lowered serum concentrations of these minerals
usually reflect the presence of a deficiency state.
From a clinical perspective, the skeleton has the dual
function of providing both structural and mechanical
support as well as being a reservoir to maintain mineral
45
homeostasis. Deficiency of Ca and/or vitamin D and in the Table 6-1 Dietary Reference Intakes for Calcium, Phosphorus and
case of small preterm infants, deficiency of P, can result in Magnesium2,5
osteopenia and rickets in infants and children.1 In addi- Life Stage Calcium* Phosphorus† Magnesium†
mg/d mg/d mg/d
tion, numerous physiological functions of all organs are
0–6 mo* 210 100 30
dependent on the maintenance of normal circulating
7–12 mo* 270 275 75
concentrations of Ca, P, and Mg, and the integrity of the
1–3 y 500 (2500) 460 (3000) 80 (65)
skeleton. 4–8 y 800 (2500) 500 (3000) 130 (110)
Males
Sources 9–13 y 1300 (2500) 1250 (4000) 240 (350)
Natural foods and a variety of foods and beverages fortified 14–18 y 1300 (2500) 1250 (4000) 410 (350)
with Ca are good sources for these minerals. Any food that Females
provides 20% or more of the daily recommended intake per 9–13 y 1300 (2500) 1250 (4000) 240 (350)
serving for a specific nutrient is considered to be “high” in 14–18 y 1300 (2500) 1250 (4000) 360 (350)
that nutrient.2 Dietary sources of minerals, including Ca Pregnancy
fortified foods and beverages, are preferred to the use of 14–18 y 1300 (2500) 1250 (3500) 400 (350)
supplements alone because the range of nutrients and the Lactation
establishment of good dietary habits are enhanced by the 14–18 y 1300 (2500) 1250 (4000) 360 (350)
use of dietary sources. Nutrient interactions also may be UL‡ § § §
less and tolerance may be greater for minerals provided by * Adequate intake (AI) = observed or experimentally determined estimates
of nutrient intake by a group or groups of healthy people. AI is the only
food sources. reference level provided for infants < 12 mo.
Mineral supplements are freely available. However, use † Recommended dietary allowance (RDA) = average daily dietary intake
of supplements does not compensate for poor food choices sufficient to meet the requirement of 97% to 98% of healthy individuals
and inadequate diet. Furthermore, the Food and Drug in a life stage and gender group.
Administration (FDA) regulates dietary supplements under ‡ Tolerable upper intake level (UL) = highest level of daily nutrient intake
a different set of regulations than drug products (prescrip- that is likely to pose no risk of adverse health effects to almost all
individuals in the general population.
tion and over-the-counter). As a result, specific contents of
§ Upper limit for each life stage is indicated in parenthesis. For
dietary supplements and contaminants are not as rigorously magnesium, applies to non-food sources only.
monitored. 3
Dietary Requirements Absorption and Excretion

Mineral requirements depend on the needs for tissue Intestinal absorption of these minerals involves a passive
synthesis in growing children and the balance among paracellular concentration-dependent process as well as
dietary supply, intestinal absorption, renal excretion, and a saturable active transcellular process. Vitamin D has
bone exchange for these minerals. There are a number of some influence on the active intestinal transport but its
unique challenges in maintaining mineral homeostasis role under normal circumstances appears to be much less
during infancy, childhood, and adolescence. All neonates than the passive diet-dependent process in the growing
must adapt successfully to extrauterine life when the child. Renal reabsorption of these minerals also has passive
continuous supply of these minerals from the placenta is and active transport components. It is highly efficient but
interrupted at birth. This adaptation is usually achieved an excessive intake can overwhelm the renal reabsorption
with appropriate nutrition support, even in critically ill capacity, leading to elevated circulating levels for each of
and preterm neonates.4 Nutrition requirements for these these minerals. Conversely, during deficient states, espe-
minerals remain high until completion of skeletal growth. cially if there is abnormal loss from the gastrointestinal
Infants and adolescents have the greatest requirements (GI) tract or the kidney, renal conservation alone is unable
because of their high growth rates. The average gain in to prevent the development of abnormally low circulating
skeletal growth over 1 year is > 25 cm for an infant and is concentrations. Normally, the growing child has net bone
even greater for the preterm infant. The peak height gain is (and soft tissue) accretion of these minerals. Some exchange
about 7 to 10 cm per year during adolescence. The recom- of these minerals occurs normally with bone modeling.
mended dietary reference intakes (DRIs) for Ca, P, and Mg The exchangeable portion may be increased during
are shown in Table 6-1. periods of stress and increased turnover. During extreme

MINERALS 47
circumstances (eg, severe Ca or P deficiency in infants) it is Table 6-2 Dietary Sources of Calcium5–7
not possible to protect the skeleton or to maintain mineral Dietary calcium (mg) Calcium–enriched food (mg)
homeostasis. Milk 240 mL (285–302) Fortified orange and other fruit
juices 180 mL (200–260)
Metabolism Yogurt 240 g (245–415) Instant drink mix with 240 mL
water (105–250)
Maintaining mineral homeostasis requires a complex inter-
Cheese single-wrapped ¾ oz Ready-to-eat cereals 1 cup
action of hormonal and non-hormonal factors; adequate (120), others (140–210/oz) (100–1,000)
functioning of various body systems, in particular the Chocolate pudding made with Breads/English muffins 30 g (30)
renal, gastrointestinal, skeletal, and endocrine systems; and 120 mL 2% milk (153)
adequate dietary intake. When assessing changes in serum Sardines with bones 90 g (270) Tortilla corn one 6” diameter
(1.2 oz) (40)
concentrations of these minerals, it is vital to understand
Salmon 90 g (181) Tortilla flour one 6” diameter
there is an interrelationship among them. For example, (1.75 oz) (58)
hypomagnesemia may cause hypocalcemia, due to the Chinese cabbage 1 cup shredded Tofu 3 oz (60–150)
decreased action of parathyroid hormone (PTH). Serum and boiled (158)
Ca and P have a reciprocal relationship, and hypoalbumin- Broccoli chopped 1 cup (100)
emia can cause hypocalcemia secondary to decreased Ca Kale 1 cup (90)
binding, while ionized calcium (unbound calcium) concen- Several servings of certain foods with less bioavailable calcium (eg,
tration remains normal. vegetables) are needed to achieve the same amount of calcium absorbed
from 1 serving (240 mL) of milk.
At the intestine-kidney-bone axis, intake of minerals
may interact with other nutrients including protein, sodium, Risks for mineral deficiency escalate with increased
potassium, vitamin D, iron, zinc, and copper. There may be requirement, decreased absorption or increased losses
significant effects on intestinal absorption, renal excretion, through the GI tract or the kidney, or disturbed metabo-
or metabolism of the minerals or on these other nutrients. lism. All rapidly growing infants, especially extremely low
Direct regulation on this axis by PTH, 1,25-dihydroxyvi- birth weight (< 1 kg) preterm infants, are at risk for mineral
tamin D, and fibroblast growth factor-23, and indirect deficiency because of increased requirement, intolerance to
regulation by growth-regulating hormones including sex multiple nutrients during acute illness, and interference with
hormones, also significantly affect growth and mineraliza- mineral retention or metabolism from therapies. Critically
tion of the skeleton, and maintenance of normal circulating ill neonates or children who require parenteral nutrition
concentrations of these minerals. A negative effect on (PN) are often intolerant to increased nutrient intake,
mineral metabolism is possible, particularly if minerals and especially the energy load. Thus, it is unrealistic to expect
other nutrients stated above are ingested in large amounts any critically ill child to achieve normal growth (ie, normal
as dietary supplements. Thus, it is vital to manage the cause anabolic state). In critically ill preterm neonates, growth
of the abnormalities in addition to providing symptomatic rarely reaches the in utero rate, thus the needs for minerals
treatment to the abnormal circulating concentration of the are correspondingly less compared to stable and growing
minerals. patients. There is no convincing evidence of mineral defi-
ciency in the stable small preterm infant who is receiving
Deficiency States adequate volumes (> 150 mL/kg/d) of high-energy preterm
Low dietary intake for Ca is common in older children. Less infant formula or mother’s milk with commercial human
than 40% of boys and < 30% of girls 6 years or older receive milk fortifier containing energy and high mineral contents
the recommended daily adequate intake for Ca. Preoccupa- and is not receiving any medications that might interfere
tion with being thin is common in adolescents, especially with mineral absorption, excretion, or metabolism.
among females, as is the misconception that all dairy foods Malabsorption states, chronic therapy with loop
are fattening. Many children and adults are unaware that diuretics and gastric acid inhibitors, or heritable disorders
low-fat milk contains at least as much Ca as does whole of mineral metabolism are associated with abnormalities in
milk. A list of foods relatively high in Ca is shown in Table mineral retention and/or metabolism.1,5 In disease states,
6-2. Low Ca intake places children at risk for fractures, and deficiency involving multiple minerals and additional
both Ca and vitamin D deficiency are factors in the develop- nutrients may be unmasked during therapy. This is best
ment of rickets in infants and young children. 8,9 represented by the development of hypophosphatemia,

hypomagnesemia, and hypokalemia simultaneously during the cellular level through the action of ionized Ca, which
refeeding of severely malnourished individuals. functions both as extra- and intracellular messenger. Its
role as a secondary messenger is critical to numerous
Excess Intake and Adverse Effects bodily functions including muscle contraction, blood vessel
The most common risk factor for excessive intake of contraction and expansion, the secretion of hormones and
minerals is associated with increased parenteral intake of enzymes, and message relay through the nervous system. 2
minerals from the unrealistic expectation of normal growth In 1993 the FDA authorized placement of a health claim
in the critically ill child. Minerals delivered via parenteral on food labels that states “adequate Ca intake throughout
routes can exceed the excretory capacity, resulting most life is linked to reduced risk of osteoporosis through the
commonly in hyperphosphatemia and hypermagnesemia mechanism of optimizing peak bone mass during adoles-
with associated hypocalcemia.1,4 These findings may in part cence and early adulthood and decreasing bone loss later in
reflect “shifts” in minerals among various compartments life,” and the addition of vitamin D to this claim is currently
but they also suggest that delivery of minerals can occur in being considered.11 Calcium may contribute among other
excess of the body’s needs. nutrition factors to the prevention of chronic diseases such
Adverse effects from excess dietary intake of minerals as hypertension.12
occur rarely in normal pediatric ages. However, it is possible
that some healthy infants may develop hyperphosphatemia Sources
and secondary hypocalcemia from feeding of standard Calcium is present in many dietary sources with dairy
infant formula. This is the result of a combination of higher products having the best bioavailability (Table 6-2) and
intake of P from infant formulas relative to breast milk, and accounting for > 70% of dietary Ca intake in the United
the inability to eliminate the excess P because of imma- States.2,5 Non-fat and reduced fat dairy products contain the
ture kidney and parathyroid gland function.1,4 Most of the same amount of Ca as regular dairy products. Some food
adverse effects of excess mineral intake are due to excessive sources (eg, fruit juices, fruit drinks, tofu, and cereals) are
intake of supplements in pharmacologic doses and may fortified with various Ca compounds that are well absorbed.
result in serious morbidity and even mortality. The deriva- Calcium is present in human milk in relatively constant
tion of the current recommendation for the upper level of amounts between 200 to 250 mg/L. Various Ca salts are
intake of Mg is based on the amount of supplement. 2 added to cow’s milk formulas for term infants to provide
at least 60 mg/100 kcal. This is about twofold higher than
Calcium the Ca density in human milk.13 Calcium fortification of
(1 mmol = 40 mg) formulas for small preterm infants may be four- to sixfold
higher than human milk.
Biochemistry and Physiology Oral supplements such as calcium compounds
Calcium is the most abundant mineral in the human containing carbonate and citrate are the most common
body and accounts for about 1% to 2% of adult human although preparations containing other anions are available.
body weight. More than 99% of total body Ca is stored Naturally occurring products (eg, oyster shell marketed as
in the bones and teeth where it functions to support their calcium supplement) contain high levels of lead, mercury,
structure. Thus, calcium is critical for normal growth and and other potentially toxic contaminants.14 Common
development of the skeleton and teeth.10 The remaining 1% parenteral supplements include calcium gluconate and
is found throughout the body in blood, muscle, and other calcium chloride but other compounds also are available.
tissues and is critical to numerous physiological functions. The proportion of elemental calcium by weight varies with
In the circulation, ~50% of Ca is ionized and the rest is the calcium compound and is 40% for carbonate, 38% for
bound to albumin or complexed to small anions such as tribasic calcium phosphate, 21% for citrate, 13% for lactate,
citrate, bicarbonate, and phosphorate. 9% for gluconate, and 6.4% for glubionate.14,15
Optimal bodily function depends on maintaining
the circulating total and especially ionized Ca concen- Absorption, Excretion, and Metabolism
tration within a narrow range. Calcium exerts its effect Gastric acid aids in the digestion of natural or Ca fortified
either through a membrane-bound Ca sensing receptor food or drink. Some Ca compounds such as calcium citrate
(a member of the G protein-coupled receptor (GPCR) are better absorbed in those individuals who have decreased
family, expressed on numerous organs and tissues) or at gastric acid when compared to calcium carbonate. About

MINERALS 49
90% of the Ca absorbed is through the small intestine and dietary intake and hormonal control of PTH and the active
< 10% is absorbed through the large intestine. Paracellular vitamin D metabolite, 1,25-dihydroxyvitamin D, with addi-
absorption takes place throughout the small intestine and is tional modulation by other factors.1 Classic target organs
dependent on concentration gradient. Transcellular absorp- critical to Ca homeostasis include the GI tract, kidney, and
tion takes place largely in the duodenum and is dependent bone. In pediatrics, the gut and kidney act primarily in the
on 1,25-dihydroxyvitamin D. capacity of retaining Ca for the growth needs of the bone,
The efficiency of Ca absorption decreases with increased hence there is always a positive Ca balance during growth.
amounts of Ca consumed and with the presence of non-Ca Dietary Ca, physical activity, and pubertal stage have inde-
components of the diet. The latter include the type and pendent effects on the rate of bone mineralization. 24,25
content of carbohydrate, phytic acid (whole grain bread, Maintenance Ca intake generally should be in the form
wheat bran, beans, seeds, nuts, grains, and soy isolates), of foods because of the range of other nutrients present in
and/or oxalic acid (spinach, collard greens, sweet potatoes, various foods. Foods fortified with Ca have increased the
rhubarb, and beans) that may bind to Ca and prevent its choices of Ca rich foods in the diet. 5
optimal absorption. These plant substances do not appear
to interfere with Ca absorption from other foods. Deficiency States
Calcium is excreted through feces, urine, and sweat. Risk factors for a deficient state include increased need, such
Calcium excretion can be increased by many factors as the rapidly growing infant, or the presence of disease
including high intake of dietary sodium, protein, and states that affect Ca digestion, absorption, or metabolism.
caffeine. High potassium intake lowers urinary Ca thereby Physically active females, particularly those with secondary
affecting the net Ca absorption. 2,16 The effect of dietary P on menstrual disorders, may have lower Ca absorption and
Ca and bone metabolism is limited if Ca intake is adequate. 5 decreased bone formation, and adequate Ca intake is impor-
The detrimental effects of consuming foods high in phos- tant to their bone health.26 Lactose-intolerant individuals
phate such as carbonated soft drinks is probably due to the may be at risk for Ca deficiency, not due to an inability to
replacement of milk with soda rather than the phosphate absorb Ca, but rather from the avoidance of dairy products. 2
level itself.17 Chronic use of Mg antacids and potent loop Drinking milk with a meal and other dietary options (eg,
diuretics such as furosemide can increase urinary Ca excre- choosing aged cheeses (such as Cheddar and Swiss) which
tion. Aluminum antacids should not be used, especially for contain little lactose, yogurt which contains live active
those with limited renal function such as infants, because cultures that aid in lactose digestion, or lactose-reduced
of potential aluminum toxicity.18 Chronic therapy with a and lactose-free milk) may allow increased Ca intake. Strict
proton pump inhibitor raises risks for fractures.19 vegans27 should include adequate amounts of non-dairy
Retention of Ca generally reflects the body’s need. It is sources of Ca in their daily diets or likely will need a Ca
usually higher in individuals undergoing rapid growth and supplement to meet the recommended Ca intake.
may be > 60% of dietary intake. Adequate intakes of Ca that Dietary Ca deficiency is a risk factor for fractures8
meet or exceed the amount needed to maintain a nutritional although it is usually not associated with clinical or biochem-
state of adequacy in nearly all members of a specific age and ical manifestations unless the Ca intake is extremely low.
gender group are shown in Table 6-1. The pregnant and Hypocalcemia does not usually occur due to low Ca intake
lactating adolescent theoretically could have an increased alone but occurs with concomitant deficiency of vitamin
need for Ca because of the need to support the bone miner- D or Mg or associated medical problems. Severe hypocal-
alization of the mother and the fetus. Limited data indicate cemia may result in clinical signs and symptoms that may
there is a compensatory increase in Ca absorption and any be subtle and vary with maturity of the individuals. Preterm
decrease in bone mass is replenished upon return of ovarian infants often manifest with non-specific symptomatology
function and no additional increase in dietary Ca intake is that may include irritability, jitteriness or lethargy, feeding
recommended.2 However, pregnant women with adequate poorly with and without feeding intolerance, abdominal
diets except for very low Ca intake can lower the fetal bone distention, apnea, cyanosis, and seizures. These features
mineral content. This is prevented by an adequate Ca intake may be confused with manifestations of hypoglycemia,
from diet or from Ca supplementation. 20 At all ages,21 partic- sepsis, meningitis, anoxia, intracranial bleeding, and
ularly in young children, dietary Ca absorption is primarily narcotic withdrawal. The degree of irritability of the infant
regulated by Ca 22 rather than vitamin23 intake. does not appear to correlate with serum Ca values. In more
Calcium homeostasis is maintained by a combination of mature individuals, other symptoms and signs may include

tetany from peripheral hyperexcitability of motor nerves. tissues of the skeleton and teeth, in biological membranes
In chronic deficient states, Ca is mobilized from the skel- as phospholipids, and in cells as nucleotides and nucleic
eton to maintain Ca levels in the blood and predisposes to acids. About 85% of P is in the skeleton, primarily in the
suboptimal bone accretion. In young children, both Ca and form of hydroxyapatite. Of the remainder, 14% is intracel-
vitamin D deficiency have a key role in the development of lular (primarily in the soft tissues) and 1% is extracellular
rickets.9 Resolution of hypocalcemia may not be possible in the circulation and interstitial fluid. Of the extracellular
until the underlying cause has been corrected. For example, P, 70% is organic and contained within phospholipids, and
hypocalcemia secondary to Mg deficit may not be correct- 30% is inorganic. 31 At pH of 7.4, the mono- and di-hydrogen
able until Mg replacement therapy is initiated. form is in a ratio of about 4:1. For that reason, P is usually
expressed in mmol rather than mEq/L.
Excess Intake and Adverse Effects The serum or plasma P concentration is ~1 to 2 mmol/L
Excess Ca intake can result in hypercalcemia (serum or (3.1–6.2 mg/dL) and is higher at younger ages. Plasma P
plasma total Ca > 11 mg/dL or ionized Ca > 5.6 mg/dL, concentrations of preterm infants is about 0.5 mmol higher
respectively) and its complications of polyuria and poly- but may be as high as 2.81 mmol/L (8.7 mg/dL) without
dipsia, renal calculi, and metastatic calcification. High affecting plasma Ca concentration.1 This minute compart-
dietary Ca intakes and routine Ca supplementation gener- ment of P is the major source of exchange of P associated
ally do not cause hypercalcemia. However, high Ca intake with dietary uptake and absorption, renal excretion and
has the potential to interfere with the absorption of other reabsorption, and bone modeling and remodeling. This
minerals such as iron, zinc, Mg, and P. Calcium supplements compartment is also the primary source of P for struc-
have the potential to interact with several prescription tural and high-energy phosphate in the cells of all tissues.
and over-the-counter medications. 28,29 Calcium decreases When extracellular fluid P concentrations are low, cellular
absorption of digoxin, fluroquinolones, levothyroxine, dysfunction follows.
tetracycline, tiludronate disodium, phenytoin, and mineral A normal level of P in the extracellular fluid is necessary
oil or stimulant laxatives when taken simultaneously with for cellular function and skeletal mineralization. The physi-
these drugs. Thiazide diuretics can interact with calcium ological functions include the maintenance of mineral and
carbonate and vitamin D supplements to increase the risk acid- base homeostasis, the temporary storage of the transfer
for hypercalcemia and hypercalciuria. Calcium supple- of energy derived from metabolic fuels, and the activation of
ments from natural products such as oyster shell should be many catalytic proteins through phosphorylation. 32 Most of
avoided because of possible toxic contaminants. these processes involve the recycling of P. Thus, the func-
Hypercalcemia may be a manifestation of P deficiency tion of dietary P is to support tissue growth and to replace
(see Phosphorus section). Metastatic deposits of calcium excretory and cellular and dermal losses.2
precipitate in the infusion delivery system, in kidneys,
and in other organs with an increased mortality have been Sources
reported in neonates who received ceftriaxone simultane- Phosphorus is ubiquitous in natural foods and is present
ously with parenteral solutions containing calcium. 30 in both organic and inorganic forms. Various phosphate
salts used in food processing for non-nutritive functions
Phosphorus (eg, moisture retention, smoothness, and binding) provide
(1 mmol = 31 mg) significant contributions to dietary P intake. Cola soft
drinks contain phosphoric acid as the acidulant and provide
Biochemistry and Physiology about 50 mg of P per 12 oz serving.2 Phosphorus intake
Phosphorus as phosphate is an essential constituent of all from soft drinks can be substantial when multiple beverages
known protoplasm. The terms phosphorus and phosphate are consumed.
are often used interchangeably, but the term phosphate Dairy and meat products have high P density. Plants,
actually means the inorganic freely available form. This nuts, and seeds also are significant sources of P. Animal or
measurable component is generally referred to as phos- synthetic protein has more bioavailable phosphorus than
phorus (P). soy or grain-based protein. Phosphorus in plants (beans,
Tissue P increases from ~0.5% of the body weight in the peas, cereals, nuts) is present in the poorly digestible
neonate to ~1% in the adult from an increase in bone and soft phytic acid. However, some phytate P is absorbed from the
tissue mass. Structurally, P is incorporated in mineralized combined effect of food phytases, colonic bacteria enzymes,

MINERALS 51
and yeast products.2 Human milk has low P content, which hormone and thyroid hormone. Renal P reabsorption is
decreases further with prolonged lactation, although the increased with 1,25-dihydroxyvitamin D.
P bioavailability is higher than all other milks for infants. The kidney can increase or decrease its P resorptive
Compared to human milk, P content is higher in cow’s milk capacity to accommodate P needs. 32,33 In infants and chil-
by five- to sixfold, standard cow milk-based infant formula dren, lower glomerular filtration rate is probably the main
by about twofold, and soy-based infant formula by about determinant of the higher serum P because P resorptive
threefold. The Ca:P ratio varies widely in natural foods. capacity is high even in the small preterm infant.1 Healthy
However, both the Ca:P ratio and absolute quantities of infants have lower serum P when breastfed compared to
these minerals are important to optimize mineral accre- those fed infant formula.1,34 The least renal excretory work
tion in bone and soft tissue. P supplements are available as to maintain normal P homeostasis during the first year is
mono- and dibasic-phosphates, in both oral and parenteral achieved with human milk as the major source of minerals.
forms. They are usually used for medical indications such as In deficient states, renal retention of filtered phosphate is
inherited metabolic defects. almost complete even in the preterm infant.1
Absorption, Excretion, and Metabolism Deficiency States

Net absorption of P ranges from 55% to 70% in adults and Cellular storage of phosphate and the portion of P that
65% to 90% in children and infants. The fractional P absorp- can be mobilized from bone are limited. Thus, dietary P
tion is virtually constant across a broad range of intake. The is required to maintain extracellular fluid P, which is the
bulk of P absorption is passive (paracellular) and concen- source of P for the tissue metabolic phosphate. Normally,
tration-dependent. A saturable, active transcellular sodium because P is ubiquitous in foods, dietary P deficiency rarely
(Na+)-dependent involving the type IIb Na+/phosphate occurs unless the individual is subjected to near total star-
cotransporter and facilitated by 1,25-dihydroxyvitamin D vation. However, small preterm infants with chronically low
also exists. P is not absorbed in the stomach but is absorbed P intake from prolonged exclusive feeding of non-supple-
throughout the small bowel. The fractional absorption of P mented mother’s milk; infants and children with poorly
and other minerals is lower from infant formulas compared managed PN with inadequate P content, inappropriate
to human milk although the absolute amounts of each administration of fluid and electrolyte therapy that causes
mineral absorbed from infant formulas are higher because excessive renal P loss; or rapid refeeding in the setting of
of the much higher mineral content in infant formulas. diabetic ketoacidosis or severe malnourishment, especially
Medications or foods that bind P (antacids, phosphate if accompanied by diarrhea, are at risk for hypophos-
binders, and calcium) can decrease the net amount of P phatemia in addition to other electrolyte abnormalities.1,2,35
absorbed by decreasing the free phosphate for absorption. Individuals with chronic aluminum antacid therapy and
Unabsorbed Ca complexes with phytic acid can inter- heritable defects of P metabolism also can manifest P defi-
fere with bacterial hydrolysis of phytate and decreases P ciency. Chronic diuretic therapy that increases urine P can
absorption.2 exacerbate the P deficit.
The kidney is a major regulator of P homeostasis. Renal Clinical manifestations of P deficiency include
P is reabsorbed primarily at proximal tubular cells (70%– anorexia, general debility, anemia, muscle weakness
80%). The remaining is reabsorbed in the distal tubules. including respiratory compromise, bone pain, rickets
Serum P increases as the total P intake and absorption and osteomalacia, increased susceptibility to infection,
exceeds the renal tubular maximum transport for P. Renal paresthesia, ataxia, confusion, and even death. 36 These
P reabsorption is modulated by changes in basolateral severe manifestations usually occur when the extracellular
basement membrane abundance of type IIa Na/phosphate fluid P is < 0.3 mmol/L (0.9 mg/dL). Plasma Ca may be
cotransporter (Npt2a) protein and requires the interaction elevated simultaneously, particularly in infants.1
of Npt2a with various scaffolding and regulatory proteins. 33
Renal P reabsorption is decreased (ie, excretion is increased) Excess Intake and Adverse Effects
by a decrease in renal Npt2a, an increase in dietary P intake, Essentially all the adverse effects of excess P intake from any
PTH, or fibroblast growth factor-23, or a loss of Phex func- source are the result of hyperphosphatemia. These include
tion. Although the effects are more minor, renal P excretion adjustments in the hormonal control system regulating
is also increased by volume expansion, metabolic acidosis, Ca homeostasis and may be complicated by hypocalcemia
glucocorticoids, and calcitonin. It is decreased by growth and its adverse effects, ectopic (metastatic) calcification,

particularly of the kidney, and possibly decreases in the Abnormalities in circulating Mg concentrations are associ-
intestinal absorption of Ca, iron, zinc, and copper but ated with widespread cellular effects.
without documented clinical adverse effects. Hyperphos-
phatemia usually occurs in the setting of kidney disease and Sources
rarely occurs under normal circumstances. One exception Magnesium is ubiquitous in foods but the Mg content of
is the development of hyperphosphatemia and secondary foods varies substantially. Green leafy vegetables are rich
hypocalcemia in some healthy infants from the use of stan- in Mg because chlorophyll is the Mg chelate of porphyrin.
dard infant formulas. This is the result of a combination of Unpolished grains and nuts also have high Mg content,
higher intake of P from infant formulas relative to breast whereas meats and milk have intermediate levels. Refined
milk, and the inability to eliminate excess P because of foods generally have the lowest Mg content.40,41 Water is a
immature renal and parathyroid functions. Clinically, this variable source of Mg depending on the source of ground
is exacerbated by the early introduction of solids or whole water. Typically, “hard” water has higher concentrations
cow’s milk to the infant.1 of Mg salts.2,41 Human milk contains adequate amounts of
Mg and infant formulas are mandated to contain at least
Magnesium 6 mg/100 kcal.13 Supplements containing various Mg salts
(1 mmol = 24 mg) are freely available in oral forms. The proportion of elemental
magnesium by weight is 60.3% for oxide; 28% for carbonate;
Biochemistry and Physiology 16% for citrate; ~12% for chloride, acetate, and lactate;
Magnesium (Mg) is the fourth most abundant cation in the 9.7% for sulfate; 6.8% for phosphate; 6.4% for ascorbate;
body and is the second most abundant intracellular cation. and 5.4% for gluconate.15 Magnesium sulfate is available in
Total body Mg content is ~25 g (1000 mmol), of which parenteral form. Mg supplements may contribute a substan-
~60% resides in bone. About one-third of the skeletal Mg tial portion of daily intake and are used as a basis for the
is exchangeable and serves as a reservoir for maintaining derivation of tolerable upper intake levels.2
extracellular Mg concentration. The rest of the Mg is in soft
tissues such as muscle and organs, and ~1% is in extracel- Absorption, Excretion, and Metabolism
lular fluid. Cellular Mg content is 6 to 9 mmol/kg net weight, The net absorption of Mg is about 40% to 60%. Frac-
and most of this Mg is localized in membrane structures tional intestinal absorption is inversely proportional to
(eg, microsome, mitochondria, plasma membrane). 37,38 the amount of Mg ingested. Intestinal absorption is via
The much smaller pool of free Mg in the cell is maintained a passive gradient-dependent paracellular and an active
at ~1 mmol/L and is in an exchanging equilibrium with saturable vitamin D-dependent transcellular mechanism.
membrane-bound Mg. This unbound intracellular Mg has a Magnesium is absorbed throughout the entire intestinal
critical role in cellular physiology. 39 Intracellular Mg usually tract with maximal absorption at the distal jejunum and
remains stable despite wide fluctuations in serum Mg. In ileum.2 Magnesium absorption is not significantly affected
Mg-deficient states, however, the intracellular content by other nutrients at the usual dietary intake. It is lowered
of Mg can be low despite normal serum concentrations. with high P intake, particularly if there is an associated high
Serum Mg has a protein-bound (~30%) and an ultrafiltrable fiber and phytate intake, and at low protein intake.2,42
(~70%) portion. Of the latter, 70% to 80% is in ionic form. The kidney plays an important role in the homeostasis
The remainder is complexed to anions, particularly phos- of divalent ions. Most of the ionized forms of Ca and Mg are
phate, citrate, and oxalate. reabsorbed at the proximal tubules and the thick ascending
Magnesium is a required cofactor for > 300 enzyme limb of Henle’s loop via a passive paracellular pathway. It
systems. It is critical for normal ATP function and glucose is dependent on salt and water reabsorption and rate of
metabolism and is necessary for both aerobic and anaerobic fluid flow. At the level of the distal convolute tubule and
metabolism. It is important in cellular cytoskeleton contrac- the connecting tubule, ionized Ca and ionized Mg are reab-
tion and at the myoneural junction, and therefore can alter sorbed via an active transcellular transport.
skeletal and cardiac muscle function. It catalyzes enzymatic Renal Mg transport also is affected by both hormonal
processes concerned with the transfer, storage, and use of (parathyroid hormone, calcitonin, glucagon, arginine vaso-
energy; regulation of movement of potassium and Ca across pressin, 17 beta estradiol) and non-hormonal factors. High
the cell membranes; and numerous other cell functions. intake of glucose, sodium, Ca, and Mg, chronic excessive

MINERALS 53
alcohol intake, as well as elevated serum Mg or Ca, deple- received Mg therapy prior to delivery.1 Acute hypotonia,
tion of potassium and phosphate, and metabolic acidosis apnea, hypotension, and refractory bradycardia mimicking
inhibit Mg and Ca reabsorption, leading to increased urine septic shock syndrome has been reported in premature
excretion of both cations.43 infants accidentally overdosed with Mg in PN.46 In adults
with hypermagnesemia, hypotension and urinary retention
Deficiency States occur at serum Mg concentrations of 1.67 to 2.5 mmol/L
Magnesium deficiency is usually associated with malab- (4–6 mg/dL); central nervous system depression, hypore-
sorption, increased losses from the gut or kidney, or during flexia, and electrocardiographic abnormalities (ie, increased
refeeding of severe and chronically malnourished indi- atrioventricular and ventricular conduction time) at 2.5 to 5
viduals. Chronic therapy with loop diuretics, cisplatin, and mmol/L (6–12 mg/dL); and respiratory depression, coma,
tacrolimus are among the increasing list of medications and cardiac arrest above 5 mmol/L (12 mg/dL).47
that result in increased renal Mg excretion and predisposi-
tion to Mg deficiency.43 There are also increasing reports of Test Your Knowledge Questions
patients with heritable defects of Mg transport that lead to 1. Which of the following statements on bioavailability of
Mg wasting and deficiency states.44 calcium is incorrect?
The typical deficit required to produce symptom- A. Highest in dairy products in the diet
atic hypomagnesemia is approximately 0.5 to 1 mmol B. Presence of phytate in plants can decrease calcium
(12–24 mg)/kg of body weight.45 Hypomagnesemia is availability
usually associated with a significant Mg deficit. These C. Calcium supplement from natural sources such
individuals often are at risk for concurrent hypocalcemia, as oyster shells may be contaminated with toxic
hypokalemia, hypophosphatemia, and possible distur- metals
bance of acid-base status. The loss of other nutrients such D. Vitamin D status is one of the determinants of
as zinc from the gastrointestinal secretion also may be calcium bioavailability
considerable. Symptoms and signs of hypomagnesemia, E. Low-fat dairy products have low calcium content
which often coexists with hypocalcemia, may be indistin- 2. Which of the following statements on calcium absorp-
guishable. Prolonged dietary Mg deprivation in human tion is incorrect?
adults leads to personality change, tremor, muscle fascicu- A. Inversely related to dietary content of calcium
lations, spontaneous carpopedal spasm, and generalized B. Lowest in pediatric ages
spasticity as well as hypomagnesemia, hypocalcemia, and C. Is diminished with steatorrhea
hypokalemia.45 In infants, acute complications associ- D. Varies with type of food consumed
ated with clinical manifestations include seizure, apnea, E. Dietary zinc decreases calcium absorption
cyanosis and hypoxia, electrocardiographic changes, 3. Which of the following statements about phosphorus
bradycardia, and hypotension. is incorrect?
A. It is ubiquitous in natural foods
Excess Intake and Adverse Effects B. Dietary intake of phosphorus is increased with
Ingestion of Mg from natural foods has not been shown to increased consumption of processed foods
exert any adverse effects. However, adverse effects of excess C. Calcium phosphorus ratio of natural foods varies
Mg intake have been reported from non-food sources such widely
as various Mg salts for pharmacologic purposes, particu- D. Phosphorus deficiency can result in hypercalcemia
larly in patients with renal dysfunction. The amount of Mg E. None of the above
supplement is the basis from which the current upper limit 4. Extracellular fluid (and serum) inorganic phosphate is
of Mg intake is derived.2 The primary initial manifestation regulated by:
of excessive Mg intake from non-food sources is diarrhea A. Renal function
(probably from its osmotic effect), and may be accompa- B. Parathyroid hormone
nied by nausea and abdominal cramping. Clinical signs of C. Fibroblast growth factor-23
neuromuscular depression with floppiness and lethargy, and D. All of the above
respiratory depression are frequent manifestations of severe E. None of the above
neonatal hypermagnesemia in infants born to mothers who

10. U.S. Department of Health and Human Services. Office of the

5. All of the following statements associated with magne-
Surgeon General. Bone Health and Osteoporosis: A Report of
sium deficit are correct except for: the Surgeon General. 2004. http://www.surgeongeneral.gov/
A. May be associated with chronic gastrointestinal library/bonehealth/content.html. Accessed March 20, 2009.
losses 11. U.S. Food and Drug Administration. Guidance for Industry:
B. May result in fecal fat loss Food Labeling: Health Claims; Calcium and Osteoporosis, and
C. May be associated with deficiency of other Calcium, Vitamin D, and Osteoporosis. http://www.fda.gov/
Food/GuidanceComplianceRegulatoryInformation/Guid-
nutrients anceDocuments/FoodLabelingNutrition/ucm152626.htm.
D. May result in hypocalcemia Accessed August 24, 2009.
E. May be asymptomatic 12. National Heart Lung and Blood Institute, National Institutes
6. Which of the following statements about hypermag- of Health. Your guide to lowering your blood pressure with
nesemia is incorrect? DASH. http://www.nhlbi.nih.gov/health/public/heart/
hbp/dash/index.htm. Accessed August 16, 2009.
A. Can occur with drinking hard water
13. U.S. Food and Drug Administration. Code of Federal Regu-
B. Can result in cardiac arrhythmia lations Title 21. Infant formula nutrient specifications.
C. Can cause respiratory failure http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/
D. Usually occurs only with pharmacologic doses of CFR Search.cfm?fr=107.100&SearchTerm=infant%20
magnesium formula. Accessed August 2, 2009.
E. Can decrease muscle tone 14. Levenson D, Bockman R. A review of calcium preparations.
Nutr Rev. 1994;52:221–232.
15. Drug Facts and Comparisons® 2009. St. Louis, MO: Wolters
See p. 487 for answers. Kluwer Health.
16. Standing Committee on the Scientific Evaluation of Dietary
References Reference Intakes, Food and Nutrition Board, Institute of
1. Koo WWK. Neonatal calcium, magnesium and phosphorus Medicine. Dietary Reference Intakes for Water, Potassium,
disorders. In: Lifshitz F, ed. Pediatric Endocrinology: A Sodium, Chloride, and Sulfate. Washington, DC: National
Clinical Guide. 5th ed. New York, NY: Marcel Dekker Inc; Academy Press; 2004.
2007:497–529. 17. Heaney RP, Rafferty K. Carbonated beverages and urinary
2. Food and Nutrition Board, Institute of Medicine. Dietary calcium excretion. Am J Clin Nutr. 2001;74:343–347.
Reference Intakes for Calcium, Phosphorus, Magnesium, Vitamin 18. Koo WWK, Kaplan LA. Aluminum and bone disorders: with
D and Fluoride. Washington, DC: National Academy Press; specific reference to aluminum contamination of infant nutri-
1997. ents. J Amer Coll Nutr. 1988;7:199–214.
3. U.S. Food and Drug Administration. Dietary supplements. 19. Yang YX, Lewis JD, Epstein S, Metz DC. Long-term proton
http://www.fda.gov/Food/DietarySupplements/default. pump inhibitor therapy and risk of hip fracture. JAMA
htm. Accessed November 20, 2009. 2006;296:2947–2953.
4. Koo WWK, McLaughlin K, Saba M. Nutrition support for 20. Koo WWK, Walters JC, Esterlitz J, Levine RJ, Bush AJ, Sibai
the neonatal intensive care patients. In: Merritt R, ed. The B. Maternal calcium supplementation and fetal bone mineral-
A.S.P.E.N. Nutrition Support Practice Manual. 2nd ed. Silver ization. Obstet Gynecol. 1999;94:577–582.
Spring, MD: American Society for Parenteral and Enteral 21. Bronner F. Recent developments in intestinal calcium absorp-
Nutrition; 2005:301–314. tion. Nutr Rev. 2009;67:109–113.
5. National Institutes of Health. Office of Dietary Supplements. 22. Oramasionwu GE, Thacher TD, Pam SD, Pettifor JM,
Dietary supplement fact sheet: Calcium. http://ods.od.nih. Abrams SA. Adaptation of calcium absorption during treat-
gov/factsheets/calcium.asp. Accessed August 14, 2009. ment of nutritional rickets in Nigerian children. Br J Nutr.
6. Pennington JAT, ed. Bowes & Church’s Food Values of Portions 2008;100:387–392.
Commonly Used. 18th ed. Philadelphia, PA: J. B. Lippincott; 23. Thacher TD, Obadofin MO, O’Brien KO, Abrams SA. The
2005. effect of vitamin D2 and vitamin D3 on intestinal calcium
7. Calcium content in foods. CalorieKing™ for Food Awareness absorption in Nigerian children with rickets. J Clin Endocrinol
Web site. http://www.calorieking.com. Accessed November Metab. 2009;94:3314-3321.
25, 2009. 24. Slemenda CW, Reister TK, Hui SL, Miller JZ, Christian
8. Greer FR, Krebs NF, Committee on Nutrition. Optimizing JC, Johnston CC Jr. Influences on skeletal mineralization
bone health and calcium intakes of infants, children, and in children and adolescents: evidence for varying effects
adolescents. Pediatrics. 2006;117:578–585. of sexual maturation and physical activity. J Pediatr.
9. Fischer PR, Thacher TD, Pettifor JM. Pediatric vitamin D and 1994;125:201–207.
calcium nutrition in developing countries. Rev Endocr Metab 25. Specker BL. Evidence for an interaction between calcium
Disord. 2008;9:181–192. intake and physical activity on changes in bone mineral
density. J Bone Miner Res. 1996;11:1539–1544.
26. Nattiv A. Stress fractures and bone health in track and field
athletes. J Sci Med Sport. 2000;3:268–279.

MINERALS 55
27. Key TJ, Appleby PN, Rosell MS. Health effects of vegetarian 38. Reinhart RA. Magnesium metabolism: a review with special
and vegan diets. Proc Nutr Soc. 2006;65:35–41. reference to the relationship between intracellular content
28. Shannon MT, Wilson BA, Stang CL. Health Professionals Drug and serum levels. Arch Intern Med. 1988;148:2415–2420.
Guide. Stamford, CT: Appleton & Lange; 2000. 39. Saris NE, Mervaala E, Karppanen H, Khawaja JA, Lewenstam
29. Jellin JM, Gregory P, Batz F, Hitchens K. Pharmacist’s Letter/ A. Magnesium. An update on physiological, clinical and
Prescriber’s Letter Natural Medicines Comprehensive Database. analytical aspects. Clin Chim Acta. 2000;294:1–26.
3rd ed. Stockton, CA: Therapeutic Research Facility; 2000. 40. Egan SK, Tao SS, Pennington JA, Bolger PM. U.S. Food and
30. U.S. Food and Drug Administration. Information for Health- Drug Administration’s Total Diet Study: intake of nutri-
care Professionals: Ceftriaxone (marketed as Rocephin tional and toxic elements, 1991-96. Food Addit Contam.
and generics). http://www.fda.gov/Drugs/DrugSafety/ 2002;19:103–125.
PostmarketDrugSafetyInformationforPatientsandPro- 41. National Institutes of Health. Office of Dietary Supplements.
viders/DrugSafetyInformationforHeathcareProfessionals/ Magnesium. http://ods.od.nih.gov/factsheets/magnesium.
ucm084263.htm#main. Accessed November 20, 2009. asp. Accessed August 14, 2009.
31. Nordin BEC. Phosphorus. J Food Nutr. 1988;45:62–75. 42. Schwartz R, Walker G, Linz MD, MacKellar I. Metabolic
32. Takeda E, Taketani Y, Sawada N, Sato T, Yamamoto H. The responses of adolescent boys to two levels of dietary magne-
regulation and function of phosphate in the human body. sium and protein. I. Magnesium and nitrogen retention. Am J
Biofactors. 2004;21:345–355. Clin Nutr. 1973;26:510–518.
33. Tenenhouse HS. Regulation of phosphorus homeostasis by 43. Quamme GA. Renal magnesium handling: new insights in
the type IIa Na/phosphate cotransporter. Annu Rev Nutr. understanding old problems. Kidney Int. 1997;52:1180–1195.
2005;25:197–214. 44. OMIM - Online Mendelian Inheritance in Man. National
34. Specker BL, Lichtenstein P, Mimouni F, Gormley C, Tsang Center for Biotechnology Information. http://www.ncbi.
RC. Calcium-regulating hormones and minerals from birth nlm.nih.gov/sites/entrez. Accessed August 20, 2009.
to 18 months of age: a cross-sectional study. II. Effects of sex, 45. Shils ME. Experimental human magnesium depletion. Medi-
race, age, season, and diet on serum minerals, parathyroid cine. 1969;48:61–85.
hormone, and calcitonin. Pediatrics. 1986;77:891–896. 46. Ali A, Walentik C, Mantych GJ, Sadiq HF, Keenan WJ,
35. Freiman I, Pettifor JM, Moodley GM. Serum phosphorus Noguchi A. Iatrogenic acute hypermagnesemia after total
in protein energy malnutrition. J Pediatr Gastroenterol Nutr. parenteral nutrition infusion mimicking septic shock
1982;1:547–550. syndrome: two case reports. Pediatrics. 2003;112:e70–72.
36. Lotz M, Zisman E, Bartter FC. Evidence for a 47. Mordes JP, Wacker WE. Excess magnesium. Pharmacol Rev.
phosphorus-depletion syndrome in man. N Engl J Med. 1978;29:273–300.
1968;278:409–415.
37. Elin RJ. Assessment of magnesium status. Clin Chem.
1987;33:1965–1970.

7
Water-Soluble Essential Micronutrients
Winston Koo, MBBS, FACN, CNS, Judith Christie, RN, MSN, May Saba, PharmD, BCNSP,
Mirjana Lulic-Botica, BSc, BCPS, and Letitia Warren, RD, CSP

Overview . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 56 1. Understand the physiological basis for the function and
Digestion, Absorption, and Metabolism. . . . . . . . . . . . . . . 57 requirement common to the group or to the individual
water-soluble essential micronutrients.
Dietary Reference Intake. . . . . . . . . . . . . . . . . . . . . . . . . . . 57
2. Understand the common risk factors and special
Increased Demands and Predisposition to Deficiency considerations in the predisposition for the develop-
States . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 58
ment of deficiency state for these nutrients.
Management of Deficiency State and Supplementation . 59 3. Understand the common manifestations and diagnosis
Specific Nutrients . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 61 of deficiency state for these micronutrients.
Thiamin (Vitamin B1) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 61 4. Understand the potential risks with excessive intake of
Riboflavin (Vitamin B2) . . . . . . . . . . . . . . . . . . . . . . . . . . . . 62 these micronutrients.
Niacin (Vitamin B3) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 63
Vitamin B6. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 64 Overview
Water-soluble essential micronutrients include the 8
Folate (Vitamin B9). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 65
B-complex vitamins: thiamin (vitamin B1), riboflavin
Vitamin B12 (Cobalamin) . . . . . . . . . . . . . . . . . . . . . . . . . . . 66 (vitamin B2), niacin (vitamin B3), vitamin B6 (pyridoxine),
Vitamin C . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 67 vitamin B12 , folate (vitamin B9), pantothenic acid (vitamin
Pantothenic Acid (Vitamin B5) . . . . . . . . . . . . . . . . . . . . . . 69 B5), biotin (vitamin B7); and vitamin C and choline. These
Biotin (Vitamin B7). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 69 micronutrients affect the function of all cells, and many
Choline . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 70 have interrelated transport mechanisms, metabolism, and
functions. In pediatric subjects, these cellular functions
additionally affect growth and development.
Some of these essential nutrients can be synthesized
de novo from other nutrients (eg, niacin from tryptophan,
choline from methylation of phosphatidylethanolamine) or
from intestinal bacteria (eg, riboflavin, pyridoxine, vitamin
B12 , pantothenic acid, and biotin), although in amounts
inadequate to meet physiological demands.
One or more of these micronutrients are used to fortify
many food and drink products, some nutrients such as
choline are added to foods as an emulsifying agent, and
all water-soluble micronutrients are available as individual
supplements or as part of multivitamin +/- multinutrient
56
WATER-SOLUBLE ESSENTIAL MICRONUTRIENTS 57
supplements.1–9 All are available as oral and parenteral varied diet assures the adequacy of intake at all life stages
preparations except for choline, which is available in oral because these essential nutrients are present in a wide range
form only. Multivitamin preparations used for parenteral of food products.1–3,7
nutrition (PN) are shown in Table 7-1. Vitamin B12 is also
available in an intranasal form. 5,6,9 Digestion, Absorption, and Metabolism
Dietary supplements in the form of multivitamins and These dietary micronutrients are released with the diges-
multiminerals are taken regularly by more than 30% of tion of foods and then absorbed in free form or as small
children in the United States with the lowest use reported molecular complexes. Absorption is usually by active trans-
among infants younger than 1 year (11.9%) and teenagers port at low nutrient intake and by passive diffusion at high
14 to 18 years old (25.7%) and highest use among 4- to intake. Absorption occurs mainly at the jejunum except for
8-year-old children (48.5%).10 Given such extensive use, cobalamin which is absorbed only at the ileum under physi-
nutrient intakes from dietary supplements must be included ological conditions. Some absorption occurs at the stomach
to obtain accurate estimates of overall nutrient intake in (niacin) and proximal colon (riboflavin, biotin).11 Postab-
children. sorptive transport usually occurs as an enzyme complex or
For healthy near-term or term infants, milk from bound to proteins. Erythrocytes may serve both as trans-
well-nourished mothers ingesting a varied diet should be porter and storage source. Tissue uptake is usually specific
sufficient to provide all water-soluble essential micronutri- to each nutrient. Some of these essential nutrients have
ents for their daily needs. Small preterm infants have greater interrelated metabolism and function. The bioavailability
needs for these and other nutrients because of minimal or of water-soluble vitamin supplements is generally similar to
absent reserves, and for catch-up growth. Human milk forti- or better than that from dietary sources when tested under
fier added to mother’s milk raises the concentration of these the same conditions.1,2,5,6,9
nutrients to multiple folds higher than what is naturally
present in human milk and should be sufficient for preterm Dietary Reference Intake
infants tolerating adequate volumes of enteral intake. 3 For The current dietary reference intake (DRI) values for
formula-fed infants, the use of commercial milk-based pediatric populations are provided in Table 7-2. However,
formula designed for term and preterm infants is expected current reference values are subject to change with
to be adequate. 3 Beyond infancy, a culturally appropriate increasing understanding of the relationship among various
Table 7-1 Content Per Unit Dose of Multivitamin Preparations for Use with Parenteral Nutrition*
Ingredient M.V.I. M.V.I. Adult® M.V.I. – 12®
Pediatric®† (for ages ≥ 11 y)‡ (no vitamin K)‡
Unit dose volume (mL) 5 10 10
Fat-soluble vitamins
Vitamin A (retinol, mg) 0.7 1 1
Vitamin D (ergocalciferol, mcg) 10 5 5
Vitamin E (dl-α-tocopheryl acetate, mg) 7 10 10
Vitamin K (phytonadione, mcg) 200 150 none
Water-soluble vitamins
Vitamin B1 (thiamin, mg) 1.2 6 6
Vitamin B2 (riboflavin 5-phosphate sodium, mg) 1.4 3.6 3.6
Niacinamide (vitamin B3, mg) 17 40 40
Vitamin B6 (pyridoxine hydrochloride, mg) 1 6 6
Folic Acid (vitamin B9, mcg) 140 600 600
Vitamin B12 (cyanocobalamin, mcg) 1 5 5
Vitamin C (ascorbic acid, mg) 80 200 200
Dexpanthenol (d-pantothenyl alcohol, provitamin B5, mg) 5 15 15
Biotin (vitamin B7, mcg) 20 60 60
* Data from manufacturer product insert (Hospira, Inc., Lake Forest, IL).
† Lyophilized powder reconstituted immediately prior to use.
‡ Dual vial liquid formulation. Vial one or lower chamber of unit vial contains fat-soluble vitamins A, D, E, and K; and water-soluble vitamins B1, B2, B6, C,
niacinamide, and dexpanthenol. Vial two or upper chamber of unit vial contains: biotin, folic acid, and vitamin B12.

Table 7-2 Dietary Reference Intake of Water-Soluble Essential Micronutrients in Pediatric Populations1,2
B6 B12
Life Thiamin Riboflavin Niacin (Pyridoxine) Folate (cobalamin) Vitamin Pantothenic Biotin Choline
Stage (B1) mg (B2) mg (B3) mg mg (B9) mcg mcg C mg acid (B5) mg* (B7) mcg* mg*
0–6 m* 0.2 0.3 2 0.1 65 0.4 40 0.2 0.7 125
7–12 m* 0.3 0.4 4 0.3 80 0.4 50 0.2 0.7 150
1–3 y† 0.5 0.5 6 (15) 0.5 (30) 150 (300) 0.9 15 (400) 2 8 200 (1000)
4–8 y† 0.6 0.6 8 (20) 0.6 (40) 200 (400) 1.2 25 (650) 3 12 250 (1000)
Males
9–13 y† 0.9 0.9 12 (20) 1.0 (60) 300 (600) 1.8 45 (1200) 4 20 375 (2000)
14–18 y† 1.2 1.3 16 (30) 1.3 (80) 400 (800) 2.4 75 (1800) 5 25 550 (3000)
Females
9–13 y† 0.9 0.9 12 (20) 1.0 (60) 300 (600) 1.8 45 (1200) 4 20 375 (2000)
14–18 y† 1.0 1.0 14 (30) 1.2 (80) 400 (800) 2.4 65 (1800) 5 25 400 (3000)
Pregnancy
14–18 y† 1.2 1.4 18 (30) 1.9 (80) 600 (800) 2.6 80 (1800) 6 30 450 (3000)
Lactation
14–18 y† 1.4 1.6 17 (30) 2.0 (80) 500 (800) 2.8 115 7 35 550 (3000)
(1800)
Highest 11 mg 11 mg 77 mg 3.9 mg 625 mcg 36.8 mcg 656 mg at NA NA NA
intake at > at at at at at 51–70 y
51 y > 70 y 51–70 y 19–30 y 51–70 y 14–55 y
UL‡ NA NA § § § NA § NA NA §
* AI, Adequate intake = observed or experimentally determined estimates of nutrient intake by a group or groups of healthy people. AI is the only reference
level provided for infants < 12 months, and for pantothenic acid, biotin, and choline at all life stages and genders.
† RDA, Recommended dietary allowance is calculated as + 2 standard deviations of the estimated average requirement or in its absence, a coefficient of
variation of 10% to 15% for each standard deviation is assumed for a life stage and gender group.
‡ UL, Tolerable upper intake level = highest level of daily nutrient intake that is likely to pose no risk of adverse health effects to almost all individuals in the
general population.
§ Upper limit for each life stage is indicated in parenthesis.
NA = not available.
Highest intake = highest reported daily mean intake from both food and supplements at 95th percentile for any life stage or gender group.
nutrients and increasing data on the type and bioavail- average daily dietary intake level that is sufficient to meet
ability of specific nutrients from naturally occurring dietary the nutrient requirement of nearly all (97% to 98%) healthy
sources, fortification of foods and drinks, and supplements. individuals. If sufficient data are available, dose response
For infants, DRI of each essential micronutrient is risk assessment to high intakes and setting of upper toler-
based on adequate intake (AI): the average daily intake of able levels of intake (UL) are made. The absence or limited
a specific nutrient in healthy infants fed principally human data in children and adolescents often necessitated the deri-
milk during the first and second 6 months after birth. For vation of EAR, RDA, and UL in these life stages and gender
ages beyond 1 year, several sets of reference values are used by extrapolation downwards from adult data, and rounded
and include AI, estimated average requirement (EAR), and up. AI is used when RDA cannot be determined.1,2
recommended dietary allowance (RDA). Establishing AI
depends on the availability of the content of the specific Increased Demands and Predisposition
essential micronutrient in food-composition data, large- to Deficiency States
scale epidemiologic studies to determine the dietary and Requirements for many water-soluble vitamins gener-
any supplement intake of the nutrient in group/s of healthy ally increase with growth, pregnancy, lactation, physical
people of both genders, and at the specific life stage. These exertion, fever, and conditions associated with increased
data in turn allow the determination of EAR which is a metabolic needs. Tobacco and alcohol also affect the needs
daily nutrient intake value estimated to meet the require- for these nutrients. More than 15% of in-school youths in the
ment of half the healthy individuals, and RDA which is the United States are reported to be current cigarette smokers12

and there is an association between cigarette smoking and have micronutrient deficiencies, 20 particularly in developed
dieting in adolescents even in non-overweight individuals.13 countries, and it is at least theoretically possible that certain
Smokers may have an increased need for antioxidant vita- micronutrients might exacerbate HIV infection.18,21 Certain
mins because of the oxidative stress from smoking.1 Also drugs including chronic diuretic therapy through its actions
there may be a concomitant decreased intake because of on excretion or metabolism of certain nutrients also predis-
inappropriate dieting.13 Alcohol is used by more young poses individuals to deficiency states (Table 7-4). Thus, the
people than tobacco and illicit drugs.14 Alcohol abuse is management of deficiency states must take into account all
often associated with poor dietary intake of many essential potential predisposing factors.1–3,22
nutrients. In addition, alcohol can directly or indirectly Isolated water-soluble vitamin deficiency is rare.
interfere with the digestion, absorption, and metabolism of However, biochemical deficiency of vitamin B12 as indicated
multiple essential water-soluble micronutrients.1,2,15–17 by increased urinary methylmalonic acid has been reported
in 2- to 14-month-old infants predominantly fed human
Table 7-3 Predispositions to Deficiency of Water-Soluble Essential milk from vegan mothers.23 Thiamin deficiency with cardiac
Micronutrients*
failure and encephalopathy was reported during a shortage
■ Limited body store particularly in infants and young children
of multivitamin preparation for patients requiring total
■ Inadequate endogenous synthesis
parenteral nutrition.24 Inborn errors of metabolism associ-
■ Decreased intake
– Parenteral nutrition without water-soluble vitamins†
ated with various aspects of digestion, absorption, transport,
– Food faddism or severe dietary restrictions and metabolism of specific essential micronutrients also
– Food refusal may result in deficiency of the specific micronutrient. These
– Anorexia nervosa heritable predispositions to deficiency or dependency states
■ Decreased bioavailability
have been reported for niacin, vitamin B6, folate, vitamin
– Cooking and storage of foods at high temperatures and
prolonged periods B12 , biotin, and vitamin C and the number of disorders is
– Addition of baking soda to vegetables expected to increase with improvements in molecular diag-
■ Decreased absorption and/or increased loss nostic techniques.
– Celiac disease, Crohn disease, cystic fibrosis, gastrointestinal Clinical manifestations of deficiency states may overlap
bypass surgery, and any malabsorption states and biochemical indicators of deficiency may be affected by
■ Nutrient-nutrient and nutrient-drug interaction (see Table 7-4) laboratory technique. Normal ranges of laboratory values
■ Mixed predispositions including some or all of above may vary with life stages and possibly other physiologic
– Hyperemesis gravidarum factors such as gender. Thus, interpretation of nutrient
– Chronic renal dialysis
– Alcohol abuse status must take into account these variables.
– Human immunodeficiency virus infection
* There is usually more than one predisposition to the development of Management of Deficiency State
deficiency state. and Supplementation
† Occurs during production shortage of parenteral multivitamin Treatment of deficient state requires an understanding
preparation.
of the primary cause, the possibility of deficiency of other
Most deficient states are associated with deficiencies in nutrients, and concomitant therapies that may interfere
more than one water-soluble essential micronutrient. There with effective replacement therapy. The initial treatment
are many potential predispositions to the development of may require an amount of micronutrient that is 10- to
deficiency states and multiple predisposing factors may be 100-fold or greater than the daily requirement and deliv-
present (Table 7-3). Deficiency of multiple micronutrients is ered via a route that will ensure delivery to the tissues, for
commonly associated with human immunodeficiency virus example, parenteral or intranasal delivery rather than oral if
(HIV) infection or acquired immunodeficiency syndrome there is a significant malabsorption state. Correction of the
(AIDS). It is likely a complex interplay of primary dietary underlying cause if possible, continued monitoring for clin-
deficiency, deficiencies secondary to antiretroviral-induced ical response, and normalization of laboratory parameters
or concomitant diarrheal diseases, and inflammation- are warranted. Thus, management of deficient state should
suppressed circulating nutrient biomarkers. Micronutrient be individualized taking into account the cause, concomi-
supplementation probably provides some overall bene- tant diet, and non-nutritional therapy. Close monitoring of
fits with respect to growth in children and pregnancy patients requiring total parenteral nutrition—particularly
outcomes.18,19 However, not all children with HIV infection those patients with abnormal gastrointestinal losses, organ

Table 7-4 Characteristics of Water-Soluble Essential Micronutrients*

Adult Biological Major Interactions Deficiency— Deficiency—Biochemical Toxicity
Tissue Half-life Interactions with Drugs† Major Clinical Erythrocyte (RC), Blood
Store with Other Manifestations (WB), Plasma (P)
Nutrients
Thiamin (B1) ~30 mg 9–18 d Not available Excess alcohol Beriberi: wet,  RC or WB Thiamin Rapid injection:
& caffeine, dry. Wernicky pyrophosphate (TPP); anaphylactoid-
diuretics Encephalopathy  RC transketolase activity like reaction
with TPP
Riboflavin Very low Minutes Folate, Anticholinergic, Ariboflavinosis:  RC Riboflavin;  RC Photo-oxidation
(B2) pyridoxine, tricyclic pharyngitis, erythrocyte glutathione of some amino
niacin antidepressant, cheilosis, angular reductase activity acids
phenothiazines, stomatitis, coefficient with FAD
phenytoin, glossitis, stimulation;  24 h urine
probenecid, seborrheic riboflavin
thiazide diuretics, dermatitis
doxorubicin
Niacin (B3) Not 45 min Riboflavin, Isoniazid Pellegra: diarrhea,  RC nicotinamide adenine Vasodilatory,
available pyridoxine dementia, dinucleotide:nicotinamide nausea &
dermatitis adenine dinucleotide vomiting,
phosphate ratio;  24 h U hepatitis,
niacin & its metabolites neurovisual
disturbance,
glucose
intolerance
B6 160 mg 25 d Riboflavin, Isoniazid, L-dopa Seizures  P pyridoxal phosphate, Peripheral
(Pyridoxine) assume niacin, folate,  RC Aspartate & alanine sensory
muscle has zinc transferase saturation neuropathy
80%
Folate 12–28 mg, Erythrocyte B12 Antifolate Seizures,  RC folate,  P Exacerbates
liver has ~8 wk medications neuromotor Homocysteine B12 deficient
~50% disorder, neuropathy
developmental
delay,
megaloblastic
anemia
B12 2–3 mg, 6d Folate Bile acid Macrocystic  P B12,  P & U Cyanocobalamin
(cobalamin) liver has sequestrants, megaloblastic Methylmalonic acid &  P worsens Leber’s
50%+ H2 receptor anemia, Homocysteine optic atrophy,
antagonist, Nervous system use hydroxy
proton pump involvement cobalamin
inhibitors
Vitamin C 2g 8–40 d Glutathione, Aspirin, warfarin, Scurvy  P ascorbate < 0.2 mg/dL, Nausea,
tocopherol, proton pump  RC and leukocyte abdominal
flavanoid, iron, inhibitors ascorbate cramps, and
copper diarrhea
Pantothenic Not Not Not Not Gastrointestinal No consistent changes in Not available
acid available available available available and nervous RC, WB or P
system
Biotin Not 2h Avidin binds Not Seizures,  U biotin, Not available
available (postingestion biotin available developmental  3-hydroxyisovaleric acid
elimination) delay, rash,
alopecia
Choline Not 43 h Folate Not Non-specific  P, RC, and tissue choline Hypotension,
available available and phosphatidylcholine cholinergic, fishy
odor
* Insufficient data to provide quantitative data in some cells.
† Selected list. For updated list.9, 35

failure, or pre-existing nutrient deficiency—is critical to the of metabolic reactions: decarboxylation of α-keto acids (eg,
clinical management. Fortification of selected nutrients, pyruvate, α-ketoglutarate, and branch-chain keto acids)
such as folic acid in the diet, is effective in the improvement and transketolation (eg, among hexose and pentose phos-
of folate status of the population. phates). Thiamin requirement is a function of carbohydrate
There is no evidence of adverse effect from the consump- intake and is critical to the metabolism of carbohydrates
tion of naturally occurring water-soluble nutrients in foods. and branched-chain amino acids, synthesis of neurotrans-
This is presumably in part the result of lowered fractional mitters glutamate and γ-amino butyric acid, nicotinamide
absorption at high intakes. The increasing practice of adenine dinucleotide phosphate (NADPH), and the
ingesting multinutrient supplements to provide an intake pentose sugars deoxyribose and ribose.1 TPP is also present
similar to daily need has no documented long-term benefit in nerve membranes and activates a chloride channel for
but is unlikely to result in any long-term side effects. Their nerve conduction.
use does not compensate for poor food choices and inad-
equate diet. Furthermore, at high intakes of supplements Source
or if the individual has an underlying metabolic disorder Thiamin in the diet includes free thiamin, phosphorylated
that enhances or interferes with the action of a specific thiamin, and protein-phosphate complexes. Dietary sources
nutrient or the drug, clinical adverse effects may result from include enriched, fortified, or whole grain rice; pasta and
nutrient-nutrient and drug-nutrient interactions (Table cereals; pork; eggs; yeast; legumes; and nuts. Thiamin is lost
7-4). Detailed descriptions of some of these interactions during processing to white flour, from milling of brown rice,
may be obtained from multiple sources.1,2,5,6,9 and during cooking.
There is limited understanding of the biochemical Thiamin in fortified foods and pharmaceutical prepa-
and genetic mechanisms whereby impaired metabolism of rations are usually thiamin salts: thiamin hydrochloride
these essential micronutrients increases the risk for devel- and thiamin mononitrate. Thiamin supplement is available
opmental anomalies and disease. Similarly, understanding in oral and injectable forms as thiamin salts or as part of
of the mechanisms whereby elevated intake of these nutri- multivitamin preparations. Lipid-soluble thiamin deriva-
ents protects against these pathologies is also limited. tives called allithiamins are also available and may be better
Current initiatives to increase intake of some essential absorbed at higher intakes.9
nutrients such as folic acid in human populations to amelio-
rate developmental anomalies and prevent disease, while Absorption, Metabolism, and Excretion
effective, lack predictive value with respect to unintended Thiamin uptake by the small intestines and by cells within
adverse outcomes. Systematic studies of excessive intake of various organs is mediated by a saturable, high-affinity
some water-soluble essential micronutrients for prolonged transport system. At high intake, absorption can occur
periods are extremely limited.1–3 The lack of reported by passive diffusion. Following absorption mainly at the
adverse effects does not mean that there is no potential jejunum, thiamin is transported by blood in both erythro-
for adverse effects from prolonged periods of high intakes. cytes (~90%) and plasma. Non-phosphorylated thiamin is
Nevertheless sufficient data are available to set the upper weakly bound to plasma proteins. The liver appears to be
limit of intake for niacin, vitamin B6, folate, vitamin C, and the major organ for phosphorylation of thiamin although
choline (Table 7-2). it can occur in all tissues. After an oral dose of thiamin,
peak urine excretion occurs in about 2 hours and is nearly
Specific Nutrients complete after 4 to 6 hours. However, the biological half-life
of the vitamin is much longer and estimated to be between
Thiamin (Vitamin B1) 9 to 18 days. Total thiamin content in the adult human is
estimated to be ~30 mg.17
Chemically, thiamin consists of substituted pyrimidine and Deficiency State
thiazole rings linked by a methylene bridge. Thiamin exists Thiamin deficiency can occur with inadequate intake
mainly in various interconvertible phosphorylated forms: particularly during PN without added water-soluble vita-
thiamin monophosphate (TMP), thiamin triphosphate mins,24 or inadequate absorption, and excessive loss from
(TTP), and ~80% as thiamin pyrophosphate (TPP). TPP, multiple causes. A state of severe depletion may occur in
the coenzyme form of thiamin, is involved in 2 main types less than 3 weeks from a strict thiamin-deficient diet but the

most common cause of thiamin deficiency in affluent coun- activity at baseline which is increased after adding TPP if
tries is alcoholism.16,17 Alcohol abuse is often associated the individual is deficient.
with poor dietary intake of many essential nutrients, and Acute symptomatic improvement occurs rapidly within
decreases the absorption and phosphorylation of thiamin. one day of treatment.27 However, neurodevelopmental
Patients with end-stage organ failure especially of the liver delay, particularly in receptive and expressive language, 31
are at risk for deficiency of thiamin and multiple nutri- and recurrent seizures32 have been noted up to 6 years of
ents. A number of inborn errors of metabolism have been follow up.
described in which clinical improvements can be docu-
mented following administration of pharmacologic doses of Supplementation
thiamin, such as thiamin-responsive megaloblastic anemia Prophylactic use of thiamin supplements may be warranted
with ringed sideroblasts. The latter is part of a clinical triad in malabsorption disorders. Occasional reports of anaphy-
including diabetes mellitus and sensorineural deafness, lactic reaction with parenteral administration of thiamin
associated with an autosomal recessive defect in thiamin has been noted but toxic effects of thiamin excess have not
transporter.15 been studied systematically.1
The classic clinical syndromes associated with
deficiency of thiamin include Beriberi or Wernicke’s Riboflavin (Vitamin B2)
encephalopathy. Beriberi is traditionally classified as “dry”
or “wet” form. Dry beriberi is characterized by a symmet Biochemistry and Physiology
rical peripheral neuropathy with progressive weakness, Riboflavin (7,8-dimethyl-10-ribityl-isoalloxazine) is a
muscle wasting, difficulty walking, and ataxia and is accom- water-soluble, yellow, fluorescent compound. The primary
panied by paresthesia and loss of deep tendon reflex. Wet form of riboflavin is an integral component of the coen-
beriberi is secondary to cardiomyopathic congestive cardiac zymes flavin mononucleotide (FMN) and flavin adenine
failure and edema. Infantile beriberi is characterized by dinucleotide (FAD), the predominant flavoenzyme in body
shock at 2 to 3 months in a breastfed child with or without tissues. These coenzymes are involved in multiple oxida-
a preceding history of weak cry and poor feeding. It gener- tion-reduction reactions integral to carbohydrate, protein,
ally occurs in the exclusively breastfed infant whose mother and fat metabolism, and are involved in the metabolism of
has a subclinical thiamin deficiency.25 Wernicke’s enceph- folate, pyridoxine, and niacin. Riboflavin-binding proteins
alopathy is characterized by altered consciousness as well expressed in fetuses of different species are evidently essen-
as the triad of ophthalmoplegia, nystagmus, and ataxia. It is tial to normal fetal development. 33
generally seen in adults with alcohol abuse and malnutrition
although it has been reported in infants and children. 25,26 Source
Thiamin deficiency from feeding of unfortified soy More than 90% of dietary riboflavin is consumed as a
infant formula due to manufacturing error has been complex of food protein with FAD and FMN and lesser
reported.27, 28 Clinical presentation occurred between 2 amounts as free vitamin and traces of glycosides and esters.
and 12 months. Initial manifestations were non-specific Animal protein (meat, dairy, and eggs) as well as green
and included vomiting, lethargy, irritability, abdominal vegetables and fortified cereals are abundant sources.4 Ribo-
distention, diarrhea, respiratory symptoms, developmental flavin may be synthesized by colonic bacteria but the extent
delay, and failure to thrive. Respiratory and gastrointestinal of its contribution to human needs is not known. 33
infections were noted in many of the reported cases. Classic
manifestation of ophthalmoplegia or death also occurred in Absorption, Metabolism, and Excretion
several infants. FAD and FMN from dietary protein are released by gastric
Laboratory investigations include abnormal magnetic acid digestion. They are then hydrolyzed to riboflavin by
resonance imaging at the frontal lobes, basal ganglia, peri- non-specific pyrophosphatases and phosphatases in the
aqueductal region, thalami, and the mammillary bodies, upper small intestine. Riboflavin absorption is relatively
while magnetic resonance spectroscopy demonstrates poor compared to other water-soluble vitamins but is
a characteristic lactate peak.28 Biochemical diagnosis of increased when ingested along with other foods and in the
thiamin deficiency is by low TPP in erythrocyte and whole presence of bile salts. Some divalent cations, such as copper,
blood29 or by the transketolase activation test. 30 The latter zinc, iron, and manganese, form chelates with riboflavin
measures the whole blood or erythrocyte transketolase and lower riboflavin absorption.

Most absorption occurs in the small intestine via an will increase the photosensitized oxidation of amino
active or facilitated transport system at low intakes and via acids and proteins in infants receiving phototherapy for
passive diffusion at high intakes. A small amount is absorbed hyperbilirubinemia.
in the large intestine. 34 There is also a small component of
enterohepatic circulation. Niacin (Vitamin B3)
Riboflavin is transported in the circulation bound to
albumin and immunoglobulins. It is phosphorylated to Biochemistry and Physiology
FMN and FAD in most tissues, in particular, in the small Niacin refers to nicotinamide (nicotinic acid amide), nico-
intestine, liver, kidney, and heart. Intracellular phosphory- tinic acid (pyridine-3-carboxylic acid), and derivatives that
lation is regulated by thyroid hormone and production of exhibit the biological activity of nicotinamide. None of the
FAD is under negative feedback control. Very little ribo- forms are related to the nicotine found in tobacco although
flavin is stored in body tissues and the excess riboflavin is their names are similar. 37 The 2 major forms of niacin are
excreted in the urine secondary to glomerular filtration and chemically modified in the mitochondria to form coen-
active tubular secretion as riboflavin (~60% to 70%) and zymes nicotinamide adenine dinucleotide (NAD) and
as a variety of flavin-related products. Riboflavin is more nicotinamide adenine dinucleotide phosphate (NADP).
heat stable than thiamin but is very photosensitive. 34 It also About 200 enzymes require the niacin coenzymes, NAD
interacts with an extensive list of drugs35 (Table 7-4). and NADP, mainly to accept or donate electrons in the
energy-producing oxidation-reduction (redox) reactions.
Deficiency State NAD functions most often in energy-producing reac-
Riboflavin deficiency is often accompanied by deficien- tions during degradation (catabolism) of carbohydrate,
cies of one or more of the other B vitamins. Chronically fat, protein, and alcohol. NADP functions more often in
limited dietary meat or dairy intake (including infants after biosynthetic (anabolic) reactions, such as in the synthesis of
weaning) is a specific risk factor for riboflavin deficiency. macromolecules including fatty acids and cholesterol. Non-
Riboflavin deficiency is also found in protein energy malnu- redox enzymatic reactions important to DNA repair, and
trition states, such as Kwashiorkor and anorexia nervosa, stress responses, cell signaling, transcription, regulation
and in patients with other risk factors that are common to all or apoptosis, chromatin structure, and cell differentiation
water-soluble micronutrients. Symptoms and signs of mild require separation of the niacin moiety from NAD and inte-
deficient state can be non-specific. The more characteristic gration of ADP-ribose in these functions.1,3,37
features of severe deficiency state of ariboflavinosis include
pharyngitis, cheilosis, angular stomatitis, glossitis (magenta Source
tongue), and seborrheic dermatitis involving nasolabial Unlike most of the water-soluble vitamins, nicotinamide
folds, flexural area of extremities, and the genital areas. can be synthesized in the liver and kidney from trypto-
Diagnosis of riboflavin deficiency is by low eryth- phan. This process requires adequate amounts of riboflavin,
rocyte riboflavin quantified by high-performance liquid pyridoxine, and iron and is highly variable depending on
chromatography and low 24-hour excretion of riboflavin. multiple other factors. For instance, tryptophan is used also
Erythrocyte glutathione reductase activity coefficient for protein synthesis which takes priority over NAD and
from in vitro stimulation by FAD increased in the ranges of NADP synthesis. An estimated average of 60 mg of trypto-
> 40%, 20% to 40%, and < 20% are considered as deficient, phan produces 1 mg of niacin or niacin equivalent. However,
low, and acceptable levels of riboflavin status. Biochemical dietary intake of niacin is needed to meet the daily require-
deficiency has been reported in infants receiving short-term ments. Good sources of niacin include yeast, meats, poultry,
phototherapy. 36 red fish (eg, tuna and salmon), cereals (especially fortified
cereals), legumes, and seeds. Lesser amounts are found in
Supplementation milk, green leafy vegetables, coffee, and tea. In corn and
Excess riboflavin turns urine yellow although there are no wheat, niacin may be bound to sugar molecules as glyco-
demonstrated functional or structural adverse effects in sides which significantly decrease niacin bioavailability. 38
vivo after excess riboflavin intake. This is in part because of
the limited absorption of ingested riboflavin. Nevertheless, Absorption, Metabolism, and Excretion
it is theoretically possible that riboflavin increases photo- Intestinal glycohydrolases catalyze the release of nicoti-
sensitivity to ultraviolet irradiation and excess riboflavin namide from NAD. Nicotinic acid and nicotinamide are

rapidly absorbed from the stomach and the intestine. They gastrointestinal effects of nausea and vomiting. Some
enter cells by simple diffusion and also by sodium-dependent improvement may occur with gradual increase in dosage,
facilitated transport across gut mucosa and erythrocytes. co-ingestion of food, or the slow-release form of supple-
The coenzymes NAD and NADP are synthesized in ment. Liver dysfunction is more common with slow-release
all tissues. Extracellular nicotinamide appears to regulate form. At high intakes of niacin, fulminant hepatitis and
the tissue NAD but is itself under hepatic control. Hepatic encephalopathy, glucose intolerance, and ocular effects of
NAD is hydrolyzed to provide nicotinamide for tissues that blurred vision, toxic amblyopia, macular edema, and cystic
lack the ability to synthesize nicotinamide from trypto- maculopathy also may occur.1
phan. Tissue store of niacin is in the form of NAD that is
not bound to enzymes or as nicotinamide adenine mono- Vitamin B6
nucleotide synthesized from tryptophan and nicotinic acid.
Excess niacin is methylated in the liver to N1-methyl-nicoti- Biochemistry and Physiology
namide and excreted in the urine either unchanged or as its Vitamin B6 comprises a group of 6 related compounds: pyri-
2-pyridone derivative. doxal (PL), pyridoxine (PN), pyridoxamine (PM), and their
respective 5’-phosphates (PLP, PNP, and PMP). The major
Deficiency State forms in animal tissues are PLP and PMP; plant-derived
Several conditions uniquely predispose to niacin deficiency. foods contain primarily PN and PNP, sometimes in the
These include carcinoid syndrome in which tryptophan is form of a glucoside.
preferentially oxidized to 5-hydroxytryptophan and sero- PLP is a coenzyme for a multitude of enzymes involved
tonin; prolonged treatment with isoniazid which competes in amino acid metabolism including aminotransferases,
with the pyridoxine-derived coenzyme required in the decarboxylases, racemases, and dehydratases. It is required
tryptophan-niacin pathway; and Hartnup’s disease, an auto- for the conversion of tryptophan to both niacin and the
somal recessive disorder that interferes with the absorption neurotransmitter serotonin; from homocysteine to cysteine,
of tryptophan. dopa to dopamine as well as the synthesis of the inhibitory
The classic manifestation of severe niacin deficiency is neurotransmitter gamma-aminobutyric acid. Pyridoxine
pellagra, an Italian term meaning “rough skin.” It is charac- is a coenzyme for δ-aminolevulinate synthase, the rate-
terized by the triad of diarrhea, dermatitis, and dementia. 39 limiting first step in heme synthesis.
Gastrointestinal manifestations include glossitis, angular
stomatitis, chelitis, and diarrhea in about 50% of patients. Source
Skin lesions begin as painful erythema in sun-exposed areas. Foods rich in pyridoxine include fruits and nuts (bananas,
Vesicle or bullae formation may occur upon re-exposure to cantaloupe, walnuts), plants (green leafy vegetables, broc-
sun and the skin eventually becomes rough, hard, and scaly. coli, peas, carrots, rice husks, brown rice, maize, wheat germ,
Hair and nails tend to be spared. Neuropsychiatric manifes- yeast), and animal products (eggs, chicken, fish, beef), as
tations include insomnia, fatigue, nervousness, irritability, well as fortified cereals. Microbial synthesis of B6 is possible
apathy, and memory impairment. Dementia and death may but the extent to which its contribution to the physiological
occur in untreated cases. need is not known.
Niacin status is determined by a decreased concentra-
tion of NAD relative to NADP in erythrocytes, and low Absorption, Metabolism, and Excretion
levels of excretion in 24-hour urine niacin and its metabo- Bioavailability of vitamin B6 in a mixed diet is ~75% with
lite N1-methyl-nicotinamide and its 2-pyridone derivative. nonphosphorylated B6 as the major form absorbed. Phos-
phatase-mediated hydrolysis of PLP and PMP precedes
Supplementation absorption by a nonsaturable passive diffusion transport of
Niacin, as a supplement or pharmacologic agent used the non-phosphorylated form primarily at the jejunum and
primarily in the treatment of hyperlipidemia, can result ileum. Pyridoxine glucoside is absorbed after deconjugation
in clinical side effects. Both forms of niacin may result by a mucosal glucosidase and some is absorbed intact, then
in similar side effects although nicotinamide results in hydrolyzed in various tissues. The unphosphorylated forms
less vasodilatory effects. Nicotinic acid as low as 30 mg of B6 are absorbed and then converted to 5’-phosphate forms
daily is associated with vasodilatory effects including by pyridoxal kinase primarily in the liver. PNP and PMP
flushing, burning, tingling, and itching sensation, and are oxidized to PLP by PNP oxidase. PMP is also generated

from PLP via aminotransferase reactions. PLP is bound to Supplementation

various proteins in tissues which protects it from the action High-dose pyridoxine supplement of 2 to 6 g daily for 2 to
of phosphatases. Muscle, plasma, and erythrocyte (hemo- 40 months46 or chronic intake even at doses < 500 mg/d47
globin) have high capacity for PLP-protein binding. may result in peripheral sensory neuropathy.
When the capacity for protein binding is exceeded, free
PLP is rapidly hydrolyzed and non-phosphorylated forms of Folate (Vitamin B9)
B6 are released from the tissues into the circulation where
albumin is the major PLP-binding protein. Free PLP in the Biochemistry and Physiology
circulation is dephosphorylated then reabsorbed or carried Folate is a generic term for this water-soluble B-complex
in the erythrocyte. Vitamin B6 is found in various subcel- vitamin. Most naturally occurring food folates are pteroyl
lular compartments but primarily in the mitochondria and glutamates containing 1 to 6 glutamate molecules joined in
cytosol. a peptide linkage to the γ-carboxyl of glutamate. Folic acid
In humans, the major excretory form is 4-pyridoxic (pteroylmonoglutamic acid) is the most oxidized and stable
acid which accounts for about half the B6 compounds in form of folate. It consists of a p-aminobenzoic acid molecule
the urine. At high doses of pyridoxine, much of the dose is linked at one end to a pteridine ring and at the other end to
excreted unchanged. The body’s B6 content is estimated to a glutamic acid molecule, and occurs rarely in food but is
be about 167 mg based on muscle biopsy data and assuming the form used in vitamin supplements and in fortified food
that muscle represents about 80% of the store. The overall products.
half-life of vitamin B6 is about 25 days but the muscle turn- Folate is critical to the metabolism of nucleic and
over for B6 is much slower.40 amino acids and promotes cellular growth in general and
is necessary for the maturation of red cells. Folate is a
Deficiency State substrate (5-methyl-tetrahydrofolate) and vitamin B12 is
Isolated deficiency of pyridoxine is rare because its metabo- a coenzyme in the formation of 5,10-methylenetetrahy-
lism is intimately involved with multiple other nutrients drofolate (MTHF) and thymidylate synthesis. In either a
including riboflavin, niacin, zinc, and folate. Special consid- folate or vitamin B12 deficiency, the megaloblastic changes
erations for predisposition to lower plasma PLP may include in bone marrow and other replicating cells result from lack
therapy with isoniazid and L-dopa (react with carbonyl of MTHF. Onset of anemia is usually gradual, and clin-
group of PLP); acetaldehyde but not ethanol decreases ical manifestation of anemia typically appears only at an
net PLP formation and may compete with PLP for protein advanced stage of anemia but may be earlier in the elderly.
binding. However, the extent to which these situations Folate and vitamin B12 deficiency are independent risk
increase B6 requirements is not known. factors for neurotube defects including anencephaly and
Clinical manifestations of the B6 deficient state spina bifida.48
include seizures in infants fed milk formulas without
fortification by pyridoxine from error in the manufac- Source
turing41,42 and abnormal electroencephalogram in adults Natural sources include fresh green vegetables, liver, yeast,
from experimental B6 deficiency.43 Both are reversed with and some fruits. Folic acid is the only water-soluble vitamin
reintroduction of B6. Intractable seizures during infancy mandated as part of prenatal supplement for the prevention
and childhood may respond to large doses of pyridoxine and of neurotube defects. The generally lower intake of vegetables
sometimes only to pyridoxal phosphate. The latter form may and fruits contributes to the potentially inadequate intake
be a result of mutations in the PNPO gene for pyridox(am) of folate. Significantly improved folate status as indicated
ine 5’-phosphate oxidase and present as neonatal epileptic by population survey of red cell and serum folate has been
encephalopathy.44 Other clinical manifestations of B6 defi- reported since the Food and Drug Administration (FDA)
ciency are non-specific and may include microcytic anemia, in 1998 required the addition of folic acid to all enriched
glossitis, seborrheic dermatitis, and depression. breads, cereals, flours, corn meal, pasta products, rice, and
Plasma PLP is probably the best indicator of B6 status other cereal grain products sold in the United States.49
because it appears to reflect tissue stores.45 Erythrocyte
aspartate and alanine aminotransferase saturation by PLP Absorption, Metabolism, and Excretion
or tryptophan metabolites is also a useful indicator of rela- Dietary folate equivalent has ~50% lower bioavailability
tive B6 status. compared to folic acid. Food folates (polyglutamate

derivatives) are hydrolyzed by conjugase enzymes to mono- concentrations increase when folate status is inadequate to
glutamate forms, then enter various cells by membrane convert homocysteine to methionine.
carrier or folate-binding protein-mediated system. The folate
transporter derives from the SLC19 gene family of solute Supplementation
carriers and shares structural homology with the thiamin Excessive folate intake may precipitate or exacerbate
transporter.15 Monoglutamates, mainly 5-methyl-tetrahy- neuropathy in vitamin B12 deficient individuals.
drofolate, are metabolized in the liver and other tissues to
polyglutamate derivatives by the enzyme folylpolygluta- Vitamin B12 (Cobalamin)
mate synthetase. Polyglutamates are the forms retained in
various tissues or found in blood or bile and are the forms Biochemistry and Physiology
needed for function as a coenzyme in single-carbon transfer The term vitamin B12 is usually restricted to cyanocoba-
reactions. lamin but can be used to refer to all potentially biologically
Folate catabolism involves cleavage of intracellular and active cobalamins, a group of cobalt-containing compounds
circulatory polyglutamates to the monoglutamate form. (corrinoids) that contains the sugar ribose, phosphate,
Approximately two-thirds of the folate in plasma is protein and a base (5,6-dimethyl benzimidazole) attached to the
bound and albumin accounts for ~50% of the bound folate. corrin ring. The cobalamin coenzymes active in human
Folates freely filter through the glomeruli, are secreted, metabolism exist as methylcobalamin and 5-deoxyadeno-
and reabsorbed by the renal tubules. The bulk of the urine sylcobalamin. Methylcobalamin is required for the methyl
excretory products are folate cleavage products mainly transfer from MTHF to homocysteine to form methi-
in the monoglutamate form. There is extensive enterohe- onine and tetrahydrofolate with the enzyme methionine
patic circulation of folate. 50 The estimated total body folate synthase. Adenosylcobalamin is required for isomerization
content is between 12 and 28 mg, of which ~50% is in the of L-methylmalonyl-CoA to succinyl-CoA with the enzyme
liver. L-methylmalonyl-CoA mutase. An adequate supply of B12
is essential for normal blood formation and neurological
Deficiency State function.
Patients receiving folate antagonists such as methotrexate
and other drugs that have antifolate activity including Source
pyrimethamine, trimethoprim, triamterene, trimetrexate, Cobalamin is found in animal foods including meat, fish,
and sulfasalazine require monitoring for folate status to poultry, cheese, milk, and eggs. Cereal and soy milks are
ensure adequate dietary intake or folate supplementa- fortified with varied amounts of B12 . Vitamin B12 content
tion. Several inborn errors in folate metabolism (MTHF in breast milk is dependent on maternal diet and mature
reductase deficiency associated with mutations of alleles on milk has lower content than colostrum. In the United States
chromosome 1)51 as well as the presence of autoantibody to and Canada, both cyanocobalamin and hydroxocobalamin
folate receptor (cerebral folate deficiency)52 predispose the are available commercially although cyanocobalamin is
affected individual to folate deficiency. Serum and red cell most commonly used in supplements and pharmaceuticals.
folate concentration are low in the former and normal in Vitamin B12 can be synthesized by intestinal bacteria but
the latter. In cerebral folate deficiency, the transfer of folate its contribution to body pool is not known but likely to be
from plasma to cerebrospinal fluid is low and cerebrospinal limited.
fluid MTHF concentration is low.
Clinical features of folate deficiency may begin during Absorption, Metabolism, and Excretion
infancy and include retarded psychomotor development, Cobalamin absorption and cellular uptake require an
poor social contact, decelerating head growth, hypotonia, intact stomach, adequate transport proteins, pancreatic
ataxia, dyskinesia, irritability, visual and hearing deficiency, sufficiency, and a normally functioning terminal ileum.11
and seizures. Some neurological manifestations may be Haptocorrin (HC), gastric intrinsic factor (IF) and transco-
reversible with folinic acid supplement. Symptomatology balamin (TC) are critical to B12 transport from food to cell.
from anemia may be present. IF and HC but not TC are glycosylated proteins. There is
Deficiency states are confirmed with low red cell folate increasing specificity for binding to cobalamin in the order
which reflects tissue folate store. Plasma folate reflects HC, TC, and IF. 53 Cobalamin released from food is bound
concurrent folate balance. Plasma total homocysteine to salivary HC. After proteolysis of HC in the duodenum,

cobalamin is then bound to IF. The cobalamin-IF complex biochemical indicators of functional B12 deficiency state.
is absorbed only in the ileum under physiological condi- Plasma B12 is considered as a less sensitive indicator of B12
tions via endocytosis mediated by a specific receptor. In deficiency compared to other biochemical changes.
the enterocyte, the cobalamin-IF complex is degraded and
cobalamin is transported to the cells bound to TC and taken Supplementation
up via endocytosis by a specific receptor on most cell types. Short-term studies up to 4 months indicate that oral B12
Vitamin B12 appears in circulation several hours after supplement has similar efficacy to intramuscular treatment
ingestion. If the circulating B12 exceeds the B12 binding for B12 deficiency. 59,60 B12 fortification of foods to improve
capacity of the blood, the excess is excreted in the urine. the population’s B12 status55 has been advocated. Intranasal
About 80% of circulating B12 is bound to the proteins delivery of B12 is possible but the bioavailability is ~10% of
transcobalamin I (TCI) and the remainder to TCII or III. intramuscular preparation. Periodic parenteral administra-
TCII is the form that delivers B12 to the tissues (~50% taken tion of high-dose B12 (1-5 mg) to patients with pernicious
up by the liver) through specific receptors for TCII. HC in anemia (lack of intrinsic factor) supports the lack of adverse
the plasma cannot facilitate cellular uptake of cobalamin effects at high doses.
except in hepatocytes. The use of cyanocobalamin is contraindicated in B12
There is an active enterohepatic circulation which deficient individuals at risk for Leber’s optic atrophy, a
reabsorbs, in the presence of intrinsic factor, almost all B12 genetic disorder caused by chronic cyanide (present in
secreted into the bile. Unlike other water-soluble vitamins, tobacco smoke, alcohol, and some plants) intoxication,
there is a large store of B12 primarily in the liver. The average because the latter may increase the risk of irreversible optic
B12 content of liver is ~1 mcg/g in healthy adults. The average atrophy. Hydroxocobalamin, a cyanide antagonist, 61 can be
total body pool of B12 is estimated to be 2 to 3 mg. Daily loss used instead of cyanocobalamin.1
of B12 is ~0.1 to 0.2% of the B12 pool regardless of the size of
the store, with the 0.2% value generally applicable to those Vitamin C
with pernicious anemia. 54
Deficiency State Ascorbic acid is the enolic form of an α-ketolactone
Breastfed infants of strict vegan mothers, children receiving (2,3-didehydro-L-threo-hexano-1,4-lactone) and the 2
macrobiotic diets, and the elderly are at risk for B12 deficiency enolic hydrogen atoms give the compound its acidic char-
as are individuals with the absence of intact stomach, ileum, acter and provide electrons for its function as a reductant
pancreatic exocrine function or intrinsic factor. 55 Chronic and antioxidant. Vitamin C refers to both ascorbic acid
use of proton pump inhibitors increases the risk for B12 and dehydroascorbic acid. Ascorbic acid is the functional
deficiency by inhibition of intragastric proteolysis, thereby and primary in vivo form of the vitamin. Ascorbate is the
inhibiting the release of B12 from food prior to binding free reduced form of ascorbic acid. Ascorbyl radical and
to haptocorrin and also inhibiting B12 binding to gastric dehydroascorbic acid are the 1- or 2-electron oxidation
intrinsic factor. 56 Autoantibodies against parietal cell H+K+- products which readily reduce back to ascorbic acid in vivo,
adenosine triphosphate causing loss of gastric parietal cells thus a relatively small amount of the vitamin is lost through
or blocking the B12 binding site for intrinsic factor result catabolism.
in B12 deficiency. Genetic defects that involve deletions Vitamin C is known to be an electron donor for 8
or defects of methylmalonic acid-CoA mutase, TCII, or human enzymes. Three enzymes participate in collagen
enzymes in the pathway of cobalamin adenosyllation have hydroxylation (also requires iron) and contribute to
been reported to be associated with B12 deficiency. 57 the biosynthesis of other connective tissue components
Clinical manifestations of B12 deficiency include macro- including elastin, fibronectin, proteoglycans, bone matrix,
cytic megaloblastic anemia and neurological problems. The and elastin-associated fibrillin. Two enzymes along with
latter include ataxia, muscle weakness, spasticity, incon- iron are required in carnitine synthesis; and 3 enzymes,
tinence, vision problems, dementia, psychosis, and mood dopamine-β-hydroxylase, peptidyl-glycine monooxygenase,
disturbance. Impaired cognitive function has been demon- and 4-hydroxyphenylpyruvatedioxygenase, are required in
strated in adolescents with marginal cobalamin. 58 hormone and amino acid biosynthesis.
Decreased plasma B12 and elevated plasma and Vitamin C is an effective antioxidant because of its
urine methylmalonic acid and plasma homocysteine are ability to donate electrons and its antioxidant effect operates

in the aqueous phase both intra- and extracellularly. It Both the 1- and 2-electron oxidation products of the
participates in redox reactions with many other dietary and vitamin are readily reduced back to ascorbic acid in vivo—
physiological compounds including glutathione, tocoph- chemically and enzymatically—by glutathione, NADH,
erol, flavonoids, and the trace metals iron and copper. and NADPH dependent reductases and relatively small
Antioxidation activities at the tissue level include protec- amounts of the vitamin are lost through catabolism.
tion of the eye, neutrophils, and sperm DNA among many Vitamin C is actively secreted in human gastric juice.
other tissues. In the circulation, it protects against oxida- Proton pump inhibitor therapy lowers the concentration of
tion of plasma low-density lipoprotein (LDL). Ascorbate vitamin C in gastric juice and may reduce the bioavailability
also provides antioxidant protection indirectly by regen- of ingested vitamin C.
erating other biological antioxidants such as glutathione The kidney is capable of reabsorption of ascorbate but
and α-tocopherol back to their active state. Ascorbic acid renal excretion of ascorbate is greater with increased intake.
functions as a reducing agent for mixed function oxidases in Aspirin may increase urinary ascorbate.6 Due to homeo-
the microsomal drug-metabolizing system that inactivates static regulation, the biological half-life of ascorbate varies
a wide variety of substrates, such as endogenous hormones widely from 8 to 40 days and is inversely related to the
or xenobiotics including drugs, pesticides, or carcinogens ascorbate body pool. A body pool of < 300 mg is associated
that are foreign to humans. The vitamin is involved in the with scurvy while maximum body pools are estimated to be
biosynthesis of corticosteroids and aldosterone and in the about 2 g.
microsomal hydroxylation of cholesterol to bile acids. 5 One
form of hereditary methemoglobinemia is reported to be Deficiency State
responsive to vitamin C.62 In developed countries, population surveys show serum
vitamin C concentrations are significantly lower in smokers
Source and low-income persons, presumably reflecting the increased
Almost 90% of vitamin C in the typical diet comes from oxidative stress of smokers and low dietary consumption of
fruits and vegetables. Citrus fruits, tomatoes, tomato juice, vitamin C foods.63 Clinical manifestation of vitamin C defi-
and potatoes are major sources. Other sources include ciency is quite rare but has been reported in children with
brussel sprouts, cauliflower, broccoli, strawberries, cabbage, severely restricted diets related to food faddism, psychiatric
and spinach. Vitamin C content of foods can vary with or developmental problems, 64 or in children with end-stage
growing condition, season, stage of maturity, cooking prac- organ disease with severely compromised nutrition.65 It
tice, and storage time prior to consumption. 22 also has been reported in young children who ingest only
well-cooked foods, few fruits and vegetables, and are supple-
Absorption, Metabolism, and Excretion mented with ultra heat-processed milk.66
Some 70% to 90% of usual dietary intake of ascorbic acid The primary clinical manifestation of vitamin C defi-
is absorbed via a sodium-dependent active transport at low ciency is scurvy and reflects deterioration of elastic tissues.
gastrointestinal ascorbate concentrations, while passive Clinical features include follicular hyperkeratosis, pete-
diffusion occurs at high concentrations. With large intakes chiae, ecchymoses, coiled hairs, inflamed and bleeding
of vitamin C, unabsorbed ascorbate is degraded in the gums, perifollicular hemorrhages, and impaired wound
intestine, a process that may account for the diarrhea and healing. Refusal to walk, with or without joint effusions and
intestinal discomfort. Dehydroascorbic acid is the form of arthralgia, dyspnoea, edema, weakness, fatigue, depres-
vitamin that primarily crosses the membranes of blood and sion and Sjogren syndrome (dry eyes and mouth) also can
intestinal cells, after which it is reduced intracellularly to occur. In experimental subjects, gingival inflammation and
ascorbic acid and localized mostly in the cytosol. Cellular fatigue were among the most sensitive markers of deficiency
transport of ascorbic acid and dehydroascorbic acid is medi- without being frankly scorbutic. Impaired bone growth,
ated by tissue-specific cellular transport systems which disturbed ossification, and subperiosteal hemorrhage may
allow for wide variation of tissue ascorbate concentrations. be present. Scurvy usually occurs at a plasma concentration
High levels are maintained in the pituitary and adrenal of < 0.2 mg/dL (11 µmol/L) although leukocyte ascor-
glands, leukocytes, eyes, and the brain, while low levels are bate concentration is considered a better measure of tissue
found in plasma and saliva. reserve than plasma ascorbate concentration and is the
Both intracellular and plasma vitamin C exist predomi- preferred indicator of vitamin C status.67
nantly in the free reduced form as ascorbate monoanion.

Supplementation pathway end products, CoA and acyl-CoA. CoA is hydro-

Gastrointestinal disturbances such as nausea, abdominal lyzed to pantothenic acid in a multiple-step reaction and is
cramps, and diarrhea have been reported at vitamin C excreted intact in the urine in proportion to dietary intake.
intake of > 3 g/d probably as a result of the osmotic effect
of unabsorbed vitamin C.68 In vivo data do not clearly show Deficiency State
a causal relationship between excess vitamin C intake by Deficiency has been reported only with feeding semisyn-
apparently healthy individuals and other adverse effects2 thetic diets70 or an antagonist to the vitamin, Ω-methyl
although increased urine oxalate excretion and development pantothenic acid.71 Clinical manifestations may be non-
of oxalate stones may be possible. However, individuals with specific and include irritability, restlessness, fatigue, apathy,
hemochromatosis, glucose-6-phosphate dehydrogenase malaise, sleep disturbances, nausea, vomiting and abdom-
deficiency, and renal disorders may be more susceptible to inal cramps, numbness, paresthesia, and staggering gait, and
adverse effects of excess vitamin C intake, which include increased sensitivity to insulin. Historically, pantothenic
excess iron absorption, pro-oxidant effects, and kidney acid was implicated in the “burning feet” syndrome that
(oxalate) stone formation. There is also risk for reduced affected prisoners of war in Asia during World War II.72
vitamin B12 and copper levels, increased oxygen demand, There are no data to support the use of whole blood,
dental enamel erosion, allergic response,2 and blocking the plasma, or red cell concentrations as a marker of deficiency
action of warfarin.6 Vitamin C intake of 250 mg/d or higher state. Urinary excretion of pantothenic acid is strongly
has been associated with false negative result for stool and dependent on dietary pantothenic acid.70
gastric occult blood.69 High-dose vitamin C supplement
should be stopped before these laboratory tests. Supplementation
There are no subgroups of population who are distinctly
Pantothenic Acid (Vitamin B5) susceptible to adverse effects of excess pantothenic acid.
Biochemistry and Physiology Biotin (Vitamin B7)

Pantothenic acid is a component of coenzyme A (CoA)
which is involved in more than 70 enzymatic pathways. Biochemistry and Physiology
CoA, in forms such as acetyl-CoA and succinyl-CoA, plays Biotin is a cofactor for 5 mammalian carboxylases. These
an important role in the tricarboxylic acid cycle and in the carboxylases catalyze the carboxylation of pyruvate to oxalo-
synthesis of fatty acids and membrane phospholipids, amino acetate which serves as an intermediate in the tricarboxylic
acids, steroid hormones, vitamins A and D, porphyrin and acid cycle, of propionyl-CoA to form D-methylmalonyl-
corrin rings, and neurotransmitters, and acetylation and CoA, then undergoes isomerization to succinyl-CoA and
acylation of proteins and the synthesis of α-tubulin. enters into the tricarboxylic acid cycle, of acetyl-CoA to
malonyl-CoA, which serves as a substrate for fatty acid elon-
Source gation; and in the degradation of leucine.
Pantothenic acid is widely distributed in foods and found
in high concentrations in organ meats, yeast, egg yolk, fresh Source
vegetables, whole grains, and legumes. Intestinal micro- Biotin is widely distributed in natural food stuffs but its
flora can synthesize pantothenic acid but its contribution in concentration varies substantially with liver having the
humans has not been quantified. highest content; fruits and most meats contain small
amounts. The contribution of biotin synthesized by intes-
Absorption, Metabolism, and Excretion tinal microflora to the body’s needs has not been defined.
CoA in the diet is hydrolyzed in the intestinal lumen to
dephospho-CoA, phosphopantethine, and pantethine, with Absorption, Metabolism, and Excretion
the latter subsequently hydrolyzed to pantothenic acid. Most dietary biotin is protein bound although it also exists
Intestinal absorption of pantothenic acid occurs through a in free form. Biotinase releases the free vitamin from the
saturable sodium-dependent active transport at low intakes, protein for absorption primarily in the proximal small
while passive diffusion occurs at high intakes. intestine but some occurs at the proximal colon. Absorp-
Tissue CoA synthesis is regulated primarily by panto tion is by active transport at low concentrations and passive
thenate kinase, an enzyme feedback inhibited by the diffusion at high concentrations. Avidin, a protein found

in appreciable amounts in raw egg white, binds to biotin Supplementation

and prevents its absorption. Specific receptors are probably Intakes of biotin at > 10 mg/d in a variety of subjects at
involved in tissue uptake of biotin. different life stages was not associated with documented
About half of biotin undergoes metabolism to bisnor- adverse effects.
biotin and biotin sulfoxide before excretion. In human
urine and plasma, they are present in molar proportions Choline
of ~3:2:1. Two additional minor metabolites, bisnorbiotin
methyl ketone and biotin sulfone, are also present in urine. Biochemistry and Physiology
The urinary excretion and serum concentrations of biotin Choline is the major source of methyl groups in the diet. It is
and its metabolites increase roughly in the same proportion a precursor for acetylcholine, phospholipids, and the methyl
in response to either intravenous or oral administration of donor betaine. Functionally, it plays a critical role in the
large doses of biotin.73 structural integrity of cell membranes, methyl metabolism,
During normal breakdown of cellular proteins, cholinergic neurotransmission, transmembrane signaling,
biotin-containing enzymes are degraded to biocytin and lipid and cholesterol transport and metabolism.
(ε-N-biotinyl-L-lysine) or short oligopeptides containing
biotin-linked lysyl residues. Biotin is released from these Source
oligopeptides by biotinidase and the biotin is reused.74 Choline in the diet is available as free choline or is bound as
water-soluble (phosphocholine, glycerophosphocholine) or
Deficiency State lipid soluble (sphingomyelin, phosphotidylcholine) esters.
Clinical deficiency of biotin is uncommon but has been It is widely distributed in foods with most in the form of
reported in individuals who consumed raw egg whites over phosphatidylcholine in membranes. Foods especially rich
long periods75 or received total parenteral nutrition before in choline compounds are milk, liver, eggs, and peanuts.
biotin supplementation.76 Infantile seizures either alone or Lecithin, a phosphatidylcholine-rich fraction prepared
with other neurological or cutaneous findings, particularly during commercial purification of phospholipids, is often
in the presence of ketolactic acidosis and organic aciduria, used interchangeably with phosphatidylcholine, and is
are typical of biotinidase deficiency.77 Infants manifest frequently added to food as an emulsifying agent and may
rash around the mouth, nose, and eyes as “biotin deficiency be a significant source of choline.
facies” after several months of biotin-free total parenteral Endogenous synthesis of choline occurs via sequential
nutrition. This rash may extend to ears and perineal orifices. methylation of phosphatidylethanolamine catalyzed by the
Alopecia totalis, hypotonia, lethargy, developmental delay, enzyme phosphatidylethanolamine N-methyltransferase
and withdrawn behavior also may occur. Similar manifes- and with S-adenosylmethionine as the methyl donor.
tations including ataxia and paresthesia may occur in older However, it is insufficient to compensate for the lack of
children and adults. The list of inborn errors of metabolism dietary choline.
that result in biotin dependency and various degrees of
neurological and dermatologic abnormalities now extends Absorption, Metabolism, and Excretion
to holocarboxylase synthetase deficiency and a defect in Choline can be absorbed as lipid-soluble esters through the
biotin transport.78 lymph or as free choline into portal circulation. Pancreatic
Biochemically, urine excretion of biotin is decreased enzymes can liberate choline from its ester forms. The
and 3-hydroxyisovaleric acid is increased.79 Plasma biotin absorption through the small intestinal mucosa is by trans-
is not a sensitive indicator of inadequate biotin intake. porter proteins, which are probably unique for choline.
Reduced expression of SLC19A3, a potential biotin trans- Some choline may be metabolized by intestinal bacteria to
porter, in leukocytes may prove to be a useful indicator of form betaine (which may be absorbed and used as a methyl
marginal biotin deficiency.80 donor) and methyl amines (which are not methyl donors).
Biotinidase deficiency results in a relative biotin defi- Choline, folate, and B12 metabolism interactions are required
ciency through lack of adequate digestion of protein-bound for methyl transfer from MTHF to homocysteine to form
biotin. It is treated with free (unbound) biotin at the esti- methionine and tetrahydrofolate with the enzyme methi-
mated typical dietary intake of 50 to 150 mcg/d.81 onine synthase. Thus, the need for choline is modified by
methionine, folic acid, and vitamin B12 .

All tissues accumulate choline by diffusion and medi- 3. Niacin can be synthesized from:
ated transport and a specific carrier mechanism transports A. Valine
free choline across the blood-brain barrier at a rate propor- B. Threonine
tional to the serum choline concentration. The liver and C. Tryptophan
kidney also readily take up choline where a large proportion D. Methionine
is oxidized to betaine. The methyl groups of betaine can be E. Linoleic acid
scavenged and reused in single-carbon metabolism. 4. Excess folate intake may exacerbate clinical manifesta-
tion of deficiency in:
Deficiency State A. Iron
Though many foods contain choline, there is at least a B. Vitamin B6
twofold variation in dietary intake in humans. When C. Thiamin
deprived of dietary choline, most men and postmenopausal D. Vitamin B12
women developed signs of organ dysfunction (fatty liver E. Choline
or muscle damage), while less than half of premenopausal 5. Inherited metabolic defects in water-soluble essential
women developed such signs.82 Individuals receiving micronutrients may present in the neonate as:
total parenteral nutrition devoid of choline but adequate A. Intractable seizures
for methionine and folate developed hepatic steatosis B. Nutritional deficiency rickets
and elevated alanine aminotransferase. These abnormali- C. Bleeding tendency
ties resolved in some individuals when a source of dietary D. Cataract
choline was provided.83 In addition to the gender influence, E. Blindness
there also appears to be genetic polymorphism and epige-
netics influence for susceptibility to choline deficiency. 82 See p. 487 for answers.
Fasting plasma, erythrocyte, and tissue content of choline
and phosphatidylcholine can be used as markers of choline References
status. 1. Institute of Medicine, Food and Nutrition Board. Dietary
Reference Intakes for Thiamin, Riboflavin, Niacin, Vitamin
B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline.
Supplementation Washington, DC: National Academy Press; 1998.
The critical adverse effect from high intake of choline is 2. Institute of Medicine, Food and Nutrition Board. Dietary
hypotension, with corroborative evidence on cholinergic Reference Intakes for Vitamin C, Vitamin E, Selenium, and Caro-
side effects (eg, sweating and diarrhea, and fishy body tenoids. Washington, DC: National Academy Press; 2000.
odor).1 3. American Academy of Pediatrics Policy. In: Kleinman RE, ed.
Pediatric Nutrition Handbook. 6th ed. Elk Grove Village, IL:
American Academy of Pediatrics; 2009.
Test Your Knowledge Questions 4. Northwestern University. Fact sheet: Nutrients and diet regi-
1. Bioavailability of water-soluble essential micronutri- mens. www.feinberg.northwestern.edu/nutrition. Accessed
ents is usually not affected by: May 28, 2009.
A. Temperature and duration of cooking 5. Drugs, Supplements, and Herbal Information, Medline Plus,
B. Storage National Institutes of Health. http://www.nlm.nih.gov/
medlineplus/druginformation.html. Accessed June 25, 2009.
C. Exposure to light 6. Micronutrient Information Center, Linus Pauling Institute,
D. Source from food or supplement Oregon State University. http://lpi.oregonstate.edu/info-
E. Maturity of the plant center/vitamins.html. Accessed May 28, 2009.
2. Clinical status of water-soluble essential micronutri- 7. USDA Agriculture Research Service. Nutrient data labora-
ents may be affected by all of the following except: tory. http://www.nal.usda.gov/fnic/foodcomp/search/.
Accessed September 23, 2009.
A. Dietary intake
8. Department of Health and Human Services. Food and Drug
B. Intact pancreatic function Administration. Parenteral multivitamin products. Federal
C. Intact stomach Register. 2000;65:21200–21201
D. Intact small bowel 9. Drug Facts and Comparisons® 2009. St Louis, MO: Wolters
E. Intact large bowel Kluwer Health.

10. Picciano MF, Dwyer JT, Radimer KL, et al. Dietary 28. Kornreich L, Bron-Harlev E, Hoffmann C, et al. Thiamine
supplement use among infants, children and adolescents deficiency in infants: MR findings in the brain. Am J Neurora-
in the United States, 1999 – 2002. Arch Pediatr Adol Med. diol. 2005;26:1668–1674.
2007;161:978–985. 29. Talwar D, Davidson H, Cooney J, St JO’Reilly D. Vitamin
11. Basu TK, Donaldson D. Intestinal absorption in health and B(1) status assessed by direct measurement of thiamin
disease: micronutrients. Best Pract Res Clin Gastroenterol. pyrophosphate in erythrocytes or whole blood by HPLC:
2003;17:957–979. comparison with erythrocyte transketolase activation assay.
12. Rudatsikira E, Muula AS, Siziya S. Current cigarette smoking Clin Chem. 2000;46:704–710.
among in-school American youth: results from the 2004 30. Bayoumi RA, Rosalki SB. Evaluation of methods of coenzyme
National Youth Tobacco Survey. Int J Equity Health. 2009 Apr activation of erythrocyte enzymes for detection of deficiency
3;8:10 of vitamins B1, B2, and B6. Clin Chem. 1976;22:327–335.
13. Seo DC, Jiang N. Associations between smoking and 31. Fattal-Valevski A, Azouri-Fattal I, Greenstein YJ, Guindy
extreme dieting among adolescents. J Youth Adolesc. M, Blau A, Zelnik N. Delayed language development due
2009;38:1364–1373. to infantile thiamine deficiency. Dev Med Child Neurol.
14. National Center for Chronic Disease Prevention and Health 2009;51:629–634.
Promotion. Healthy youth! Alcohol and drug use. http:// 32. Fattal-Valevski A, Bloch-Mimouni A, Kivity S, et al. Epilepsy
w w w.cdc.gov/HealthyYouth/alcoholdrug/index.htm. in children with infantile thiamine deficiency. Neurology.
Accessed September 25, 2009. 2009;73:828–833.
15. Ganapathy V, Smith SB, Prasad PD. ��
SLC19: the folate/thia- 33. Powers HJ. Riboflavin (vitamin B-2) and health. Am J Clin
mine transporter family. Pflugers Arch. 2004;447:641–646. Nutr. 2003;77:1352–1360.
16. Singleton CK, Martin PR. Molecular mechanisms of thia- 34. Jusko WJ, Levy G. Absorption, metabolism, and excretion of
mine utilization. Curr Mol Med. 2001;1:197–207. riboflavin-5’-phosphate in man. J Pharm Sci. 1967;56:58–62.
17. Ariaey-Nejad MR, Balaghi M, Baker EM, Sauber- 35. Erlich SD. Possible interactions with vitamin B2 (riboflavin).
lich HE. Thiamin metabolism in man. Am J Clin Nutr. (2007). www.umm.edu/altmed/articles/vitamin-b2-000989.
1970;23:764–778. htm. Accessed May 28, 2009.
18. Mehta S, Fawzi W. Effects of vitamins, including vitamin A, 36. Amin HJ, Shukla AK, Snyder F, Fung E, Anderson NM,
on HIV/AIDS patients. Vitam Horm. 2007;75:355–383. Parsons HG. Significance
��
of phototherapy-induced ribo-
19. Allen LH, Peerson JM, Olney DK. Provision of multiple rather flavin deficiency in the full-term neonate. Biol Neonate.
than two or fewer micronutrients more effectively improves 1992;61:76–81.
growth and other outcomes in micronutrient-deficient chil- 37. Drake VJ, Jacobson EL (2007) “Niacin”. Micronutrient
dren and adults. J Nutr. 2009;139:1022–1030. Information Center, Linus Pauling Institute, Oregon State
20. Malik ZA, Abadi J, Sansary J, Rosenberg M. Elevated levels University. http://lpi.oregonstate.edu/infocenter/vitamins/
of vitamin B12 and folate in vertically infected children with niacin. Accessed May 28, 2009.
HIV-1. AIDS. 2009;23:403–407. 38. Gregory JF 3rd. Nutritional Properties and significance of
21. Nevado J, Tenbaum SP, Castillo AI, Sánchez-Pacheco A, vitamin glycosides. Annu Rev Nutr. 1998;18:277–296.
Aranda A. Activation of the human immunodeficiency virus 39. Hegyi J, Schwartz RA, Hegyi V. Pellagra: dermatitis,
type I long terminal repeat by 1 alpha, 25-dihydroxyvitamin dementia, and diarrhea. Int J Dermatol. 2004;43:1–5.
D3. J Mol Endocrinol. 2007;38:587–601. 40. Coburn SP. Location and turnover of vitamin B6 pools and
22. Ball GFM. Vitamins in Foods: Analysis, Bioavailability, and vitamin B6 requirements of humans. Ann N Y Acad Sci.
Stability. Boca Raton, FL: Taylor and Francis; 2006. 1990;585:76–85.
23. Specker BL, Black A, Allen L, Morrow F. Vitamin B-12: low 41. Coursin DB. Convulsive seizures in infants with pyridoxine-
milk concentrations are related to low serum concentrations deficient diet. J Am Med Assoc. 1954;154:406–408.
in vegetarian women and to methylmalonic aciduria in their 42. Bessey OA, Adam DJ, Hansen AE. Intake of vitamin B6 and
infants. Am J Clin Nutr. 1990;52:1073–1076. infantile convulsions: a first approximation of requirements of
24. Hahn JS, Berquist W, Alcorn DM, Chamberlain L, Bass D. pyridoxine in infants. Pediatrics. 1957;20:33–44.
Wernicke encephalopathy and beriberi during total parenteral 43. Kretsch MJ, Sauberlich HE, Newbrun E. Electroencepha-
nutrition attributable to multivitamin infusion shortage. Pedi- lographic changes and periodontal status during short-term
atrics. 1998;101:E10. vitamin B-6 depletion of young, nonpregnant women. Am J
25. Luxemburger C, White NJ, ter Kuile F, et al. Beri-beri: the Clin Nutr. 1991;53:1266–1274.
major cause of infant mortality in Karen refugees. Trans R Soc 44. Gospe SM Jr. Pyridoxine-dependent seizures: new genetic
Trop Med Hyg. 2003;97:251–255. and biochemical clues to help with diagnosis and treatment.
26. Davis RA, Wolf A. Infantile beriberi associated with Curr Opin Neurol. 2006;19:148–153.
Wernicke’s encephalopathy. Pediatrics. 1958;21:409–420. 45. Lui A, Lumeng L, Aronoff GR, Li TK. Relationship between
27. Fattal-Valevski A, Kesler A, Sela BA, et al. Outbreak of body store of vitamin B6 and plasma pyridoxal-P clear-
life-threatening thiamine deficiency in infants in Israel ance: metabolic balance studies in humans. J Lab Clin Med.
caused by a defective soy-based formula. Pediatrics. 1985;106:491–497.
2005;115:e233–e238. 46. Schaumburg H, Kaplan J, Windebank A, et al. Sensory neurop-
athy from pyridoxine abuse. A new megavitamin syndrome. N
Engl J Med. 1983;309:445–448.

47. Parry GJ, Bredesen DE. Sensory neuropathy with low-dose 66. Ratanachu-Ek S, Sukswai P, Jeerathanyasakun Y, Wong-
pyridoxine. Neurology. 1985;35:1466–1468. tapradit L. Scurvy in pediatric patients: a review of 28 cases. J
48. Stover PJ. Physiology of folate and vitamin B12 in health and Med Assoc Thai. 2003;86:S734–740.
disease. Nutr Rev. 2004;62:S3–S12. 67. Thurnham DI. Micronutrients and immune function: some
49. McDowell MA, Lacher DA, Pfeiffer CM, et al. Blood folate recent developments. J Clin Pathol. 1997;50:887–891.
levels: the latest NHANES results. NCHS Data Brief. 2008 68. Wandzilak TR, D’Andre SD, Davis PA, Williams HE. Effect
May;(6):1–8. of high dose vitamin C on urinary oxalate levels. J Urol.
50. Weir DG, McGing PG, Scott JM. Folate metabolism, the 1994;151:834–837.
enterohepatic circulation and alcohol. Biochem Pharmacol. 69. Gogel HK, Tandberg D, Strickland RG. Substances
��
that inter-
1985;34:1–7. fere with guaiac card tests: implications for gastric aspirate
51. Tonetti C, Burtscher A, Bories D, Tulliez M, Zittoun J. Meth- testing. Am J Emerg Med. 1989;7:474–480.
ylenetetrahydrofolate reductase deficiency in four siblings: a 70. Fry PC, Fox HM, Tao HG. Metabolic response to a pantoth-
clinical, biochemical, and molecular study of the family. Am J enic acid deficient diet in humans. J Nutr Sci Vitaminol (Tokyo).
Med Genet. 2000;91:363–367. 1976;22:339–346.
52. Ramaekers VT, Rothenberg SP, Sequeira JM, et al. Autoan- 71. Hodges RE, Bean WB, Ohlson MA, Bleiler R. Human pantoth-
tibodies to folate receptors in the cerebral folate deficiency enic acid deficiency produced by omega-methyl pantothenic
syndrome. N Engl J Med. 2005;352:1985–1991. acid. J Clin Invest. 1959;38:1421–1425.
53. Wuerges J, Geremia S, Fedosov SN, Randaccio L. Vitamin 72. Glusman M. The syndrome of “burning feet” (nutritional
B12 transport proteins: crystallographic analysis of beta-axial melagia) as a manifestation of nutritional deficiency. Am J
ligand substitutions in cobalamin bound to transcobalamin. Med. 1947;3:211–223.
IUBMB Life. 2007; 59:722–729. 73. Wolf B, Grier RE, Secor McVoy JR, Heard GS. Biotinidase
54. Amin S, Spinks T, Ranicar A, Short MD, Hoffbrand AV. deficiency: a novel vitamin recycling defect. J Inherit Metab
Long-term clearance of [57Co]cyanocobalamin in vegans and Dis. 1985;8 (suppl 1):53–58.
pernicious anaemia. Clin Sci (Lond). 1980;58:101–103. 74. Mock DM, Heird GM. Urinary biotin analogs increase in
55. Allen LH. How common is vitamin B-12 deficiency? Am J Clin humans during chronic supplementation: the analogs are
Nutr. 2009;89:693S–696S. biotin metabolites. Am J Physiol. 1997;272:E83–85.
56. Termanini B, Gibril F, Sutliff VE, Yu F, Venzon DJ, Jensen 75. Baugh CM, Malone JH, Butterworth CE Jr. Human biotin
RT. Effect of long-term gastric acid suppressive therapy on deficiency. A case history of biotin deficiency induced by
serum vitamin B12 levels in patients with Zollinger-Ellison raw egg consumption in a cirrhotic patient. Am J Clin Nutr.
syndrome. Am J Med. 1998;104:422–430. 1968;21:173–182.
57. Kapadia CR. Vitamin B12 in health and disease: part 76. Mock DM, Baswell DL, Baker H, Holman RT, Sweetman
I-inherited disorders of function, absorption, and transport. L. Biotin deficiency complicating parenteral alimentation:
Gastroenterologist. 1995;3:329–344. diagnosis, metabolic repercussions, and treatment. J Pediatr.
58. Louwman MW, van Dusseldorp M, van de Vijver FJ, et al. Signs 1985;106:762–769.
of impaired cognitive function in adolescents with marginal 77. Wolf B, Heard GS, Weissbecker KA, McVoy JR, Grier RE,
cobalamin status. Am J Clin Nutr. 2000;72:762–769. Leshner RT. Biotinidase deficiency: initial clinical features
59. Vidal-Alaball J, Butler CC, Cannings-John R, et al. Oral vita- and rapid diagnosis. Ann Neurol. 1985;18:614–617.
min B12 versus intramuscular vitamin B12 for vitamin B12 78. Mardach R, Zempleni J, Wolf B, et al. Biotin dependency due to a
deficiency. Cochrane Database Syst Rev. 2005;(3):CD004655. defect in biotin transport. J Clin Invest. 2002;109:1617–1623.
60. Andrès E, Dali-Youcef N, Vogel T, Serraj K, Zimmer J. Oral 79. Mock NI, Malik MI, Stumbo PJ, Bishop WP, Mock DM.
cobalamin (vitamin B12) treatment. An update. Int J Lab Increased urinary excretion of 3-hydroxyisovaleric acid
Hematol. 2009;31:1–8. and decreased urinary excretion of biotin are sensitive early
61. Shepherd G, Velez LI. Role of hydroxocobalamin in acute indicators of decreased biotin status in experimental biotin
cyanide poisoning. Ann Pharmacother. 2008;42:661–669. deficiency. Am J Clin Nutr. 1997;65:951–958.
62. Jamal A. Hereditary methemoglobinemia. J Coll Physicians 80. Vlasova TI, Stratton SL, Wells AM, Mock NI, Mock DM.
Surg Pak. 2006;16:157–159. Biotin deficiency reduces expression of SLC19A3, a potential
63. Schleicher RL, Carroll MD, Ford ES, Lacher DA. Serum biotin transporter, in leukocytes from human blood. J Nutr.
vitamin C and the prevalence of vitamin C deficiency in the 2005;135:42–47.
United States: 2003-2004 National Health and Nutrition 81. Wolf B, Heard GS, McVoy JR, Raetz HM. Biotinidase defi-
Examination Survey (NHANES). Am J Clin Nutr. 2009; Aug ciency: the possible role of biotinidase in the processing of
12 [Epub ahead of print]. dietary protein-bound biotin. J Inherit Metab Dis. 1984;7
64. Willmott NS, Bryan RA. Case report: scurvy in an epileptic (suppl 2):121–122.
child on a ketogenic diet with oral complications. Eur Arch 82. Zeisel SH. Gene response elements, genetic polymorphisms
Paediatr Dent. 2008;9:148–152. and epigenetics influence the human dietary requirement for
65. Samonte VA, Sherman PM, Taylor GP, et al. Scurvy diagnosed choline. IUBMB Life. 2007;59:380–387.
in a pediatric liver transplant patient awaiting combined 83. Buchman AL, Dubin MD, Moukarzel AA, et al. Choline ��
defi-
kidney and liver retransplantation. Pediatr Transplant. ciency: a cause of hepatic steatosis during parenteral nutrition
2008;12:363–367. that can be reversed with intravenous choline supplementa-
tion. Hepatology. 1995;22:1399–1403.

8
Fat-Soluble Vitamins
Winston Koo, MBBS, FACN, CNS, May Saba, PharmD, BCNSP, Mirjana Lulic-Botica, BSc, BCPS, and Judith Christie, RN, MSN

Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 74 1. Understand the physiological basis for the function and
Vitamin A. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .76 requirement for fat-soluble vitamins, as a group or for
Biochemistry and Physiology each vitamin individually.
Sources 2. Understand the common risk factors and special
Absorption and Metabolism considerations in the predisposition to develop fat-
Deficiency soluble vitamin deficiency states.
Adverse Effects
3. Understand the common manifestations and diagnosis
Vitamin D . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 78 of deficiency states for these fat-soluble vitamins.
Sources
4. Understand the potential risks of excessive intake of
Absorption and Metabolism fat-soluble vitamins.
Deficiency
Adverse Effects Introduction
Vitamin E. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 81 Achievement of adequate status for fat-soluble vitamins (A,
Biochemistry and Physiology D, E, and K) depends on adequate intake, intestinal digestion
Sources and absorption, cellular uptake, and metabolism. Vitamins
Absorption and Metabolism
D and K are produced endogenously in substantial, but vari-
Deficiency
Adverse Effects able, amounts. Fortification of some vitamins (eg, vitamin
D) is widely practiced because of their limited distribution
Vitamin K . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 83
Biochemistry and Physiology in commonly consumed natural foods. However, a varied
Sources dietary intake generally assures an adequate supply of fat-
Absorption and Metabolism soluble vitamins meeting the dietary reference intake (DRI)
Deficiency values in the normal population (Table 8-1).
Adverse Effects Fat-soluble vitamins have metabolic interactions with
one another, and with other nutrients. These interactions
may affect the requirements for and biological actions of fat-
soluble vitamins. For example, other antioxidants including
vitamin C, glutathione, and ubiquinols, can affect the regen-
eration of α-tocopherol and the requirement for vitamin E;
zinc, energy, and protein metabolism affect vitamin A status
through their effect on production of retinol-binding protein
(RBP) and transthyretin; novel ligands (eg, secondary
bile acids and long-chain polyunsaturated fatty acids) can
74
FAT-SOLUBLE VITAMINS 75
activate vitamin D receptors leading to additional potential to decrease the absorption of all fat-soluble vitamins and
biological function for vitamin D. Thus nutrient require- predisposes an individual to a deficiency state. Mineral oil
ments and functions of fat-soluble vitamins should not be and other nonabsorbable lipids interfere with absorption
considered in isolation; they must be considered as part of of fat-soluble vitamins. The adverse effects are potentially
total nutrition support. greater during periods of increased metabolic demands (eg,
pediatric age ranges).
Table 8-1 Dietary Reference Intake for Fat-Soluble Vitamins1-4 Certain groups of individuals are at risk for fat-soluble
Life stage Vitamin A VITAMIN D* VITAMIN E VITAMIN K* vitamin deficiency. Individuals with any disease state that
mcg RAE IU (1 mcg = mg mcg
(1 mcg = 3.3 40 IU)
impairs biliary and pancreatic secretions, intestinal mucosal
IU) function, micelle formation, uptake into enterocytes,
0–6 mo* 400 (600) 400 (1000) 4 2.0 and chylomicron secretion can impair the digestion and
7–12 mo* 500 (600) 400 (1000) 5 2.5 absorption of all fat-soluble vitamins. Thus, severe hepato-
1–3 y† 300 (600) 400 (2000) 6 (200) 30 biliary disorders, cystic fibrosis, and Whipple’s disease are
4–8 y† 400 (900) 400 (2000) 7 (300) 55 some of the diseases that predispose the individual to fat-
9–13 y† 600 (1700) 400 (2000) 11 (600) 60 soluble vitamin deficiency. Increasingly, inherited defects
MALES in absorption or metabolism of various vitamins are docu-
14–18 y† 900 (2800) 400 (2000) 15 (800) 75 mented to contribute to deficiency states in an individual.
FEMALES Deficiency states from limited intake are more common
14–18 y† 700 (2800) 400 (2000) 15 (800) 75
for vitamins A and D than for vitamins E and K. Restrictions
PREGNANCY
in the variety of foods due to limited financial resources or
14–18 y† 750 (2800) 400 (2000) 15 (800) 75
fad diets is a risk factor for deficiency states. Concomitant
LACTATION
14–18 y† 1200 (2800) 400 (2000) 19 (800) 75
deficit in other nutrients is also common in these circum-
UL § § § NA stances. The at-risk life stages include the very young and
adolescence. For example, prolonged exclusively breastfed
For the individual:
infants living at higher latitudes are at risk for vitamin D
* Adequate intake (AI) = observed or experimentally determined estimates
of nutrient intake by a group or groups of healthy people. Applicable for deficiency. This is the result of lack of endogenous produc-
all ages for vitamins D and K. tion from inadequate sunlight exposure and poor exogenous
† Recommended dietary allowance (RDA) = average daily dietary intake intake because of the low vitamin D content of breast milk.
sufficient to meet the requirement of 97% to 98% of healthy individuals Pregnancy and lactation result in added demands to the
in a life stage and gender group. RDA = EAR + 2SDEAR or 1.2 EAR or 1.3
EAR. body’s nutritional requirements.
For a group: In certain disease states, supplementation of fat-soluble
Estimated average requirement (EAR) = daily intake of a nutrient estimated vitamins under medical supervision is appropriate. Bioavail-
to meet the nutrient requirement of half of the healthy individuals in a life ability of the enteral supplement may be improved with the
stage and gender group. water miscible form or with alteration in the physical form, 5
Dose response assessment although parenteral supplementation still may be needed
UL = § Upper limit for each life stage is indicated in parenthesis. in some patients. In healthy populations, ingestion of fat-
NA = not available soluble vitamins, often in some combination of multiple
vitamins, is a common practice among adults and chil-
Consideration of special circumstances including the dren.1–3,6 Supplementation in amounts similar to the daily
effect of medication is warranted. Chronic glucocorticoid requirements (ie, doubling the intake to twice the daily
and phenobarbital therapy affects vitamin D metabolism. recommendation), is unlikely to result in any adverse effect,
Alternately, marked alteration in vitamin K intake can although there is also no consistent benefit.
adversely affect coumarin anticoagulant therapy. Treatment Adverse effects from consumption of fat-soluble vita-
of extreme obesity with increasingly severe dietary restric- mins naturally occurring in foods has been reported for
tion and bariatric surgery can result in decreased intake and vitamin A.7 Chronic exposure to excess intake of vitamins
absorption of fat-soluble vitamins and other nutrients. The A and D is well known to have toxic effects affecting many
use of bile salt or fat sequestrants, such as cholestyramine organ systems. In some cases, single exposure to large doses
and orlistat, as adjunct therapy for hypercholesterolemia, of some fat-soluble vitamins may be toxic and occasionally
hepatobiliary disorders, or extreme obesity has the potential may be lethal. Certain individuals (eg, those with chronic

alcohol abuse and liver dysfunction) may be at greater risk green and yellow vegetables, oils, and fruits. Ripe, colored
for adverse effects of excess intake or deficiency in fat-soluble fruits and cooked, yellow tuber vegetables are more effi-
vitamins and other nutrients. Cigarette consumption ciently converted to vitamin A compared to dark green
increases the demand on antioxidants in addition to its leafy vegetables. 3 Current estimates of vitamin A intake
other adverse effects. from vegetable sources is about 26% to 34% based on retinol
activity equivalent (RAE). 3
Vitamin A Supplements are available as retinol, retinyl esters
(palmitate, acetate, and N-formyl aspartamate), retinalde-
Biochemistry and Physiology hyde or β-carotene, either alone or in a multivitamin, and in
Vitamin A, or retinoids, refers to retinol and its derivatives oral and parenteral forms.11,12
including synthetic analogs that have the same β-ionone Vitamin A activity is expressed as RAEs (1 mcg RAE
ring and similar biological activities. They also include = 1 mcg all-trans-retinol = 2 mcg supplemental all-trans-β-
provitamin A carotenoids that are the dietary precursor of carotene = 12 mcg dietary all-trans-β-carotene = 24 mcg
retinol. The all-trans isomer is the most common and stable other dietary provitamin A carotenoids = 3.3 IU of vitamin
form although many cis isomers also exist. A activity). 3 The bioconversion of dietary provitamin caro-
Retinoids are critical to the maintenance of proper tenoids to RAE is estimated to be 12:1 (mcg:mcg) based
vision in the signal transmission of images to the visual on the relative absorption efficiency of β-carotene from
cortex. They are necessary for cell differentiation and integ- food and the functional carotene:retinol equivalency ratio.
rity of epithelial cells throughout the body including normal One RAE for dietary provitamin A carotenoids other than
differentiation of the cornea and conjunctival membranes, β-carotene is lower and set at 24 mcg. 3 The use of mcg RAE
as well as for the photoreceptor rod and cone cells of the is preferred to mcg retinol equivalent (RE) or International
retina. Other critical functions include maintenance of Units when calculating and reporting the amount of total
immune function, expression of various genes that encode vitamin A in mixed foods or assessing the amount of dietary
for structural- and extracellular matrix-proteins, enzymes, and supplemental vitamin A consumed. RE was based on
RBPs and receptors, and embryonic development of hind- the earlier erroneous two times higher estimate of biocon-
brain, eyes, ears, heart, and limbs. Provitamin A carotenoids version of dietary carotenoids. 3
must be converted to retinoids to exert vitamin A function.
In addition, carotenoids are excellent antioxidants and may Absorption and Metabolism
have other biological properties unrelated to their vitamin The efficiency of absorption of preformed vitamin A is
A activity. about 70% to 90%. Vitamin A supplements, particularly
β-carotene, are generally better absorbed than the dietary
Sources vitamin sources. There may be a maturation lag in the ability
Vitamin A is present in the diet as retinyl esters derived to absorb vitamin A in the preterm infant13 and the only
almost exclusively from animal sources (liver and fish effective means to elevate plasma retinol concentrations
liver oils, dairy products, kidney, and eggs). Most of the in preterm infants is via parenteral route.14 Dietary retinyl
vitamin A in breast milk is in the form of retinyl palmitate esters are freed by acidic digestion and emulsified by bile
in milk fat and is in greatest concentration in colostrum salts to form micelles. These micelles are transported to the
and transition milk. The vitamin A content of breast milk intestinal cells, where the retinyl ester is moved across the
is generally lower in vitamin A deficient populations but is mucosal membrane and hydrolyzed, re-esterified, and then
still sufficient to prevent subclinical deficiency in exclusively incorporated into chylomicrons within the cell and secreted
breastfed infants during the first 6 months. 8 Cow’s milk has into lymph. At physiological concentrations, cellular uptake
relatively lower vitamin A content than human milk and and efflux of unesterified retinol by enterocytes is medi-
averages ~40 International Units (IU)/g fat.9 The U.S. Food ated by lipid transporters and saturable, whereas at high
and Drug Administration encourages dairy producers to pharmacological doses, the absorption of retinol is non-
fortify reduced fat milk to 2000 IU/L.9 Infant formulas are saturable.15 Portal route of absorption is possible under
fortified with vitamin A at 250 to 750 IU/100 kcal.10 High- some circumstances.
temperature sterilization of milk increases isomerization Carotenoids are solubilized into micelles, from which
of trans- to cis-retinol by as much as 34%. 3 Provitamin A they are absorbed into duodenal mucosal cells. Absorption
carotenoids (mainly β-carotene) are distributed widely in of carotenoids is by passive diffusion and by a facilitated

process that requires, at least for lutein, the class B-type 1 health and survival of infants, young children, and preg-
scavenger receptor (SR-B1).16 The intestine, liver, lung, nant and lactating women. These life-stage groups represent
adipose, and other tissues possess β,β-carotene 15,15’ periods when both nutrition stress is high and the diet is
monooxygenase activity that allows the central cleavage of likely to be chronically deficient in vitamin A. There are
the β-carotene to form 2 molecules of retinal. The latter can numerous clinical effects of vitamin A deficiency (Table
be converted to other retinoids. Eccentric cleavage of caro- 8-2) but the most specific manifestation is xerophthalmia.
tenoids by other enzymes is also possible. The absorption In developed countries, risk factors for vitamin A deficiency
efficiency of β-carotene has wide inter-individual variation include fat malabsorption conditions, strict vegan diets,
and is usually < 20%. 3,16 It is higher in the presence of dietary fad diets, and severely restricted preformed- or provitamin
fat, from homogenized, juiced, or cooked vegetables which A. Ethanol decreases liver vitamin A stores by increasing
allow the release of carotenoids, and during poor vitamin release of hepatic retinol independent of dietary intake
A status. It is lower in the presence of intestinal infections and decreasing conversion of β-carotene to retinol, thus
or infestations, and at high dietary carotenoid intake.17 promoting vitamin A deficiency. 3
β-carotene significantly reduces lutein absorption when
given simultaneously. 3 Table 8-2 Clinical Effects of Vitamin A Deficiency3,19,20
Retinyl esters and carotenoids are transported to the ■ Xerophthalmia*
liver in chylomicron remnants. Apoprotein E and several XN: Impaired dark adaptation (from slowed regeneration of
specific hepatic membrane receptors are required for the rhodopsin) to night blindness
uptake of chylomicron remnants by the liver. Retinyl esters XCj: Conjunctival dryness (xerosis), XB: keratinization (Bitot’s spot)
are hydrolyzed to retinol then bound to RBP for release XCo: Corneal xerosis, XU/K: Corneal ulceration and/or keratomalacia
of any part, XSc: Corneal scar in central part, XSp: Corneal scar
into the circulation. In the blood, holo-RBP associates with in peripheral part
transthyretin to form a trimolecular complex with retinol XF: Xerophthalmia fundus
in a 1:1:1 molar ratio for delivery to peripheral tissues. ■ Generalized dysfunction of cellular and humoral immunity
Retinoic acid, nuclear retinoic acid receptor and retinoid X with increased morbidity and mortality especially from
receptors, cellular retinol, and retinoic acid binding proteins measles and diarrhea
I and II are critical to the function of retinoids. Carotenoids ■ Impairs iron mobilization from stores
are incorporated into very low density lipoproteins and ■ Defects in lung function
■ Follicular hyperkeratosis
exported from the liver into the blood. They enter periph-
eral tissues via receptor uptake of lipoproteins and undergo * Classification according to reference 19.
further metabolism.
Retinoids are stored in the liver and other tissues The level of retinol in the blood is under homeostatic
including adipose tissue, bone marrow, lung, eye, kidney, control over a broad range of body stores and reflects body
and other organs. When vitamin A intake is adequate, stores only when these are very low or very high. 8 In addition,
> 90% of total body vitamin A is present in the liver. Vitamin low plasma retinol concentration can result from an inad-
A concentration of at least 20 mcg/g of liver in adults is equate supply of dietary protein, energy, or zinc because of
suggested as the minimal acceptable reserve.18 Regenera- decreased rate of synthesis of RBP; or from acute or chronic
tion of retinyl esters to form local storage pools (eg, in the infection because of decreases in the concentrations of the
retinal pigment epithelium) also occurs. negative acute phase proteins, RBP and transthyretin, even
Typically, the majority of vitamin A metabolites when liver retinol is adequate. 3 Changes over time in plasma
are excreted in the urine and almost all of the excreted retinol concentration distributions within a population can
metabolites are biologically inactive. Thus elevated plasma be helpful to determine vitamin A status.8 Plasma retinol at
concentrations of retinol, RBP, and transthyretin can occur < 0.70 μmol/L (1 μmol/L = 28.6 mcg/dL) reflects vitamin
in chronic renal disease. Some retinoid metabolites are A inadequacy and at < 0.35 μmol/L is considered as indica-
conjugated with glucuronic acid or taurine in the liver for tive of vitamin A deficiency.20 Simultaneous measurement
excretion in bile. of plasma RBP is helpful to assess the vitamin A status.4
Other measures of vitamin A status such as the relative
Deficiency dose response (RDR) and modified relative dose response
Vitamin A deficiency is an endemic nutrition problem (MRDR), immune function tests, conjunctival impres-
throughout much of the developing world and affects the sion cytology, dark adaptation test, pupillary response test,

and total liver reserve by isotope dilution, are abnormal in 3 months. 3,25 In adults, there are inconsistent findings for
clinical vitamin A deficiency. However, none of the above bone mineral loss and fractures. 3
measures have sufficient data relating to the usual dietary Ethanol, while promoting a deficiency of vitamin A, also
intakes of individuals or populations to allow adequate enhances vitamin A hepatotoxicity.27 Care is needed with
determination of the vitamin A status. Some of these tests vitamin A supplementation in patients with renal dysfunc-
(eg, RDR and MRDR) are subjected to other factors such as tion to avoid vitamin A toxicity because the kidney is the
RBP production that can influence the outcome. 3,8,21 main route of excretion of vitamin A and its metabolites.
Night blindness significantly improved in a majority of Both acute and chronic vitamin A toxicity are associated
affected persons with vitamin A or β-carotene supplemen- with increased plasma retinyl ester concentrations. 28
tation.22 Vitamin A supplementation reduces the risk of In humans, teratogenic effects, particularly neural crest
mortality among infants, young children, and pregnant and defects, from naturally occurring metabolites of vitamin
postpartum women in developing countries. Intramuscular A (trans-retinoic acid, 13-cis retinoic acid, and their oxo-
vitamin A supplement has a modest effect on reduction in derivatives) are well documented in women exposed during
oxygen requirement at 36 weeks postmenstrual age in those the first trimester. There are limited data to link terato-
with birth weights < 1 kg.14 Deficiency in other nutrients genic effects to high-dose preformed vitamin A (retinol
also should be treated as they also may detrimentally affect and retinyl esters) and insufficient data to determine the
vitamin A status. For example, zinc deficiency decreases presence of toxic non-teratogenic developmental effects. 29
the synthesis and secretion of RBP and transthyretin, and Adolescents using vitamin A or derivatives for the treatment
synthesis of rhodopsin. of acne must be informed of the potential teratogenic effects
There is no evidence for a certain percentage of provi- and counseled on the need to avoid pregnancy during this
tamin A carotenoids to meet the vitamin A requirement. therapy.
However, in view of the health benefits of consumption of High β-carotene intake has not been shown to cause
fruits and vegetables, 5 servings of fruits and vegetables hypervitaminosis A but carotenodermia (a yellowish
daily could provide 5.2 to 6 mg/d of provitamin A which is discoloration of the skin from hypercarotenemia) has been
~50% to 65% of the men’s RDA for vitamin A. 3 reported30,31 and is reversed when the intake is discon-
tinued. Clinical intervention trial of β-carotene supplement
Adverse Effects based on its antioxidant activity has resulted in a significant
There are substantial data on the adverse effects of high increase in the rate of lung cancer in smokers. This would
vitamin A intake.18,23 Individuals with pre-existing liver suggest that excessive intake of the provitamin A carote-
disease, hyperlipidemia, severe protein malnutrition, or noids may have unintended consequences on the complex
high alcohol intake, may be distinctly susceptible to the and intricately balanced natural antioxidant defense
adverse effects of preformed vitamin A intake. Short-term system. 32 Also, the combination of excess β-carotene and
large doses and even a single dose > 150,000 mcg in adults24 ethanol may result in hepatotoxicity. 3
and proportionately lower in children can result in acute
toxicity characterized by nausea, vomiting, headache, Vitamin D
vertigo, blurred vision, muscular incoordination, and raised
intracranial pressure. In infants, there is also bulging of Biochemistry and Physiology
fontanels.18,25 Animal studies demonstrated that a similarly Vitamin D (calciferol) refers to two fat-soluble seco-sterols:
large single dose of vitamin A can be lethal.26 cholecalciferol (vitamin D3) photosynthesized in the skin of
Chronic toxicity is usually associated with ingestion of vertebrates, and ergocalciferol (vitamin D2) from the yeast
large doses > 30,000 mcg/day for months or years. Clinical and plant sterol. The term vitamin D without the subscript
manifestations of chronic toxicity are varied and non-specific is frequently used generically to describe vitamins D2 and
and may include irritability, anorexia, skin desquamation, D3 and, correspondingly, their metabolites. The parent
and liver abnormalities including elevated liver enzymes, vitamin D compounds are biologically inert and require
fibrosis, and cirrhosis. In infants, additional non-hepatic two obligatory hydroxylation steps primarily in the liver
manifestations include bulging fontanel, craniotabes, and and kidney to 25 hydroxyvitamin D (25 OHD) and 1,25
laboratory findings of cortical hyperostosis, hypercalcemia, dihydroxyvitamin D (1,25 (OH)2D), respectively. Quanti-
and hyperphosphatemia, and metastatic calcifications may tatively, 25 OHD is the major circulating metabolite. It is a
occur at an intake between 5,500 to 6,750 mcg/d for 1 to good marker of vitamin D status as it reflects the cumulative

effects of exposure to sunlight and dietary intake of vitamin individuals, endogenous synthesis of vitamin D is possible
D. 33 At physiological concentrations, 1,25 (OH)2D is the although the rate of production is lower than less pigmented
metabolite responsible for most, if not all, biological func- individuals. In any case, adequate endogenous production
tions of vitamin D. of vitamin D3 is not assured for all populations because of
The classic actions of vitamin D include the mainte- multiple factors that affect its endogenous synthesis.
nance of calcium homeostasis and bone mineralization in Foods naturally rich in vitamin D are limited to the
the prevention of rickets in children and osteomalacia in flesh of fatty fish and fish liver oil, and the liver and fat from
adults. These effects are mediated primarily through 1,25 aquatic mammals (eg, seals and polar bears). Thus, dietary
(OH)2D binding of nuclear vitamin D receptor (VDR) intake of vitamin D from foods comes primarily from forti-
and from participation in various feedback loops involving fied milk products and other fortified foods such as breakfast
parathyroid hormone, calcitonin, and fibroblast growth cereals.41,42 The average intake of vitamin D is about 200 to
factor (FGF)-23. There is also 1,25 (OH)2D3 -mediated 400 IU per day with children tending to have greater intake
gene regulation for several bone anabolic and resorbing than adults.41 Human milk and cow’s milk have very low
factors. VDR is widely distributed in numerous organ vitamin D content (< 50 IU/L). In the United States, a vast
systems and 1,25 (OH)2D3 -VDR effects at the local level majority of natural milk and all infant formulas are fortified
include immunomodulation, antimicrobial action, detoxi- with vitamin D3 at 400 IU (10 mcg)/L9 and 40 to 100 IU/100
fication, cell proliferation, apoptosis regulation, insulin kcal,10 respectively. The amounts of vitamin D added to the
secretion, skin integrity and β-oxidation. 34 VDR stimula- milk products were erratic during the early 1990s but more
tion independent of 1,25 (OH)2D3 controls hair cycling and recent testing of samples indicates that vitamin D fortifica-
brain development. Novel ligands other than 1,25 (OH)2D3 tion is more uniform.9
including lithocolic acid, curcumin, γ-tocotrienol, and Vitamin D supplements as vitamin D2 or D3 are available
essential fatty acid derivatives may play additional specific either alone or as multivitamins in oral preparations. The
roles in physiological functions. 35 Despite the numerous parent vitamin D compound is available in parenteral form
physiological functions mediated by VDR, the evidence for only as part of a multivitamin. The more potent vitamin D
major dysfunction from vitamin D deficiency other than analog or hydroxylated vitamin D metabolites are available
the classic actions of mineral homeostasis and bone miner- in the oral and parenteral forms and are most often used as
alization is limited. part of the management of specific medical conditions. For
Biological activity of vitamin D is expressed in Inter- example, there are vitamin D analogs with minimal or no
national Units based on bioassay using cholecalciferol. The calcemic effects that are used for their antiproliferative and
biological activity of 1 mcg of vitamin D is 40 IU and 1 mcg pro-differentiation actions.11,12
25 OHD is 200 IU (ie, 5 times more potent than cholecalcif-
erol).1 Both forms of vitamin D undergo the same metabolic Absorption and Metabolism
fate and function similarly at least for the classic actions Intestinal absorption of vitamin D and its metabolites
in the clinical prevention and treatment of rickets and requires normal bile and pancreatic secretions. Once
osteomalacia. 36,37 The role of vitamin D2 in other actions is absorbed from the intestine, it is incorporated into chylomi-
not well defined. crons and transported through the lymphatic system. Both
the endogenously synthesized and absorbed dietary vitamin
Sources D and its metabolites are transported in the circulation
Endogenous synthesis of vitamin D3 requires exposure primarily by specific vitamin D binding protein and also
to sunlight or irradiation in the ultraviolet B range. It is by albumin to the various tissues. Structural differences in
extremely effective and a 10- to 15-minute whole-body the parent vitamin D3 and vitamin D2 and their metabolites
exposure to peak summer sun will generate and release up alter their binding to the carrier protein vitamin D binding
to 20,000 IU vitamin D3 into the circulation. 38,39 However, protein (DBP) and their metabolism. Data on bioavailability
prolonged sunlight exposure increases the conversion of of vitamin D3 versus D2 is controversial with respect to the
previtamin D3 to inactive metabolites. Cutaneous produc- maintenance of circulating 25 OHD concentrations.43,44
tion of vitamin D3 is substantially diminished by decreased Circulating parent vitamin D is short-lived as it is either
exposure to sunlight from seasonal changes, or time of day, stored in the fat or metabolized in the liver.45 In the hepatic
clouds, aerosols, thick ozone, higher latitude, aging, clothing, mitochondria, vitamin D 25 hydroxylase is regulated by
sunscreen use, and melanin pigmentation.40 In dark-skinned vitamin D and its metabolites. The half-life of circulating

25 OHD is 10 days to 3 weeks.46 Subsequent hydroxyla- including hydroxyproline, pyridinoline, deoxypyridinoline,

tion at the 1-carbon position to 1,25 (OH)2D in the kidney N- and C-teleopeptides, and osteocalcin in the circulation
is tightly regulated, principally through the action of para- and/or urine.
thyroid hormone in response to calcium and phosphorus Based on the traditional Gaussian distribution, the
levels. The half-life of 1,25 (OH)2D is ~4 to 6 hours.47 It is lower limit of serum or plasma 25 OHD is considered to be
possible that activated macrophages, some lymphoma cells, in the range of 10 to 15 ng/mL (1 nmol/L = 0.4 ng/mL).
and cultured skin and bone cells also make 1,25 (OH)2D However, the lower limit in adults is recommended to be
and exert paracrine or autocrine actions. Excessive unregu- ~80 nmol/L (32 ng/mL) based on changes in biomarkers
lated production of 1,25 (OH)2D by activated macrophages such as parathyroid hormone, calcium absorption, and
and lymphoma cells is responsible for hypercalciuria and bone mineral density38 and in children to be ~60 nmol/L
hypercalcemia. (24 ng/mL).4 Low circulating 25 OHD is common in chil-
Enterohepatic circulation of vitamin D and its metab- dren50 and adults.42 Non-calcium and non-bone related
olites is present but probably has a limited role in their clinical outcomes including cancer risk and immune defects
conservation.48 Further hydroxylation at the 24-carbon of from population-based studies in vitamin D status are not
25 OHD and 1,25 (OH)2D is the initial step in the meta- well defined. The widespread occurrence of low circulating
bolic degradation of these 2 vitamin D metabolites, with the 25 OHD concentrations in children and the occasional clin-
major metabolite (calcitroic acid) excreted in the urine.49 ical manifestation of rickets in non-supplemented infants
have prompted the recommendation to raise the daily
Deficiency vitamin D intake to 400 IU.4 However, beneficial effects
Clinical deficient states can result from lack of cutaneous of having values of serum or plasma 25 OHD concentra-
production of vitamin D3 with inadequate intake, impaired tions higher than the current recommended levels remain
absorption or metabolism of vitamin D to its active form undefined.
1,25 (OH)2D, or impaired recognition of 1,25 (OH)2D by
its receptor. Drugs such as glucocorticoids inhibit vitamin Adverse Effects
D dependent calcium absorption. Phenobarbital and Vitamin D toxicity from prolonged exposure to natural
phenytoin can alter the metabolism and circulating half- sunlight has not been reported. Increased sunlight exposure
life of vitamin D metabolites. Chronic therapy with these leads to a decrease in endogenous production of vitamin
medications predisposes patients to the effects of vitamin D3 by conversion of previtamin D3 to inactive metabolites,
D deficiency. inhibition of 25-hydroxylase enzymes results in decreased
Vitamin D deficiency results in inadequate mineraliza- production of 25 OHD3, and stimulation of 24-hydroxy-
tion, or demineralization, of the skeleton with occurrence lase enzyme results in increased metabolic degradation of
of rickets in the developing skeleton and osteomalacia in vitamin D metabolites. These processes contribute to the
adults. Rickets is characterized by widening at the ends of prevention of hypervitaminosis D and vitamin D toxicity.
long bones, rachitic rosary, deformations include bowed Excessive vitamin D intake from supplements can
legs and knock-knees, and frontal bossing of the skull. result in hypervitaminosis D and is characterized by a
In addition, secondary hyperparathyroidism occurs as a considerable increase in plasma 25 OHD in the range of
homeostatic response to prevent a decrease in circulating 400 to 1250 μmol/L (160–500 ng/mL). 51,52 Other vitamin
ionized calcium from vitamin D deficiency. Parathyroid D metabolites are also elevated although the increase in
hormone mobilizes calcium from the skeleton resulting in 1,25 (OH)2D is generally elevated to a much lower extent. 52
porotic bones, and conserves renal calcium but increases Clinical toxicity is manifested through hypercalcemia and
phosphorus excretion as reflected by low or absent urine its multiple debilitating effects include polyuria, polydipsia,
calcium and increased urine phosphorus. Thus, vitamin D depression, and metastatic calcification of soft tissues
deficiency is characterized by a low circulating concentra- including the kidney, blood vessels, heart, and lung. These
tion of 25 OHD, normal fasting circulating calcium with effects generally are seen with chronic supplementation in
low or low normal phosphorus, and elevated parathyroid excess of 20,000 IU daily53 although toxicity can occur at
hormone, although hypocalcemia can occur in chronic lower doses. Toxicity from chronic intake of ergocalciferol
vitamin D deficiency. Increased bone turnover with appears to require significantly higher doses. 54 It is possible
vitamin D deficiency is reflected by elevated bone alkaline that this lower toxicity may be a result of its relatively low
phosphatase, collagen, and non-collagenous bone proteins bioactivity compared to cholecalciferol.

Vitamin E = mg α-TE in a meal × 0.8 and/or

= IU of the RRR-α-tocopherol compound × 0.67
Biochemistry and Physiology = IU of all rac-α-tocopherol compound × 0.45
There are 8 naturally occurring forms of vitamin E with
4 (α-, β-, γ-, and δ-) tocopherols, all in the RRR- form, If diets vary considerably from what might be considered
and 4 (α-, β-, γ-, and δ-) tocotrienols. The RRR- form of typical in the United States or Canada, a conversion factor
α-tocopherol is maintained in human plasma and occurs other than 0.8 might be more appropriate.2
naturally in foods. Eight different stereoisomers in equal All forms of supplemental α-tocopherol are used to
amounts are found in synthetic vitamin E (all rac-α- establish the tolerable upper intake level for vitamin E as all
tocopherol): RRR-, RSR-, RRS-, RSS-, SRR-, SSR-, SRS-, forms of vitamin E are absorbed.2
and SSS- forms with structural differences at the side chain
and at the ring/tail junction. Sources
The various forms of vitamin E are not interconvert- The main dietary sources of vitamin E are edible vegetable
ible in the human. The plasma concentration and biological oils. All of the α-tocopherol present in natural foods is in the
activity of different forms of vitamin E are dependent RRR-α-tocopherol form. Oils from wheat germ, sunflower,
primarily on the affinity of α-tocopherol transfer protein safflower, canola, olive, and cottonseed contain > 50% of the
(α-TTP) for them. RRR-α-tocopherol has the highest tocopherol as α-tocopherol. Soybean and corn oils contain
affinity for α-TTP. Other forms of vitamin E stereoisomers ~10 times as much γ-tocopherol as α-tocopherol. Palm and
have much lower binding affinity to α-TTP.2 They may have rice bran oils contain high proportions of α-tocopherol,
some biological functions55,56 and their intake are reported as well as various tocotrienols. Meat, poultry, fish, dairy
as α-tocopherol equivalent.2 products, nuts, grains and fruit, especially the oils or fatty
Vitamin E functions primarily as a non-specific chain- portions, are other sources of α-tocopherol. 2 Colostrum and
breaking antioxidant acting as a peroxyl radical scavenger breast milk are rich sources of vitamin E. 58 Infant formulas
that prevents the propagation of free radical reaction and are fortified with a minimum of 0.7 IU/100 kcal.10 Infant
lipid peroxidation. 57 Vitamin E also may play important formulas fortified with the natural form of α-tocopherol have
roles in cell proliferation and differentiation, cell adhesion better bioavailability compared to the synthetic forms. 59
and arachidonic acid cascade through inhibition of protein Estimation of dietary intake of vitamin E is difficult
kinase C activity, downregulating expression of intercel- because the source of oil is not always known with certainty
lular cell adhesion molecule (ICAM-1) and vascular cell and most nutrient databases, as well as nutrition labels, do
adhesion molecule (VCAM-1), and upregulating expres- not distinguish among the different tocopherols in food.
sion of cytosolic phospholipase A 2 and cyclooxygenase-1.2 Food preparation, such as deep frying using vegetable oil,
Current recommendations for vitamin E intake include leads to chemical structure modification and may result
only the 2R-stereoisomeric forms of α-tocopherol (RRR-, in functional discrepancy. 56 Vitamin E esters usually as
RSR-, RRS-, RSS-) since they are maintained in human acetate of either natural RRR- or the synthetic mixture (all
plasma or tissue. Data on intakes from current surveys and rac-) of α-tocopherol are used in food fortification, supple-
nutrient content of foods are presented as α-tocopherol ments, and pharmacological agents. Vitamin E supplements
equivalents (α-TE) and include all 8 naturally occurring are available alone or as multivitamins in oral preparation.
forms of vitamin E, after adjustment for bioavailability Vitamin E is available in parenteral form only as part of a
using previously determined equivalency. For example, multivitamin.11 A water-miscible formulation of vitamin E,
γ-tocopherol is estimated to have only 10% of the bioac- tocopheryl polyethylene glycol succinate 1000 (TPGS), is
tivity of α-tocopherol. absorbed, metabolized, and reverses signs of vitamin E defi-
Based on the NHANES III (Third National Health and ciency in children60 with severe fat malabsorption.
Nutrition Examination Survey 1988 to 1994) data, ~80%
of the α-TE from foods is contributed by foods containing Absorption and Metabolism
α-tocopherol. Thus, the intake of α-TE is usually greater Reports of vitamin E absorption from the intestinal lumen
than the intake of α-tocopherol alone.2 Milligrams of vary widely from 21% to 86%. In healthy humans, the esters
α-tocopherol in a meal including fortified food or multivita- are hydrolyzed and absorbed as efficiently as α-tocopherol.
mins is based on the following conversion factors: The absorption of various forms of vitamin E is indepen-
dent and shows similar apparent efficiency. 2 Efficiency of

absorption depends upon biliary and pancreatic secretions, flavonoids may add to the total antioxidant pool. Cellular
micelle formation, uptake into enterocytes, and chylo- redox cycling is coupled to the energy status of the organism.
micron secretion. 2 Vitamin E absorption is facilitated by Thus dietary deficiencies of niacin or riboflavin might result
dietary fat and is lowered following vitamin E supplemen- in insufficient reducing equivalents for recycling oxidized
tation.61 During chylomicron catabolism, some vitamin E products.2
is distributed to all of the circulating lipoproteins. Chylo- Clinical deficiency from low dietary intake of vitamin E
micron remnants, containing newly absorbed vitamin in normal individuals without undue oxidative stresses has
E, are taken up by the liver. The high affinity of hepatic not been reported.2 Clinical vitamin E deficiency occurs
α-TTP to α-tocopherol over all other vitamin E isomers is with fat malabsorption syndromes or with genetic defect
responsible for the preferential secretion of α-tocopherol in α-TTP or abetalipoproteinemia where there is decreased
with very low-density lipoprotein from the liver, 62 which is hepatic reserve and circulating vitamin E.
the main determinant of plasma vitamin E concentrations. Vitamin E deficiency causes axonal degeneration of
Adipose tissue and muscle are other major storage sites for the large myelinated axons and results in posterior column
vitamin E. and spinocerebellar symptoms. Peripheral neuropathy is
Vitamin E rapidly transfers between lipoproteins and initially characterized by areflexia, with progression to
between lipoproteins and cell membranes, which may ataxic gait, and by decreased vibration and position sensa-
enrich cell membranes with vitamin E. The human plasma tions. Ophthalmoplegia, skeletal myopathy, and pigmented
phospholipid transfer protein accelerates this process.63 The retinopathy also may occur.60 Neurological symptoms
RRR-stereoisomer has roughly twice the availability of the can progress if untreated and may be reversed if treated
all-rac forms. Tissue α-tocopherol concentrations largely early. Increased erythrocyte fragility in vitro and hemo-
reflect changes in plasma concentrations of α-tocopherol.64 lytic anemia with vitamin E deficiency are reversible with
The 4 tocopherols are ultimately degraded by omega- adequate replacement of vitamin E.
oxidation and subsequent beta-oxidations followed by the Plasma α-tocopherol is decreased in vitamin E depleted
elimination of the metabolites in the bile and in the urine. subjects and a level > 12 μmol/L (0.5 mg/dL; 1 μmol/L
Excess α-tocopherol as well as forms of vitamin E not prefer- = 0.042 mg/dL) is consistent with vitamin E adequacy. 2
entially used is excreted unchanged in the stool and in bile. In subjects with elevated serum lipids, for example in
The decreased intestinal absorption and increased excre- cholestasis, a ratio of serum α-tocopherol to serum total
tion of urinary vitamin E metabolites may limit the rise in lipids of < 0.6 mg/g indicates vitamin E deficiency regard-
plasma α-tocopherol (~ threefold) and vitamin E supple- less of serum α-tocopherol concentrations. In subjects with
ments providing > 150 to 200 mg daily may not promote normal serum lipid concentrations (328–573 mg/dL),
higher tissue concentrations.65 corrections are not necessary to assess whether α-tocopherol
When vitamin E intercepts a radical, α-tocopherol is concentrations are within the normal range. 60,66 Hydrogen
oxidized to the tocopheryl radical, a 1-electron oxidation peroxide induced hemolysis and lipid peroxidation
product. A tocopherol radical can be reduced (ie, to regen- biomarkers in plasma, urine, or breath are elevated during
erate α-tocopherol) by other antioxidants including vitamin vitamin E depletion and are normalized upon vitamin E
C, glutathione, and ubiquinols. The tocopherol radical can repletion. However, these markers are non-specific and may
undergo further metabolism and is excreted in urine. It also vary with intake of other antioxidants.
may act as a prooxidant in the absence of a water-soluble Routine supplementation of vitamin E is recommended
antioxidant and oxidize other lipids in vitro. Whether this for specific disorders. However, there are no conclusive data
occurs in vivo is inconclusive. Vitamin E compounds other to support a high intake of vitamin E in the management
than RRR-α-tocopherol are preferentially metabolized and of chronic illnesses involving the cardiovascular system,
excreted.2 diabetes mellitus, cancer, central nervous system, cataracts,
or immune function.2
Deficiency
Vitamin E requirements increase with increased intake of Adverse Effects
polyunsaturated fatty acids, high-level physical activity, and All forms of vitamin E are absorbed and could contribute
cigarette smoking. However, the extent of increased require- to vitamin E toxicity although not all forms are maintained
ment and the compensatory effects of other antioxidants in plasma. Normal adults appear to tolerate oral tocopherol
are not defined. Intake of plant phenolic compounds and intake of 100 to 800 mg/d67 but adverse effects from the

consumption of vitamin E as a supplement, food fortifier, prevalent in margarines, infant formulas, and prepared
or pharmacological agent are possible. There are contra- foods. Long-chain menaquinones are produced in substan-
dictory reports in humans on hemorrhagic complications tial amounts endogenously but are probably insufficient to
from high vitamin E intake. It is possible that individuals meet the daily requirement for vitamin K.72 Vitamin K is
deficient in vitamin K or on anticoagulant therapy are at present in low concentrations in breast milk (< 5 mcg/L).
an increased risk for coagulation defects. 2 Preterm infants Commercial infant formulas are fortified with vitamin K
with birth weights < 1.5 kg with elevated plasma vitamin E (50–100 mcg/L) based on a minimum of 4 mcg/100 kcal.10
at a mean of 5.1 mg/dL have an increased incidence of Intravenous fat emulsions are another source of vitamin K
sepsis and necrotizing enterocolitis.68 Plasma α-tocopherol although the content varies with composition of the fat emul-
concentrations are not informative for assessing adverse sion and manufacturing process.73 Vitamin K supplement is
effects because they plateau at ~3 to 4 times the values for available alone or as part of many, but not all, multivitamin
non-supplemented individuals. 2 preparations in oral and parenteral forms.
Vitamin K Absorption and Metabolism

Phylloquinone absorption in the jejunum is dependent
Biochemistry and Physiology on the presence of bile and pancreatic secretions and is
There are 2 naturally occurring compounds with vitamin enhanced by dietary fat. Free phylloquinone is almost
K activity: phylloquinone (vitamin K1) from plants and completely absorbed but absorption of vitamin K from food
long-chain menaquinones (vitamin K 2) synthesized from sources is much lower and is generally < 20%. 3 Absorbed
intestinal bacteria. Menadione (vitamin K 3) is chemi- phylloquinone is secreted into lymph and enters the circula-
cally synthesized and has better water solubility than the 2 tion. In the postprandial state, phylloquinone is transported
natural forms. Structural differences in the isoprenoid side mainly by triglyceride-rich lipoproteins (TRLs) and long-
chain govern many facets of the metabolism of K vitamins, chain menaquinones mainly by low-density lipoproteins.
including the way they are transported, taken up by target Liver uptake and turnover of phylloquinone is rapid. TRL-
tissues, and subsequently excreted.69 borne phylloquinone uptake by some extrahepatic tissues
Vitamin K in its reduced form is a cofactor for gamma- (eg, osteoblasts) is an apoE-mediated process with the
glutamyl carboxylase enzymes responsible for the LRP1 receptor playing a predominant role.
posttranslational conversion of specific glutamic acid (Glu) Both phylloquinone and menaquinones activate the
residues to γ-carboxyglutamyl (Gla) residues in a subclass steroid and xenobiotic receptor that initiates their catabo-
of proteins known as vitamin K dependent proteins (also lism. Vitamin K is excreted primarily in bile and also in
known as γ-carboxylated proteins or Gla-proteins). The urine after oxidative degradation of the phytyl side chain
major Gla proteins include certain proteins of the blood followed by glucuronide conjugation. The liver has the
coagulation system: prothrombin (coagulation factor II), highest concentration of phylloquinone and significant
factors VII, IX, and X, protein C, protein S, and protein Z; amounts are also present in the heart and other tissues.
and proteins expressed in mineralized tissues: osteocalcin Hepatic reserve is rapidly depleted from restricted dietary
and matrix Gla-protein.70,71 Other putative non-cofactor intake.
functions of vitamin K include suppressing inflammation,
preventing brain oxidative damage, and playing a role in Deficiency
sphingolipid synthesis. 3,71 Individuals at risk for vitamin K deficiency include those
with severe fat malabsorption conditions (eg, hepatobiliary
Sources disorders) or after bariatric surgery, especially those with
Vitamin K content in most foods is very low (< 10 mcg/ severe diet restriction. Prolonged use of broad-spectrum
100 g), and the majority is obtained from a few leafy green antibiotics may decrease vitamin K synthesis by intestinal
vegetables and 4 vegetable oils (soybean, cottonseed, canola, bacteria. Long-term differences in dietary vitamin K intake
and olive) that contain high amounts. Hydrogenation of modulate the response to coumarin anticoagulants, which
plant oils to form solid shortenings results in some conver- act by blocking the vitamin K recycling. Elevated intake of
sion of phylloquinone to 2’,3’-dihydrophylloquinone but vitamin E antagonizes vitamin K action probably through
it is uncertain whether these forms are metabolically and its effect on vitamin K absorption and metabolism.2,74
functionally identical. These forms of vitamin K are most The classic sign of vitamin K deficiency is an increase in

prothrombin time, and in severe cases, a hemorrhagic event. D. Carotenoids have a different extent of vitamin A
Both abnormalities are responsive to vitamin K. However, activity.
other than the exclusively breastfed infant without vitamin E. Retinoids and carotenoids have similar potency for
K prophylaxis therapy, it is almost impossible to achieve this bioactivity.
level of deficiency by simple restriction of vitamin K intake 3. All of the following statements on endogenous synthesis
in any nutritionally adequate, self-selected diet in healthy of vitamin D are correct except:
individuals. The role of vitamin K in matrix-Gla formation A. It occurs following exposure to sunlight.
would support its physiological activity in the metabolism B. A brief period of sunlight exposure can generate a
of multiple organ systems but to date its role in chronic large amount of vitamin D.
diseases such as osteoporosis and atherosclerosis remains C. Dark-skinned individuals cannot produce vitamin
to be defined. D.
Prothrombin time, vitamin K dependent factors II, VII, D. Vitamin D toxicity does not occur following chronic
IX, and X, plasma phylloquinone and menaquinone concen- sunlight exposure.
trations, and proteins induced in vitamin K deficiency E. Sunscreen, clothing, and winter can decrease the
such as under-γ-carboxylated prothrombin (PIVKA-II) capacity to produce vitamin D.
and osteocalcin (ucOC), respond to alterations in dietary 4. Which of the following statements concerning vitamin
vitamin K and are helpful to assess relative changes in E is correct?
vitamin K status. However, prothrombin time is the only A. Various forms of vitamin E are interconvertible.
indicator of vitamin K status associated with adverse clinical B. Natural RRR-α-tocopherol has similar biopo-
effects. Vitamin K prophylaxis is recommended in newborn tency to all other naturally occurring vitamin E
infants75 and in conditions that predispose the patient to fat- stereoisomers.
soluble vitamin deficiency states. C. Synthetic (all-rac-tocopherol) vitamin E has greater
biopotency than the natural RRR-α-tocopherol.
Adverse Effects D. Soybean and safflower oils have much higher
Vitamin K toxicity is rare. Parenteral administration of a content of γ-tocopherol versus α-tocopherol.
large amount of water-soluble synthetic vitamin K (vitamin E. Vegetable oils are poor sources of vitamin E.
K 3) has been associated with hemolytic anemia, hyper- 5. Which of the following may interfere with vitamin K
bilirubinemia, and kernicterus4 and with liver damage. 3 No action?
adverse effects associated with other vitamin K supplements A. Chronic antibiotic therapy
or from food have been reported in healthy individuals B. Cholestyramine
although high dietary intake or supplemental vitamin K can C. Orilstat
inhibit the anticoagulation effect of vitamin K antagonists. D. Coumarin
E. All of the above
Test Your Knowledge Questions
1. Human milk is a good source of which fat-soluble See p. 487 for answers.
vitamins?
A. A and E References
B. D and A 1. Food and Nutrition Board, Institute of Medicine. Dietary
C. E and D Reference Intakes for Calcium, Phosphorus, Magnesium, Vitamin
D, and Fluoride. Washington, DC: National Academy Press;
D. K and D 1997.
E. K and A 2. Food and Nutrition Board, Institute of Medicine. Dietary
2. All of the following statements about vitamin A are Reference Intakes for Vitamin C, Vitamin E, Selenium, and Caro-
correct except: tenoids. Washington, DC: National Academy Press; 2000.
A. Absorption increases with presence of dietary fat. 3. Food and Nutrition Board, Institute of Medicine. Dietary
Reference Intakes for Vitamin A, Vitamin K, Arsenic, Boron,
B. Vitamin A metabolizes into various forms with
Chromium, Copper, Iodine, Iron, Manganese, Molybdenum,
biological action. Nickel, Silicon, Vanadium, and Zinc. Washington, DC: National
C. Vitamin A activity of carotenoids is mediated Academy Press; 2001.
through its conversion to retinoids.

4. American Academy of Pediatrics, Committee on Nutrition. 21. Wasantwisut E. Application of isotope dilution tech-
Kleinman RE, ed. Pediatric Nutrition Handbook. 6th ed. Elk nique in vitamin A nutrition. Food Nutr Bull. 2002; 23(3
Grove Village, IL: American Academy of Pediatrics; 2009. Suppl):103–106.
5. Papas KA, Sontag MK, Pardee C, et al. A pilot study on the 22. World Health Organization, United Nations Childrens Fund,
safety and efficacy of a novel antioxidant rich formulation in VACG Task Force. Vitamin A Supplements: A Guide to Their
patients with cystic fibrosis. J Cyst Fibros. 2008;7:60–67. Use in the Treatment and Prevention of Vitamin A Deficiency and
6. Picciano MF, Dwyer JT, Radimer KL, et al. Dietary Xerophthalmia. 2nd ed. Geneva: World Health Organization;
supplement use among infants, children and adolescents 1997. http://www.who.int/nutrition/publications/micronu-
in the United States, 1999 – 2002. Arch Pediatr Adol Med. trients/vitamin_a_deficieny/9241545062/en/index.html.
2007;161:978–985. Accessed July 25, 2009.
7. Mahoney CP, Margolis MT, Knauss TA, Labbe RF. Chronic 23. Penniston KL, Tanumihardjo SA. The acute and chronic toxic
vitamin A intoxication in infants fed chicken liver. Pediatrics. effects of vitamin A. Am J Clin Nutr. 2006;83:191–201.
1980;65:893–897. 24. Bendich A, Langseth L. Safety of vitamin A. Am J Clin Nutr.
8. World Health Organization. Brown E, Akre J, eds. Indicators 1989;49:358–371.
for Assessing Vitamin A Deficiency and Their Application in Moni- 25. Persson B, Tunell R, Ekengren K. Chronic vitamin A intoxi-
toring and Evaluating Intervention Programmes. Geneva: World cation during the first half year of life; description of 5 cases.
Health Organization; 1996. http://www.who.int/nutrition/ Acta Paediatr Scand. 1965;54:49–60.
publications/micronutrients/vitamin_a_deficieny/WHO_ 26. Macapinlac MP, Olson JA. A lethal hypervitaminosis A
NUT_96.10/en/index.html. Accessed July 25, 2009. syndrome in young monkeys (Macacus fascicularis) following
9. Murphy SC, Whited LJ, Rosenberry LC, Hammond BH, a single intramuscular dose of a water-miscible prepara-
Bandler DK, Boor KJ. Fluid milk vitamin fortification compli- tion containing vitamins A, D2 and E. Int J Vitam Nutr Res.
ance in New York state. J Dairy Sci. 2001;84:2813–2820. 1981;51:331–341.
10. U.S. Food and Drug Administration. Code of Federal Regu- 27. Leo MA, Lieber CS. Alcohol, vitamin A, and beta-carotene:
lations Title 21. Infant formula nutrient specifications. adverse interactions, including hepatotoxicity and carcinoge-
http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/ nicity. Clin Nutr. 1999;69:1071–1085.
CFR Search.cfm?fr=107.100&SearchTerm=infant%20 28. Krasinski SD, Russell RM, Otradovec CL, et al. Relationship
formula. Accessed August 2, 2009. of vitamin A and vitamin E intake to fasting plasma retinol,
11. Drug Facts and Comparisons® 2009. St. Louis, MO: Wolters retinol-binding protein, retinyl esters, carotene, alpha-tocoph-
Kluwer Health. erol, and cholesterol among elderly people and young adults:
12. Drugs, Supplements, and Herbal Information. Medline Plus, increased plasma retinyl esters among vitamin A-supplement
National Institutes of Health. http://www.nlm.nih.gov/ users. Am J Clin Nutr. 1989;49:112–120.
medlineplus/druginformation.html. Accessed June 25, 2009. 29. World Health Organization, The Micronutrient Initia-
13. Koo WWK, Krug-Wispe S, Succop P, Tsang RC, Neylan M. tive. Safe Vitamin A Dosage During Pregnancy and Lactation.
Effect of different vitamin A intakes in very low birth weight Geneva: World Health Organization; 1998. http://www.who.
infants. Am J Clin Nutr. 1995;62:1216–1220. int/nutrition/publications/micronutrients/vitamin_a_defi-
14. Darlow BA, Graham PJ. Vitamin A supplementation to cieny/WHO_NUT_98.4/en/index.html. Accessed July 25,
prevent mortality and short and long-term morbidity in 2009.
very low birthweight infants. Cochrane Database Syst Rev. 30. Lascari AD. Carotenemia. A review. Clin Pediatr.
2007;4:CD000501. 1981;20:25–29.
15. Harrison EH. Mechanisms of digestion and absorption of 31. Bendich A. The safety of beta-carotene. Nutr Cancer.
dietary vitamin A. Annu Rev Nutr. 2005;25:87–103. 1988;11:207–214.
16. Borel P, Drai J, Faure H, et al. ��
Recent knowledge about intes- 32. Black HS. Reassessment of a free radical theory of cancer with
tinal absorption and cleavage of carotenoids. Ann Biol Clin. emphasis on ultraviolet carcinogenesis. Integr Cancer Ther.
(Paris) 2005;63:165–177. 2004;3:279–293.
17. Tang G, Qin J, Dolnikowski GG, Russell RM. Vitamin A 33. Haddad JG Jr, Hahn TJ. Natural and synthetic sources
equivalence of beta-carotene in a woman as determined by a of circulating 25-hydroxyvitamin D in man. Nature.
stable isotope reference method. Eur J Nutr. 2000;39:7–11. 1973;244:515–517.
18. Olsen JA. Adverse effects of large doses of vitamin A and retin- 34. Jurutka PW, Bartik L, Whitfield GK, et al. Vitamin D receptor:
oids. Semin Oncol. 1983;10:290–293. key roles in bone mineral pathophysiology, molecular mecha-
19. Singh K. Modified classification of xerophthalmia. Indian J nism of action, and novel nutritional ligands. J Bone Miner Res.
Ophthalmol. [serial online] 1991 [cited November 24, 2009]; 2007;22 Suppl 2:v2–10.
39:105–107. http://www.ijo.in/text.asp?1991/39/3/105/24460. 35. Haussler MR, Haussler CA, Bartik L, et al. Vitamin D receptor:
20. World Health Organization. Global prevalence of vitamin A molecular signaling and actions of nutritional ligands in
deficiency in populations at risk 1995–2005. WHO Global disease prevention. Nutr Rev. 2008;66 (10 Suppl 2):S98–112.
Database on Vitamin A Deficiency. Geneva: World Health 36. Gordon CM, Williams AL, Feldman HA, et al. Treatment of
Organization; 2009. http://whqlibdoc.who.int/publications/ hypovitaminosis D in infants and toddlers. J Clin Endocrinol
2009/9789241598019_eng.pdf. Accessed July 25, 2009. Metab. 2008;93:2716–2721.

37. Bischoff-Ferrari HA, Willett WC, Wong JB, et al. Prevention 57. Traber MG, Atkinson J. Vitamin E, antioxidant and nothing
of nonvertebral fractures with oral vitamin D and dose depen- more. Free Radic Biol Med. 2007;43:4–15.
dency: a meta-analysis of randomized controlled trials. Arch 58. Debier C. Vitamin E during pre- and postnatal periods. Vitam
Intern Med. 2009;169:551–561. Horm. 2007;76:357–373.
38. Hollis BW. Circulating 25-hydroxyvitamin D levels indica- 59. Stone WL, LeClair I, Ponder T, Baggs G, Barrett Reis B.
tive of vitamin D sufficiency: implications for establishing a Infants discriminate between natural and synthetic vitamin
new effective dietary intake recommendation for vitamin D. J E. Am J Clin Nutr. 2003;77:899–906.
Nutr. 2005;135:317–322. 60. Sokol RJ, Butler-Simon N, Conner C, et al. Multicenter trial
39. Lehmann B. The vitamin D3 pathway in human skin and its of d-alpha-tocopheryl polyethylene glycol 1000 succinate for
role for regulation of biological processes. Photochem Photo- treatment of vitamin E deficiency in children with chronic
biol. 2005;81:1246 –1251. cholestasis. Gastroenterology. 1993;104:1727–1735.
40. Engelsen O, Brustad M, Aksnes L, Lund E. Daily duration of 61. Lodge JK, Hall WL, Jeanes YM, Proteggente AR. Physiolog-
vitamin D synthesis in human skin with relation to latitude, ical factors influencing vitamin E biokinetics. Ann N Y Acad
total ozone, altitude, ground cover, aerosols and cloud thick- Sci. 2004;1031:60–73.
ness. Photochem Photobiol. 2005;81:1287–1290. 62. Traber MG, Burton GW, Hamilton RL. Vitamin E trafficking.
41. Calvo MS, Whiting SJ, Barton CN. Vitamin D fortification in Ann N Y Acad Sci. 2004;1031:1–12.
the United States and Canada: current status and data needs. 63. Kostner GM, Oettl K, Jauhiainen M, Ehnholm C, Esterbauer
Am J Clin Nutr. 2004;80:1710S–6S. H, Dieplinger H. Human plasma phospholipid transfer protein
42. Yetley EA. Assessing the vitamin D status of the US popula- accelerates exchange/transfer of alpha-tocopherol between
tion. Am J Clin Nutr. 2008;88:558S–564S. lipoproteins and cells. Biochem J. 1995;305:659–667.
43. Holick MF, Biancuzzo RM, Chen TC, et al. Vitamin D2 is as 64. Burton GW, Traber MG, Acuff RV, et al. Human plasma and
effective as vitamin D3 in maintaining circulating concen- tissue alpha-tocopherol concentrations in response to supple-
trations of 25-hydroxyvitamin D. J Clin Endocrinol Metab. mentation with deuterated natural and synthetic vitamin E.
2008;93:677–681. Am J Clin Nutr. 1998; 67: 669–684.
44. Armas LA, Hollis BW, Heaney RP. Vitamin D2 is much less 65. Schultz M, Leist M, Petrizika M, Gassmann B, Brigelius-
effective than vitamin D3 in humans. J Clin Endocrinol Metab. Flohe R. A novel urinary metabolite of α-tocopherol,
2004;89:5387–5391. 2,5,7,8-tetramethyl-2(2’ carboxyethyl)-6-hydroxychroman,
45. Mawer EB, Backhouse J, Holman CA, Lumb GA, Stanbury as an indicator of adequate vitamin E supply? Am J Clin Nutr.
SW. The distribution and storage of vitamin D and its metabo- 1995;62:1527S–1534S.
lites in human tissues. Clin Sci. 1972;43:413–431. 66. Sokol RJ, Heubi JE, Iannaccone ST, Bove KE, Balistreri WF.
46. Mawer EB, Schaefer K, Lumb GA, Stanbury SW. The metabo- Vitamin E deficiency with normal serum vitamin E concen-
trations in children with chronic cholestasis. N Engl J Med.
lism of isotopically labeled vitamin D3 in man: the influence of 1984;310:1209–1212.
the state of vitamin D nutrition. Clin Sci. 1971;40:39–53. 67. Farrell PM, Bieri JG. Megavitamin E supplementation in man.
47. Kumar R. The metabolism and mechanism of action of Am J Clin Nutr. 1975;28:1381–1386.
1,25-dihydroxyvitamin D3 . Kidney Int. 1986;30:793–803. 68. Johnson L, Bowen FW Jr, Abbasi S, et al. Relationship
48. Clements MR, Chalmers TM, Fraser DR. Enterohepatic of prolonged pharmacologic serum levels of vitamin E
circulation of vitamin D: a reappraisal of the hypothesis. to incidence of sepsis and necrotizing enterocolitis in
Lancet. 1984;1:1376–1379. infants with birth weight 1,500 grams or less. Pediatrics.
49. DeLuca HF. Evolution of our understanding of vitamin D. 1985;75:619–638.
Nutr Rev. 2008;66 (10 Suppl 2):S73–S87. 69. Shearer MJ, Newman P. Metabolism and cell biology of
50. Rovner AJ, O’Brien KO. Hypovitaminosis D among healthy vitamin K. Thromb Haemost. 2008;100(4):530–547.
children in the United States: a review of the current evidence. 70. Suttie JW. Synthesis of vitamin K dependent proteins. FASEB
Arch Pediatr Adolesc Med. 2008;162:513–519. J. 1993;7:445–452.
51. Jacobus CH, Holick MF, Shao Q , et al. Hypervita- 71. Benzakour O. Vitamin K dependent proteins: func-
minosis D associated with drinking milk. N Engl J Med. tions in blood coagulation and beyond. Thromb Haemost.
1992;326:1173–1177. 2008;100:527–529.
52. Jones G. Pharmacokinetics of vitamin D toxicity. Am J Clin 72. Booth SL, Suttie JW. Dietary intake and adequacy of vitamin
Nutr. 2008;88:582S–586S. K. J Nutr. 1998;128:785–788.
53. Heaney RP. Vitamin D: criteria for safety and efficacy. Nutr 73. Chambrier C, Bannier E, Lauverjat M, Drai J, Bryssine S,
Rev. 2008;66 (10 Suppl 2):S178–S181. Boulétreau P. Replacement of long-chain triglyceride with
54. Stephenson DW, Peiris AN. The lack of vitamin D toxicity medium-chain triglyceride/long-chain triglyceride lipid
with megadose of daily ergocalciferol (D2) therapy: a case emulsion in patients receiving long-term parenteral nutrition:
report and literature review. South Med J. 2009;102:765–768. effects on essential fatty acid status and plasma vitamin K1
55. Sen CK, Khanna S, Roy S. Tocotrienols: vitamin E beyond levels. J Parenter Enteral Nutr. 2004;28:7–12.
tocopherols. Life Sci. 2006;78:2088–2098. 74. Traber MG. Vitamin E and K interactions — a 50-year-old
56. Cornwell DG, Ma J. Studies in vitamin E: biochemistry and problem. Nutr Rev. 2008;66:624–629.
molecular biology of tocopherol quinones. Vitam Horm. 75. American Academy of Pediatrics Policy Statement. Committee
2007;76:99–134. on Fetus and Newborn. Controversies concerning vitamin K
and the newborn. Pediatrics. 2003;112:191–192.
9
Fluids and Electrolytes
Gerald L. Schmidt, PharmD, BCNSP

Background . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 87 1. Describe factors that influence movement of fluid and
Fluid Distribution. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 87 electrolytes between the intracellular and extracellular
fluid compartments.
Fluid Regulation. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 88
Hypervolemia 2. Recommend appropriate treatments for fluid and elec-
Hypovolemia trolyte abnormalities.
Fluid Considerations/Requirements in Children. . . . . . . . 89 3. Describe the differences in the treatment of acute and
chronic electrolyte abnormalities.
Treatment of Fluid Imbalances. . . . . . . . . . . . . . . . . . . . . . 90
Electrolyte Assessment. . . . . . . . . . . . . . . . . . . . . . . . . . . . 90
Sodium
Background
Water is the most abundant and probably the most impor-
Potassium. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 94
tant substance in the body. It is essential for digestion,
Hyperkalemia
Hypokalemia absorption, transport, and utilization of nutrients as well as
the excretion of waste products. The regulation of fluids and
Magnesium. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 95
Hypermagnesemia electrolyte balance is maintained by an elaborate system
Hypomagnesemia of interrelated regulatory systems to ensure proper cell
Calcium. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 97 function. Unfortunately, fluid and electrolyte imbalances
Hypercalcemia are common, and when severe, these imbalances can have
Hypocalcemia a detrimental effect on major organ systems. This chapter
Phosphorus. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 98 will focus on fluid and electrolyte homeostasis as well as
Hyperphosphatemia commonly encountered fluid and electrolyte abnormalities
Hypophosphatemia and the treatment of these disorders.
Fluid Distribution
Water, being the most abundant component of the body,
makes up a large portion of total body weight. The actual
percentage of total body water (TBW) varies depending on
age, weight, gender, and body fat percentage. Adipose tissue
is the least hydrated body tissue; therefore, obese patients
will have a lower percentage of TBW content.1–3 Water
accounts for about 80% of total body weight in premature
infants and this proportion decreases slowly to 55% to 60%
of total body weight by age 18 years.4,5 TBW is divided into
87
3 separate compartments: intracellular fluid (ICF) (32%– volume would increase as would the ECF and ICF osmo-
52% of total body weight), transcellular fluid (1.5%–2.5% of lality. However, the ICF volume would decrease due to the
total body weight), and extracellular fluid (ECF) (16%–26% fluid shift caused by the hypertonic fluid. The volume of the
of total body weight). The ECF is further divided into the ECF increase would be determined by the tonicity and the
interstitial space (12%–19% of total body weight) and the volume of the hypertonic solution given.7
intravascular space (4%–6% of total body weight).6 Relative The balance between the ECF and ICF is important in
percentages in each compartment at various ages can be fluid homeostasis, but these are not the only compartments
found in Table 9-1. that must be maintained. The ECF components, the intra-
The primary factor that determines the water distribu- vascular space and the interstitial space, are maintained
tion between the ICF and ECF compartments is osmotic by Starling forces. Starling forces consist of plasma oncotic
pressure. Sodium is the predominant extracellular osmotic pressure and hydrostatic pressure. When fluid moves from
agent, and potassium is the predominant intracellular the plasma to the interstitial space, edema occurs.9 As
osmotic agent. The sodium-potassium-adenosine triphos- vascular permeability increases, albumin leaks from the
phatase (Na+-K+-ATPase) pump maintains the sodium plasma to the interstitial space. This capillary leak causes a
and potassium gradient in normal conditions by pumping reduction in plasma oncotic pressure which in turn causes
3 sodium ions extracellularly for every 2 potassium ions it fluid to move from the plasma to the interstitial space. If this
pumps intracellularly. A disruption in the function of the happens quickly, and the plasma volume is not replaced,
Na+-K+-ATPase pump can have a significant effect on fluid intravascular volume depletion can occur resulting in
distribution between the compartments. 3 hypotension and poor perfusion.
Fluid composition also plays an important role in fluid
dynamics between the ICF and ECF. For example, when Fluid Regulation
100 mL of 5% dextrose (a solute-free solution) is adminis- The primary source of fluid intake is usually the diet,
tered intravenously to a patient, the dextrose is metabolized although some water will be generated from the oxidation
and the resultant water gets distributed proportionally to of carbohydrates, proteins, and fat. 3,10 The majority of fluid
all compartments. Approximately 65% of the fluid volume losses are through urinary output, but fluid losses also occur
(65 mL) would go into the ICF, 32% (32 mL) would remain via the skin and the respiratory and gastrointestinal (GI)
in the ECF, and 3% (3 mL) would go into the transcellular tracts. Sodium and fluid balance are closely intertwined.
fluid compartment. Of the 32 mL that remained in the ECF, Disturbances of water balance lead to changes in plasma
25% (8 mL) would remain in the intravascular space and osmolarity and sodium balance, and changes in sodium
75% (24 mL) would be in the interstitial space. If 100 mL of balance result in changes in plasma osmolarity and fluid
0.9% sodium chloride were given, all 100 mL would stay in volume. In order to maintain a relatively normal serum
the ECF: 25% (25 mL) in the intravascular space and 75% osmolarity (290 ± 5 mOsm/L), the sodium-to-TBW ratio
(75 mL) in the interstitial space.7,8 The administration of a must be maintained in a relatively narrow range. When a
hypertonic solution (eg, 3% sodium chloride) has a different fluid deficit or excess occurs, physiological feedback mecha-
effect on fluid distribution. The increased tonicity of the nisms are activated to either increase or decrease renal
3% sodium chloride would create an osmotic gradient, water excretion or to increase or decrease thirst, thereby
pulling fluid into the ECF from the ICF. Thus, the ECF influencing fluid intake.11–15 An abnormality in either of
Table 9-1 Distribution of Total Body Water as a Percent of Total Body Weight
Age/Life Stage Total Body Water Intracellular Extracellular Transcellular
Premature infant 80% 52% 26% Intravascular 6% 2.5%
Interstitial 19%
3-month-old infant 70% 46% 22% Intravascular 5.5% 2%
Interstitial 16.5%
6-month-old infant 60% 39% 19% Intravascular 5% 1.8%
Interstitial 14%
10- to 18-year-old child/adolescent Male 59% 38% 18% Intravascular 4.5% 1.7%
Female 57% 36% Interstitial 13.5%
Elderly patient 50% 32% 16% Intravascular 4% 1.5%
Interstitial 12%

FLUIDS AND ELECTROLYTES 89
these 2 mechanisms can have a significant effect on water increases the permeability of water in the collecting tubule,
and sodium balance. The treatment of a fluid deficit or a resulting in water reabsorption in the collecting tubule
fluid excess requires the identification of the condition (ie, water retention). The resultant water retention will
that caused the abnormality and determination of the result in a more concentrated urine.20,21 Signs and symp-
time frame during which the abnormality occurred. Acute toms of hypovolemia include thirst, altered mental status,
disturbances, changes occurring in 48 hours or less, are weakness, fatigue, neuromuscular irritability, agitation,
more frequently associated with signs and symptoms and seizures, and coma.22 Other conditions that may lead to
can be corrected acutely. Chronic disturbances developing hypovolemia include GI hemorrhage, vomiting, diarrhea,
over a longer period of time are typically asymptomatic excessive sweating, burns, diabetes insipidus, and excessive
and should be replaced less aggressively.16 When assessing diuresis.23 The fluid deficit can be calculated by using the
or treating fluid and electrolyte imbalances, the patient’s following equation:
volume status must be assessed to determine if he or she
is euvolemic, hypervolemic, or hypovolemic. Patients who Fluid deficit = {(Patient serum sodium – 140) × body weight in
are euvolemic usually have the ability to self-regulate fluid kilograms} ÷ 140
status and require little more than maintenance fluids and
electrolyte supplementation. Patients who are either hyper- Fluid Considerations/Requirements
or hypovolemic require additional assessment and may in Children
require additional treatment as well. Normal daily fluid requirements can be estimated in
a variety of ways. One of the most common ways, the
Hypervolemia Holliday-Segar formula, is a weight-based method (Table
Hypervolemia, or increased TBW, causes a decreased 9-2).24,25 For example, using this method, a child weighing
serum osmolarity resulting in dilute urine by suppressing 27 kg would require a minimum of 1640 mL of fluid per day.
the levels of circulating antidiuretic hormone (ADH). The This method is commonly used to estimate fluid require-
precise mechanism by which plasma osmolarity suppresses ments; however, it does not address fluid requirements in
ADH is unclear, but it probably is related to specialized cells abnormal circumstances such as kidney failure or conges-
that sense osmolarity changes and send messages to the tive heart failure.
neuroendocrine cells located in the hypothalamus or the
organum vasculosum.17 In most cases, the thirst response Table 9-2 Calculating Estimated Fluid Requirements
will be suppressed, ADH will be suppressed, and the excess (Holliday-Segar Formula)
water will be excreted by the kidneys. However, in condi- Body Weight Daily Fluid Requirement Fluid Requirements
tions where the low plasma osmolarity fails to inhibit ≤ 10 kg 100 mL/kg 4 mL/kg/h
ADH secretion (such as in severe low-output congestive > 10 kg to 1000 mL + 50 mL/kg for 40 mL/h + 2 mL/kg/h
≤ 20 kg wt > 10 kg > 10 kg
heart failure), cell expansion, hypervolemia, and hypona-
> 20 kg 1500 mL + 20 mL/kg for 60 mL/h + 1 mL/kg
tremia continue to progress.18 Symptoms include headache, wt > 20 kg > 20 kg
nausea, vomiting, muscle twitching, convulsion, and if
severe, death.19 Other conditions that may result in hyper- There are a number of conditions that require adjust-
volemia include kidney or liver failure with ascites, sepsis, ments in fluid intake in order to provide optimal care. After
cardiac failure, and syndrome of inappropriate antidiuretic birth, a contraction of the ECF compartment takes place due
hormone (SIADH). to the loss of interstitial fluid, which results in a 5% to 10%
weight loss in healthy neonates, possibly more in premature
Hypovolemia infants.26–31 Prematurity affects fluid balance. Premature
Hypovolemia is a condition where TBW is decreased signif- infants may require as much as 200 mL/kg/d to maintain
icantly enough to result in symptoms. The body can correct fluid balance due to their large insensible fluid losses. These
the problem by stimulating the thirst response, increasing losses are due partially to the large skin-to-body surface area
ADH release, or both. When the plasma osmolarity is ratio and partially to the immaturity of the skin which leads
increased or when the blood volume or pressure is reduced, to increased evaporative fluid loss. 32,33 In addition, photo-
the thirst response is stimulated.17 In hypovolemia, the therapy and radiant warmers increase water losses, often as
serum osmolarity increases and the blood volume decreases, much as 20 to 40 mL/kg/d. 34–37 Insensible fluid losses may
which results in the release of ADH. The presence of ADH remain greater than 100 mL/kg/d for weeks in neonates

weighing less than 750 g. In patients weighing between 750 treatment of significant hypovolemia (dehydration) will be
g and 1000 g, insensible fluid losses can decrease to 60 mL/ covered in the Hypernatremia section of this chapter.
kg over the first week of life, and in those neonates weighing
between 1001 g and 1250 g, insensible fluid losses usually Electrolyte Assessment
decrease to 35 mL/kg over the first week. 38 This decrease in Changes in the ECF compartment are responsible for the
insensible fluid losses is due mainly to maturation and thick- signs and symptoms associated with fluid and electrolyte
ening of the skin shortly after birth. Antenatal steroids that imbalances. Therefore, it is the ECF compartment that must
help progress lung maturation will also affect skin thick- be corrected to alleviate those signs and symptoms. There are
ening, which reduces fluid losses via the skin. Therefore, 5 basic steps or criteria that are essential in the assessment
premature infants whose mothers did not receive antenatal and treatment of fluid and electrolyte abnormalities (Table
steroids prior to birth may have excessive fluid losses for an 9-3). The first step is to determine the cause of the electro-
extended period of time. 37 Other conditions that increase lyte imbalance. For example, is the hypokalemia a result of
insensible water loss include omphalocele, gastroschisis, chronic diuretic therapy or is it the result of an intracellular
tachypnea, and administration of non-humidified oxygen. shift secondary to a large dextrose infusion? Once the cause
Conditions that may require fluid restriction due to has been identified, the second step is to classify the event as
decreased fluid losses include but are not limited to kidney either acute or chronic. The prescriber can then determine
and lung dysfunction and heart failure. whether a supplemental infusion or a change in the mainte-
One relatively simple way to assess fluid balance is by nance solution (step 3) is a more appropriate intervention to
assessing daily weights. It is important to use the same scale correct the abnormality. Acute problems should usually be
and to make sure that the patient has the same equipment treated with supplemental infusions whereas chronic prob-
attached to accurately assess daily weights. Rapid weight lems should usually be treated with maintenance solutions.
changes typically reflect changes in water balance. Another The next step is to determine the therapeutic index of the
useful indicator for assessing fluid status is serum sodium electrolyte to be corrected. If treating a severe hypokalemia,
concentrations. An increase in the serum sodium concentra- it is typically safer to administer a relatively moderate
tion with little weight gain or weight loss typically indicates potassium infusion and then recheck the serum potassium
dehydration, whereas a low serum sodium concentration concentration before repeating the dose rather than giving
along with weight gain typically indicates fluid overload. one large potassium supplemental infusion. If the deficit
was inappropriately assessed and the single supplementa-
Treatment of Fluid Imbalances tion was too high, the patient could develop hyperkalemia
Conditions that affect the serum sodium concentration will and its associated consequences. In a patient with severe
affect fluid balance. Likewise, conditions that affect fluid hypomagnesemia, overestimating the magnesium supple-
balance will have an effect on the serum sodium concen- mentation will have little clinical impact on the patient.
tration. When addressing fluid issues, assessing trends in Therefore the prescriber can be more aggressive when
the serum sodium concentration is essential to making the supplementing magnesium and phosphate versus potas-
appropriate adjustment. Whenever possible the underlying sium. The final step or criterion is to assess the acuity of the
cause of the electrolyte disturbance should be treated, electrolyte imbalance. If the serum electrolyte concentra-
rather than just treating the serum sodium concentration. tion is critical or life-threatening, then the problem should
Dilutional hyponatremia (one form of hypervolemia) can be treated acutely. After initial treatment, then the mainte-
occur from conditions where fluid accumulates, such as in nance solution can be adjusted, if necessary.
sepsis, and in kidney or liver dysfunction, especially when
ascites is present. 39 In general, chronic fluid disturbances Table 9-3 Five Steps or Criteria for Correcting Electrolyte Abnormalities
take longer than 48 hours to develop, and patients typically 1. Determine the cause of the electrolyte abnormality.
do not exhibit signs and symptoms unless the fluid overload 2. Classify the electrolyte abnormality as acute or chronic.
is severe, resulting in a very low serum sodium concentra- 3. Determine whether a supplemental infusion (bolus) or an increase in
tion (typically less than 120 mEq/L). Overzealous diuresis the maintenance infusion or intake is appropriate for treatment.
or administration of hypertonic saline can result in an 4. Determine the therapeutic index of the electrolyte.
osmotic demyelination syndrome, causing brain injury 5. If the serum electrolyte concentration is critical or life-threatening,
if serum sodium is increased (or decreased) faster than treat acutely, then determine if an adjustment is needed in the
0.5 mEq/L/h or by more than 10 mEq/L in 24 hours.19 The maintenance fluid intake.

Reference values for normal serum electrolyte concen- loop diuretics can cause hyponatremia. Diuretics can also
trations based on age appear at the beginning of each cause sodium imbalances. Loop diuretics cause a hypo
electrolyte section below. These values are included to volemic hypernatremia due to increased water loss relative
illustrate the differences in electrolyte concentrations for to sodium loss, and overzealous use of thiazide diuretics
various age groups. Laboratory reference values will vary causes a hypovolemic hyponatremia. Sodium require-
from institution to institution, and practitioners should use ments vary depending on age group and also vary from
the reference values listed at their individual institutions for patient to patient. In general, parenteral requirements for
adjusting serum electrolyte values. sodium are about 2 to 5 mEq/kg in term infants, children,
and adolescents. In preterm infants, as little as 1 mEq/kg
Sodium of sodium may maintain sodium concentrations, but in
Preterm: 130–140 mEq/L general 3 to 4 mEq/kg is recommended for the first week of
Older Infants: 133–146 mEq/L life and then 3 to 6 mEq/kg in preterm infants less than 28
Children and Adolescents: 135–145 mEq/L weeks gestation.42,43 Oral sodium requirements vary with
age (Table 9-4).
Sodium is the most abundant extracellular cation in the
body. It has 2 primary functions: fluid balance and main- Hypernatremia
tenance of the membrane potential of cells. The body Hypernatremia is defined as serum sodium concentration
maintains sodium homeostasis primarily by the renin- greater than 145 mEq/L. Hypernatremia usually develops
angiotensin-aldosterone system and ADH secretion. Other under conditions of low or normal total body sodium but
systems involved in sodium maintenance include the it can also develop with an increase in total body sodium.
sympathetic nervous system, atrial natriuretic peptide, the Hypernatremia is typically a result of net water loss or hypo-
kallikrein-kinin system, various intrarenal mechanisms, tonic fluid loss. Causes of hypernatremia include lack of oral
and other factors that regulate renal and medullary blood hydration, diarrhea, vomiting, overzealous diuresis, fever,
flow.40 The body maintains cell membrane potential by the and the inability to express a need for water (eg, infants,
Na+-K+-ATPase pump. Three sodium ions are pumped out children, or patients who have an altered mental status).
of the cell for every 2 potassium ions that are pumped into An algorithm for the evaluation and treatment of hyperna-
the cell, which produces the negative charge in the cells tremia can be found in Figure 9-1. If the hypernatremia is
necessary for normal functioning of nerves and muscle cells due to sodium intake, then intake must be decreased. If the
and the active transport of nutrients, such as glucose and hypernatremia is associated with dehydration, then rehy-
amino acids.41 dration should be started immediately. If the dehydration is
In normal situations the body’s sodium losses match mild and asymptomatic, then rehydration can be addressed
the body’s sodium intake. The kidney has the ability to by simply altering the oral fluid intake. If the dehydration is
reabsorb up to 99% of the sodium presented to the renal moderate to severe or if the patient is symptomatic, aggres-
tubules, so in times of a sodium intake deficit, serum sodium sive treatment should begin immediately.
concentrations can be maintained. Daily sodium losses in In order to treat the patient appropriately, classi-
these instances may be only a few milliequivalents. Medi- fying dehydration as mild, moderate, or severe is helpful.
cations can also affect sodium balance. Lactulose, normal Mild dehydration can be identified by the presence of dry
saline, and hypertonic saline can cause hypernatremia, and mucous membranes with normal hemodynamic param-
medications such as chlorpropamide, demeclocycline, and eters. Moderate dehydration can be defined as the presence
Table 9-4 Oral Electrolyte Requirements by Age (mg)

Age Sodium Potassium Age Magnesium Age Calcium Phosphorus
0–0.5 y 120 500 0–0.5 y 30 0–0.5 y 210 100
0.5–1 y 200 700 0.5–1 y 75 0.5–1 y 270 275
1–2 y 225 1000 1–3 y 80 1–3 y 500 460
2–5 y 300 1400 4–8 y 130 4–8 y 800 500
6–9 y 400 1600 9–13 y 240 8 y or older 1300 1250
10 y or older 500 2000 > 13 y (M) 400
> 13 y (F) 360

of changes in hemodynamic parameters suggesting intra- replacement, usual maintenance fluids (Column 3 in Table
vascular depletion like tachycardia, mild hypotension, and 9-2) must be administered. If severely volume depleted, the
orthostasis. Severe volume depletion is defined by the pres- patient will require more than one 20 mL/kg fluid bolus to
ence of more profound hemodynamic compromise, such resolve the tachycardia, hypotension, and other symptoms.
as moderate to severe hypotension, tachycardia, and poor Once the tachycardia and hypotension have resolved, the
perfusion. Clinical symptoms of mild, moderate, and severe fluid deficit and maintenance requirements can be calcu-
dehydration generally correspond to a 5%, 10%, and 15% lated. In a teenager, the fluid deficit associated with mild,
weight loss in infants, respectively, which can be detected moderate, and severe dehydration is generally about 50% of
if pre- and post-dehydration weights are available. In teen- that seen in an infant; therefore the initial bolus is generally
agers, mild, moderate, and severe dehydration correspond 10 mL/kg rather than 20 mL/kg. Alternatively, as in adults,
to a 3%, 5%, and 7% loss in body weight, respectively.44 Fluid a fluid bolus of 500 mL to 1000 mL is given initially and
therapy must include replacement of the deficit as well as repeated based on hemodynamic response.
provision of maintenance fluids. Hypertonic dehydration (hypernatremia) must be
There are various methods used for correcting volume managed differently. In hypertonic dehydration, the fluid
depletion, but 3 principles always apply: (1) the fluid deficit from the ICF compartment is drawn into the intravascular
must be replaced with an appropriate fluid; (2) mainte- space. Rapid administration of fluid as described above may
nance fluids must be provided on an ongoing basis; and (3) cause rapid fluid shifts that can result in cerebral edema and
if there are continued ongoing losses (eg, gastric drainage, intracranial bleeding. In hypertonic dehydration, the fluid
vomiting, diarrhea), these losses must be replaced on an volume deficit is calculated and gradually replaced (usually
ongoing basis to prevent further fluid deficits. For example, over 48 hours).45 The need for a fluid bolus as described
an infant weighing 5 kg has a 500 mL (10%) fluid deficit. above is based on hemodynamic parameters. If the patient
Given the degree of fluid deficit (10% or more), an isotonic is hemodynamically compromised (hypotension, severe
fluid bolus (20 mL/kg or 2% of the patient’s body weight tachycardia), then a 10 to 20 mL/kg bolus of an isotonic
= 100 mL) would be indicated initially. After this bolus, fluid is imperative to restore perfusion and normalize hemo-
the remaining deficit (8% or 400 mL) would be replaced as dynamic parameters. When correcting severe symptomatic
follows: 50% (200 mL) over the next 8 hours and 50% (200 hypovolemic hypernatremia, the underlying cause of the
mL) over the subsequent 16 hours. In addition to the deficit hypernatremia should be treated. In general, to prevent
Figure 9-1 Hypernatremia
Adapted from Matarese LE, Gottschlich MM, eds. Contemporary Nutrition Support Practice: A Clinical Guide. Whitmire SJ. Fluids and electrolytes, p. 130.

cerebral edema, the serum sodium should not be corrected below 125 mEq/L. Severe acute hyponatremia is life-threat-
at a rate that exceeds 0.5mEq/L/h or more than 10 mEq/L ening; fortunately the more common type of hyponatremia
in 24 hours. seen in hospitalized patients is slow-developing and less
severe. The 2 most common causes of hyponatremia include
Hyponatremia hypervolemic hyponatremia where the total body sodium is
Hyponatremia is defined as a serum sodium concentra- normal to high and TBW is high, and hyponatremia due to
tion less than 135 mEq/L. It is one of the most common actual sodium and water losses. In kidney failure, liver failure
electrolyte disturbances found in the hospitalized patient. with ascites, hyperaldosteronism, and congestive heart
Signs and symptoms include headache, nausea, vomiting, failure, the body accumulates sodium and fluid, resulting
muscle cramps, lethargy, restlessness, disorientation, and in hypervolemic hyponatremia, sometimes referred to as
depressed reflexes and are more commonly seen with an dilutional hyponatremia. Diarrhea and other GI losses such
acute decrease in the serum sodium concentration typically as gastric suction, enterocutaneous fistulas, or necrotizing
Figure 9-2 Hyponatremia
Adapted from Matarese LE, Gottschlich MM, eds. Contemporary Nutrition Support Practice: A Clinical Guide. Whitmire SJ. Fluids and electrolytes, p. 129.

enterocolitis; thiazide diuretic-induced hyponatremia; and solutions or maintenance intravenous (IV) fluids should
salt-wasting nephropathy are examples of conditions that start at about 2 to 4 mEq/kg and may increase depending
cause hypovolemic hyponatremia. In premature neonates, on kidney function, GI losses, and medication use.42, 44 Oral
the salt-wasting nephropathy can be severe, often requiring potassium requirements vary with age (Table 9-4).
delivery of sodium equal to 6 mEq/kg or more daily to
maintain sodium and fluid balance.27 An algorithm for the Table 9-5 Medications Affecting Potassium and Magnesium
evaluation and treatment of hyponatremia can be found Hyperkalemia Hypokalemia
in Figure 9-2. Treatment with hypertonic saline may be Potassium-sparing diuretics Loop diuretics
indicated if the serum sodium concentration is below Nonsteroidal anti-inflammatory Thiazide diuretics
125 mEq/L or if the patient is symptomatic. The sodium drugs Fludrocortisones
deficit is calculated by using the equation: Angiotensin converting enzyme High-dose glucocorticoids
inhibitors
High-dose penicillins
Angiotensin-II receptor blockers
sodium deficit (mEq) = TBW × wt × (Nadesired – Naactual) Phenolphthalein
Trimethoprim
where TBW is the percentage of the body weight found in Table 9-1 Sodium polystyrene sulfonate
Pentamidine
divided by 100, and weight is in kg. Sorbitol
Cyclosporine
β2–adrenergic agonists
Tacrolimus
Typically no more than 50% of the sodium deficit should Tocolytic agents
Heparin
be replaced over 12 hours. In general, the serum sodium Theophylline
Penicillin G potassium
should not be corrected at a rate that exceeds 0.5 mEq/L/h Caffeine
β-blockers
or more than 10 mEq/L in 24 hours in order to prevent the Insulin/dextrose
Succinylcholine
development of central pontine myelinolysis.46
Hypermagnesemia Hypomagnesemia
Tocolytic agents Cisplatinum
Potassium
Magnesium-containing antacids Foscarnet
Newborn: 3.7–5.9 mEq/L
Magnesium-containing enemas Amphotericin B
Infant: 4.1–5.3 mEq/L
Aminoglycosides
Children and Adolescents: 3.4–4.7 mEq/L
Thiazide diuretics
Potassium is the primary ICF cation. Potassium is essential

for cell metabolism and maintenance of resting membrane Hyperkalemia
potential. Intracellular potassium concentrations are Hyperkalemia is defined as a serum potassium concen-
approximately 140 mEq/L (ICF potassium concentrations tration greater than 4.7 to 5.9 mEq/L, depending on
equal ECF sodium concentrations due to the action of the the patient’s age. Signs and symptoms of hyperkalemia
Na+-K+-ATPase pump).47 Other factors that affect potassium include muscle twitching, cramping, weakness, ascending
distribution include those affecting the Na+-K+-ATPase paralysis, electrocardiogram (ECG) changes (eg, peaked
pump, such as insulin, catecholamines, and ECF pH; T-waves, prolonged PR interval), and dysrhythmias (eg,
exercise; and cell breakdown. 3,48,49 Potassium is primarily bradyarrhythmias, ventricular fibrillation, and asystole).
excreted via the kidney. Potassium excretion varies based Hyperkalemia is one of the most dangerous electrolyte
on serum potassium concentrations and the release of imbalances that develop in premature infants. The immatu-
aldosterone and angiotensin II. A lack of aldosterone causes rity of the kidneys results in a reduced glomerular filtration
potassium retention, whereas an excess causes potassium rate, urinary potassium excretion, acidosis, and immature
depletion. 50 In times of a potassium deficit, urinary excre- renal tubular response to aldosterone. 54 Hyperkalemia can
tion drops significantly, but not entirely. If potassium intake occur from excessive potassium intake in the presence of
significantly increases, urinary potassium excretion will altered kidney excretion or metabolic acidosis caused by
increase as well as potassium excretion via non-renal mecha- conditions such as diabetic ketoacidosis and renal tubular
nisms (GI tract), a process known as potassium adaptation. acidosis. Metabolic acidosis causes hyperkalemia by causing
In chronic kidney insufficiency, GI potassium losses may a shift of potassium from the ECF to the ICF in order to
increase to 30% to 50% of the ingested potassium. 51–53 Medi- balance the excess hydrogen ions that are moving into the
cations that affect potassium concentrations can be found ICF. Clinically significant hyperkalemia can also develop as
in Table 9-5. Supplementation in parenteral nutrition (PN) a result of cell lysis (hemolysis) or tissue injury and death

(eg, burns, rhabdomyolysis) in vivo due to the release of the catecholamines, and inadequate intake. Signs and symp-
ICF potassium into the serum. toms are non-specific but include dysrhythmias, paralysis,
Treatment of hyperkalemia depends on both the muscle necrosis, and possibly death. The treatment of
severity and the cause. All sources of potassium intake hypokalemia depends on both the severity and the cause
should be discontinued immediately and, if feasible, any of the hypokalemia. Oral potassium supplements are avail-
medication that may contribute to hyperkalemia should able as a variety of salts, and the choice of agent depends
be stopped or the dose reduced. If the potassium is signifi- on other concomitant electrolyte imbalances, cost, and
cantly elevated or if the patient is symptomatic, IV calcium patient preference. In an asymptomatic patient with mild to
chloride should be administered immediately to reduce the moderate hypokalemia, oral supplementation is preferred
excitability of the cardiac muscle. (Note: Calcium gluconate because of safety reasons (eg, there is no risk for potas-
is generally not recommended in emergency situations.) sium extravasation). Oral supplementation also reduces the
There are two basic mechanisms used to treat hyperkalemia: risk of overcorrection causing hyperkalemia and too rapid
shifting potassium into the ICF and removing potas- correction causing dysrhythmias. Oral potassium can be
sium from the body. Insulin in combination with glucose, irritating to the GI tract. For mild to moderate potassium
β2-adrenergic agonists, and sodium bicarbonate will shift the depletion, doses of 2 to 5 mEq/kg/d in divided doses, not
potassium into the ICF. Loop and thiazide diuretics (loop to exceed 1 to 2 mEq/kg as a single dose, taken with plenty
to a greater extent than thiazide), cation exchange resins of water, are recommended. 55,56 Serum potassium should
like sodium polystyrene, and dialysis all reduce potassium be rechecked approximately 2 hours after the initial dose is
concentrations by directly removing potassium from the completed, and additional doses given, if needed.
body (exchange resins and dialysis) or by increasing renal The use of IV potassium supplementation should be
potassium excretion (diuretics). Serum potassium concen- reserved for patients who are symptomatic, who have severe
trations should be monitored frequently during treatment, hypokalemia, or when administration via the GI tract is
especially in patients being treated with dextrose and contraindicated. Dosages range from 0.5 to 1 mEq/kg
insulin, β2-adrenergic agonists, and sodium bicarbonate depending on the severity of the hypokalemia and kidney
because once these therapies are discontinued, potassium function. Generally, infusion rates should not exceed
will shift back to the ECF compartment. Potassium concen- 0.5 mEq/kg/h, unless continuous cardiac monitoring is
trations should be monitored for at least 12 hours after the available. Potassium can be caustic to the vein, so to minimize
hyperkalemia has resolved to ensure that equilibration of irritation, the concentration for administration through a
potassium between the ICF and ECF is complete. 3 peripheral vein should not exceed 0.06 mEq/mL. 56,57 When
Pseudohyperkalemia is common in infants and young administering IV potassium supplementation, co-admin-
children and can occur when red blood cells break down istration with dextrose may worsen the hypokalemia by
during the blood-drawing process. In other words, the serum stimulating insulin release, which promotes the intracel-
potassium detected in the sample is higher than the actual lular shift of potassium. Concurrent hypomagnesemia may
serum potassium concentration due to hemolysis of the red result in refractory hypokalemia due to increased renal
blood cells during the blood-drawing process or while in potassium losses due to the kidney’s attempt to conserve
the collection tube. This form of hyperkalemia is the most magnesium and impairment of the Na+-K+-ATPase pump. 58
common form detected in pediatric patients with normal As such, it is important to correct a low magnesium level
kidney function. If pseudohyperkalemia is suspected, and while treating hypokalemia. Serum potassium should be
if the patient is asymptomatic and has normal kidney func- rechecked approximately 2 hours after the initial dose is
tion, the serum potassium concentration should be repeated completed, and additional doses given, if needed.
(avoiding rapid aspiration and use of narrow gauge needles
if possible) before starting any treatment for hyperkalemia. Magnesium
All Age Groups: 1.6–2.3 mg/dL
Hypokalemia
Hypokalemia is defined as a serum potassium concentration Magnesium is an essential cofactor in more than 300
less than 3.4 mEq/L. It is a common electrolyte abnor- enzymatic reactions, including those involved in glucose
mality seen in clinical practice. Causes of hypokalemia metabolism, fatty acid synthesis and breakdown, and DNA
include medications, metabolic alkalosis, abnormal and protein metabolism. Magnesium plays a critical role in
GI losses, hyperaldosteronism, hypomagnesemia, the functioning of the Na+-K+-ATPase pump, thus affecting

neuromuscular transmission, cardiovascular excitability, Hypermagnesemia occurs primarily in the setting

vasomotor tone, and muscle contraction. Magnesium is also of kidney insufficiency in combination with continued
an integral component of bone and parathyroid hormone magnesium intake. In the premature infant, the most
(PTH) secretion. 59,60 More than 50% of the magnesium in common cause of hypermagnesemia results from placental
the body resides in bone. Magnesium is found primarily transfer of magnesium during the treatment of premature
in the ICF with only about 2% of total body stores found labor contractions with magnesium sulfate. The effect that
in the ECF. About 61% of serum magnesium is physiologi- hypermagnesemia has on the ability to relax smooth muscle
cally active in the ionized form, 33% protein bound, and 5% makes magnesium a viable treatment due to the low risk of
complexed to phosphate, citrate, and other compounds. harm to the neonate. The neonate with hypermagnesemia
Magnesium homeostasis is maintained and regu- will have poor muscle tone, which will return to normal
lated by the GI tract, kidney, and bone via PTH. Healthy as the serum magnesium concentration decreases over
individuals absorb between 30% and 40% of ingested approximately 2 to 5 days, depending on the severity of the
magnesium. Magnesium is absorbed in the distal jejunum initial hypermagnesemia.66
and ileum, and absorption is inversely proportional to the
magnesium intake. Magnesium is primarily excreted via the Hypomagnesemia
kidneys with about 35% of ingested magnesium excreted in Hypomagnesemia is defined as serum magnesium concen-
the urine. In the presence of high magnesium intake, renal tration less than 1.3 mg/dL. It is a common condition seen in
excretion increases to maintain normal serum magnesium hospitalized patients. Signs and symptoms include apathy,
concentrations. Very little magnesium (1%–2%) is excreted depression, psychosis, muscle weakness, vertigo, ataxia,
via the feces. Bone is very important to the homeostasis seizures, confusion, leg cramps, hyperactive tendon reflexes,
of serum magnesium concentrations. If a patient becomes anorexia, nausea, vomiting, paresthesias, Chvostek’s and
magnesium depleted, the mineral is leached from the bone to Trousseau’s sign, spontaneous carpal-pedal spasm, and
maintain ECF magnesium concentrations. ECF magnesium cardiac complications including dysrhythmias.67 Hypo-
is then sacrificed to the ICF to maintain normal metabolic magnesemia can also cause other electrolyte abnormalities.
functions.61 Medications that affect magnesium concentra- Hypomagnesemia may result in refractory hypokalemia
tions are listed in Table 9-5. IV magnesium supplementation because of increased renal potassium losses due to the
in PN solutions ranges from 0.25 mEq/kg to 0.5 mEq/kg kidney’s attempt to conserve magnesium and impairment
daily but may be higher in patients with abnormal magne- of the Na+-K+-ATPase pump. 58 Hypomagnesemia may also
sium losses. Oral magnesium requirements vary with age result in hypocalcemia. Magnesium deficiency can impair
(Table 9-4). parathyroid function, and hypomagnesemia accompanied
by hypoparathyroidism is a common cause of neonatal
Hypermagnesemia hypocalcemia.68,69
Hypermagnesemia is defined as serum magnesium greater Hypomagnesemia can be caused by decreased intake,
than 2.4 mg/dL. Hypermagnesemia is usually well toler- increased excretion, or intracellular shifts of magnesium.70
ated but can affect neurological, neuromuscular, and Excessive renal losses may occur in patients with acute
cardiac function when magnesium concentrations exceed tubular necrosis, renal tubular acidosis, Bartter syndrome,
3 mg/dL.62,63 Physical findings include nausea, vomiting, or hyperaldosteronism, or may be induced by medications
diaphoresis, flushing, depressed mental function, drowsi- such as amphotericin, cisplatin, cyclosporine, aminogly-
ness, muscular weakness, hypotension, and bradycardia. If cosides, and foscarnet.71 Intracellular shifts can be caused
patients with severe hypermagnesemia are symptomatic, by dextrose and/or insulin administration. Because only
IV calcium chloride should be administered immediately about 1% to 2% of total body magnesium is found in the
to reduce the excitability of the cardiac muscle. (Note: ECF, serum concentrations are not a good reflection of total
Calcium gluconate is generally not recommended in emer- body magnesium stores. Treatment of hypomagnesemia is
gency situations.) Hemodialysis may be required to reduce therefore empirical. The IV route is preferred in patients
the magnesium concentration to a safer value. Treatments with moderate to severe hypomagnesemia because of the
for hypermagnesemia in an asymptomatic patient include GI intolerance generally seen with large oral doses. Recom-
dietary magnesium restriction, administration of a loop mended doses are 0.2 to 0.4 mEq/kg (25–50 mg/kg), up to
diuretic, and possibly hemodialysis if kidney dysfunction is 2 mEq (2 g) every 8 to 12 hours for 2 to 3 doses.72 There is
present.64, 65 a renal magnesium threshold for magnesium reabsorption;

thus up to 50% of an individual magnesium dose can be the calcium bound to albumin, and the free or ionized
eliminated via the kidneys if the magnesium is not distrib- calcium. Therefore, if the serum albumin is low, the serum
uted intracellularly.73,74 In asymptomatic adults, a maximum total calcium also will be low. Although not completely reli-
infusion rate of 1 g (8 mEq)/h is recommended. 3,75 This infu- able in critically ill patients, serum calcium concentrations
sion rate would equate to about 0.1 mEq/kg/h in children. can be corrected for the degree of hypoalbuminemia using
Supplemental magnesium doses may be reduced by 50% in the equation:
patients with kidney dysfunction to lessen the risk of hyper-
magnesemia. However, reducing the dose by 50% may not Corrected calcium = measured total calcium (mg/dL) +
be necessary in all cases because, if only a one-time dose is 0.8 [4 – albumin (g/dL)]
given, the magnesium will not continue to accumulate, and
mild hypermagnesemia is well tolerated. Serum magnesium Alternatively, if the patient’s albumin is low, then the
should be rechecked approximately 2 hours after the infu- serum ionized calcium should be checked as this is the most
sion is completed, and additional boluses given, if needed. accurate laboratory test for assessing the physiologically
active calcium status. The serum pH and the phosphorus
Calcium and albumin concentrations affect the amount of calcium
Age Group Total Calcium Age Group Ionized (SI Units) that is ionized.77–79 Supplementation of calcium in PN solu-
Preterm 6.2–11 mg/dL Preterm 1.75–2 mmol/L tions ranges from 1 to 4 mEq/kg. Oral calcium requirements
Full Term 7.6–10.4 mg/dL Full Term 1.05–1.37 mmol/L vary with age and can be found in Table 9-4.
< 36 h
Full Term 1.1–1.42 mmol/L Hypercalcemia
36–84 h Hypercalcemia is most often seen in patients with hyper-
10 d – 2 y 9–11 mg/dL > 84 h 1.2–1.38 mmol/L
parathyroidism or cancer with bone metastases. It can
2–12 y 8.8–10.8 mg/dL
also occur with toxic serum concentrations of vitamin A
> 12 y 8.6–10 mg/dL
or vitamin D, chronic ingestion of milk and/or calcium
carbonate-containing antacids in the setting of kidney
Calcium is one of the most abundant ions in the body. insufficiency, immobility, tuberculosis, and medications.
It accounts for 1% to 2% of total body weight. Calcium Clinical signs and symptoms include fatigue, nausea,
is necessary for many physiological functions including vomiting, constipation, anorexia, and confusion. In severe
neuromuscular activity, preservation of the integrity of cell cases, cardiac dysrhythmias may be present. Mild hypercal-
membranes, regulation of endocrine secretory activities, cemia typically responds to fluid and ambulation. In severe
blood coagulation, activation of the complement system, hypercalcemia, immediate treatment should be started
and bone metabolism. Serum calcium concentrations are to prevent acute kidney failure, obtundation, ventricular
controlled by the parathyroid gland. When serum calcium dysrhythmias, coma, and death. If a loop diuretic and IV
is low, PTH secretion is stimulated, which increases bone fluid are used to treat hypercalcemia (eg, to increase calcium
resorption, augments renal calcium conservation, and acti- excretion), IV hydration with 0.9% sodium chloride should
vates vitamin D, which increases calcium absorption from be started immediately to prevent dehydration. Hemodi-
the GI tract. When serum calcium is increased, the thyroid alysis may be necessary for patients with life-threatening
releases calcitonin, which acts to inhibit bone resorption and hypercalcemia or those with kidney failure. 80
increase renal calcium excretion. Generally, serum calcium
concentrations are maintained by either renal excretion of Hypocalcemia
excess calcium or leaching of calcium from the bone.76 Measured hypocalcemia is commonly encountered in
About 99% of the body’s calcium is found in teeth and patients with hypoalbuminemia but does not require treat-
bone, with only 1% found in the serum. There are 3 forms ment unless the corrected calcium or ionized calcium is
of calcium in the body: complexed, protein-bound, and found to be low. Signs and symptoms of hypocalcemia
ionized. Complexed calcium is that combined with non- include hypotension, decreased myocardial contractility,
protein anions such as phosphate, carbonate, and citrate. It prolonged QT interval, paresthesias, Chvostek’s and
is not available for physiological activity. Slightly less than Trousseau’s signs, muscle cramps, tetany, and seizures.
half of the serum calcium is bound to protein, primarily Causes of hypocalcemia include vitamin D deficiency or
albumin. The serum calcium measures total serum calcium, the inability to activate vitamin D, hyperphosphatemia,

pseudohypoparathyroidism, decreased PTH activity, destruction and acidosis cause a shift to the ECF.77 Intra-
sepsis, rhabdomyolysis, and massive blood transfusions.81 venous phosphorus requirements are 1 to 2.5 mmol/kg in
Medications can also cause hypocalcemia. Of particular premature infants and 0.5 to 1 mmol/kg/d in term infants
importance to the premature infant are furosemide, and children up to 18 years of age. Oral phosphorus require-
phenobarbital, and phenytoin. 82 Sulfur-containing amino ments vary with age (Table 9-4).
acids (eg, cysteine) also increase renal calcium excretion.
The increased renal calcium excretion seen with cysteine Hyperphosphatemia
supplementation in PN solutions is counterbalanced by the Hyperphosphatemia is defined as a serum phosphate
increased solubility of calcium and phosphorus in PN solu- concentration greater than 4.5 to 9 mg/dL, depending on
tions supplemented with cysteine hydrochloride due to the the patient’s age. Most patients are asymptomatic, but signs
lower pH of the solution after cysteine is added.83, 84 and symptoms may include anorexia, nausea, vomiting,
Patients with severe hypocalcemia or acute symptom- dehydration, and neuromuscular irritability. The biggest
atic hypocalcemia require immediate treatment. IV calcium concern with hyperphosphatemia is metastatic calcifica-
comes in two salt forms: chloride and gluconate. Calcium tion from elevated serum concentrations of calcium and
chloride contains 13.6 mEq of elemental calcium per gram; phosphate.91 Although various equations for predicting
calcium gluconate contains 4.65 mEq of elemental calcium metastatic calcification are used, the equations are not
per gram. Because there is 3 times the elemental calcium accurate because of the variety of factors that determine
in calcium chloride compared to calcium gluconate, in vivo calcium/phosphate solubility. Ionized calcium is
calcium chloride is associated with a higher incidence of much more reactive than phosphate, so hypercalcemia
tissue necrosis if extravasation occurs. 85 For hypocalcemic with a mild hyperphosphatemia has a higher probability of
tetany, 0.5 to 1 mEq/kg of calcium chloride infused over causing metastatic calcification than hyperphosphatemia
5 to 10 minutes may be used; this dose may be repeated with slightly increased serum calcium. With the newer
in 6 hours or followed with a continuous infusion with phosphate-binding agents available, aluminum-containing
2.5 mEq/kg/d of calcium chloride.86, 87 If hypomagnesemia antacids are no longer recommended for the treatment or
is present, magnesium supplementation should be given to prevention of hyperphosphatemia in patients with kidney
facilitate correction of hypocalcemia. In cases of hypocal- insufficiency because of the anemia, osteomalacia, and
cemia secondary to hyperphosphatemia, treating with a central nervous system toxicity experienced with the use of
phosphate binder should be considered prior to giving IV aluminum-containing agents in this patient population.92
calcium to prevent calcium/phosphate precipitation in soft
tissues. Hypophosphatemia
Hypophosphatemia can be defined as a serum phosphorus
Phosphorus concentration below 2.7 mg/dL to 4.5 mg/dL, depending
Newborn: 4.5–9 mg/dL on the patient’s age.47 Hypophosphatemia is common in
10 days–2 years: 4.5–6.7 mg/dL critical illness, malnutrition, alkalosis, and in patients
2–12 years: 4.5–5.5 mg/dL receiving phosphate binders (eg, aluminum- , magnesium- ,
> 12 years: 2.7–4.5 mg/dL and calcium-containing products, sevelamer, or sucralfate).
Signs and symptoms of hypophosphatemia include neuro-
Phosphorus, mainly in the form of phosphate, is the primary logical, neuromuscular, cardiopulmonary, and hematologic
intracellular anion in the body. It has many important func- dysfunction.88–90 Primary causes of hypophosphatemia
tions including bone and cell membrane composition, include inadequate intake of phosphate or the administra-
maintenance of normal pH, and provision of energy-rich tion of large amounts of dextrose solutions in malnourished
bonds (adenosine triphosphate, or ATP), and it is needed patients who are at risk for developing refeeding syndrome
in all cellular functions that require energy. Phosphorus is (Chapter 19).
required for glucose utilization, glycolysis, 2,3-diphospho- Treatment of hypophosphatemia varies, depending
glycerate synthesis, neurological function, and muscular on the serum phosphorus concentration and the presence
function.88-90 Phosphorus homeostasis is maintained by GI of signs and symptoms. Mild asymptomatic hypophos-
absorption, renal excretion, PTH, and distribution between phatemia can be treated with oral phosphate supplements,
the ICF and ECF. Glucose and insulin, catecholamines, and assuming that the GI tract is functional. However, oral
alkalosis all cause intracellular shifts of phosphorus. Cell supplements are not well absorbed and often cause diarrhea.

Patients with symptomatic or moderate to severe hypo- birth. On day 7, the patient’s serum sodium concentra-
phosphatemia should be treated with IV phosphate. Two tion is 137 mEq/L. The patient continues to receive
salt forms are available for replacing phosphate: sodium 160 mL/kg/d of IV fluids that contain 3 mEq/kg/d
phosphate and potassium phosphate. Sodium phosphate of sodium. Over the next 3 days, the patient’s serum
provides 4 mEq sodium for every 3 mmol phosphate, and sodium concentration has decreased to 129 mEq/L.
potassium phosphate provides 4.4 mEq potassium for The patient does not appear to be fluid overloaded,
every 3 mmol phosphate. When ordering phosphate, the septic, or suffering from necrotizing enterocolitis. The
dose should be ordered in millimoles of phosphate rather patient’s weight has remained around 1250 g. What is
than milliequivalent of the sodium or potassium compo- the most appropriate way to correct the serum sodium
nent of the salt. Common recommendations for replacing concentration?
phosphate provide up to 0.32 mmol/kg of phosphate for A. Increase the sodium concentration in the IV solution
serum phosphorus levels < 1.5 mg/dL. This dose is often because the current sodium intake is inadequate to
inadequate and may require multiple boluses to reach keep up with the renal and GI sodium losses.
normal phosphorus levels.93,94 Higher doses have been B. Decrease the maintenance IV fluid rate by 25%
recommended for phosphorus replacement in adults, and because the decrease in the serum sodium concen-
the higher supplemental doses have been used successfully tration is probably due to fluid overload.
in pediatric patients (Table 9-6). Serum phosphate levels C. Give sodium chloride orally to replace the sodium
should be checked 2 hours after the infusion is completed deficit.
and the patient should be redosed if needed. Phosphate D. Decrease the maintenance IV fluid by 25% and
should be replaced no faster than 0.1 to 0.2 mmol/kg/h give sodium chloride orally because the decrease
to allow the phosphate time to move intracellularly and to in the serum sodium concentration is probably due
prevent possible hypocalcemia.95 If potassium phosphate to fluid overload, but the serum sodium concentra-
is used to replace the phosphate, the infusion rate should tion is a critical value; thus treatment must begin
be based on the potassium infusion rate. ECG monitoring immediately.
should accompany infusion of individual doses greater than 3. An 8-year-old child who weighs 27 kg is admitted for
0.5 mEq/kg/h. Sodium phosphate is the preferred salt for nausea, vomiting, and failure to thrive. The patient is
phosphate supplementation. started on maintenance IV fluids containing D5W/0.2
NaCl with 20 mEq KCl per liter. The following morning,
Table 9-6 Phosphate Replacement in Adults the serum phosphorus concentration is 1.2 mg/dL and
Mild Depletion (2.3–3 mg/dL) 0.16 mmol/kg the serum potassium concentration is 3.4 mEq/L.
Moderate Depletion (1.6–2.2 mg/dL) 0.32 mmol/kg What is the most appropriate way to correct the serum
Severe Depletion (< 1.5 mg/dL) 0.64 mmol/kg phosphorus concentration?
A. Add sodium phosphate 1 mmol/kg to the mainte-
nance IV fluid.
Test Your Knowledge Questions B. Add potassium phosphate 1 mmol/kg to the main-
1. The intravenous administration of 100 mL of 0.9% tenance IV fluid.
sodium chloride to a patient will: C. Give sodium phosphate 27 mmol (36 mEq sodium)
A. Increase the intracellular fluid (ICF) compartment intravenously over 8 hours.
by 100 mL but will not increase the extracellular D. Give potassium phosphate 27 mmol (40 mEq potas-
fluid (ECF) compartment. sium) intravenously over 8 hours.
B. Increase the ECF compartment by 100 mL, with a
75 mL increase in intravascular volume. See p. 487 for answers.
C. Increase the ECF compartment by 100 mL, with a
25 mL increase in intravascular volume. References
D. Increase the ICF compartment by 50 mL, with a 1. Steijaert M, Deurenberg P, Van Gaal L, De Leeuw I. The use
25 mL increase in intravascular volume. of multi-frequency impedance to determine total body water
and extracellular water in obese and lean female individuals.
2. A 1340-g neonate is placed on IV fluids/nutrition at Int J Obes Relat Metab Disord. 1997;21(10):930–934.
160 mL/kg/d. Over the next 5 days the weight decreased
to 1250 g due to the contraction of the ECF seen after

2. Sartorio A, Malavolti M, Agosti F, Marinone PG, Caiti O, 20. Knepper MA, Rector CF. Urinary concentration and dilu-
Bedogni G. Body water distribution in severe obesity and its tion. In: Brenner BM, Rector FC, eds. The Kidney. 4th ed. Vol
assessment from eight-polar bioelectrical impedance analysis. 1. Philadelphia, PA: Saunders; 1991:445–482.
Eur J Clin Nutr. 2005;59(2):155–160. 21. Mange K, Matsuura D, Cizman B, et al. Language guiding
3. Rose BD, Post TW. Clinical Physiology of Acid-Base and Elec- therapy: the case of dehydration versus volume depletion. Ann
trolyte Disorders. 5th ed. New York, NY: McGraw-Hill; 2001. Intern Med. 1997;127(9):848–853.
4. Whitmire SJ. Fluids and electrolytes. In: Gottschlich MM, ed. 22. Heitz U, Horne M. Pocket Guide to Fluid, Electrolytes, and Acid-
Science and Practice of Nutritional Support: A Case-Based Core Base Balance. 5th ed. St Louis, MO: Mosby-Year Book; 2004.
Curriculum. Dubuque, IA: Kendall/Hunt; 2001:53–84. 23. Mirtallo J, Canada T, Johnson D, et al. Safe practices for paren-
5. Bhatia J. Fluid and electrolyte management in the very low teral nutrition. J Parenter Enteral Nutr. 2004;28(6):S39–S70.
birth weight neonate. J Perinatol. 2006;26(Suppl 1):S19–S21. 24. Holliday MA, Segar WE. The maintenance need for water in
6. Bakris GL, Stein JH. Sodium metabolism and maintenance of parenteral fluid therapy. Pediatrics. 1957;19:823–832.
extracellular fluid volume. In: Arieff AI, DeFronzo RA, eds. 25. Choong K, Bohn D. Maintenance parenteral fluids in the criti-
Electrolyte and Acid-Base Disorders. 2nd ed. New York, NY: cally ill child. J Pediatr (Rio J). 2007;83(2 Suppl):S3–S10.
Churchill Livingstone; 1995:29–50. 26. Lorenz JM, Kleinman LI, Ahmed G, et al. Phases of fluid and
7. Soheyl B, Klaus Z, Zoltan S, et al. Small-volume fluid resusci- electrolyte homeostasis in the extremely low birth weight
tation with hypertonic saline prevents inflammation but not infant. Pediatrics. 1995;96(3):484–489.
mortality in a rat model of hemorrhagic shock. Shock. 2006; 27. Modi N. Sodium intake and preterm babies. Arch Dis Child.
25(3):283–289. 1993;69:87–91.
8. Mange K, Matsuura D, Cizman B, et al. Language guiding 28. Bauer K, Bovermann G, Roithmaier A, Gotz M, Proiss A,
therapy: the case of dehydration versus volume depletion. Ann Versmold HT. Body composition, nutrition and fluid balance
Int Med. 1997; 127(9):848–853. during the first two weeks of life in preterm neonates weighing
9. Hansen M. Fluid balance. In: Hansen M, ed. Pathophysiology: less than 1500 grams. J Pediatr. 1991;118(4):615–620.
Foundations of Disease and Clinical Intervention. Philadelphia, 29. Sankar MJ, Agarwal R, Mishra S, Deorari AK, Paul VK.
PA: Saunders; 1998:160–175. Feeding of low birth weight infants. Indian J Pediatr.
10. Toney GM, Chen QH, Cato MJ, Stocker SD. Central osmotic 2008;75(5):459–469.
regulation of sympathetic nerve activity. Acta Physiol Scand. 30. Shaffer SG, Brandt SK, Hall RT. Postnatal changes in
2003; 177(1):43–55. total body water and extracellular volume in the preterm
11. Sutsch G, Bertel O, Rickenbacher P, et al. Regulation of aldos- infant with respiratory distress syndrome. J Pediatr.
terone secretion in patients with chronic congestive heart 1986;109(3):509–514.
failure by endothelins. Am J Cardiol. 2000; 85(8):973–976. 31. Tang W, Ridout D, Modi N. Influence of respiratory distress
12. Quinn SJ, Williams GH. Regulation of aldosterone secretion. syndrome on body composition after preterm birth. Arch Dis
Annu Rev Physiol. 1988; 50:409–426. Child Fetal Neonatal Ed. 1997;77(1):F28–F31.
13. Weber KT. Aldosterone in congestive heart failure. N Engl J 32. Rutter N, Hull D. Water loss from the skin of term and preterm
Med. 2001;345(23):1689–1697. babies. Arch Dis Child. 1979;54(11):858–868.
14. Thomson CJ, Bland J, Burd J, Baylis PH. The osmotic thresh- 33. Costarino AT, Baumgart S. Modern fluid and electrolyte
olds for thirst and vasopressin release are similar in healthy management of the critically ill premature infant. Ped Clin
man. Clin Sci. 1986;71:651–656. North Am. 1986;33(1):153–178.
15. Robertson GL. Thirst and vasopressin function in normal 34. Kjartansson S, Hammarlund K, Sedin G. Insensible water
and disordered states of water balance. J Lab Clin Med. loss from the skin during phototherapy in term and preterm
1983;101(3):351–371. infants. Acta Paediatr. 1992;81(10):764–768.
16. Langley G. Fluid, electrolytes, and acid-base disorders. 35. Grunhagen DJ, de Boer MG, de Beaufort AJ, Walther FJ.
In: Gottschlich MM, DeLegge MH, Mattox T, Mueller C, Transepidermal water loss during halogen spotlight therapy
Worthington P, eds. The A.S.P.E.N. Nutrition Support Core in preterm infants. Pediatr Res. 2002;51(3):402–405.
Curriculum: A Case-Based Approach – The Adult Patient. Silver 36. Maayan-Metzger A, Yosipovitch G, Hadad E, Sirota L. Trans
Spring, MD: American Society for Parenteral and Enteral epidermal water loss and skin hydration in preterm infants
Nutrition; 2007:104–128. during phototherapy. Am J Perinatol. 2001;18(7):393–396.
17. Zimmerman EA, Ma LY, Nilaver G. Anatomical basis of thirst 37. Hartnoll G. Basic principles and practical steps in the
and vasopressin secretion. Kidney Int. 1987; 21:S14–S19. management of fluid balance in the newborn. Semin Neonatal.
18. Uretsky BF, Verbalis JG, Generalovich T, Valdes A, 2003;8(4): 307–313.
Reddy PS. Plasma vasopressin response to osmotic and 38. Davis ID, Avner ED. Neonatal-perinatal medicine: diseases of
hemodynamic stimuli in heart failure. Am J Physiol. the fetus and infant. In: Fanaraff AA, Martin RJ, eds. Fluid and
1985;248(3):H395–H402. Electrolyte Management. 7th ed. St. Louis, MO: CV Mosby;
19. Sterns RH, Spital A. Disorders of water balance. In: Kokko JP, 2002:619–627.
Tannen RL, eds. Fluids and Electrolytes, 2nd ed. Philadelphia, 39. Kumar V, Cotran RS, Robbins SL. Disorders of vascular flow
PA: Saunders; 1990:139–194. and shock. In: Kumar V, Cotran RS, Robbins SL, eds. Basic
Pathology. 5th ed. Philadelphia, PA: Saunders; 1992:61–91.

40. Pincus MR, Preuss HG, Henry JB. Evaluation of renal func- 58. Whang R, Whang DD, Ryan MP. Refractory potassium reple-
tion, water, electrolytes, acid-base balance and blood gasses. tion. A consequence of magnesium deficiency. Arch Intern
In: Henry JB, ed. Clinical Diagnosis and Management by Med. 1992;152(1):40–45.
Laboratory Methods. 19th ed. Philadelphia, PA: Saunders; 59. Reinhart RA. Magnesium metabolism. A review with special
1996:139–149. reference to the relationship between intracellular content
41. Hwai-Ping S. Sodium, chloride, and potassium. In: Stipanuk and serum levels. Arch Intern Med. 1988;148(11):2415–2420.
M, ed. Biochemical and Physiological Aspects of Human Nutri- 60. Zaloga GP, Roberts PR. Calcium, phosphorus, and magne-
tion. Philadelphia, PA: Saunders; 2000:686–710. sium disorders. In: Ayres SM, Grenvik NA, Holbrook PR,
42. Wilkins BH. Renal function in sick very low birthweight Shoemaker WC, eds. Textbook of Critical Care. 4th ed. Phila-
infants: 3. Sodium, potassium, and water excretion. Arch Dis delphia, PA: Saunders; 2000:905–928.
Child. 1992; 67(10):1154–1161. 61. Quamme GA. Laboratory evaluation of magnesium status.
43. Hartnoll G, Betremieux P, Modi N. Randomised controlled Renal function and free intracellular magnesium concentra-
trial of postnatal sodium supplementation on body composition. Clin Lab Med. 1993;13(1):209–223.
tion in 25 to 30 week gestational age infants. Arch Dis Child 62. Teng RJ, Wu TJ, Sharma R, Garrison RD, Hudak ML. Early
Fetal Neonatal Ed. 2000;82(1):F24–F28. neonatal hypotension in premature infants born to preec-
44. Roberts KB. Fluids and electrolytes: parenteral fluid therapy. lamptic mothers. J Perinatol. 2006;26(8):471–475.
Pediatr Rev. 2001;22(11):380–387. 63. Whang R, Ryder KW. Frequency of hypomagnesemia and
45. Finberg L. Hypernatremic (hypertonic) dehydration in hypermagnesemia. Requested vs routine. JAMA. 1990;
infants. N Engl J Med. 1973;289(4):823–832. 263(22):3063–3064.
46. Holliday MA, Kalayci MN, Harrah J. Factors that limit brain 64. Reinhart RA. Magnesium metabolism. A review with special
volume changes in response to acute and sustained hyper- and reference to the relationship between intracellular content
hyponatremia. J Clin Invest. 1968;47(8):1916–1928. and serum levels. Arch Intern Med. 1988;148:(11)2415–2420.
47. Robertson J. Blood chemistries and body fluids. In: Robertson 65. Van Hook JW. Endocrine crises. Hypermagnesemia. Crit Care
J, Shilkofski N, eds. The Harriet Lane Handbook. 7th ed. Phila- Clin. 1991;7(1):215–223.
delphia, PA: Elsevier Mosby; 2006:661–672. 66. Ramsey PS, Rouse DJ. Magnesium sulfate as a Tocolytic
48. Horisberger J, Lemas V, Kraehenbuhl J, Rossier BC. Struc- agent. Semin Perinatol. 2002;25(4):236–247.
ture-function relationship of Na,K-ATPase. Annu Rev Physiol. 67. Weisinger JR, Bellorin-Font E. Magnesium and phosphorus.
1991;53:565–584. Lancet. 1998;352(9125):391–396.
49. Rodriguez-Soriano J. Potassium homeostasis and its distur- 68. Lee CT, Tsai WY, Tung YC, Tsau YK. Transient
bance in children. Pediatr Nephrol. 1995;9(3):364–374. pseudohypoparathyroidism as a cause of late-onset
50. Ganguly A. Primary aldosteronism. N Engl J Med. hypocalcemia in neonates and infants. J Formos Med Assoc.
1998;339(25):1828–1834. 2008;107(10):806–810.
51. Kelvay LM, Bogden JD, Aladjem M, et al. Renal and gastroin- 69. Desai TK, Carlson RW, Geheb MA. Prevalence and
testinal potassium excretion in humans: new insight based on clinical implications of hypocalcemia in acutely ill
new data and review and analysis of published studies. J Am patients in a medical intensive care setting. Am J Med.
Coll Nutr. 2007;26(2):103–110. 1988;84(2):209–214.
52. Mathialahan T, Sandle GI. Dietary potassium and laxatives as 70. Ryzen E, Wagers PW, Singer FR, Rude RK. Magnesium
regulators of colonic potassium secretion in end-stage renal deficiency in a medical ICU population. Crit Care Med.
disease. Nephrol Dial Transplant. 2003;18(2):341–347. 1985;13(1):19–21.
53. Brown RS. Extrarenal potassium homeostasis. Kidney Int. 71. Dacey MJ. Hypomagnesemic disorders. Crit Care Clin.
1986;30(1):116–127. 2001;17(1):155–173, viii.
54. Subramanian S, Agarwal R, Deorari AK, Paul VK, 72. Magnesium sulfate. In: Taketomo CK, Hodding JH, Kraus
Bagga A. Acute renal failure in neonates. Indian J Pediatr. DM, eds. Pediatric Dosage Handbook. 15th ed. Hudson, OH:
2008;75(4):385–391. Lexi-Comp; 2008:1090–1092.
55. Strom BL, Carson JL, Schinnar R, et al. Upper gastrointestinal 73. Topf MJ, Murray PT. Hypomagnesemia and hypermag-
tract bleeding from oral potassium chloride. Comparative risk nesemia. Rev Endocr Metab Disord. 2003;4(2):195–206.
from microencapsulated vs wax matrix formulations. Arch 74. Oster JR, Epstein M. Management of magnesium depletion.
Intern Med. 1987;147(5):954–957. Am J Nephrol. 1988;8(5):349–354.
56. Potassium chloride. In: Taketomo CK, Hodding JH, Kraus 75. Herbert P, Mehta N, Wang J, Hindmarsh T, Jones G, Cardinal
DM, eds. Pediatric Dosage Handbook. 15th ed. Hudson, OH: P. Functional magnesium deficiency in critically ill patients
Lexi-Comp; 2008:1432–1435. identified using a magnesium-loading test. Crit Care Med.
57. Potassium chloride. In: Phelps SJ, Hak EB, Crill CM, eds. The 1997;25(5):749–755.
Teddy Bear Book: Pediatric Injectable Drugs. 8th ed. Bethesda, 76. Chattopadhyay N, Mithal A, Brown EM. The calcium-
MD: American Society of Health-System Pharmacists; sensing receptor: a window into the physiology and
2007:368–369. pathophysiology of mineral ion metabolism. Endocrinol Rev.
1996;17(5):289–307.

77. Popovtzer MM. Disorders of calcium, phosphorus, vitamin D, 87. Davis KD, Attie MF. Management of severe hypercalcemia.
and parathyroid hormone activity. In: Schrier RW, ed. Renal Crit Care Clin. 1991;7(1):175–190.
and Electrolyte Disorders. 6th ed. Philadelphia, PA: Lippincott 88. Peppers MP, Geheb M, Desai T. Endocrine crises. Hypo-
Williams & Wilkins; 2003:216–277. phosphatemia and hyperphosphatemia. Crit Care Clin.
78. Jain A, Agarwal R, Sankar MJ, Deorari AK, Paul VK. Hypocal- 1991;7(1):201–214.
cemia in the newborn. Indian J Pediatr. 2008;75(2):165–169. 89. Knochel JP. The pathophysiology and clinical charac-
79. Bushinsky DA, Monk RD. Electrolyte quintet: Calcium. teristics of severe hypophosphatemia. Arch Intern Med.
Lancet. 1998; 352(9124):306–311. 1977;137(2):203–220.
80. Zivin JR, Gooley T, Zager RA, Ryan MJ. Hypocalcemia: a 90. Worley G, Claerhout SJ, Combs SP. Hypophosphatemia
pervasive metabolic abnormality in the critically ill. Am J in malnourished children during refeeding. Clin Pediatr.
Kidney Dis. 2001;37(4):689–698. 1998;37(6):347–352.
81. Guise TA, Mundy GR. Clinical review 69: Evaluation of 91. Clark Cl, Sacks GS, Dickerson RN, Kudsk KA, Brown RO.
hypocalcemia in children and adults. J Clin Endocrinol Metab. Treatment of nutrition support using a graduated dosing
1995;80(5):1473–1478. scheme: results from a prospective clinical trial. Crit Care
82. Schmidt GL, Baumgartner TG, Fischlschweiger W, Sitren Med. 1995;23(9):1504–1511.
HS, Thakker KM, Cerda JJ. Cost containment using cysteine 92. Sperschneider H, Gunther K, Marzoll I, Kirchner E, Stein G.
HCl acidification to increase calcium/phosphate solubility Calcium carbonate (CaCO3): an efficient and safe phosphate
in hyperalimentation solutions. J Parenter Enteral Nutr. binder in haemodialysis patients? A 3-year study. Nephrol Dial
1986;10(2):203–207. Transplant. 1993;8(6):530–534.
83. Wood RJ, Sitrin MD, Cusson GJ, Rosenberg IH. Reduction 93. Potassium phosphate. In: Phelps SJ, Hak EB, Crill CM,
of total parenteral nutrition-induced urinary calcium loss by eds. The Teddy Bear Book: Pediatric Injectable Drugs. 8th ed.
increasing the phosphorus in the total parenteral nutrition Bethesda, MD: American Society of Health-System Pharma-
prescription. J Parenter Enteral Nutr. 1986;10(2):188–190. cists; 2007:370–371.
84. Semple P, Booth C. Calcium chloride; a reminder. Anaesthesia. 94. Goodman WG, Goldin J, Kuzion BD, et al. Coronary-
1996;51(1):93. artery calcification in young adults with end-stage renal
85. Calcium chloride. In: Phelps SJ, Hak EB, Crill CM, eds. The disease who are undergoing dialysis. N Engl J Med.
Teddy Bear Book: Pediatric Injectable Drugs. 8th ed. Bethesda, 2000;342(20):1478–1483.
MD: American Society of Health-System Pharmacists; 95. Ritz E. The clinical management of hyperphosphatemia. J
2007:70–71. Nephrol. 2005;18(3):221–228.
86. Calcium chloride. In: Taketomo CK, Hodding JH, Kraus
DM, eds. Pediatric Dosage Handbook. 15th ed. Hudson, OH:
Lexi-Comp; 2008:290–291.

PART II
AGE-SPECIFIC NUTRITION FOR

GROWTH AND DEVELOPMENT
10. Nutrition and Early Development. . . . . . . . . . . . . . 105

Russell J. Merritt, MD, PhD, FAAP
Barbara Marriage, PhD, RD
Ricardo Rueda, MD, PhD
11. Human Milk . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 120
12. Infant Formulas and Complementary Feeding. . . . 129
Kelly Green Corkins, MS, RD, CNSD
13. Growth Assessment and Monitoring . . . . . . . . . . . 143
14. Obesity and Metabolic Disorders. . . . . . . . . . . . . . 149
Michelle Battista, BS, PhD Candidate
Robert Murray, MD
15. Lipid Disorders. . . . . . . . . . . . . . . . . . . . . . . . . . . . 162
Shirley Huang, MD
Melanie Katrinak, RD, CSP, LDN
16. Use of Fad and Popular Diets. . . . . . . . . . . . . . . . . 169
Catherine Christie, PhD, RD
Julia A. Watkins, PhD, MPH
Judith C. Rodriguez, PhD, RD
17. Sports Nutrition . . . . . . . . . . . . . . . . . . . . . . . . . . . 178
Jackie Buell, PhD, RD, LD, ATC, LAT
Diane L. Habash, PhD, RD, LD
10
Nutrition and Early Development
Russell J. Merritt, MD, PhD, FAAP, Barbara Marriage, PhD, RD, and Ricardo Rueda, MD, PhD

Nutrition Physiology of Pregnancy . . . . . . . . . . . . . . . . . . 105 1. Achieve familiarity with the normal physiology and
Impact of Maternal Dietary Deficiencies on the Fetus. . 107 metabolism of the fetus and know nutrient deficiencies
Macronutrients associated with adverse pregnancy outcomes.
Calcium 2. Know common late adverse manifestations of early
Iron programming observed in epidemiologic and animal
Folic Acid and Vitamin B12 studies.
Vitamin E
Multiple Micronutrients
3. Be aware of potential mechanisms involved in late and
transgenerational effects of early life programming.
Impact of Nutrition and Other Stresses on Fetal
Metabolism, Organ Growth, and Development . . . . . . . . 109
Nutrition Physiology of Pregnancy
History and Epidemiology of the Fetal
Origins of Disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 110 Pregnancy proceeds from fertilization to implantation
Hypothesis through development and maturation of the placenta (of
Expansion to Postnatal Growth Period fetal origin) and the fetus. A healthy pregnancy is depen-
Integration of Pre- and Postnatal dent on maternal nutrition status at conception, adequate
Programming Effects. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 112 oxygen delivery (blood-flow dependent) to the placenta
Early Programming in the Premature Infant and fetus, and the availability of appropriate amounts of
Animal Models . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 112 nutritional substrates in the hormonal matrix that facili-
Animal Models of Dietary Manipulation tates development of the placenta and the fetus. Early in
Animal Models Induced by Glucocorticoid Exposure gestation, placental mass is high relative to that of the fetus,
Animal Models Induced by Surgical Manipulation
and in later gestation this ratio declines. Initially, placental
Third and Future Generation Effects . . . . . . . . . . . . . . . . 114 transport is largely dependent on increases in placental size,
Implications for Future Health . . . . . . . . . . . . . . . . . . . . . 115 but later in pregnancy, both placental transport function
Implications for Current Practice. . . . . . . . . . . . . . . . . . . 115 and placental size must increase to meet the needs of the
Future Research Needs. . . . . . . . . . . . . . . . . . . . . . . . . . . 116 rapidly growing fetus.
The uterus and placenta are perfused by the maternal
uterine arteries, and the placenta transfers nutrients and
gasses bi-directionally across the microvillous maternal-
facing membranes and fetal-facing baso-lateral membranes
of the syncytiotrophoblast and into the fetal venous
circulation. The placenta has a relatively higher glucose
requirement than the fetus to perform its important func-
tions of substrate regulation, transport, and hormone
105
secretion. In intrauterine growth restriction (IUGR) preg- acids except tryptophan are in much higher concentration
nancies, placental weight is reduced more than fetal weight. in the placenta than in maternal blood. Leucine appears to
In contrast, the placenta may be increased in mass in gesta- have specific trophic effects on the placenta and the fetus,
tional diabetes.1 possibly because of its impact on “mammalian target of
Much of what we know about fetal substrate metabo- rapamycin” (mTOR), which is a critical regulator of protein
lism comes from extensive studies of the late gestation synthesis. IUGR fetuses have reduced fetal enrichment of
ovine fetus initiated by Battaglia and many other investiga- leucine relative to the maternal circulation.4 Other specific
tors associated with the Perinatal Research Center at the amino acids such as arginine have not only nutrient, but,
University of Colorado School of Medicine.2–8 The umbilical similarly, regulatory and developmental effects.10 The fetal
vein transports oxygen and nutrients to the fetus toward the liver makes glutamate (largely from glutamine), aspar-
fetal liver and ductus venosus, which variably shunts blood tate, and serine; the flux of glutamate and serine is in the
around the liver to the fetal heart and brain. Until the time direction of the placenta, where they are metabolized, the
of birth, when the lungs expand and pulmonary artery glutamate oxidized to CO2 . Serine is important to the one-
resistance increases, the lungs are also partly bypassed. This carbon pool for nucleotide biosynthesis and as a precursor
increases oxygenated blood flow to the fetal brain via the for glycine and gluconeogenesis. 5
ductus arteriosus that connects the pulmonary artery and When there is reduced oxygen, glucose, and amino
the aorta. Blood containing amino acids, metabolites, and acid availability to the fetus by virtue of reduced umbilical
carbon dioxide (CO2) returns to the placenta by way of the vein blood flow (associated with placental transport insuf-
2 umbilical arteries. ficiency), fetal weight gain slows. There are compensatory
The major energy source for the fetus is glucose, which increases in fetal amino acid catabolism such that changes
normally all comes from maternal transport to the fetus and in fetal blood amino acid concentrations are minimized.
placenta.2 It also uses lactate produced in the placenta and This situation is associated with altered substrate distribu-
endogenously.9 Glucose uptake by placental and fetal tissues tion and changes in relative organ growth. When glucose
and fetal growth are proportional to glucose delivery. 2 The (and other substrate) supply is limited and the fetus is
fetal pancreas secretes insulin by mid-gestation and responds relatively hypoglycemic, growth of the brain, kidney, and
to variations in the glucose delivery rate. Normally the fetal adrenals is relatively maintained. Growth of the spleen,
liver is not active in gluconeogenesis. Fetal tissue glucose liver, pancreas, and lung are reduced in excess of the
transporters and intracellular downstream metabolic regu- (primate) body weight decrement.11 More blood is shunted
lators are modulated by glucose and insulin levels in the through the ductus venosus, reducing splanchnic substrate
fetus. Insulin-responsive fetal tissues include the heart, availability. This leads to slower growth and altered fetal
liver, skeletal muscle, and adipose tissue. Placental glucose liver metabolism and reduced pancreatic beta cell mass or
uptake is not regulated by insulin. When fetal glucose supply function, depending on the stage of pregnancy. The most
is limited, fetal glucose oxidation is maintained by virtue of common cause of IUGR is placental transport insufficiency
increased uterine artery/umbilical vein glucose gradient (oxygen, glucose, amino acids), which may be related to
and gluconeogenesis from amino acids in the fetus: “…the local uterine factors, maternal malnutrition, advanced
fetus develops with mechanisms that tend to keep its energy maternal diabetes, hypertension, or other maternal or
metabolism relatively constant, while growth is, at times of placental pathology.12,13
deficient energy supply, expendable.”3 Central metabolic mediators for regulatory hormone
Amino acids are the second most important macro- and metabolic changes in the fetus are fetal insulin, cortisol
nutrient in the fetus with at least 14 complex amino acid (increased levels of which are associated with reduced
transporter systems on both of the syncytiotrophoblast glucose uptake, increased gluconeogenesis, and slower fetal
membranes.10 The large neutral and branched-chain amino growth),14 and insulin-like growth factors (IGFs), which are
acids are transported most directly proportional to their critical for placental development and function and protein
maternal concentration. 5 Because of shared transporters synthesis in fetal tissues.15,16 The increased insulin levels
and competition among amino acids for specific trans- seen in response to acute hyperglycemia (in sheep) diminish
porters, an increase in delivery of multiple amino acids with sustained hyperglycemia, and glucose transporters
sharing the same transporter to the uterine artery may have in liver, muscle, and adipose tissue decline, although total
a different effect than an increase of a single amino acid on fetal glucose uptake remains elevated. The liver volume may
the uptake and transport of a specific amino acid. All amino be increased. Many of these fetal adaptations may persist,

NUTRITION AND EARLY DEVELOPMENT 107
alter postnatal substrate metabolism, and determine the placental synthesis of nitric oxide, a major vasodilator and
metabolic response to postnatal and later diet. angiogenesis factor, and polyamines, key regulators of DNA
Specific common metabolic/hormonal derangements and protein synthesis, may provide an explanation for IUGR
that influence organ growth and metabolic development of in response to the 2 extremes of nutrition problems with
the fetus include hypoglycemia, hyperglycemia, maternal the same pregnancy outcome. Placental and fetal growth
or gestational diabetes, and activation of the fetal hypo- is most vulnerable to maternal nutrition status during the
thalamic-pituitary-adrenal (HPA) axis (summarized by peri-implantation period and the period of rapid placental
McMillen17) by a variety of intrauterine insults. The fetus development (the first trimester of gestation).
and its uteroplacental support system are highly adaptive There has been extensive clinical research, using both
to their vascular supply, oxygenation state, and metabolic observational and interventional study designs, that allows
substrate availability. In this formative stage of life, thou- some quantification of the effects of maternal anthropo-
sands of responses at the fetal, organ, tissue, membrane, metric indices, dietary intake in pregnancy, and nutritional
cytosolic, and nuclear levels determine the survival, health, supplements with respect to measures of fetal size and
and function of the fetus. These responses are regulated at maturity at birth. Overall, these studies find a strong posi-
the enzyme substrate level, others at the level of messenger tive association between maternal pre-pregnancy nutrition
ribonucleic acid (mRNA) transcription, and some at the status and the ability of a mother to nourish her growing
nuclear level by way of epigenetic modification. Some of fetus. Recent evidence also suggests that periconceptional
these adaptations are transient and others, particularly with undernutrition, as well as pregnancy undernutrition, are
prolonged exposure, appear to be permanent. Epigenetic important determinants of the length of gestation. Gesta-
changes involve gene regulation effects that are inherited tional weight gain and nutritional interventions during
from one cell generation to the next. These gene expres- pregnancy appear able to modify this association by
sion modifications do not change the deoxyribonucleic acid altering the rate of fetal growth, although the extent of the
(DNA) sequence.18 Examples of epigenetic mechanisms modification appears to be dependent on maternal baseline
include DNA methylation, histone modification, and altera- nutrition status, and is modest.23 Current estimates of nutri-
tions in noncoding RNAs.19 Epigenetic modifications of tion needs are provided in Table 10-1.
cells in specific organs help determine the final metabolic
phenotype, which is a product of both genetic inheritance Macronutrients
and developmental environmental influences on gene In terms of maternal macronutrient status, there is some
expression. Vulnerability to environmental and dietary evidence that balanced protein/energy supplementation
influences appears to continue well past the time of birth. may be beneficial for decreasing rates of low birth weight
Fetal and early postnatal plasticity allows survival, but may (LBW) and small for gestational age (SGA) deliveries,
also set the stage for later maladaptive metabolic responses, especially in populations where women have chronically
particularly to metabolic environments different from that marginal nutrition status prior to pregnancy.15 However,
experienced early in development (eg, food surfeits versus overall analysis of the available evidence suggests that
scarcity).20 maternal supplementation with balanced or high-protein
diets had no beneficial effects on fetal growth. There is
Impact of Maternal Dietary Deficiencies limited evidence that protein supplementation adversely
on the Fetus affected fetal growth rate (as measured by mean birth
Maternal nutrition during pregnancy can exert long-lasting weight) and therefore potentially increased LBW deliveries.
effects on the health of the offspring.21 These effects may The effect of energy/protein restriction has been also evalu-
be due to undernutrition or deficit of specific nutrients, or ated in women who were classified as obese pre-pregnancy
to an excess of energy or nutrients. Epidemiological and or had rapid early gestational weight gain. In women who
animal studies suggest that fetal adaptive responses to the were obese before pregnancy, there have been no benefits to
intrauterine environment, including maternal malnutrition, fetal growth of restricting energy and protein during gesta-
overnutrition, or diabetes, may increase the risk of many tion, although evidence from controlled trials is limited. 23
chronic diseases in adulthood, including Type 2 diabetes and It has also been reported that high intakes of protein and
coronary heart disease (CHD).22 Animal studies also show fat during pregnancy may impair development of the
that both maternal undernutrition and overnutrition reduce fetal pancreatic beta cells and lead to insulin deficiency in
placental-fetal blood flow and slow fetal growth. Impaired the offspring.16

On the other hand, very recent studies have demon- Calcium

strated that a low-protein diet in utero had a deleterious In terms of specific micronutrients, maternal calcium
effect on bone development in the offspring that persisted supplementation may have a beneficial effect on fetal
into adulthood.24 The offspring displayed significant differ- growth, particularly in women with low calcium status at
ences in bone structure and density at various sites. These the outset of pregnancy or who were classified as being at
differences are indicative of significantly altered bone risk of gestational hypertension. Calcium supplementa-
turnover.25 tion during pregnancy can be linked directly to increased
bone density and bone length of neonates.26 The effects on
Table 10-1 Recommended Daily Nutrient Intakes During Pregnancy fetal growth appeared to come partly from a reduction in
Water 3L preeclampsia and resultant lengthened gestation.23
Energy Varies by age, pregnancy stage, BMI, activity
Carbohydrate 175 g Iron
Total fiber 28 g Some studies have reported that iron deficiency anemia
Linoleic acid 13 g early in pregnancy was associated with greater than a
Linolenic acid 1.4 g twofold increase in the risks of LBW and preterm delivery.21
Protein 71 g In addition, reduced iron availability for brain iron accre-
Vitamin A 750–770 mcg* tion is associated with persisting developmental and
Vitamin C 80–85 mg/d* behavioral changes. A number of conditions associated with
Vitamin D 5 mcg fetal growth retardation or macrosomia such as diabetes,
Vitamin E 15 mg
placental insufficiency, and smoking restrict iron availability
Vitamin K 75–90 mcg*
during gestation and predispose to later iron deficiency. 27
Thiamin 1.4 mg
Riboflavin 1.4 mg
Niacin 18 mg
Folic Acid and Vitamin B12
Vitamin B6 1.9 mg In well-nourished populations, folic acid needs are usually
Folate 600 mcg met by dietary intake. However, in some countries (eg, the
Vitamin B12 2.6 mcg United States), it is recommended that pregnant women
Pantothenic acid 6 mg consume 600 mcg of folic acid per day to reduce the risk
Biotin 30 mcg of neural tube defects (Table 10-1). A dietary deficiency of
Choline 450 mg folate interferes with the growth of the fetus. Low maternal
Calcium 1000–1300 mg* folate intake (< 240 mcg/d) has been associated with a
Chromium 29–30 mcg* greater than threefold increase in the risk of LBW and
Copper 1000 mcg preterm delivery. A metabolic effect of folate deficiency is
Fluoride 3 mg elevation of homocysteine, and women with high homo-
Iodine 220 mcg cysteine levels are more likely to have a reproductive history
Iron 27 mg
of preeclampsia, preterm delivery, LBW, or fetal growth
Magnesium 350–400 mg*
restriction.21 A recent study carried out in India has high-
Manganese 2 mg
Molybdenum 50 mcg
lighted that dietary methyl donors including B12 and folate
Phosphorus 700–1250 mg*
seem to play a major role in fetal programming. Maternal
Selenium 60 mcg low B12 status along with normal to high folate status
Zinc 11–12 mg* predicted later adiposity and insulin resistance in children.
Potassium 4.7 g Thus, 1-C (methyl) metabolism seems to play a key role in
Sodium 1.5 g fetal programming.28
Chloride 2.3 g
* Varies by age group. Vitamin E
Adapted from U.S. Dietary Reference Intakes (www.nap.edu). The plasma concentration of α-tocopherol, the most
common isomer of vitamin E, was positively related to fetal
growth (birth weight for gestation), reduced small-for-
gestation births, and increased risk of large-for-gestation
births. Concentrations of α-tocopherol were positively

related to the use of prenatal multivitamins before and (eg, cortisol, catecholamines, glucagons, and GH). The
during pregnancy and to vitamin E in the maternal diet. anabolic hormones tend to increase the uptake and utili-
Emerging evidence suggests that the effect of vitamin E on zation of glucose and reduce the oxidation of amino acids.
fetal growth may be via increased blood flow and nutrient They also enhance protein accretion by stimulating protein
supply to the fetus.21 synthesis, by reducing proteolysis, or both. The catabolic
hormones tend to increase fetal glucose production by acti-
Multiple Micronutrients vating hepatic gluconeogenesis. They also reduce protein
There have been few studies published to examine whether accretion and fetal uptake of amino acids.
multiple micronutrient supplements might be more The fetal HPA axis is particularly vulnerable to changes
beneficial than single micronutrients. There is evidence of in the intrauterine environment. In humans, most brain and
interactions of several micronutrients at the metabolic level. HPA development occurs in utero. However, in species often
Little is yet known about the significance of these interac- used as models of in utero manipulation that give birth to
tions for pregnancy outcomes, especially in developing immature offspring (eg, rodents), most brain development
countries where nutrient deficiencies rarely occur in isola- occurs in the early postnatal days. 33,34
tion and multiple micronutrient deficiencies are common. 29 Prenatal stress has a profound effect on neuroendocrine
A meta-analysis of global multinutrient supplementation development and function. Exposure of the fetus to elevated
studies found a small effect on birth weight between iron- glucocorticoids appears to be the central link between
folate supplementation or placebo. 30 prenatal stress and modification of HPA axis develop-
ment and function. There is evidence that antenatal stress/
Impact of Nutrition and Other Stresses anxiety has a programming effect on the fetus that lasts
on Fetal Metabolism, Organ Growth, at least until mid-childhood and results in higher rates of
and Development behavioral and emotional problems. 35 Cognitive and behav-
Deprivation of nutrients and/or oxygen in utero alters fetal ioral modifications have also been linked to alterations in
metabolism in a manner that changes body growth and HPA axis activity and prenatal glucocorticoid exposure.
the development of individual fetal tissues. 31 The effects of Prenatal stress has been associated with changes in memory
varying nutrient availability on fetal metabolism depend and behavior, and with depression, anxiety, chronic fatigue
on the specific nature of the nutrition variation and on syndrome, and schizophrenia. 33 These alterations in HPA
the duration, severity, and gestational age at onset of the axis function, behavior, and cognition as a result of prenatal
insult. Deprivation of oxidative substrates such as glucose stress have been related to changes in brain corticosteroid
produces a different metabolic response in the fetus from receptor populations and alterations in hippocampal and
that seen from oxygen deprivation alone or when there is hypothalamic neuronal development. 36
combined oxygen and substrate deficiency. These different Numerous studies in animals and humans have demon-
nutrition challenges also have different effects on the utero- strated that synthetic glucocorticoid administration can
placental tissues and on the fetal hormonal environment, also promote HPA hyperactivity. Synthetic glucocorticoids
both of which influence the availability and metabolic fate are poorly catabolized by placental 11β-hydroxysteroid
of specific nutrients in the fetus. 32 dehydrogenase type 2 (11β−HSD2), and readily pass to the
Many of the nutritionally induced alterations in fetus. 37 Fetal glucocorticoid exposure alters the expression
fetal metabolism and growth are likely to be mediated of glucocorticoid receptors, and impacts every level of the
by hormonal changes in either the mother or the fetus. HPA axis. Synthetic glucocorticoids are often administered
Dietary restriction is known to alter maternal concentra- to women threatened with preterm delivery to enhance
tions of growth hormone (GH), insulin-like growth factors fetal lung maturation to reduce morbidity and mortality
(IGFs), insulin, glucocorticoids, leptin, thyroid hormones, at a time in gestation when endogenous fetal cortisol levels
and placental lactogen. 31 These hormones alter maternal would normally be quite low. Due to recent clinical obser-
metabolite concentrations that in turn influence fetal vations and animal studies of this practice, concerns have
substrate availability, particularly for those metabolites been voiced by international expert groups. In spite of
crossing the placenta against a concentration gradient. In these concerns, administration of repeated doses of ante-
general, reducing fetal delivery of oxygen and nutrients natal corticosteroids to pregnant patients continues to be
lowers anabolic hormones (eg, insulin, IGFs, and thyroid common clinical practice. 33
hormones) and increases catabolic hormone concentrations Programming of the fetal HPA axis appears to play a

central role in the link between fetal growth and long-term exposed to food restriction, the more permanent the effects
disease in adulthood (Figure 10-1). Stress-induced prenatal on adult size, despite attempts to obtain catch-up growth.40
programming of HPA axis function can increase the risk Competition among fetuses for intrauterine food supply or
of developing cardiovascular and metabolic diseases. On littermates for milk can lead to periods of undernutrition
another front, evidence is also accumulating rapidly that during critical periods of development. The fetus or neonate
chronic stimulation of the HPA axis and resulting excess adapts by slowing the rate of cell division in certain organs
glucocorticoid exposure may play a role in the develop- in such a way as to permanently change or program metabo-
ment of visceral obesity. Because regulation of energy and lism and growth potential.
food intake under stress is important for survival, it is not Barker and colleagues proposed the “developmental
surprising that the HPA axis is not only the conductor of or fetal origins of adult disease” in humans in 1986. The
appropriate stress responses, but also tightly intertwined hypothesis was based on observations that the highest rates
with the regulation of appetite. 38 of CHD in a geographical region of England were associ-
ated with increased infant mortality in the same population
History and Epidemiology of the decades earlier.41 Further epidemiological evidence was
Fetal Origins of Disease provided from 2 large studies of males from Hertfordshire
and Sheffield, England, that demonstrated a strong corre-
Hypothesis lation between LBW, low weight for length at 1 year, and
Early nutrition programming is the concept that nutri- small head circumference with death from CHD.42,43 It
tion experiences in early life can program an individual’s is of interest to note that the relationship between LBW
metabolism and development and influence later health and CHD was related to slow fetal/infant growth rather
outcomes. In 1962, McCance39 observed that the size of a than prematurity. The association between reduced size at
weanling rat varied inversely with the number of littermates birth and risk factors for CHD including obesity, hyperten-
suckled by the dam. Further experimental work in both rats sion, hyperlipidemia, and non-insulin-dependent diabetes
and pigs illustrated that the earlier in life the animal was mellitus (NIDDM) has been confirmed from cohort
Figure 10-1 Scheme of the role that programming of the fetal hypothalamic-pituitary-adrenal (HPA) axis during development plays in the link between
fetal growth and long-term disease in adulthood. Gc: Glucocorticoids; Dex: Dexamethasone.

studies in various countries.44–49 A systematic review of 80 size. 54 A systematic review of 15 studies examining the role
studies found that there was a 2-mmHg decrease in systolic of rapid growth in infancy and childhood on later obesity
blood pressure per kilogram increase in birth weight.48 found 13 publications that demonstrated a significant asso-
A review of 48 papers examining the relationship of birth ciation of early rapid growth with obesity prevalence in later
weight and later glucose and insulin metabolism demon- life. 59 Another systematic review that evaluated both size at
strated that LBW was correlated with adverse glucose and birth and rate of growth in infancy concluded that infants
insulin metabolism, possibly related to insulin resistance.49 who are at the highest end of the distribution for weight,
Fetal overnutrition in infants of diabetic mothers may also or who grew rapidly during infancy, are at increased risk
cause an increased risk of glucose intolerance and NIDDM of subsequent obesity.60 Although controversy exists as to
in later life. 50 A study in Pima Indians demonstrated a the specific periods of infancy and childhood that predict
U-shaped relationship between birth weight and prevalence later adiposity, several observational studies have indi-
of NIDDM with high birth weight explained by the pres- cated that weight gain in the first half of infancy may be a
ence of gestational diabetes. 51 critical period.61–63 In formula-fed infants in whom repeated
measures of infant weight gain were available, Stettler and
Expansion to Postnatal Growth Period colleagues showed that rapid weight gain in the first week of
Although nutrition effects during fetal life have been shown life was associated with risk of overweight in adulthood.64
to be important determinants of susceptibility to later health Several reviews have demonstrated that breastfeeding
effects, postnatal events modify the influence of prenatal may reduce the risk of later obesity. It has been suggested
growth. In evaluating the fetal origins of disease hypothesis that the benefits of breastfeeding may be due to slower
it has been recognized that it is important to adjust for early growth in the breastfed compared to the formula-fed infant.
weight gain and current body size. Numerous epidemio- The differences in growth rate between breastfed and
logical studies show that the highest risk for cardiovascular formula-fed infants are greatest in the first few weeks of life,
disease (CVD) and associated disorders is in adults who a critical period for programming of obesity.64
were small at birth and became overweight or obese during Observational studies support the hypothesis that early
childhood or adulthood.44,52–55 The “thrifty phenotype” postnatal nutrition plays an important role in the develop-
hypothesis proposed by Hales and Barker postulates that ment of obesity and related cardiovascular risk factors,
the fetus selectively distributes nutrients to certain organs but limited clinical evidence exists on the effects of early
during periods of undernutrition, leading to permanent nutrition programming in term infants. In a recent study,
metabolic changes that enhance its chance of survival SGA term infants randomly assigned to a nutrient-enriched
during periods of limited postnatal nutrition. 56 If adequate formula at birth had higher diastolic blood pressure at 6 to
food becomes available postnatally, the prenatal meta- 8 years.65 In a secondary analysis, the diastolic blood pres-
bolic adaptations to undernutrition are detrimental in that sure was greater in children who had more rapid weight
obesity and related metabolic disorders may develop. 57 gain from birth to 9 months.65 Support for the “growth
Lucas and colleagues proposed the term “program- acceleration hypothesis” in term infants was demonstrated
ming” to explain the mechanism whereby an early stimulus in a study that utilized multiple measurements of growth
or insult occurring at a critical or sensitive period results in from birth to 5 years in relation to blood pressure.66 Rapid
a permanent or long-term change. 58 Current research seeks increases in weight in the first 6 months of life predicted
to identify critical periods during prenatal and postnatal life elevated diastolic blood pressure in adults, independent of
when nutrition deficiencies or excesses may influence the fetal growth.66 LBW and rapid postnatal growth are asso-
risk of chronic adult disease. ciated with later elevated blood pressure indicating the
Recent evidence suggests that rapid weight gain during importance of both prenatal and postnatal factors in the
infancy may be associated with an increased incidence of programming of later health effects. Improved maternal
childhood or adult obesity and cardiovascular risk factors. nutrition and prevention of rapid percentile-crossing weight
The majority of the studies show consistent associations gain in infants could have a substantial impact on the devel-
between LBW and rapid weight gain in infancy with opment of adult chronic diseases.
increased risk of CHD. In addition, an observational study
from Helsinki demonstrated that slow weight gain during
infancy followed by a rapid weight gain after 1 year of age
increased the risk of coronary disease, irrespective of birth

Integration of Pre- and Postnatal growth and a nutrient-dense diet may be a risk factor for
Programming Effects later CVD.
Gluckman and colleagues use the term “developmental Although slower growth in preterm infants may
plasticity” (defined as the ability of an organism to develop have benefits for later health outcomes,69 the risks of
in various ways, depending on the particular environment adverse consequences on cognition must be considered.
or setting) to provide a framework for the observations on Numerous studies have demonstrated that growth restric-
the impact of early growth on later health.20 tion in preterm infants is associated with long-term short
The first models to explain the developmental origins of stature and cognitive deficits. Preterm infants fed standard
health and disease (DOHaD) idea were the “thrifty pheno- formula compared to nutrient-enriched formula demon-
type” and the “fetal salvage” hypothesis in which a fetus strated a significant reduction in intelligence quotient (IQ )
adapts to survive a deprived intrauterine environment. 56,67 and neurocognitive impairment at 7 to 8 years of age.74
These theories were later expanded to include the postnatal Higher bone mineralization and improved linear growth
environment and termed a “predictive adaptive response.”68 in childhood has been reported in preterm infants fed a
The risk of disease is increased when the postnatal environ- preterm formula versus unfortified breast milk or standard
ment does not match what is predicted prenatally. Animal formula.75,76 There are clear benefits for the use of special-
studies—in which nutritional, endocrinologic, or surgical ized formulas in preterm infants relative to term formulas to
manipulation from conception to weaning have been used support brain development that outweigh the later risks of
to induce permanent changes in the offspring—provide cardiovascular disorders. Short-term advantages of dietary
biological support for the concept of “developmental plas- supplementation of at-risk infants have also been demon-
ticity” and its role as a key determinant in the risk of later strated in developing countries where more rapid weight gain
chronic disease. up to 2 years of age was associated with decreased hospital
admissions and reduced mortality.77 Further research is
Early Programming in the Premature Infant needed to determine optimal growth to achieve cognitive
Prospective interventional studies performed by Singhal, benefits (in preterm infants) and short-term health benefits
Lucas et al in preterm infants have demonstrated the impor- in at-risk populations while minimizing the longer-term
tance of early nutrition for long-term health outcomes.69 risk of chronic disease.
More than 900 preterm infants were randomly assigned in
2 parallel trials to receive (a) banked breast milk or preterm Animal Models
formula or (b) standard term formula or preterm formula. Animal models of early growth restriction have been used to
The preterm infants fed breast milk for a period of 4 weeks better understand its relationship with adult human disease
had improved lipid profiles,70 lower blood pressure,71 lower and to provide insight into underlying molecular mecha-
leptin concentrations, and decreased insulin resistance72,73 nisms. Nutritional, hormonal, and surgical insults during
at 13 to 16 years compared to the infants fed preterm pregnancy have been shown to result in growth restriction
(nutrient-enriched) formula. The lipoprotein profile, in various species.78
C-reactive protein (a marker for the low-grade inflamma-
tory response associated with the atherosclerotic process), Animal Models of Dietary Manipulation
and blood pressure did not differ significantly between Dietary manipulation by global caloric restriction, reduc-
infants randomized to standard infant formula and those tion of dietary protein content, iron restriction, or dietary
fed preterm formula.70,71 The ratio of leptin to fat mass (a fat supplementation have all been studied in rodents and
marker of obesity) was significantly higher in children fed ovine models. The most common model is the pregnant
the preterm formula compared to the children who received rat subjected to malnutrition. However, a limitation of
breast milk or standard term formula.72 Fasting 32-33 the rodent model is that the rat is an altricial animal, born
proinsulin concentration (a marker of insulin resistance) with a poorly developed central nervous system and auto-
was significantly higher in children who received preterm crine system, with significant maturation during weaning.
formula, and further analysis demonstrated that differences The guinea-pig may be a more relevant model as these
in weight gain (or loss) in the first 2 weeks of life was the animals are precocial and born with well-developed central
only factor related to later proinsulin concentrations, irre- nervous, endocrine, and cardiovascular systems. Because
spective of size at birth.73 These landmark studies provide of the polytocous nature of rats and guinea-pigs, there may
the first experimental clinical evidence that faster postnatal be considerable variability in fetal and neonatal nutrient

supply to individual offspring within a litter. In contrast, is associated with adult central adiposity.82 Less severe
sheep pregnancies are usually singleton or twin.79 food restriction (to 50% of ad libitum intake) from day 15
In the maternal low-protein animal models there are of pregnancy to weaning has been shown to result in insu-
striking parallels with the development of type 2 diabetes linopenia and an age-dependent loss of glucose tolerance in
and/or the metabolic syndrome. In this model, rats are 12-month-old male offspring.83
fed a low-protein (5%-8%) diet during pregnancy that
restricts the growth of the offspring. If such offspring are Iron
cross-fostered to mothers fed a control diet (20% protein) Feeding rats and sheep iron-deficient diets during preg-
during lactation, they gain weight rapidly and, by weaning nancy leads to anemia and growth restriction of the fetus.
(21 days of age), have similar body weights to controls. The offspring have decreased iron concentrations in brain
However, this catch-up growth has a detrimental effect on tissue that cannot be normalized by iron treatment after
longevity. Permanent growth restriction results if maternal weaning. In addition, behavioral differences and alterations
protein restriction is continued during lactation, even after in cardiovascular development have been noted.78 Gesta-
the offspring are weaned to a control diet. Maternal protein tional conditions that compromise fetal iron status include
restriction has been shown to have long-term effects on maternal iron deficiency, diabetes mellitus, and hyperten-
the structure and function of individual organs. Beta-cell sion. Animal models have demonstrated that early iron
proliferation and islet size were significantly reduced in deficiency affects neuronal and glial energy metabolism,
the pancreas. However, a functional defect in glucose- monoamine metabolism, and myelination.19 It also induces
stimulated insulin secretion from islets of adult low-protein genomic changes coding for signal transduction, dendritic
offspring is only observed when an additional dietary insult structure, and energy metabolism that last well into adult-
such as high fat or sucrose feeding is introduced post hood, in spite of later iron repletion. Early iron sufficiency
natally.80 Maternal protein restriction has also been shown may be critical for long-term neurologic health.19
to have long-term effects on insulin-sensitive tissues. There Animal models are also used to study early life influ-
are structural and functional changes in the liver. Skeletal ences on appetite and feeding behavior. Studies of rodent
muscle is more sensitive to insulin in terms of its ability to models indicate that fetal undernutrition determines adult
stimulate glucose uptake. Adipocytes have an elevated basal adiposity. It is unclear whether the increase in central
and insulin-stimulated glucose uptake and increased levels adiposity is related to increased food intake or reduced
of insulin receptors.78 energy expenditure, although evidence exists to suggest
Nutrition restriction is also one of the most common that both may be involved. Rats subjected to intrauterine
experimental methods of fetal insult used for investigation protein restriction exhibited increased preference for high-
into the mechanisms of programmed hypertension. This was fat foods. Feeding of energy-dense foods to rats that were
one of the first methods to demonstrate that the timing of undernourished in utero promoted a greater degree of
the insult is critical to the programming response. A reduc- obesity than noted in animals with adequate nutrition in
tion of nephron number was observed when the nutrition fetal life. Programming of appetite may stem from remod-
insult coincided with the nephrogenic period. Slow fetal eling of hypothalamic structures that control feeding
growth also leads to alterations in the normal regulatory and programming of the expression of genes involved in
systems involved in the long-term control of blood pressure responses to orexigenic hormones. Recent work has defined
regulation. The pathogenesis of hypertension programmed circuitry in the hypothalamus that appears to mediate many
by in utero insult is multi-factorial and appears to involve of the effects of the adipocyte-derived hormone leptin on
intrinsic intrarenal defects and alterations in extrarenal feeding and glucose homeostasis. Evidence accumulated
regulatory systems critical to renal sodium excretion. A role primarily in mice indicates that these circuits develop as
for sex steroids was also demonstrated.81 projections from the arcuate nucleus of the hypothalamus.
Severe food restriction (to only 30% of ad libitum Leptin appears to play a crucial neurotrophic role governing
intake) during pregnancy has also been shown to induce development of these pathways that regulate food intake
severe intrauterine growth restriction in rats. In addition and adiposity.84 Early programming of appetite and obesity
to expressing hypertension in adulthood, these offspring is a complex phenomenon and the understanding of how
have increased fasting plasma insulin compared to control maternal nutrition determines later energy balance is at a
offspring. They also have increased food intake, consistent very early stage.85
with findings in humans suggesting early growth restriction

Animal Models Induced by Glucocorticoid Exposure Animal Models Induced by Surgical Manipulation
Several animal studies have shown that prenatal glucocor- Reduction in placental blood flow and consequent restric-
ticoid excess, either from endogenous overproduction from tion of oxygen, nutrient transport, and fetal growth can
maternal stress or through exogenous administration to the be produced in the rat by uterine artery ligation in late
mother or fetus, reduces birth weight and causes hyperten- gestation, uterine and umbilical artery embolism, or
sion, hyperglycemia, and behavioral abnormality in the carunclectomy.78,79 At 2 weeks of age, growth-retarded
offspring. These effects are transmitted across generations offspring in this model have reduced nephron number. This
without further exposure to glucocorticoids, an observa- nephron deficit was associated with impaired renal func-
tion that supports an epigenetic mechanism.86 tion at 2 weeks of age despite compensatory hypertrophy
Rat offspring that have been exposed to excess prenatal of remaining nephrons. Also, molecular analysis of skeletal
glucocorticoids undergo catch-up growth postnatally muscle from fetuses and 21-day-old offspring following
and normalize body weight by weaning. Outcomes from uterine artery ligation revealed that this mode of growth
such offspring when they are adults are consistent with restriction is associated with changes in both mitochon-
the hypothesis that rapid postnatal catch-up growth is drial gene expression and function. In female offspring,
deleterious to health.78 There are also accumulating data in after uterine artery ligation, growth restriction was associ-
rodents to suggest that prenatal glucocorticoid overexpo- ated with increased fasting blood glucose levels and with
sure programs an adverse adult cardiovascular, metabolic, impaired glucose tolerance and lower insulin secretion
neuroendocrine, and behavioral phenotype. The pheno- during a glucose tolerance test.78
typic outcome is similar to that of the low-protein model.
Fetal glucocorticoid overexposure may be a common Third and Future Generation Effects
mechanism for mediating fetal growth retardation and Adverse events during pregnancy can affect not only the
metabolic programming. This suggestion is based on the offspring of the pregnancy but also the next generation. In a
observation that dietary protein restriction during rat UK study examining the relationship of adult blood pressure
pregnancy reduces 11β-HSD2 activity. This enzyme, as to the mother’s fetal growth and size at birth, it was demon-
mentioned earlier, serves as a placental barrier to maternal strated that reduced fetal growth was associated with raised
glucocorticoids by rapidly metabolizing maternal glucocor- blood pressure in the next generation. 88 The researchers
ticoids to inert 11-keto forms to minimize fetal exposure to concluded that if the growth of a female fetus is restricted,
glucocorticoids.78 there are changes in her physiology and metabolism that
HPA regulation can be programmed by nutrient restric- lead to elevated blood pressure in the next generation.
tion. In fetal rats nutrient restriction results in blunted Adults who were born during the Dutch famine and
diurnal patterns of adrenocorticotropic hormone (ACTH) whose mothers had inadequate nutrition during the first 2
at 4 weeks postnatal age, alterations in basal plasma corticos- trimesters of pregnancy were more likely to be obese and
terone in adulthood, and altered basal HPA axis activity. 33 have abnormal lipid profiles than adults whose mothers had
Normally, the presence of 11β-HSD2 in the placental syncy- poor nutrition during the third trimester. 89 Infants born to
tiotrophoblasts protects the fetus from maternally derived mothers who were malnourished during the third trimester
glucocorticoids. Maternal glucocorticoid levels are much were leaner but had impaired glucose tolerance. Infants who
higher than fetal levels for most of pregnancy, so a relative were of normal birth weight born to severely malnourished
deficiency in placental 11β-HSD2 would put the fetus at mothers went on to deliver smaller babies in the next gener-
great risk of increased glucocorticoid exposure. 87 In some ation. One explanation for the intergenerational effects on
studies, a strong positive correlation has been reported birth weight is that the hormonal environment of the uterus
between placental 11β-HSD2 activity and fetal weight at of the undernourished mother may affect the reproduc-
term and birth weight in preterm infants. Maternal protein tive tract of the fetus. A possibly similar transgenerational
restriction in rodents reduces the activity of 11β-HSD2 in transmission of longevity propensity has been identified for
the placenta. 11β-HSD2 activity is influenced by multiple males in epidemiologic studies of food supply during early
maternal environmental factors and its modulation may spermatogenesis.90 Although the mechanisms behind these
be a mechanism through which a variety of environmental relationships are poorly understood, epigenetic dysregula-
insults exert their programming effects. 86 tion of the insulin-like growth factor 2 (IGF-2) gene has
been proposed. IGF-2 is a key factor in human develop-
ment and growth and is maternally imprinted. Individuals

who were prenatally exposed to malnutrition during the a driver of morbidity and mortality, as well as a potential
Dutch famine had less DNA methylation of the IGF-2 source of economic and political instability. Already, it is
gene compared with their unexposed same-sex siblings 6 estimated that today’s children in the United States will,
decades later.91 These data support the hypothesis that early for the first time in generations, not live longer than their
life environmental conditions cause epigenetic changes in parents.
humans that persist throughout life. The most frequent of the DOHaD-associated condi-
tions include hypertension, diabetes, coronary artery
Implications for Future Health disease, and the complications of obesity. For each of these
Dietary inadequacy, imbalance, or excess can all impact fetal conditions, primary prevention is far preferable to, and far
development. Some of these changes persist throughout less expensive than, treatment and secondary or tertiary
life or leave the individual vulnerable to later environ- preventive measures. However, medical treatments have
mental and dietary conditions that can adversely impact developed far faster than the behavioral, cultural, and social
health and longevity. Underlying fetal morphological and changes required to alter the trajectory of the development
functional changes related to pregnancy, postnatal diet, of these conditions. In light of this, medical solutions should
and various stressors and their adult consequences have be sought along with the broader public health initiatives
been delineated. Now we are beginning to understand the that will be required to improve the quality of life for the
molecular determinants of these changes and the dietary developing fetus and neonate.
and environmental factors controlling them. Both over- and
undernutrition in utero and in early life can increase risks Implications for Current Practice
for adverse metabolic outcomes including type 2 diabetes, What implications can be drawn from current knowledge
CVD, and obesity. The seriousness of these events is ampli- in this area for nutrition advice in the practice of obstet-
fied by evidence that certain potentially adverse epigenetic rics, pediatrics, neonatology, and public health? Given that
effects induced in the female fetus may persist through at preconceptual nutrition status is at least as important as
least an additional generation. nutrition status during pregnancy, planned pregnancies in
Current agricultural production and food distribution mature women with good nutrition status is a highly desir-
and changes in diet and activity patterns are associated with able starting point. This requires approaches to maximizing
a historically high prevalence of obesity, diabetes, and their nutrition status of fertile women of childbearing age beyond
complications. As many as a third of today’s children in an exclusive focus on pregnancy and lactation, especially
some states are destined to become diabetic, given obesity where pregnancies are unlikely to be planned. During
rates and genetic predisposition. In developed countries, pregnancy, adequate energy, protein, and micronutrients,
many of these may now be in the second or third genera- including methyl donors, can be expected to have a salutary
tion of families expressing this phenotype. Many come effect on developmental outcomes related to fetal nutrition
from environments with a history of food and micronu- status. There is some evidence to indicate excesses of fat and
trient scarcity. In many parts of the world, these contrasting protein during pregnancy are to be avoided, and long-chain
nutrition states coexist contemporaneously. In the course n-3 fatty acids, especially docosahexaneoic acid, may have
of a lifetime, individuals can be expected to pass from beneficial impact on mental, visual, and behavioral develop-
one dietary camp to the other, magnifying the potential ment. Monitoring fetal growth, maternal weight gain, and
adverse developmental impacts inherent to both. In India maternal blood sugar can detect deviations from expected
we now have the phenomenon of the “thin, fat Indian” that developmental patterns.
has given India the distinction of the world’s highest rate For term infants, it appears to be desirable to continue
of diabetes, despite a lower ranking for obesity. Based on on a relative growth trajectory (percentile) similar to
what is emerging from the DOHaD literature and the inves- that experienced in utero. Traditionally, “normalizing”
tigation of epigenetics, we can expect the consequences of the growth of in utero growth-retarded infants has been
dietary scarcity and surfeit and their coexistence to exert accepted as the de facto goal of good nutrition. Based on
their adverse effects in future generations in the absence of more recent findings, these children may be metabolically
fresh insights on how to intervene to break this cycle. An more suited to a slower rate of growth. Percentile crossing in
inability to meet potential major population increases in infancy, and later, appears to increase risk of the DOHaD-
health care costs related to morbidity patterns associated associated conditions. In the first 2 weeks of life and after
with DOHaD-associated conditions could itself become about 4 months of age, breastfeeding may lead to less weight

gain than formula feeding and can be viewed as particu- growth. The recent U.S. data from Ehrenkranz on the posi-
larly beneficial in this population. An important medical tive developmental outcome of encouraging early growth in
concern in such infants is to support brain development, premature infants dictates against any go-slow approach for
but most of the data on the importance of early nutrition for these infants to possibly reduce markers of future cardio-
brain development come from studies of premature infants. vascular risk (to below values observed in healthy term
It remains largely unknown if nutritional supplementation infants).93
and growth acceleration are beneficial in this regard for term
growth-retarded infants. For infants in underdeveloped Future Research Needs
countries who develop extrauterine growth retardation This is a rich area for potential investigation at all levels
later in infancy and early childhood, short-term nutritional of biological research. At the molecular level, we need
supplementation has been found to reduce acute morbidity specific descriptions of the molecular changes underlying
and mortality (as well as progression of their malnutrition). the DOHaD phenomenon in various organs and the mech-
Premature infants, especially extremely low birth anisms controlling these molecular changes, including
weight (ELBW) infants, are at high risk of extrauterine nutrition influences. In physiology, there remain opportu-
growth retardation. Their nutrition requirements exceed nities to explore the developmental impact of organ-specific
those of term infants, given their immature development effects of general and nutrient-specific under- and overnu-
and body composition. In these infants, developmental trition at various stages of fetal and infant development.94
achievement and reduced neurological complications are Beardsall et al lists opportunities for studies of glucose
associated with higher growth rates. Premature infants, control in the fetus relative to body composition, pancre-
both in-hospital and following hospital discharge, are very atic development, and in utero programming of glucose
responsive to nutritional supplementation. Data from Lucas control.94 The epidemiologists, who did much to initiate
and Singhal have been taken by some to demonstrate that this field of research, can tell us more about the simi-
rapid growth should not be encouraged for this population, larities and differences of effects of different stressors (eg,
based on higher blood pressure, leptin, blood lipids, and gestational malnutrition versus diabetes) on the expres-
split proinsulin values in premature infants when fed prema- sion of the DOHaD-related morbidity. More remains
ture formula compared to term formula or human milk. to be done to elucidate the relation of intrauterine and
However, in their studies, these markers of cardiovascular postnatal effects (and their interaction). Clinical investi-
risk were not elevated above those for typical term infants. gators can prospectively study the developmental impact
These same investigators demonstrated developmental of growth acceleration in various populations and age
disadvantages in these infants at least through childhood groups of infants and young children looking at infection
from receiving standard term formulas versus more nutrient- and immune outcomes, cardiovascular and metabolic risk
rich premature formula. Interestingly, while premature factors, bone health, and neurodevelopment. There may be
infants fed premature formula grew faster than breastfed better versus worse times or target populations for catch-
infants, their neuro-developmental status was not better up growth. There appears to be great potential in exploring
than that of breastfed infants. Bone mineralization is very early or later drug or hormonal interventions to reverse
improved in premature infants given mineral-rich prema- the underlying molecular basis of some DOHaD-associ-
ture and post-discharge formulas compared to standard ated conditions. For example, administration of leptin (a
term formulas. However, this may not persist into pleomorphic hormone during gestation) in late gestation
adulthood.92 or shortly after birth may reverse the development of the
Human milk with human milk fortifier is the current expected postnatal phenotype of the growth-retarded
recommended approach for small premature infants as it can fetus or alter the development of appetite regulation.95,96
preserve the beneficial nutrition and immunologic effects There is also the potential to alter the epigenetic pheno-
of human milk while providing additional energy, protein, type through controlled exposure to methyl donors or
minerals, and other micronutrients. For formula-fed prema- other agents directly affecting epigenetic mechanisms.97,98
ture infants, premature, not term, formula is recommended.
However, there is no evidence postdischarge formulas have
improved developmental outcomes versus infants fed stan-
dard term formulas after hospital discharge. However, in the
smallest infants, they have been observed to enhance head

10. Grillo MA, Lanza A, Colombatto S. Transport of amino

Test Your Knowledge Questions acids through the placenta and their role. Amino Acids.
1. The dominant fuel source for the healthy fetus is: 2008;34(4):517–523.
A. Fatty acids because they are the richest source of 11. Myers RE, Hill DE, Holt AB, Scott RE, Mellits ED, Cheek DB.
energy Fetal growth retardation produced by experimental placental
B. Amino acids because they promote rapid growth insufficiency in the rhesus monkey. I. Body weight, organ size.
C. Galactose, because the fetus cannot utilize glucose Biol Neonate. 1971;18(5):379–394.
12. Howarth C, Gazis A, James D. Associations of Type 1 diabetes
D. Glucose transported from the maternal circulation mellitus, maternal vascular disease and complications of preg-
2. Nutrition programming is a process that: nancy. Diabet Med. 2007;24(11):1229–1234.
A. Is specific to the fetus 13. Kanaka-Gantenbein C, Mastorakos G, Chrousos GP. Endo-
B. Occurs only in animals crine-related causes and consequences of intrauterine growth
C. Occurs early in life and may extend beyond a single retardation. Ann N Y Acad Sci. 2003;997:150–157.
14. Ward JW, Wooding FB, Fowden AL. Ovine feto-placental
generation
metabolism. J Physiol. 2004; 554(Pt 2):529–541.
D. Is a transient response to nutrient availability 15. de Onis M, Villar J, Gulmezoglu M. Nutritional interventions
3. Upward growth percentile-crossing in infancy and to prevent intrauterine growth retardation: evidence from
early childhood: randomized controlled trials. Eur J Clin Nutr. 1998;52(Suppl
A. Reduces short-term infectious mortality and leads 1):S83–S93.
to lower adult blood pressure 16. Shiell AW, Campbell DM, Hall MH, Barker DJ. Diet in late
pregnancy and glucose-insulin metabolism of the offspring 40
B. Has been associated with increased risk for devel- years later. BJOG 2000;107(7):890–895.
opment of features of the metabolic syndrome 17. McMillen IC, MacLaughlin SM, Muhlhausler BS, Gentili
C. Helps prevent subsequent rebound obesity S, Duffield JL, Morrison JL. Developmental origins of adult
D. Improves glucose control later in life health and disease: the role of periconceptional and foetal
nutrition. Basic Clin Pharmacol Toxicol. 2008;102(2):82–89.
18. Wu G, Bazer FW, Cudd TA, Meininger CJ, Spencer
See p. 487 for answers.
TE. Maternal nutrition and fetal development. J Nutr.
2004;134(9):2169–2172.
References 19. Georgieff MK. The role of iron in neurodevelopment: fetal
1. Pardi G, Cetin I. Human fetal growth and organ devel- iron deficiency and the developing hippocampus. Biochem Soc
opment: 50 years of discoveries. Am J Obstet Gynecol. Trans. 2008;36(pt 6):1267–1271.
2006;194(4):1088–1099. 20. Gluckman PD, Hanson MA, Cooper C, Thornburg KL.
2. Hay WW Jr. Placental-fetal glucose exchange and fetal Effect of in utero and early-life conditions on adult health and
glucose metabolism. Trans Am Clin Climatol Assoc. disease. N Engl J Med. 2008;359(1):61–73.
2006;117:321–340. 21. Scholl TO. Maternal nutrition before and during pregnancy.
3. Hay WW Jr. Recent observations on the regulation of fetal Nestle Nutr Workshop Ser Pediatr Program. 2008;61:79–89.
metabolism by glucose. J Physiol. 2006;572(pt 1):17–24. 22. Martin-Gronert MS, Ozanne SE. Maternal nutrition during
4. Battaglia FC. Clinical studies linking fetal velocimetry, blood pregnancy and health of the offspring. Biochem Soc Trans.
flow and placental transport in pregnancies complicated 2006;34(pt 5):779–782.
by intrauterine growth retardation (IUGR). Trans Am Clin 23. Morton SMB. Maternal nutrition and fetal growth and devel-
Climatol Assoc. 2003;114:305–313. opment. In: Gluckman P, Hanson M, eds. Developmental
5. Battaglia FC. In vivo characteristics of placental amino acid Origins of Health and Disease. UK: Cambridge Univer-
transport and metabolism in ovine pregnancy--a review. sity Press; 2006:98–129.
Placenta. 2002;23(Suppl A):S3–S8. 24. Lanham SA, Roberts C, Cooper C, Oreffo RO. Intrauterine
6. Battaglia FC, Wilkening R, Meschia G. Unique organ specific programming of bone. Part 1: alteration of the osteogenic
characteristics of amino acid metabolism in early develop- environment. Osteoporos Int. 2008;19(2):147–156.
ment. Trans Am Clin Climatol Assoc. 1995;106:141–149. 25. Lanham SA, Roberts C, Perry MJ, Cooper C, Oreffo RO.
7. Barry JS, Anthony RV. The pregnant sheep as a model for Intrauterine programming of bone. Part 2: alteration of skel-
human pregnancy. Theriogenology 2008;69(1):55–67. etal structure. Osteoporos Int. 2008; 19(2):157–167.
8. Regnault TR, Friedman JE, Wilkening RB, Anthony RV, Hay 26. Thomas M, Weisman SM. Calcium supplementation during
WW Jr. Fetoplacental transport and utilization of amino acids pregnancy and lactation: effects on the mother and the fetus.
in IUGR--a review. Placenta. 2005;26(Suppl A):S52–S62. Am J Obstet Gynecol. 2006;194(4):937–945.
9. Sparks JW, Hay WW Jr, Bonds D, Meschia G, Battaglia 27. Rao R, Georgieff MK. Iron in fetal and neonatal nutrition.
FC. Simultaneous measurements of lactate turnover rate Semin Fetal Neonatal Med. 2007;12(1):54–63.
and umbilical lactate uptake in the fetal lamb. J Clin Invest. 28. Yajnik CS, Deshmukh US. Maternal nutrition, intrauterine
1982;70(1):179–192. programming and consequential risks in the offspring. Rev
Endocr Metab Disord. 2008;9(3):203–211.

29. Ramakrishan U, Manjrekar R, Rivera J, Gonzales-Cossio 47. Forsen T, Osmond C, Eriksson JG, Barker DJ. Growth
T. Micronutrients and pregnancy outcome : A review of the of girls who later develop coronary heart disease. Heart.
literature. Nutr Res. 1999;19:103–159. 2004;90(1):20–24.
30. Shah PS, Ohlsson A. Effects of prenatal multimicronutrient 48. Huxley RR, Shiell AW, Law CM. The role of size at birth and
supplementation on pregnancy outcomes: a meta-analysis. postnatal catch-up growth in determining systolic blood
CMAJ. 2009;180(12):E99–108. pressure: a systematic review of the literature. J Hypertens.
31. Fowden AL, Ward JW, Forhead A. Control of fetal metabo- 2000;18(7):815–831.
lism: relevance to developmental origins of health and disease. 49. Newsome CA, Shiell AW, Fall CH, et al. Is birth weight related
In: Gluckman P, Hanson M, eds. Developmental Origins to later glucose and insulin metabolism?—A systematic
of Health and Disease. UK: Cambridge University Press; review. Diabet Med. 2003;20(5):339–348.
2006:143–158. 50. Dabelea D, Pettitt DJ. Intrauterine diabetic environment
32. Fowden AL, Forhead A. The role of hormones in intrauterine confers risks for type 2 diabetes mellitus and obesity in the
development. In: Barker DJP, ed. Fetal Origins of Cardiovas- offspring, in addition to genetic susceptibility. J Pediatr Endo-
cular and Lung Disease. New York, NY: Marcel Dekker Inc; crinol Metab. 2001;14(8):1085–1091.
2000:199–228. 51. McCance DR, Pettitt DJ, Hanson RL, et al. Birth weight
33. Sloboda D, Newnham J, Moss T, Challis J. The fetal hypo- and non-insulin dependent diabetes: thrifty genotype,
thalamic-pituitary-adrenal axis: relevance to developmental thrifty phenotype, or surviving small baby genotype? BMJ.
origins of health and disease. In: Gluckman P, Hanson M, eds. 1994;308(6934):942–945.
Developmental Origins of Health and Disease. UK: Cambridge 52. Fall CH, Osmond C, Barker DJ, et al. Fetal and infant
University Press; 2006:191-205. growth and cardiovascular risk factors in women. BMJ.
34. Dobbing J, Sands J. Comparative aspects of the brain growth 1995;310(6977):428–432.
spurt. Early Hum Dev. 1979;3(1):79–83. 53. Eriksson JG, Forsen T, Tuomilehto J, Winter PD, Osmond
35. O’Conner TG, Heron J, Golding J, Glover V. Maternal C, Barker DJ. Catch-up growth in childhood and death
antenatal anxiety and behavioural/emotional problems in from coronary heart disease: longitudinal study. BMJ.
children: A test of a programming hypothesis. J Child Psychol 1999;318(7181):427–431.
Psychiatry. 2003;44:1025–1036. 54. Eriksson JG, Forsen T, Tuomilehto J, Osmond C, Barker DJ.
36. Welberg L, Seckl J. Prenatal stress, glucocorticoids Early growth and coronary heart disease in later life: longitu-
and the programming of the brain. J Neuroendocrinol. dinal study. BMJ. 2001;322(7292):949–953.
2001;13(2):113–128. 55. Rich-Edwards JW, Kleinman K, Michels KB, et al. Longi-
37. Seckl JR, Holmes MC. Mechanisms of disease: glucocorti- tudinal study of birth weight and adult body mass index in
coids, their placental metabolism and fetal ‘programming’ predicting risk of coronary heart disease and stroke in women.
of adult pathophysiology. Nat Clin Pract Endocrinol Metab. BMJ. 2005;330(7500):1115.
2007;3(6):479–488. 56. Hales CN, Barker DJ. Type 2 (non-insulin-dependent)
38. Adam TC, Epel ES. Stress, eating and the reward system. diabetes mellitus: the thrifty phenotype hypothesis. Diabeto-
Physiol Behav. 2007;91(4):449–458. logia. 1992;35(7):595–601.
39. McCance RA. Food, growth, and time. Lancet. 57. Ozanne SE, Hales CN. Early programming of glucose-insulin
1962;2(7258):671–676. metabolism. Trends Endocrinol Metab. 2002;13(9):368–373.
40. Widdowson EM, McCance RA. A review: new thoughts on 58. Lucas A. Programming by early nutrition in man. Ciba Found
growth. Pediatr Res. 1975;9(3):154–156. Symp. 1991;156:38–50.
41. Barker DJ, Osmond C. Infant mortality, childhood nutrition, 59. Monteiro PO, Victora CG. ��
Rapid growth in infancy and child-
and ischaemic heart disease in England and Wales. Lancet. hood and obesity in later life—a systematic review. Obes Rev.
1986;1(8489):1077–1081. 2005;6(2):143–154.
42. Barker DJ, Winter PD, Osmond C, Margetts B, Simmonds SJ. 60. Baird J, Fisher D, Lucas P, et al. Being big or growing fast:
Weight in infancy and death from ischaemic heart disease. systematic review of size and growth in infancy and later
Lancet. 1989;2(8663):577–580. obesity. BMJ. 2005;331(7522):929.
43. Barker DJP, Osmond C, Simmonds SJ, Wield GA. The rela- 61. Stettler N, Zemel BS, Kumanyika S, Stallings VA. Infant
tion of small head circumference and thinness at birth to weight gain and childhood overweight status in a multicenter,
death from cardiovascular disease in adult life. Br Med J. cohort study. Pediatrics. 2002;109(2):194–199.
1993;306:422–426. 62. Stettler N, Kumanyika SK, Katz SH, Zemel BS, Stallings
44. Frankel S, Elwood P, Sweetnam P, Yarnell J, Smith GD. Birth- VA. Rapid weight gain during infancy and obesity in young
weight, body-mass index in middle age, and incident coronary adulthood in a cohort of African Americans. Am J Clin Nutr.
heart disease. Lancet. 1996; 348(9040):1478–1480. 2003;77(6):1374–1378.
45. Stein CE, Fall CH, Kumaran K, Osmond C, Cox V, Barker 63. Dennison BA, Edmunds LS, Stratton HH, Pruzek RM. Rapid
DJ. Fetal growth and coronary heart disease in south India. infant weight gain predicts childhood overweight. Obesity.
Lancet. 1996;348(9037):1269–1273. 2006;14(3):491–499.
46. Leon DA, Lithell HO, Vagero D, et al. Reduced fetal growth 64. Stettler N, Stallings VA, Troxel AB, et al. Weight gain in the
rate and increased risk of death from ischaemic heart disease: first week of life and overweight in adulthood: a cohort study
cohort study of 15,000 Swedish men and women born 1915- of European American subjects fed infant formula. Circula-
29. BMJ. 1998;317(7153):241–245. tion. 2005;111(15):1897–1903.

65. Singhal A, Cole TJ, Fewtrell M, et al. Promotion of faster 82. Vickers MH, Breier BH, Cutfield WS, Hofman PL, Gluckman
weight gain in infants born small for gestational age: is PD. Fetal origins of hyperphagia, obesity, and hypertension
there an adverse effect on later blood pressure? Circulation. and postnatal amplification by hypercaloric nutrition. Am J
2007;115(2):213–220. Physiol Endocrinol Metab. 2000;279(1):E83–E87.
66. Ben Shlomo Y, McCarthy A, Hughes R, Tilling K, Davies D, 83. Woodall SM, Johnston BM, Breier BH, Gluckman PD.
Smith GD. Immediate postnatal growth is associated with Chronic maternal undernutrition in the rat leads to delayed
blood pressure in young adulthood: the Barry Caerphilly postnatal growth and elevated blood pressure of offspring.
Growth Study. Hypertension. 2008;52(4):638–644. Pediatr Res. 1996;40(3):438–443.
67. Cianfarani S, Germani D, Branca F. Low birthweight and adult 84. Bouret SG, Simerly RB. Developmental programming of
insulin resistance: the “catch-up growth” hypothesis. Arch Dis hypothalamic feeding circuits. Clin Genet. 2006;70(4):295–301.
Child. Fetal Neonatal Ed. 1999;81(1):F71–F73. 85. Langley-Evans SC, Bellinger L, McMullen S. Animal models
68. Gluckman PD, Hanson MA. The consequences of being born of programming: early life influences on appetite and feeding
small—an adaptive perspective. Horm Res. 2006;65(Suppl behaviour. Matern Child Nutr. 2005;1(3):142–148.
3):5–14. 86. Drake AJ, Tang JI, Nyirenda MJ. Mechanisms underlying the
69. Singhal A, Lucas A. Early origins of cardiovas- role of glucocorticoids in the early life programming of adult
cular disease: is there a unifying hypothesis? Lancet. disease. Clin Sci. (Lond) 2007;113(5):219–232.
2004;363(9421):1642–1645. 87. Fowden AL, Forhead AJ. Endocrine mechanisms of intra-
70. Singhal A, Cole TJ, Fewtrell M, Lucas A. Breastmilk uterine programming. Reproduction. 2004;127(5):515–526.
feeding and lipoprotein profile in adolescents born preterm: 88. Barker DJ, Shiell AW, Barker ME, Law CM. Growth in utero
follow-up of a prospective randomised study. Lancet. and blood pressure levels in the next generation. J Hypertens.
2004;363(9421):1571–1578. 2000;18(7):843–846.
71. Singhal A, Cole TJ, Lucas A. Early nutrition in preterm infants 89. Stein AD, Lumey LH. The relationship between maternal
and later blood pressure: two cohorts after randomised trials. and offspring birth weights after maternal prenatal famine
Lancet. 2001;357(9254):413–419. exposure: the Dutch Famine Birth Cohort Study. Hum Biol.
72. Singhal A, Farooqi IS, O’Rahilly S, Cole TJ, Fewtrell M, Lucas 2000;72(4):641–654.
A. Early nutrition and leptin concentrations in later life. Am J 90. Pembrey ME, Bygren LO, Kaati G, et al. Sex-specific, male-
Clin Nutr. 2002;75(6):993–999. line transgenerational responses in humans. Eur J Hum Genet.
73. Singhal A, Fewtrell M, Cole TJ, Lucas A. Low nutrient intake 2006;14(2):159–166.
and early growth for later insulin resistance in adolescents 91. Heijmans BT, Tobi EW, Stein AD, et al. Persis-
born preterm. Lancet. 2003;361(9363):1089–1097. tent epigenetic differences associated with prenatal
74. Lucas A, Fewtrell MS, Morley R, et al. Randomized trial of exposure to famine in humans. Proc Natl Acad Sci. USA
nutrient-enriched formula versus standard formula for post- 2008;105(44):17046–17049.
discharge preterm infants. Pediatrics. 2001;108(3):703–711. 92. Fewtrell MS, Williams JE, Singhal A, Murgatroyd PR, Fuller
75. Chan GM. Growth and bone mineral status of discharged N, Lucas A. Early diet and peak bone mass: 20 year follow-up
very low birth weight infants fed different formulas or human of a randomized trial of early diet in infants born preterm.
milk. J Pediatr. 1993;123(3):439–443. Bone. 2009;45(1):142–149.
76. Fewtrell MS, Prentice A, Jones SC, et al. Bone mineralization 93. Ehrenkranz RA, Dusick AM, Vohr BR, Wright LL, Wrage LA,
and turnover in preterm infants at 8-12 years of age: the effect Poole WK. Growth in the neonatal intensive care unit influ-
of early diet. J Bone Miner Res. 1999;14(5):810–820. ences neurodevelopmental and growth outcomes of extremely
77. Victora CG, Barros FC, Horta BL, Martorell R. Short-term low birth weight infants. Pediatrics. 2006;117(4):1253–1261.
benefits of catch-up growth for small-for-gestational-age 94. Beardsall K, Diderholm BM, Dunger DB. Insulin and carbo-
infants. Int J Epidemiol. 2001;30(6):1325–1330. hydrate metabolism. Best Pract Res Clin Endocrinol Metab.
78. Ozanne SE. Metabolic programming in animals. Br Med Bull. 2008; 22(1):41–55.
2001;60:143–152. 95. Alexe DM, Syridou G, Petridou ET. Determinants of early life
79. Armitage JA, Khan IY, Taylor PD, Nathanielsz PW, Poston L. leptin levels and later life degenerative outcomes. Clin Med
Developmental programming of the metabolic syndrome by Res. 2006;4(4):326–335.
maternal nutritional imbalance: how strong is the evidence 96. Palou A, Pico C. Leptin intake during lactation prevents
from experimental models in mammals? J Physiol. 2004;561(Pt obesity and affects food intake and food preferences in later
2):355–377. life. Appetite. 2009;52(1):249–252.
80. Desai M, Crowther NJ, Lucas A, Hales CN. Organ-selective 97. Stocker CJ, Cawthorne MA. The influence of leptin on
growth in the offspring of protein-restricted mothers. Br J early life programming of obesity. Trends Biotechnol.
Nutr. 1996;76(4):591–603. 2008;26(10):545–551.
81. Ojeda NB, Grigore D, Alexander BT. Developmental 98. Zeisel SH. Nutrigenomics and metabolomics will change
programming of hypertension: insight from animal models of clinical nutrition and public health practice: insights from
nutritional manipulation. Hypertension. 2008; 52(1):44–50. studies on dietary requirements for choline. Am J Clin Nutr.
2007;86(3):542–548.

11
Human Milk

Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 120 1. List 3 benefits of the use of human milk for the infant.
Breastfeeding. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 121 2. Describe the 10 steps to successful breastfeeding.
3. State the American Academy of Pediatrics recom-
Preterm Breast Milk. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 122
mendation for the use of vitamin D with an exclusively
Fortification . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 122
human milk fed infant.
Banked Human Milk. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 123
Vitamin D . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 123 Introduction
Growth of Breastfed Infants. . . . . . . . . . . . . . . . . . . . . . . 123 Breastfeeding is advocated throughout the world. The
Breast Milk Safety and Administration . . . . . . . . . . . . . . 124 American Academy of Pediatrics (AAP), the Canadian
Breast Milk and Maternal Medications . . . . . . . . . . . . . . 125
Pediatric Society, the International Pediatric Associa-
tion, the World Health Organization (WHO), and others
all have policies that recommend breastfeeding as the
preferred method of feeding for infants.1–4 The Healthy
People 2010 goals proposed by the United States Surgeon
General include breastfeeding initiation rates of 75% and
continued breastfeeding rates of 50% at 6 months and 25%
at 12 months5 which are close to being achieved nationally
although significant state-to-state variability remains.6
The advantages of breastfeeding are numerous and
include nutritional, immunologic, bonding, and societal
benefits (Table 11-1). Some of this may be attributed to the
establishment of beneficial bacteria in the gastrointestinal
tract of the infant through the use of breast milk which
contains probiotics, especially Bifidobacterium bifidum and
Lactobacillus. Breastmilk also contains growth factors,
including oligosaccharides, that promote the growth of these
bacteria and are generally called probiotics.7 The bifidus flora
of the breastfed infant is thought to activate the immune
system and defend against pathogens.8 The colonization of
breastfed infants’ gastrointestinal tracts has been different
than that of formula-fed infants. This may be changing as
prebiotics and probiotics have now been added to some infant
formulas in an effort to duplicate this benefit.9
120
HUMAN MILK 121
Table 11-1 Benefits of Breastfeeding Table 11-2 Ten Steps to Successful Breastfeeding3
Improved mother-infant bonding Every facility providing maternity services and care for
newborn infants should:
More rapid uterine involution
1. Have a written breastfeeding policy that is routinely communicated
Postpartum weight loss to all health care staff.
Mother
Decreased incidence of premenopausal breast cancer 2. Train all health care staff in skills necessary to implement this policy.
Decreased incidence of ovarian cancer 3. Inform all pregnant women about the benefits and management
of breastfeeding.
May protect against development of osteoporosis
4. Help mothers initiate breastfeeding within 30 minutes after birth.
Antibacterial factors: Secretory IgA, IgM, IgG, IgD,
Bifidobacterium growth factor, lactoferrin, complement 5. Show mothers how to breastfeed and how to maintain lactation
C1-9, factor binding proteins, lysozyme, lactoperoxidase, even if they should be separated from their infants.
macrophages, neutrophils, B and T lymphocytes, lipid, 6. Give newborn infants no food or drink other than breast milk,
growth factors, nucleotides, vitamins A, E, C1,10,11 unless medically indicated.
Decreased incidence of gastrointestinal illness, respiratory 7. Practice rooming in—allow mothers and infants to remain
Infant illness, otitis media, urinary tract infections, sudden infant together—24 hours a day.
death syndrome12–17
8. Encourage breastfeeding on demand.
Lower incidence of allergies, even with a family history 9. Give no artificial teats or pacifiers (also called dummies or
of atopy18–22 soothers) to breastfeeding infants.
May have lower incidence of later chronic diseases such 10. Foster the establishment of breastfeeding support groups and
as Crohn’s disease, lymphoma, specific genotypes of refer mothers to them on discharge from the hospital or clinic.
diabetes mellitus type 123–26
Reprinted with permission from Baby-Friendly USA Web site,
Reduced time off work for mothers of breastfed infants http://www.babyfriendlyusa.org. Accessed December 31, 2009.
Society for infant’s illness
Reduced health care costs1
The management of the breastfeeding dyad requires
skill and knowledge to achieve a successful outcome for
For the premature infant the use of breast milk may both the mother and infant. Unfortunately, there are still
offer a particular advantage in decreasing the incidence of reports of hypernatremic dehydration among exclusively
necrotizing enterocolitis (NEC).27–29 Research by Meinzen- breastfed neonates due to inadequate intake with poten-
Derr suggested a dose-related association of breast milk tially devastating consequences. The recommendation from
feeding with a reduction in risk of NEC or death in extremely analyses of these reports is for close and regular follow-up of
low birthweight infants.28 However, in a randomized trial of breastfed infants by a health care provider. 33–35
extremely premature infants, there was no difference in the Evidence-based guidelines from the Academy of
incidence of NEC between the group of infants fed donor Breastfeeding Medicine are available that provide recom-
human milk and those fed preterm formula. 30 Kleinman, mendations for best practice in the management of term,
Walker, and Schanler have suggested a protective effect near-term (35–37 week), and premature infants. 36–38 Late
against infection in premature infants who are fed their preterm (near-term) infants with gestational ages between
own mother’s milk. 31,32 34–36 6/7 weeks are at particular risk for lactation problems
as these infants may appear to be competent early in breast-
Breastfeeding feeding when they are not and may fool even experienced
In 1991 the WHO and United Nations International mothers. These infants may have difficulty extracting milk
Children’s Fund (UNICEF) established an international and stimulating the mother to produce an adequate milk
program to promote breastfeeding, the Baby Friendly supply. 39 Late preterm infants are more likely to require
Hospital Initiative (BFHI).3 This incorporated a 10-step rehospitalization in the first 2 weeks after birth and have
program to promote and support breastfeeding (Table 11-2). poor lactation outcomes such as early cessation of breast-
feeding, jaundice, dehydration, and poor growth.40 Their
mothers are also at risk for delayed lactogenesis.40 Meier et
al. and Wight describe strategies to work with the mother-
infant dyad in establishing and maintaining maternal milk
supply and adequate intake for the infant. 39,40

The mothers of premature or sick term infants have the Table 11-3 Nutrient Composition of Human Milk and Fortified Human Milk
challenge of pumping breast milk. Strategies to facilitate Based on Intake of 150 mL/kg54–59
pumping are available.41 A discussion of these is beyond the Calories Protein Calcium Phosphorus
scope of this chapter and interested readers are referred to Preterm Milk 101 cal/kg 2.1 g/kg 37.5 mg/kg 19.5 mg/kg
Term Milk 102 cal/kg 1.5 g/kg 42 mg/kg 21 mg/kg
the book by Wight et al and to several works by Paula Meier
Preterm milk with
PhD RN. She has written extensively on the promotion Enfamil® Human mixed to 172.5 mg/
of lactation in an inner-city newborn intensive care unit 3.75 g/kg 94.5 mg/kg
Milk Fortifier with 120 cal/kg kg
(NICU) setting,42 evaluation of the efficiency of different iron
breast pumps,43 and the role of nipple shields in facilitating Preterm milk with
Similac® Human 120 cal/kg 3.6 g/kg 207 mg/kg 117 mg/kg
milk transfer for preterm infants.44 Milk Fortifier
Preterm/term 4.35 g/kg
Preterm Breast Milk milk 1:1 with
125 cal/kg
preterm milk
174 mg/kg 95.6 mg/kg
Breast milk from mothers of preterm infants often may Similac® Special 3.75 g/kg
Care® 30 cal/oz term milk
have increased amounts of protein, sodium, chloride, and
Prolact+4 Fortifies up Added Added
iron for 3 weeks45 to approximately 1 month after delivery.46 120 cal/kg
H2MF™ to 3.45 g/kg minerals minerals
For optimal growth preterm infants need augmentation of
Recommended
breast milk due to their increased needs for protein, phos- Intake for 120 cal/kg 3-4 g/kg/d
120-230 60-140 mg/
phorus, calcium, and zinc.47–49 Previously it was thought mg/kg kg
preterm infants
that, at least in terms of bone mineralization, as infants born
prematurely grew into childhood their bone density would
normalize. A new study by Chan et al demonstrated that Fortification
premature infants, < 1.5 kg at birth, continue to show lower Sometimes due to a disease process a term infant
bone mineral content and density and tend to be signifi- cannot tolerate full volume feedings. In this case higher
cantly smaller for age than their term counterparts when calorie human milk can be made, but not using the same
studied at 5 to 9 years of age. 50 Fortification is an accept- products that are used for the preterm infant as the levels
able method of augmenting breast milk for a premature of calcium and phosphorus may be too high. An individual-
infant.27,47,48 ized approach is necessary based on the prescribed volume
There are different methods of fortification that can be and the calorie, protein, and mineral needs for that infant.
utilized including powdered human milk fortifier or mixing Term infant formula may be used to augment breast milk to
higher calorie (30 calorie) premature formula in a 1:1 keep a good protein, carbohydrate, and lipid ratio.
mixture or other ratios with breast milk. The final nutrient A concept sometimes called lacto engineering may also
content can vary significantly depending on the fortifier be used to increase calories, using the higher calorie hind
selected (Table 11-3). Many prefer human milk fortifier in milk to augment the caloric content of the milk. This will not
order to use the maximal amount of human milk. There is an alter the need for fortification for a preterm infant, but it can
increase in osmolality when the fortifier is added to breast help supply additional calories. A creamatocrit is a measure-
milk, 51 but there appears to be no difference in the inci- ment for estimating the fat content and therefore the caloric
dence of side effects,48 NEC, 52 or altered gastric emptying. 53 content of a human milk sample. A microhematocrit tube is
A liquid fortifier, Prolact+4 H 2MF™, is made from human filled with milk and spun in a centrifuge. The layer of fat is
milk and comes as +6, +8, and +10 with increasing amounts measured as with a blood hematocrit.60,61 Regression equa-
of calories and protein. 54 This product is much more expen- tions are as follows:
sive than traditional human milk fortifiers. • Fresh breast milk: Energy(kcal/dL) = 5.99 × creamat-
ocrit (%) + 32.5 and
• Frozen breast milk: Energy (kcal/dL) = 6.20 × creama-
tocrit (%) + 35.1.62
Research is being conducted on the content of hind
milk. There appear to be no significant differences in cream-
atocrit values of the milk of mothers of preterm, small for
gestational age, and term infants.63 The creamatocrit values
appear to increase until 16 weeks postpartum and then

HUMAN MILK 123
decline.63 The circadian variation of fat content in human beginning in the first 2 months after birth.77 Rickets, an
milk has been evaluated, and although spot values may be example of extreme vitamin D deficiency, continues to
misleading, consistent sampling does show a trend in 2 be reported in the United States and other Western coun-
studies for samples expressed at night to have greater fat tries, predominantly in the breastfed population and in
content.64,65 The vitamin A and E levels also appear to be 1.6 infants with darker skin pigmentation.78,79 Historically we
times higher in hind than foremilk, something to consider relied upon the effect of sunlight on our skin to stimulate
when planning fortification.66 Medela has a commercial, synthesis of vitamin D from cholesterol as our main source.
easy-to-use creamtocrit instrument that also computes There is normally very little vitamin D in breast milk. In
the calories per ounce and fat grams.67 Validation studies a lactating mother supplemented with 400 International
and tests using creamatocrit measurements performed by Units of vitamin D, the vitamin content of her own milk
mothers have also been done.68–70 ranges from < 25 to 78 International Units/L.80 There is
There has been controversy concerning the effect of some research on providing women with very large doses of
iron as one of the ingredients in human milk fortifiers on vitamin D, thereby increasing the content of their milk. At
the antimicrobial properties of human milk. A reduced this time there is a need for research concerning the safety
antimicrobial effect of human milk with an iron-containing and efficacy of this method prior to recommendation to a
fortifier has been demonstrated against Escherichia coli (E. larger population.80 There is also now concern about the
coli), Staphylococcus, Enterobacter sakazakaii (E. sakazakaii), age at which direct sunlight exposure is initiated, with the
and Group B streptococcus in one study,71 and against E. current recommendation that infants under 6 months be
coli, Staphylococcus aureus, Pseudomonas aeruginosa, and kept out of direct sunlight.81 In following these guidelines,
Candida albicans in a second study 72 when these organisms vitamin D supplementation is necessary. More vitamin
were added to human milk. A proposed explanation is the D-only products are now made and are included in the new
effect of iron on the antibacterial effects of lactoferrin, which paper on vitamin D.76
is diminished when lactoferrin is saturated with iron.71 In The iron content in human milk is very low, although
another study, no effect was seen in the counts of resident more bioavailable compared to iron in iron-fortified
flora and E. sakazakaii using fortifiers added to fresh milk in infant formula.82 Iron needs in the first 6 months of life
a time span of 6 hours.73 The human milk-derived fortifier for a breastfed infant rely on the infant’s stores at birth. 82
when added to breast milk did not affect the antimicrobial In healthy breastfed term infants iron deficiency before
properties of the milk.74 6 months of age is observed but uncommon. Typically at
4 to 6 months, iron-rich complementary foods are added,
Banked Human Milk although the newer guidelines are for exclusive breast-
Banked donor pasteurized human milk is used in many feeding for 6 months.83
nurseries, either as a bridge to feed early if the mother’s own Premature infants do not have the same iron stores as
milk is not yet in, or as a substitute for the mother who cannot term infants, and infants who are hospitalized may have
supply sufficient milk or who has chosen not to pump. Some blood sampled for testing, further depleting their iron stores.
nurseries use donor milk in the first few weeks after delivery Premature infants typically receive iron supplementation
as that is the peak time for contracting NEC. Donor milk may due to their low stores at birth and beneficial effect has been
be collected from preterm or term mothers; obviously there documented in the literature.84 Iron deficiency in infants
is a much greater pool available from mothers of term infants. is concerning as it appears to lead to developmental delay,
The pasteurization in particular alters some of the proper- which is irreversible.84 Infants who are breastfed exclusively
ties of human milk.46 If donor-banked term milk is used for a for 6 months may be at increased risk of iron deficiency. 82
preterm infant, there will be increased needs for supplemental Ziegler et al studied the effect of early (at 1 month) iron
protein, calcium, and phosphorus as the levels of these nutri- administration on breastfed term infants. 85 Early supple-
ents are lower in donor term milk than in preterm milk.75 mentation was feasible and well tolerated by most infants. 86
Vitamin D Growth of Breastfed Infants

The latest statement regarding vitamin D from the Growth of breastfed infants differs from formula-fed
AAP is to supplement with 400 International Units per infants. The WHO has published a growth curve87 based
day beginning soon after birth.76 This replaces the 2003 on infant growth data from one site in the United States as
statement that recommended 200 International Units well as sites in Brazil, Ghana, India, Norway, and Oman.

The intention was to choose sites where breastfeeding increase hormone levels, leading to increased milk
was commonly practiced and provide lactation support to production.93–95
mothers to help them comply with the feeding standards • Breast milk should be stored in sterile or aseptic food
required to construct this growth curve. The factors were: grade plastic or glass containers that are built to with-
exclusive or predominate breastfeeding for the first 4 stand long-term freezing. They need to have close-fitting
months, introduction of complementary food between 4 and caps that provide an airtight closure; a nipple is not an
6 months, and partial breastfeeding to be continued until at acceptable cap.93
least 12 months.88 Comparing the 2000 Centers for Disease • Labels should include the name of the contents:
Control and Prevention (CDC) growth curve to the WHO expressed breast milk, infant’s name, medical record or
curve, there are notable differences in the growth trajec- identification number, date and time of milk expressed,
tory of breastfed infants, with breastfed infants growing medications or supplements taken by the mother,
more rapidly in the first 2 months and less rapidly from 3 whether the milk is fresh or frozen, date and time of milk
to 12 months in relation to the CDC curve. Linear growth thawed, and expiration. The expiration will depend on
is higher until 4 months. The growth trajectories show that whether the milk is fresh or frozen. Labels should be
infants in the CDC curve are heavier and shorter than the made of a material that the writing on the label can still
WHO reference population.89 be read after freezing and moisture.93
• Frozen milk should not be transported in ice as ice is
Breast Milk Safety and Administration warmer than frozen milk and could thaw the milk. Blue
In 2001, a powdered infant formula, Portagen® (which ice containers freeze at a colder temperature and are
was not a standard formula for preterm infants), was used acceptable for use.93
and prepared in a NICU for preterm infants. A 33-week • Length of time milk may be stored at different storage
infant became ill and died; the cerebral spinal culture grew temperatures93:
E. sakazakaii. Because this is a rare cause of neonatal menin-
Length of Time
gitis, the state health board and the CDC became involved. Storage Method Temperature
Recommended
In the investigation it was shown that not only opened cans Room temperature 25°C, 75°F <4h
of the formula contained the bacteria but also the unopened Cooler with ice packs 15°C, 59°F 24 h
cans as well. This launched an investigation into the bacterial Refrigerator, 24 h feeding when
4°C, 39°F
counts of powdered formula, for unlike liquid concentrate thawed milk possible
or ready to feed, it is not sterile.90,91 In the guidelines issued Refrigerator,
4°C, 39°F 24 hours
fortified milk
by the CDC in 2002, it stated that formula products should
Refrigerator,
be based on nutrition needs with alternatives to powder fresh milk
4°C, 39°F 48 h
forms used whenever possible; and hang times limited to 4 Freezer, home unit 3 mo
hours.90 The Food and Drug Administration issued a letter Freezer −20°C, −4°F 6–12 mo
to professionals with similar recommendations.92 This has Freezer −70°C, −94°F > 12 mo
implications for the use of powdered human milk fortifiers
as well as the use of expressed breast milk. Safety remains a • As breast milk is not homogenized, separation of fat
paramount concern in the provision of any nutrition to the may occur when breast milk is used in tube feedings.
preterm or term infant. Detailed guidelines published by Research has shown a 17% fat loss in intermittent
the American Dietetic Association (ADA) have been estab- feeding but a 34% loss in a continuous tube feeding.95
lished for the collection, labeling, transporting, storage, While some nurseries never use human milk in a
and administration of expressed breast milk.93 The Human continuous feeding setup due to the losses, others
Milk Banking Association of North America also published believe that although it is not ideal it is the best therapy
guidelines for the handling of breast milk in hospitals, for the infant and they will accept, and try to minimize,
daycare settings, and the home.94 The following are some of the losses via the tube. These techniques include using
the ADA key points: a shortened tubing length and tilting the feeding pump
• Mothers are encouraged to express milk ideally as soon as syringe upward,96 as well as transitioning to bolus feed-
possible after birth (or breastfeed if the infant is able).93 ings when possible.93
• Mothers are encouraged to pump every 2 to 3 hours • The hang time for breast milk should be 4 hours and the
or at least 8 times in 24 hours using a hospital grade syringe and tubing should be changed every 4 hours
pump, using a double kit to not only save time but also as well.93

HUMAN MILK 125
• Only the milk to be given per feed should be warmed. Test Your Knowledge Questions
Excessive heat could harm the infant and destroy 1. Why is the late preterm infant at particular risk for
factors such as IgA and enzymes. Any milk left in a lactation problems?
bottle should be discarded.93 A. The infant may be mislabeled as a term infant and
• Hospitals should have policies to cover the treated as such.
misadministration of breast milk. Unfortunately this B. The infant may have difficulty extracting milk
continues to be a problem in nurseries, and strategies sufficiently.
have been employed to decrease the incidence of C. The infant appears competent at breastfeeding
misadministration.97–99 A thorough schematic is when he or she is not.
presented in the ADA manual.93 D. The mothers of these infants are at risk for delayed
In addition to concerns about bacterial contamination, lactogenesis.
cytomegalovirus (CMV) in breast milk has been addressed. E. All of the above.
Freezing at −20°C has been discussed as a method of 2. Can the use of higher calorie hind milk from the use
decreasing the viral load of CMV in breast milk. Freezing of lactoengineering replace fortification in a preterm
at this temperature does not appear to decrease secretory infant?
IgA, lysozyme, lactoferrin, C3 complement, or the function A. Yes
of cells in breast milk.100 While freezing at −20°C for various B. No
time periods does appear in studies to decrease viability of 3. Could there be nutrition problems affecting growth
CMV, it is not certain what freezing time period is safe for with the use of donor banked human milk for preterm
high viral loads and what would be necessary to achieve 100% infants?
inactivity. A full discussion of this issue is beyond the scope of A. Yes
this article, and a review of the topic is available.101 B. No
Breast Milk and Maternal Medications See p. 487 for answers.

Health professionals are often asked questions about the
use of medications in mothers who are lactating. Riordan References
and Auerbach state that there are 3 “knowns” about medica- 1. American Academy of Pediatrics, Committee on Nutri-
tions and breast milk: (1) most drugs pass into breast milk; tion. Kleinman RE, ed. Pediatric Nutrition Handbook. 6th
ed. Elk Grove Village, IL: American Academy of Pediatrics;
(2) almost all medication appears in only small amounts, 2009:55.
usually less than 1% of the maternal dosage; and (3) very few 2. Canadian Paediatric Society Nutrition Committee, American
drugs are contraindicated for breastfeeding women.102,103 Association of Pediatrics Committee on Nutrition. Breast-
That does not mean, however, that caution should not be feeding; a commentary in celebration of the international year
taken when prescribing medications to lactating women. of the child.1979. Pediatrics. 1978;65:591–601.
3. International Pediatric Association: Recommendations for
Hale’s Medications and Mother’s Milk is a useful reference
action programmes to encourage breastfeeding. Acta Paediatr
that is updated regularly and compiles the known data Scand. 1976;65:275–277.
about medications, assigning a risk code.104 The evaluation 4. WHO/UNICEF. Protecting, promoting, and supporting
of the safety of medications for premature infants depends breastfeeding; the special role of maternity services, a joint
on 3 factors according to Hale: the amount of medication WHO/UNICEF statement. Geneva Switzerland 1989, World
in the milk, the oral bioavailability of the medication, and Health Organization.
5. US Department of Health and Human Services. Healthy
the ability of the infant to clear the medication.105 Some of People 2010: Understanding and Improving Health and Objec-
the drugs of concern in general are the chemotherapeutic tives for Improving Health. Vols. 1, 2. 2nd ed. Washington, DC:
agents, radioactive isotopes, drugs of abuse, lithium, ergot- US Dept of Health and Human Services; 2000.
amine, and drugs that suppress lactation. Antihistamines 6. Centers for Disease Control and Prevention. Breastfeeding
may reduce milk supply.105 Report Card, United States: Outcome Indicators. http://www.
cdc.gov/breastfeeding/data/report_card2.htm. Accessed
November 12, 2009.
7. Lawrence RA, Lawrence RM. Breastfeeding: A Guide for the
Medical Profession. 6th ed. St. Louis, MO: Mosby; 2005:187.

8. Fanaro S, Vigi V. Infant formulas supplemented with prebi- 28. Meinzen-Derr J, Poindexter B, Wrage L, et al. Role of human
otics: intestinal microbiota and immune responses. Minerva milk in extremely low birth weight infants’ risk of necrotizing
Pediatr. 2008;60:327–335. enterocolitis or death. J Perinatol. 2009;29:57–62.
9. Hatakka K, Savilahti E, Ponka A, et al. Effect of long-term 29. Sisk PM, Lovelady CA, Dillard RG, et al. Early human
consumption of probiotic milk on infections in children milk feeding is associated with a lower risk of necrotizing
attending day care centres: double blind, randomized trial. enterocolitis in very low birth weight infants. J Perinatol.
BMJ. 2001;322:1327. 2007;27428–433.
10. May JT. Microbial contaminants and antimicrobial properties 30. Schanler RJ, Lau C, Hurst NM, et al. Randomized trial of
of human milk. Microbiol Sci. 1988;5:42–46. donor human milk versus preterm formula as substitutes for
11. Goldman AS, Garza C, Nichols BJ, et al. Immunologic factors mothers’ own milk in the feeding of extremely low birthweight
in human milk during the first year of lactation. J Pediatr. infants. Pediatrics. 2005;116:400–406.
1982;100:563. 31. Schanler RJ. Mother’s own milk, donor human milk, and
12. Howie PW, Forsyth JS, Ogston SA, et al. Protective effect of preterm formulas in the feeding of extremely premature
breastfeeding against infection. BMJ. 1990;336:92. infants. J Pediatr Gastroenterol Nutr. 2007;48:S175–S177.
13. Duncan B, Ey J, Holberg CJ, Wright AJ, et al. Exclusive breast- 32. Kleinman RE, Walker WA. The enteromammary immune
feeding for at least 4 months protects against otitis media. system. Dig Dis Sci. 1979;24:876–882.
Pediatrics. 1993;91:867–872. 33. Wang AC, Chen SJ, Yuh YS. Breastfeeding associated
14. Aniansson G, Alni B, Andersson A, et al. A prospective cohort neonatal hypernatremic dehydration in a medical center: a
study on breastfeeding and otitis media in Swedish infants. clinical investigation. Acta Paediat Taiwan. 2007;48:186–190.
Pediatr Infectious Dis J. 1994;12:183–188. 34. Unal S, Arhan E, Kara N, et al. Breastfeeding associated
15. Paradise JL, Elster BA, Tan L. Evidence in infants with cleft hypernatremia: retrospective analysis of 169 term newborns.
palate that breast milk protects against otitis media. Pediatrics. Pediatr Int. 2008;50:29–34.
1994;94:853–860. 35. Yaseen H, Salem M, Darwich M. Clinical presentation of
16. Pisacane A, Grazione L, Mazzarella G, et al. Breastfeeding and hypernatremic dehydration in exclusively breastfed neonates.
urinary tract infections. J Pediatr. 1992;120:87–89. Indian J Pediatrics. 2004;71:1059–1062.
17. Vennemann MM, Bajanowski T, Brinkman B, et al. Does 36. Academy of Breastfeeding Medicine. Guidelines for
breastfeeding reduce the risk of sudden infant death hospital discharge of the breastfeeding term newborn and
syndrome? Pediatrics. 2009;123:e406–e410. mother. “Going home protocol.” 2007, Sep 2 (3)158–165.
18. Saarinen IJM, Kajosaari M, Backnman A, et al. Prolonged http://www.guideline.gov/summary/summary.aspx?doc_
breastfeeding as prophylaxis for atopic disease. Lancet. id=11556&nbr=5987&ss=15. Accessed November 12, 2009.
1979;2:163–166. 37. Academy of Breastfeeding Medicine. Breastfeeding the near
19. Kramer MS. Does breastfeeding help protect against atopic term infant (35 to 37 weeks gestation). 2004 Aug 22. http://
disease? Biology, methodology and a golden jubilee of contro- www.guideline.gov/summary/summary.aspx?ss=15&doc_
versy. J Pediatr. 1988;112:181–190. id=11227&nbr=5874. Accessed November 12, 2009.
20. Thygarejan A, Burks AW. American Academy of Pediatrics 38. Academy of Breastfeeding Medicine. Transitioning the breast-
recommendations on the effect of early nutritional interven- feeding/breastmilk-fed premature infant from the neonatal
tions on the development of atopic disease. Curr Opin Pediatr. intensive care unit to home. 2004 Sep 17. http://www.guide-
2008;20:698–702. line.gov/summary/summary.aspx?doc_id=11229. Accessed
21. Greer FR, Sicherer SH, Burks W, et al. Effects of nutritional November 12, 2009.
interventions on the development of atopic disease in infants 39. Wight N. Breastfeeding the borderline near term infant. Pedi-
and children; the role of maternal diet restriction, timing atric Ann. 2003;32:329–336.
of introduction of complementary foods, and hydrolyzed 40. Meier PP, Furman LM, Deenhardt M. Increased lactation risk
formulas. Pediatrics. 2008;121:183–190. for late preterm infants and mother: evidence and manage-
22. Hanson LA, Adlerberth I, Carlsson B, et al. Host defense of ment strategies to protect breastfeeding. J Midwifery Womens
the neonate and the intestinal flora. Acta Peadiatric Scand. Health. 2007;52:579–587.
1989; 351(suppl):122–125. 41. Wight NE, Morton JA, Kim JH. ‘Best Medicine’ Human Milk in
23. Koletzko S, Sherman P, Corey M, et al. Role of infant feeding the NICU. Amarillo, TX: Hale Publishing, LP; 2008.
practices in development of Crohn’s disease in childhood. 42. Meier PP, Engstrom JL, Mingolelli SS, et al. The Rush
BMJ. 1989;298:1617–1618. Mothers’ Milk Club: Breastfeeding interventions for mothers
24. Gerstein HC. Cow’s milk exposure and type I diabetes with very-low-birthweight infants. J Obstet Gynecol Neonatal
mellitus. Diabetes Care. 1994;17:1319. Nurs. 2004;33:164–172.
25. Savilahti E, Saarinen KM. Early infant feeding and type I 43. Meier PP, Engstrom JL, Hurst NM, et al. A comparison of the
diabetes. Eur J Nutr. 2009;48(4):243–249. efficiency, comfort and convenience of two hospital-grade
26. Davis MK, Savitz DA, Graubard BI. Infant feeding and child- electric breast pumps for mothers of very low birth weight
hood cancer. Lancet. 1988;2:365–368. infants. Breastfeed Med. 2008;3:141–120.
27. Schanler RJ. The use of human milk for premature infants. 44. Meier PP, Brown LP, Hurst NN, et al. Nipple shields for
Pediatr Clin N Am. 2001;48:207–219. preterm infants: effect on milk transfer and duration of breast-
feeding. J Hum Lact. 2000;16:106–114.

HUMAN MILK 127
45. Chazpak N, Ruiz JG, KMC Team. Breast milk composition in 65. Weber A, Loui A, Jochum F, et al. Breast milk from mothers
a cohort of preterm infants’ mothers followed in a ambulatory of very low birthweight infants: variability in fat and protein
program in Colombia. Acta Paediatr. 2007;96:1735–1739. content. Acta Paediatr. 2001;90:772–775.
46. Lawrence RA, Lawrence RM. Breastfeeding: A Guide for the 66. Bishara R, Dunn MS, Merko SE, et al. Nutrient composition
Medical Profession. 6th ed. St. Louis, MO: Mosby; 2005:445. of hindmilk is produced by mothers of very low birth weight
47. Morales Y, Schanler RJ. Human milk and clinical outcomes infants born at less than 28 weeks gestation. J Hum Lact.
in VLBW infants: how compelling is the evidence of benefit? 2008;24:159–167.
Semin Perinatol. 2007;31:83–88. 67. Medala Web site. http://www.medelabreastfeedingus.com/
48. Mukhopadhyay K, Narang A, Mahajan R. Effect of human for-professionals/lc-information. Accessed February 2009.
milk fortification in appropriate for gestation and small for 68. Meier PP, Engstrom JL, Zuleger JL, et al. Accuracy of a user-
gestation preterm babies: a randomized trial. Indian Pediatrics. friendly centrifuge for measuring creamatocrit on mothers’
2007;44:286–290. milk in a clinical setting. Breastfeed Med. 2006;1:79–87.
49. Carey DE, Rowe JS, Goetz CA, et al. Growth and phosphorus 69. Griffith TL, Meier PP, Bradford LP, et al. Mothers’ performing
metabolism in premature infants fed human milk, fortified creamatocrit measures in the NICU: accuracy, reactions, and
human milk, or special premature formula. Am J Dis Child. cost. J Obstet Gynecol Neonatal Nurs. 2000;29:249–257.
1987;141:511. 70. Meier PP, Engstrom JL, Murtaugh MA, et al. Mothers’ milk
50. Chan GM, Armstrong C, Moyer-Mileur L, et al. Growth and feedings in the neonatal intensive care nursery: accuracy of
bone mineralization in children born prematurely. J Perinatol. the creamatocrit technique. J Perinatol. 2002; 22:646–649.
2008; 28:619–623. 71. Chan GM. Effect of powdered human milk fortifier
51. Janjindami W, Chotsampancharoen T. Effect of fortification on the antibacterial actions of human milk. J Perinatol.
on the osmolality of human milk. J Med Assoc Thai. 2006; 2003;23:620–623.
99:1400–1403. 72. Ovali F, Ciftci I, Cetinkaya Z, et al. Effects of human milk
52. Bhat BA, Gupta B. Effects of human milk fortification on fortifier on the antimicrobial properties of human milk. J Peri-
mortality factors in very low birthweight infants. Ann Saudi natol. 2006;26:761–763.
Med. 2003;23:28–31. 73. Telang S, Berseth CL, Ferguson PW, et al. Fortifying fresh
53. Yigit S, Akgoz A, Memisoglu A, et al. Breast milk fortifica- human milk with commercial human milk fortifiers does not
tion: effect on gastric emptying. J Matern Fetal Neonatal Med. affect the bacterial growth during 6 hours at room tempera-
2008;21;843–846. ture. J Am Diet Assoc. 2005;105:567–572.
54. Prolacta Web site. http://www.Prolacta.com. Accessed 74. Chan GM, Lee MI, Rechman DJ. Effects of a human milk-
January 2009. derived human milk fortifier on the antibacterial actions of
55. Sapsford A. Composition of human milk and selected enteral human milk. Breastfeed Med. 2007;2:205–208.
products. In: Groh Wargo S, Thompson M, Cox J, eds. Nutri- 75. Wojcik KY, Rechtman DJ, Lee, ML, et al. Macronutrient
tional Care for High Risk Newborns. 3rd ed. Chicago, IL: analysis of a nationwide sample of breast milk. J Am Diet Assoc.
Precept Press; 2000:664 2009; 109:137–140.
56. Abbott Nutrition Web site. http://www.abbottnutrition.com/ 76. Wagner CL, Greer FR; American Academy of Pediatrics
products. Accessed January 2009. Section on Breastfeeding; American Academy of Pediatrics
57. MeadJohnson Nutrition Web site. http://www.mjn.com. Committee on Nutrition. Prevention of rickets and vitamin
Accessed January 2009. D deficiency in infants, children, and adolescents. Pediatrics.
58. Groh Wargo S. Recommended enteral nutrient intakes. In: 2008:122:1142–1152.
Groh Wargo S, Thompson M, Cox J, eds. Nutritional Care 77. Gartner LM, Greer FR; American Academy of Pediatrics
for High Risk Newborns. 3rd ed. Chicago, IL: Precept Press; Section on Breastfeeding; American Academy of Pediatrics
2000:234. Committee on Nutrition. Prevention of rickets and vitamin
59. Ziegler EE. Protein requirements of very low birth weight D deficiency: new guidelines for vitamin D intake. Pediatrics.
infants. J Pediatric Gastroenterol Nutr. 2007;45:S170–S174. 2003;111:908–910.
60. Lawrence RA, Lawrence RM. Breastfeeding: A Guide for the 78. Kreiter SR, Schwartz RP, Kirkman HN, et al. Nutritional
Medical Profession. 6th ed. St. Louis, MO: Mosby; 2005:693. rickets in African American breastfed infants. J Pediatr.
61. Lucas A, Gibbs JAH, Lyster RLI, et al. Creamatocrit: simple 2000;137:153–157.
clinical technique for estimating fat concentration and energy 79. Ward LM. Vitamin D deficiency in the 21st century: a persis-
value of human milk. Br Med J. 1978;1:1018. tent problem among Canadian infants and mothers. CMAJ.
62. Wang CD, CHU PS, Mellen BG, et al. Creamatocrit and 2005;172:769–770.
the nutrient composition of human milk. J Perinatol. 80. Wagner CL, Hulsey TC, Fanning D, et al. High dose vitamin
1999;19:343–346. D supplementation in a cohort of breastfeeding mothers and
63. Chatterjee R, Chatterjee S, Datta T, et al. Longitudinal study their infants; a six month follow-up pilot study. Breastfeed
of human milk creamatocrit and weight gain in exclusively Med. 2006;1:59–70.
breastfed infants. Indian Pediatrics. 1997; 34:901–904. 81. American Academy of Pediatrics, Committee on Envi-
64. Lubetsky R, Mimouni FB, Dollberg S, et al. Consistent ronmental Health. Ultraviolet light: a hazard to children.
circadian variations in creamatocrit over the first 7 weeks of Pediatrics. 1999;104:328–333.
lactation: a longitudinal study. Breastfeed Med. 2007;2:15–18.

82. American Academy of Pediatrics, Section on Breastfeeding. 93. Sapsford A, Lessen R. Expressed human milk. In: Robbins
Breastfeeding and the use of human milk. Pediatrics. ST, Beker LT, eds. Infant Feedings: Guidelines for Preparation of
2005;115:496–506. Formula and Breastmilk in Health Care Facilities. Chicago, IL:
83. Chantry CJ, Howard CR, Auinger P. Full breastfeeding dura- American Dietetic Association; 2004.
tion and risk for iron deficiency in U.S. infants. Breastfeeding 94. Human Milk Banking Association of North America. 2006
Med. 2007;2:63–73. Best Practice for Expressing, Storing and Handling of Mother’s
84. Steinmacher J, Pohlandt F, Bode H, et al. Randomized trial Own Milk in Hospital and at Home. Raleigh, NC: Human Milk
of early versus late enteral iron supplementation in infants Banking Association of North America; 2006.
with a birth weight of less than 1301 grams: neurocogni- 95. Martinez FE, Desai ID, Davidson AGF, et al. Ultrasonic
tive development at 5.3 years’ corrected age. Pediatrics. homogenization of expressed human milk to prevent fat loss
2007;120:538–546. during tube feeding. J Pediatr Gastroenterol Nutr. 1987;6:593.
85. Ziegler EE, Nelson SE, Jeter JM. Iron supplementation 96. Narayan I, Singh B, Harvey D. Fat loss during feeding of
of breastfed infants from an early age. Am J Clin Nutr. human milk. Arch Dis Child. 1984; 59:475–477.
2009;89(2):525–532. 97. Zeilhofer UB, Frey B, Zandee J, Bernet V. The role of critical
86. Lozoff B, Jimenez E, Hagen J, et al. Poorer behavioral and incident monitoring in detection and prevention of breast
developmental outcome more than 10 years after treatment milk confusions. Eur J Pediatr. 2009;168(10):1277–1279.
for iron deficiency. Pediatrics. 2000;105:E51. 98. Dougherty D, Giles V. From breast to bottle: quality assur-
87. World Health Organization. The WHO Child Growth Stan- ance for breast milk management. Neonatal Network. 2000;
dards. www.who.int/childgrowth/standards/en. Accessed 19:21–25.
January 30, 2009. 99. Drenckpohl D, Bowers L, Cooper B. Use of the six signs meth-
88. WHO Multicentre Growth Reference Study Group. Breast- odology to reduce incidence of breast milk administration
feeding in the WHO Multicentre Growth Reference Study. errors in the NICU. Neonatal Network. 2007; 26:161–166.
Acta Paediaticia. 2006;(Suppl)450:1626. 100. Lawrence RA. Storage of human milk and the influence of
89. de Onis M, Onyango AW. The Centers for Disease Control and procedures on immunological components of human milk.
Prevention 2000 growth charts and the growth of breastfed Acta Paediatr Suppl. 1999;88:14–18.
infants. Acta Paediatrica. 2003;92:413–419. 101. Lawrence RM. Cytomegalus in human breast milk: risk to the
90. Enterobacter sakazakaii infections associated with the use of premature infant. Breastfeeding Med. 2006;1:99–107.
powdered infant formula–Tennessee 2001. MMWR Weekly. 102. Riordan J. Drugs and breastfeeding. In: Riordan J, Auerbach
April 12, 2002;298–300. K, eds. Breastfeeding and Human Lactation. 2nd ed. Sudbury,
91. Bowen AB, Braden CR. Invasive Enterobacter sakazakaii MA: Jones and Bartlett; 1998,163–219.
disease in infants. Emerging Infectious Diseases. August 2006. 103. American Academy of Pediatrics, Committee on Nutrition.
http://www.cdc.gov/ncidod/EID/vol12no08/05-1509.htm. Kleinman RE, ed. Pediatric Nutrition Handbook. 6th ed. Elk
Accessed November 12, 2009. Grove Village, IL: American Academy of Pediatrics; 2009:71.
92. Food and Drug Administration. Health professionals letter 104. Hale T. Medications and Mothers Milk. 13th ed. Amarillo, TX:
on Enterobacter sakazakii infections associated with use of Hale Publishing, LP; 2008.
powdered (dry) infant formulas in neonatal intensive care 105. Hale T. Medication in breastfeeding mothers of preterm
units. April 11, 2002, revised October 10, 2002. infants. Pediatric Ann. 2003;337–347.

12
Infant Formulas and
Complementary Feeding
Kelly Green-Corkins, MS, RD, CNSD and Timothy Sentongo, MD

Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 129 1. Explain the basis for and regulation of infant formulas.
Regulation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 130 2. Discuss reasons for functional ingredients in infant
formulas.
Types of Infant Formulas. . . . . . . . . . . . . . . . . . . . . . . . . . 130
Standard Milk-Based Term Infant Formulas 3. Differentiate infant formulas and target populations.
Term Formulas Designed for Symptoms of Intolerance 4. Describe how increased caloric concentrations may
Premature or Low Birth Weight Formulas influence tolerance.
Premature Discharge Formulas 5. Summarize reasoning behind current guidelines for
Specialized Infant Formulas introducing complementary foods to an infant’s diet.
Functional Ingredients in Infant Formulas. . . . . . . . . . . . 135
DHA/ARA Introduction
Forms of Infant Formula and Mixing Guidelines . . . . . . . 137 The World Health Organization recommends human milk
Introducing Complementary Foods as the sole source of nutrition for healthy full-term infants
to the Infant’s Diet. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 139 birth to 6 months of age.1 Breastfeeding provides benefits
Toddler Formulas . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 139 to the infant that infant formula can not. Breastfeeding
promotes gastrointestinal development and function,
immune support, and neurodevelopment. 2 It is not always
possible for a mother to breastfeed, or a mother may
choose not to breastfeed due to cultural, social, or health
reasons. Iron-fortified infant formulas are appropriate
substitutes for human milk. No matter what the choice or
reason for not breastfeeding, a mother should be supported
in her decision. 3
Because human milk is the optimal source of nutrition
for an infant, infant formulas are designed to be similar to
human milk and/or to promote a similar response as seen
in the breastfed infant.4 Even with the latest functional
ingredients added (docosahexaenoic acid [DHA] and
arachidonic acid [ARA], nucleotides, probiotics, prebiotics),
infant formulas are still not able to provide the hormones,
immunoglobulins, enzymes, and live cells that are in human
milk. 3 Infant formulas are designed using cow’s milk or
soy as a base. Although infant formula manufacturers will
129
never be able to completely replicate human milk, research Table 12-1 Infant Formula Manufacturer Web Sites
continues and there are modifications to improve the quality Manufacturer Product Line Web Site
of infant formulas. 3 Abbott Similac® www.abbottnutrition.com
Nutritionals
Regulation Mead Johnson Enfamil® www.meadjohnson.com
An infant formula is defined by the Federal Food, Drug, Nestle Gerber GOOD START® www.gerber.com
Nutricia Neocate® and www.nutricia-na.com
and Cosmetic Act (FDCA) as “a food which purports to be other products
or is represented for special dietary use solely as a food for PBM Nutritionals Bright Beginnings™ www.pbmproducts.com
infants by reason of its simulation of human milk or its suit- Parent’s Choice®
ability as a complete or partial substitute for human milk.”5 Vitaflo some modulars www.vitaflousa.com
Infant formulas designed to meet a specific medical need
(ie, premature infant formulas) are considered “exempt”
because the nutrition requirements of infants with certain Standard Milk-Based Term Infant Formulas
medical conditions differ from those of healthy infants. Standard milk-based infant formulas (Table 12-2) are
Exempt formulas are not exempt from monitoring or regu- designed to meet the needs of healthy infants birth to 1 year
lation and need to meet certain criteria. All infant formula of age. The protein source is cow’s milk, which is iron-forti-
manufacturers must begin with safe ingredients that are fied. Most formula-fed infants will consume one of these
approved for use in infant formulas, or are generally recog- products.
nized as safe (GRAS). 5 A subgroup of the standard infant formulas is organic.
The Infant Formula Act of 1980 (revised 1986), an In order to be labeled organic, the formula ingredients must
amendment to the FDCA, was developed due to an incident be certified organic and meet U.S. Department of Agricul-
involving inadequate chloride in a soy-based formula that ture regulations. Ingredients must be produced without
resulted in metabolic acidosis in several infants.6 The Food pesticides, added growth hormones, or antibiotics.
and Drug Administration (FDA) is responsible for moni-
toring the manufacturers that make infant formulas. There Term Formulas Designed for Symptoms of Intolerance
are federal regulations on quality control, labeling, nutrient Formulas designed for symptoms of intolerance (Table
levels, formula recall, new product notification, and exempt 12-3) are milk-based and are appropriate for the full-term
products. There are established levels for 29 nutrients and infant. Modifications include partial hydrolysis of the
maximum levels for 9 nutrients. Manufacturers are required protein, reduced lactose or lactose-free, and added rice
to declare on the label the levels of each nutrient provided, starch.
and the manufacturer must analyze each batch of formula
to ensure the declared levels of all essential nutrients are Partially Hydrolyzed Protein
being provided. The FDA reviews the analysis records and Formulas containing partially hydrolyzed protein are not
will perform tests on the formula to monitor the manufac- considered hypoallergenic and are not intended to be used
turers. 5 The concentration of nutrients in infant formula for treatment of any allergic condition or disease. Partially
is higher than in human milk because of the decreased hydrolyzed formulas contain reduced or no lactose and
bioavailability in infant formula. 3,7 each product is different in the type of protein hydrolyzed
and degree of hydrolysis. Therefore, assumptions can not
Types of Infant Formulas be made that all partially hydrolyzed protein formulas offer
Information included in this section and the accompanying identical benefits.8
tables is up-to-date as of the time of publication. For the The benefits of partially hydrolyzed 100% whey protein
most current information, please visit the manufacturers’ have been studied and research demonstrates that it may
Web sites (Table 12-1). decrease the risk of atopic dermatitis in infants with a
family history of allergic disease. 8 The product containing
the partially hydrolyzed 100% whey protein is considered a
routine milk-based infant formula.
Another product on the market contains partially
hydrolyzed whey and casein. This product is marketed
for intolerances but does not have research to suggest the

INFANT FORMULAS AND COMPLEMENTARY FEEDING 131
Table 12-2 Standard Milk Based Infant Formulas (per 100 calories) The standard dilution for these products is 0.67 kcal/mL (20 kcal/oz).
Product Protein g (% kcal) CHO g (% kcal) Fat g (% kcal) Na K Ca Phos Fe Osmolal- Comments
(Manufacturer) Source Source Source mg mg mg mg mg ity mOsm
Bright Beginnings™ 2.2 (9%) 10.9 (43.6%) 5.3 (47.7%) 27 108 82 43 1.8 added nucleotides
Milk-based nonfat milk, whey lactose palm olein, soy oil,
(PBM Nutritionals) protein concentrate coconut oil, high
oleic safflower or
sunflower oil
Bright Beginnings™ 2.2 (9%) 10.6 (42%) 5.3 (48%) 23 84 63 42 1.8 added nucleotides, DHA
Organic organic reduced lactose organic palm or 17 mg, ARA 34 mg
(PBM Nutritionals) minerals whey, palm olien, high
nonfat milk oleic safflower
or sunflower oil,
coconut oil, soy oil
Enfamil LIPIL® w/iron 2.1 (8.5%) 10.9 (43.5%) 5.3 (48%) 27 108 78 43 1.8 300 DHA 17 mg, ARA 34 mg
(Mead Johnson) (liquid): reduced lactose palm olein, soy oil, PRSL 18.9/100 cals
minerals whey, coconut oil, high
nonfat milk oleic sunflower oils
(powder): whey
protein concentrate,
nonfat milk
Enfamil® PREMIUM™ 2.1 (8.5%) 11 (43.5%) 5.3 (48%) 27 108 78 43 1.8 300 added nucleotides
(Mead Johnson) whey, nonfat milk lactose, galacto- palm olein, soy oil, 28 mg/L, DHA 17 mg,
oligosaccharides coconut oil, high ARA 34 mg
oleic sunflower oils PRSL 19.1/100 cals
added prebiotic – galacto-
oligosaccharide (GOS)
GOOD START® Gentle 2.2 (9%) 11.2 (45%) 5.1 (46%) 27 108 67 38 1.5 250 46 mg added
PLUS™ whey protein lactose, corn palm olein, soy oil, nucleotides, DHA 0.32%,
(Nestle/Gerber) concentrate maltodextrin coconut oil, high ARA 0.64% PRSL
(enzymatically oleic safflower or 19.5/100 cals
hydrolyzed, reduced sunflower oil
in minerals)
GOOD START® Nourish 2.2 (9%) 11.2 (45%) 5.1 (46%) 27 108 67 38 1.5 250 5 mg added nucleotides
PLUS™ whey protein lactose, corn palm olein, soy oil, PRSL 19.5/100 cals
(Nestle/Gerber) concentrate maltodextrin coconut oil, high No DHA and ARA
(enzymatically oleic safflower or
in minerals)
GOOD START® Protect 2.2 (9%) 11.2 (45%) 5.1 (46%) 27 108 67 38 1.5 250 46 mg added
PLUS® whey protein lactose, corn palm olein, soy oil, nucleotides, DHA 0.32%,
(Nestle/Gerber) concentrate maltodextrin coconut oil, high ARA 0.64%
(enzymatically oleic safflower or PRSL 19.5/100 cals
in minerals)
Parent’s Choice® Milk 2.1 (8.4%) 10.9 (43.6%) 5.3 (47.7%) 27 108 78 43 1.8 DHA, ARA
Formula DHA & ARA nonfat milk, whey lactose palm olein, soy oil,
(PBM Nutritionals) protein concentrate coconut oil, high
oleic safflower or
sunflower oil
Parent’s Choice® Organic 2.2 (9%) 10.6 (42%) 5.3 (48%) 23 84 63 42 1.8 DHA, ARA
(PBM Nutritionals) organic reduced organic lactose organic vegetable
mineral whey oils (palm or
palm olein, high
oleic safflower or
sunflower, coconut,
soy)
Similac® Advance® 2.07 (8%) 11.2 (43%) 5.4 (49%) 24 105 78 42 1.8 310 added nucleotides,
EarlyShield™ nonfat milk, whey lactose, high oleic safflower DHA 0.15%, ARA 0.40%
(Abbott Nutritionals) protein concentrate galactose oligo- oil, soy oil, coconut PRSL 18.7/100 cals
saccharides oil added prebiotics, GOS
(GOS)
Similac® Organic 2.07 (8%) 10.56 (42%) 5.49 (49%) 24 105 78 42 1.8 225 DHA 0.15%, ARA 0.40%
(Abbott Nutritionals) organic nonfat dry organic corn organic high oleic PRSL 18.8/100 cals
milk maltodextrin, sunflower oil, unmodified whey:casein
organic lactose, organic soy oil, 18:82
organic sugar organic coconut oil

Table 12-3 Infant Formulas for Symptoms of Intolerance (per 100 calories) Standard dilution is 0.67 kcal/mL (20 kcal/oz).
Bright Beginnings™ 2.3 (9%) 10.8 (43%) 5.3 (48%) 32 108 82 46 1.8 added nucleotides,
Gentle nonfat milk, whey corn syrup solids, palm olein, coconut DHA, ARA
(PBM Nutritionals) protein hydrolysate lactose oil, soy oil, high
oleic safflower or
sunflower oil
Enfamil AR® LIPIL 2.5 (10%) 11 (44%) 5.1 (46%) 40 108 78 53 1.8 240 RTU DHA 17 mg,
(Mead Johnson) nonfat milk lactose, palm olein, soy oil, 230 ARA 34 mg
rice starch, cocnut oil, high oleic Powder PRSL 22/100 cals
maltodextrin sunflower oil
Enfamil® 2.3 (9%) 10.8 (43%) 5.3 (48%) 32 108 82 46 1.8 220 DHA 17 mg,
Gentlease® LIPIL partially corn syrup solid, palm olein, soy oil, ARA 34 mg
(Mead) hydrolyzed lactose coconut oil, high PRSL 20/100 cals
nonfat milk and oleic sunflower oil
whey protein
concentrate
Parent’s Choice® 2.3 (9%) 10.8 (43%) 5.3 (48%) 32 108 82 46 1.8 DHA, ARA
Gentle nonfat milk, whey corn syrup solids palm olein, cocnut
(PBM Nutritionals) protein hydrolysate oil, soy oil, high
oleic safflower or
sunflower oil
Lactose Free whey protein corn syrup solids palm olein, coconut
with Lipids concentrate, milk oil, soy oil, high
(PBM Nutritionals) protein isolate oleic safflower or
sunflower oil
Parent’s Choice® 2.6 (10%) 10.5 (42%) 5.3 (48%) 36 130 195 130 2 DHA, ARA
Sensitivity™ milk protein corn syrup solids, palm olein, coconut
(PBM Nutritionals) isolate sucrose oil, soy oil, high
oleic safflower or
sunflower oil
Similac® Isomil® DF 2.66 (11%) 10.1 (40%) 5.46 (49%) 44 108 105 75 1.8 240 no DHA or ARA,
(Abbott Nutritionals) soy protein isolate, corn syrup solids, soy oil, cocnut oil soy protein
L-methionine sucrose
Similac Sensitive® 2.14 (9%) 10.7 (43%) 5.4 (49%) 30 107 84 56 1.8 200 DHA 0.15%,
(Abbott Nutritionals) milk protein corn maltodextrin, high oleic safflower ARA 0.40%
isolate sugar oil, soy oil, coconut PRSL 19.9/100 cals
oil
Similac 2.14 (9%) 10.7 (43%) 5.4 (49%) 30 107 84 56 1.8 180 DHA 0.15%,
Sensitive® RS milk protein corn syrup, rice high oleic safflower ARA 0.40%
(Abbott Nutritionals) isolate starch, sugar oil, soy oil, coconut PRSL 19.9/100 cals
oil
same potential benefits as the partially hydrolyzed 100% lactose intolerant. However, most babies make adequate
whey protein. amounts of lactase and congenital lactase deficiency is
extremely rare. Milk-based lactose-free formulas are not
Lactose-free indicated in galactosemia.
Lactose is only present in mammalian milk. Lactose-
free formulas have similar calorie, protein, fat, and Added Rice Starch
micronutrient content as standard milk-based formulas. Added rice starch formulas are standard milk-based infant
Lactose-free formulas, including soy formulas, may be indi- formulas designed to thicken in the acidic environment of
cated in infants with suspected transient lactase deficiency the stomach to decrease spitting-up episodes.9 Rice starch
secondary to gastroenteritis or protracted diarrhea. Parents is added as part of the carbohydrate content; therefore,
with lactose intolerance may assume their infants are also the macronutrient distribution remains consistent with

Table 12-4 Soy-Based Infant Formulas (per 100 calories) Standard dilution for soy-based formulas is 0.67 kcal/mL (20 kcal/oz).
Enfamil® ProSobee® 2.5 (10%) 10.6 (42%) 5.3 (48%) 36 120 105 69 1.8 liquid 200 DHA 34 mg,
LIPIL soy protein isolate, corn syrup solid palm olein, soy oil, powder ARA 17 mg
(Mead Johnson) L-methionine coconut oil, high oleic 170 PRSL 23/100 cals
sunflower oil
GOOD START® 2.5 (10%) 11 (44%) 5.1 (46%) 40 116 105 63 1.8 180 DHA, ARA
Soy PLUS™ enzymatically corn maltodextrin, palm olein, soy oil, PRSL 22.9/100 cals
(Nestle/Gerber) hydrolyzed soy sucrose coconut oil, high
protein isolate, oleic safflower or
L-methionine sunflower oil
Similac® Isomil® 2.45 (10%) 10.3 (41%) 5.46 (49%) 44 108 105 75 1.8 200 DHA 0.15%,
Advance® soy protein isolate, corn syrup solids, high oleic safflower ARA 0.40%
(Abbott Nutritionals) L-methionine sugar oil, soy oil, cocnut oil PRSL 22.8/100 cals
Bright Beginnings™ 2.5 (10%) 10.6 (42%) 5.3 (48%) 36 120 105 83 1.8 DHA 17 mg,
Soy soy protein isolate, corn syrup solids palm olein, coconut ARA 34 mg PRSL
(PBM Nutritionals) L-methionine oil, soy oil, high oleic
safflower or sunflower
oil
Soy DHA and ARA soy protein isolate corn syrup solids palm olein, coconut PRSL 22.9/100 cals
(PBM Nutritionals) oil, soy oil, high
oleic safflower or
sunflower oil
standard milk-based infant formulas. Rice cereal may be infant’s specific needs.12 Soy milk protein is no less aller-
added to standard infant formula to achieve a similar effect; genic than cow’s milk protein. 3 Infants with documented
however, it increases the caloric density and may result in cow’s milk allergy should not be given a soy formula
clogged nipples. Added rice starch formulas are not substi- because 10% to 14% of these babies will also have a sensi-
tutes for thickened formula indicated for risk of aspiration. tivity to soy protein.13,14 Infants with acute gastroenteritis
Currently there are 2 added rice starch products on the who were previously well can be managed with rehydration
market; one of the products is lactose-free while the other and continued use of human milk or their usual cow’s milk-
has reduced lactose. Each product has studies to support based formula at the standard dilution.12
that the added rice starch decreases episodes of spitting
up.9,10 Premature or Low Birth Weight Formulas
Premature or low birth weight (LBW) formulas (Table
Soy-Based Formulas 12-5) come in ready-to-feed nurser bottles that are avail-
Soy-based formulas (Table 12-4) are designed to meet the able for hospital use only. These formulas are milk-based
needs of healthy infants birth to 1 year of age. The protein and designed to meet the special nutrition needs of preterm
source is soy, supplemented with methionine to make it a infants (born less than 37 weeks gestation) and/or infants
complete protein source. These formulas are fortified with born less than 1500 g (which is considered very low birth
iron and are lactose-free. It is estimated that about 25% weight [VLBW]) while in the hospital, if human milk is
of infants consuming formula will consume a soy-based not available. The unique characteristics of this group of
formula. Soy-based infant formulas have higher calcium formulas include increased protein, carbohydrate blends
and phosphorus than standard cow’s milk-based formulas of lactose and glucose polymers, fat blends containing
because of reduced bioavailability secondary to phytates.11 a portion of fat as medium-chain triglycerides (MCTs)
Soy-based formulas offer no advantage over cow’s milk- to promote fat absorption, and increased calcium and
based formulas except for a few indications. Indications for phosphate to promote net mineral retention and bone
soy-based formula are infants with galactosemia or heredi- mineralization.15,16 Premature infant formulas are available
tary lactase deficiency (rare), or if a vegetarian human milk with low iron or iron-fortified. One of the 3 formulas avail-
substitute is requested.12 able has partially hydrolyzed 100% whey protein. The other
Soy-based formulas are not recommended for prema- 2 formulas contain intact whey and casein proteins.
ture infants as they are not designed to meet the premature

Premature Discharge Formulas acids and small peptides. The fat content is made up of long-
Premature discharge formulas (Table 12-6) are designed to chain triglycerides (LCTs), varying amounts of MCTs, and
meet the nutrition needs of the infant born prematurely or polyunsaturated vegetable oils to supply essential fatty acids
the LBW infant who is transitioning home. These formulas (EFAs). These formulas are lactose-free and because of the
are milk-based with higher levels of calcium and phos- hydrolyzed protein have a higher osmolarity. Protein hydro-
phorus than standard term infant formulas. They provide a lysates are recommended in infants intolerant of cow’s milk
nutrient intake that is between a preterm and term formula. and soy proteins, and those with significant malabsorption
The American Academy of Pediatrics (AAP) supports the due to gastrointestinal or hepatobiliary disease (eg, cystic
use of preterm discharge formulas to postnatal age of 9 to12 fibrosis, short gut syndrome, biliary atresia, cholestasis,
months corrected age or until weight for length is main- protracted diarrhea). 3,17
tained above the 25th percentile. 3
Amino Acid Based
Specialized Infant Formulas Amino acid-based infant formulas (Table 12-8) are indicated
in extreme protein hypersensitivity or when intolerance
Extensively Hydrolyzed Protein symptoms persist on an extensively hydrolyzed formula.18
Formulas containing extensively hydrolyzed protein (Table Approximately 2% to 10% of infants with cow’s milk protein
12-7) are considered hypoallergenic according to AAP and allergy develop persistent symptoms despite therapy with
FDA standards, meaning that most children with cow’s partially hydrolyzed formula and thus require an amino
milk protein sensitivity will not have an allergic reaction to acid-based formula.19 There is no additional benefit to using
these formulas. The protein in these formulas is extensively an amino acid-based formula if an extensively hydrolyzed
hydrolyzed by heat or enzymes, resulting in free amino casein formula is effective. Other indications for the amino
Table 12-5 Premature Infant Formulas (per 100 calories) Standard dilution varies and can be 0.67 kcal/mL (20 kcal/oz) or 0.8 kcal/mL (24 kcal/oz).
Enfamil® Premature 3 (12%) 11 (44%) 5.1 (44%) 58 98 165 83 0.5 240 DHA 17 mg, ARA
LIPIL non-fat milk, whey corn syrup solids, MCT oil, soy oil, high 1.8 34 mg, PRSL 27/100
20 cal/oz (low iron or protein concentrate lactose oleic vegetable oil cals, nucleotides
iron fortified) 28 mg/L, Ca:Phos
(Mead Johnson) ratio – 2:1
Enfamil® Premature 3 (12%) 11 (44%) 5.1 (44%) 58 98 165 83 0.5 300 DHA 17 mg, ARA
LIPIL non-fat milk, whey corn syrup solids, MCT oil, soy oil, high 1.8 34 mg, PRSL 27/100
24 cal/oz protein concentrate lactose oleic vegetable oil cals, nucleotides
(low iron or iron 34 mg/L, Ca:Phos
fortified) ratio – 2:1
(Mead Johnson)
GOOD START® 3 (12%) 10.5 (42%) 5.2 (46%) 55 120 164 85 1.8 275 Ca:Phos
Premature enzymatically corn maltodextrin, MCT oil, soy oil, high ratio – 1.9:1
24 cal/oz hydrolyzed whey lactose oleic safflower or
(Nestle/Gerber) protein isolate sunflower oil
(from cow’s milk)
Similac Special 3 (12%) 10.3 (41%) 5.43 (47%) 43 129 180 100 0.37 235 DHA 0.25%,
Care® nonfat milk, whey corn syrup solids, MCT, soy oil, 1.8 ARA 0.40%, PRSL
20 cal/oz (low iron protein concentrate lactose coconut oil 27.8/100 cals
or iron fortified)
(Abbott Nutritionals)
Care® nonfat milk, whey corn syrup solids, MCT, soy oil, 1.8 ARA 0.40%, PRSL
24 cal/oz (low iron protein concentrate lactose coconut oil 27.8/100 cals
or iron fortified)
Care® nonfat milk, whey corn syrup solids, MCT, soy oil, ARA 0.40%, PRSL
30 cal/oz protein concentrate lactose coconut oil 27.8/100 cals

Table 12-6 Premature Discharge Infant Formulas (per 100 calories) Standard dilution for these formulas is 0.73 kcal/mL (22 kcal/oz).
Enfamil® 2.8 (11%) 10.4 (42%) 5.3 (47%) 35 105 120 66 1.8 powder 42 mg added
EnfaCare® LIPIL whey protein powder: lactose, high oleic sunflower 260 nucleotides, DHA
(Mead Johnson) concentrate, corn syrup solids or safflower oil, soy liquid 250 17 mg, ARA 34 mg,
nonfat milk RTU: maltodextrin, oil, MCT, coconut oil PRSL 24/100 cals
lactose
Similac® NeoSure® 2.8 (11%) 10.1 (40%) 5.5 (49%) 33 142 105 62 1.8 250 DHA 0.15%,
(Abbott Nutritionals) nonfat milk, whey corn syrup solids, soy oil, coconut oil, ARA 0.40%, PRSL
protein concentrate lactose MCT 25.2/100 cals
acid-based formulas include eosinophilic gastrointestinal of a physician. Evaluation of triene:tetraene ratio may be
disorders and transitioning from parenteral to enteral feed- needed to detect EFAD, and addition of EFAs at a volume of
ings and short bowel syndrome (SBS).19 3% to 5% of total kilocalories may be indicated with some of
the formulas with lower levels of the long-chain fatty acids.
Carbohydrate Free
These formulas (Table 12-9) are designed for the Reduced Mineral
management of carbohydrate metabolism disorders and The mineral content of this formula (Table 12-11) is close
carbohydrate malabsorption issues (eg, glucose-galactose to the mineral content of human milk and is designed to
malabsorption).20 The physician or healthcare professional treat calcium disorders.21 The formula may also be used for
prescribes a carbohydrate to be added to the formula and it infants with impaired renal function. An additional source
is usually titrated up to make the formula 20 kcal/oz.21 of iron may need to be considered. Infants consuming this
formula should be monitored by a medical professional.
Reduced Fat/Modified Fat
These reduced or modified fat formulas (Table 12-10) can Functional Ingredients in Infant Formulas
be used in conditions of decreased bile salts, fat malabsorp-
tion, defective lymphatic transport of fat, chylothorax, or DHA/ARA
long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency. Long-chain polyunsaturated fatty acids (LCPUFAs) in
Due to the risk of essential fatty acid deficiency (EFAD), infant feeding refer to docosahexaenoic acid (DHA) and
these formulas should only be used under the supervision arachidonic acid (ARA). DHA and ARA are synthesized
Table 12-7 Extensively Hydrolyzed Protein Infant Formulas (per 100 calories)
Nutramigen® LIPIL 2.8 (11%) 10.3 (41%) 5.2 (48%) 47 110 94 52 1.8 liquid 320 DHA 17 mg,
(Mead Johnson) extensively corn syrup solids, palm olein, soy oil, powder ARA 34 mg,
hydrolyzed casein, modified corn coconut oil, high oleic 300 PRSL 25/100 cals,
L-cystine, L-tyrosine, starch sunflower oil lactose and sucrose
L-tryptophan free
Nutramigen® with 2.8 (11%) 10.3 (41%) 5.3 (48%) 47 110 94 52 1.8 300 DHA 17 mg,
Enflora™ LGG extensively corn syrup solids, palm olein, soy oil, ARA 34 mg,
(Mead Johnson) hydrolyzed casein, modified corn coconut oil, high oleic PRSL 16.8/100 cals,
L-cystine, L-tyrosine, starch sunflower oil *added probiotic
L-tryptophan Lactobacillus GG
Pregestimil® LIPIL 2.8 (11%) 10.2 (41%) 5.6 (48%) 47 110 pwdr pwdr 1.8 RTU 280 DHA 17 mg,
(Mead Johnson) casein hydrolysate, corn syrup solids, MCT, soy oil, corn oil, 94 52 ARA 34 mg pwdr,
amino acids dextrose, modified high oleic safflower or RTU RTU PRSL 25/100 cals,
corn starch sunflower oil 115 75 RTU - PRSL
RTU-no dextrose RTU-no corn oil 26/100cals
Similac® Alimentum® 2.75 (11%) 10.2 (41%) 5.54 (48%) 44 118 105 75 1.8 370 DHA 0.15%,
Advance casein hydrolysate, sugar, modified high oleic safflower ARA 0.40%,
(Abbott Nutritionals) L-cystine, L-tyrosine, tapioca starch oil, MCT, soy oil PRSL 25.3/100 cals
L-tryptophan

Table 12-8 Free Amino Acid Infant Formulas (per 100 calories)
Similac® EleCare® 3.1 (15%) 10.7 (43%) 4.8 (42%) 45 150 116 84.2 1.5 350 DHA, ARA
(Abbott Nutritional) free L-aa corn syrup solids high oleic safflower PRSL 28/100 cals
oil, MCT oil, soy oil
Neocate® Infant 3.1 (12%) 11.7 (47%) 4.5 (41%) 37.3 155.1 124 93.1 1.85 375 available without
DHA & ARA free aa corn syrup solids refined vegetable oil DHA & ARA also
(Nutricia) (soy oil, coconut oil,
high oleic sunflower
oil)
Nutramigen® AA LIPIL 2.8 (11%) 10.3 (41%) 5.3 (48%) 47 110 94 52 1.8 350 DHA 17 mg,
(Mead Johnson) free amino acids corn syrup solids, palm olein, soy oil, ARA 34 mg,
modified tapioca coconut oil, high oleic PRSL 16.8/100 cals
starch sunflower oil
Table 12-9 Carbohydrate-Free Formulas (per 100 calories)

RCF* 3.0 (12%) 10.1 (40%) 5.3 (48%) 44 108 105 75 1.8 168 no DHA/ARA
(Abbott Nutritionals) soy protein isolate, selected by high oleic safflower PRSL 25.8/100cals
L-methionine physician or health oil, coconut oil, soy oil
care professional
3232A 2.8 (11%) 13.5 (54%) 4.2 (35%) 43 109 94 63 1.88 type of 59 gm CHO added
(Mead Johnson) extensively choice by physician, MCT, corn oil CHO will to 1 quart prepared
hydrolyzed casein, modified tapioca influence product, PRSL
L-cystine, L-tyrosine, starch as stabilizer 25/100 cals
L-tryptophan
*based on 100 calories when 52 gm of CHO are added to 13 oz of concentrate
from the dietary EFAs alpha-linolenic acid (ω-3) and linoleic the intestinal mucosa, and may contribute to the pool of
acid (ω-6), respectively. Endogenous synthesis of LCPUFAs nucleotides available to the proliferation of lymphocytes.27
begins in the first days of life.22 A source of dietary nucleotides may be important for infants
DHA and ARA are present in human milk. Breastfed whose tissue turnover rates may be higher (eg, the preterm
infants have higher plasma and erythrocyte lipid concen- infant or infants with chronic diarrhea).26 There is still a
trations of DHA and ARA compared to infants fed formula question as to what the appropriate level of dietary nucle-
without DHA and ARA.23 Furthermore, DHA and ARA are otides should be and which ones should be used. The levels
the major fatty acids in neural tissues and DHA is a major and types of nucleotides that are currently being provided
component of photoreceptor cells.24 The major supply of in infant formulas have not shown any deleterious effects.28
LCPUFAs to the fetus during development is from maternal
plasma.25 Therefore, the clinical significance of this seems Prebiotics and Probiotics
to be more prominent for the preterm infant as compared to Prebiotics are complex dietary carbohydrates present
the term infant.22 in breast milk and several foods that are not digestible or
absorbable by the human gastrointestinal tract.29,30 They
Nucleotides include fructo-oligosaccharides (FOS) and galacto-oligo-
Nucleotides are compounds formed of phosphoric acid, saccharides (GOS). Prebiotics become the fuel for beneficial
a sugar, and a purine or pyrimidine base that are synthe- bacteria in the gut and stimulate their growth. This gives the
sized, degraded, and salvaged in the body. This continuous beneficial bacteria a competitive advantage over the other
process takes place to a larger degree in the gut and immune bacteria in the gut. 31
system than the rest of the body because cells are more Probiotics are defined as non-pathogenic organisms
rapidly turning over.26 Dietary nucleotides are thought to in the food supply that provide a benefit to the host. 32
have effects on intestinal growth and development, healing Bifidobacteria is the most prevalent species that colonizes

the intestines of breastfed infants. 33,34 It is thought that manufacturers provide many different formulas in stan-
the higher percentage of bifidobacteria may be associated dard caloric dilution and some formulas at higher caloric
with some health benefits. 35 Bifidobacteria lactis added to concentrations in convenient ready-to-feed nurser bottles.
infant formula has been shown to be safe and increases the Consumers can purchase ready-to-feed formula at stan-
percentage of bifidobacteria in the microflora. 35 dard dilution in quart-sized bottles or single-serving nurser
Lactobacillus GG (rhamnose) is another species of bottles. Ready-to-feed formula is the most expensive form
bacteria prevalent in the intestines of healthy infants. as the consumer is paying for the convenience.
Studies suggest that an extensively hydrolyzed protein Liquid concentrate is also considered commercially
formula with supplemented LGG may be more effective in sterile, but because it needs to be mixed with water to make
the treatment of cow’s milk protein allergy than the same a standard dilution, it offers more opportunity for potential
formula without supplementation. 36 contamination than ready-to-feed. Liquid concentrate is the
second choice in hospitals and can be used to make higher-
Forms of Infant Formula caloric concentrations. It is easy to mix for consumers and
and Mixing Guidelines offers some financial savings over ready-to-feed.
Infant formula is available in 3 forms: ready-to-feed, liquid Powder is not sterile and must be mixed with water.
concentrate, and powder. All forms are nutritionally Because it is not sterile, it may contain pathogenic bacteria. 37
complete and are regulated. There are small differences Powder formula has been associated with Enterobacter saka-
between the 3 forms for technical reasons.7 Liquid concen- zakii contamination in immunocompromised neonates in
trate and powder forms require the addition of potable water healthcare facilities.38 Because of the population that they
to reconstitute and can be mixed to various caloric dilutions serve, hospitals only use powder when there is no other option
according to the special need of the infant. available.39 Reconstituted powder formulas have been safely
Ready-to-feed is the most commonly used form in consumed by millions of infants worldwide over the past half
hospitals as it is considered commercially sterile. It is century, so parents of healthy newborns should continue
convenient and limits opportunity for contamination. The to feel comfortable using powder infant formulas. The
Table 12-10 Modified Fat Formulas (per 100 calories)

Enfamil® Enfaport® 3.5 (14%) 10.2 (41%) 5.4 (45%) 30 115 94 52 1.8 280 (30 DHA, ARA
LIPIL calcium caseinate, corn syrup solids MCT (84%), soy oil cal/oz) PRSL 29/100 cals
(Mead Johnson) sodium caseinate *comes in RTU, 30
cal/oz. Water can be
added to dilute to
lower concentrations
Monogen 2.7 (11%) 16 (64%) 2.8 (25%) 48 86 62 48 1 250-22 essential fatty acid
(Nutricia) whey protein corn syrup solids MCT (as fractionated cal/oz ratio n6:n3 of 4.6:1
concentrate, coconut oil), walnut 370-30 *for > 1 y old
L-amino acids oil cal/oz
Lipistart 3 (12%) 12 (47%) 4.6 (41%) 55 108 105 77 1 180-22 *for > 1 y old
(vitaflo) cal/oz
205-24
cal/oz
272-30
cal/oz
Table 12-11 Reduced Mineral Infant Formula (per 100 calories)

Similac PM 60/40 2.2 (9%) 10.2 (41%) 5.6 (50%) 24 80 56 28 0.7 280 no DHA & ARA
(Abbott Nutritionals) whey protein lactose high oleic safflower PRSL 18.3/100 cals
concentrate, oil, soy oil, coconut oil
sodium caseinate

ESPGHAN (European Society for Pediatric Gastroenter- Table 12-12 Increasing Caloric Concentration of Term Infant Formulas
ology, Hepatology, and Nutrition) Committee on Nutrition with Standard Dilution of 20 kcal/oz or 0.67 kcal/mL
recommends that in the home powder infant formulas should Concentration Amount of Powder/Liquid Water
(oz)
be freshly prepared for each feeding and any remaining milk
20 kcal/oz 4 scoops powdered formula* 8
discarded to minimize potential risk of contamination.40 (0.67 kcal/mL) 13 oz liquid concentrate 13
Consumers choose it because it is the least expensive form
24 kcal/oz 5 scoops powdered formula* 8
and can be quickly mixed at any location when needed. (0.8 kcal/mL) 13 oz liquid concentrate 9
27 kcal/oz 5.5 scoops powdered 8
Water (0.9 kcal/mL) formula*
Tap water or boiled and cooled water is adequate to use when 13 oz liquid concentrate 6
preparing formula for healthy infants with a normal immune *Use only the scoop provided with the specific formula. Scoop sizes vary
system and who are fed orally.41 Municipal tap water is more from product to product.
regulated than bottled water. Municipal tap water is fluori-
dated whereas most bottled water is not. Bottled water or Modular Macronutrients
infant fluoridated bottled water may be a good choice when Modular macronutrients can be used to increase caloric
tap water is from a well because well water may contain high concentration. Modulars are available as protein, carbo-
levels of certain minerals. In hospitals only chilled, sterile hydrate, fat, and combinations of macronutrients. The fat
water is recommended in formula preparation.42 and/or carbohydrate modulars may not add as significantly
Infants consuming either human milk or infant formula to the potential renal solute load (PRSL) and osmolality as
exclusively do not have a need for additional water in their diets. concentrating the formula with less water, and fat and/or
Human milk or infant formula provides adequate free water for carbohydrate modulars should be considered when concen-
hydration in hot or dry climates and if the infant is febrile.3 trating calories higher than 24 calories per ounce. Modular
macronutrients will not increase the concentration of
Standard Dilution micronutrients like concentrating just the formula powder
When mixing formulas, healthcare professions should or concentrate. This may be desirable in some situations
suggest that parents read the manufacturer instructions (renal insufficiency) and not desirable in other situations
on the can as instructions may vary by manufacturer and (increased calcium and phosphorus needs in prematurity).
by product. In powdered formulas, only use the scoop that Modulars can be added to the formula when mixing
comes with that particular formula because scoop sizes are or they can be mixed with water and delivered as a bolus
different for each formula. Standard dilution for term infant through the tube separate from formula. To boost caloric
formulas is 20 kcal/oz, or 0.67 kcal/mL, and can be made intake of formula, some common food products or ingredi-
by mixing 1 scoop of powder for each 2 oz of water, or by ents may also be used (eg, table sugar, vegetable oil, or corn
mixing a 13-oz can of concentrate with 13 oz of water. starch). These ingredients may not be ideal, but they are
much less expensive than the manufactured modulars.
Increasing Caloric Concentration
For special feeding situations, both powdered infant Increasing Concentration of Breast Milk
formula or infant formula concentrate can be reconstituted Infants born prematurely often have caloric and nutrient
(Table 12-12) to provide formula with more concentrated deficits, even at discharge, and although breast milk is the
calories than standard dilution. 21 Concentrated liquids best choice for feeding these infants, it may not meet all of
from all manufacturers contain 40 kcal/oz, so the same the caloric and nutrient needs of the infant with signifi-
instructions for preparation and caloric concentration can cant comorbidities.43 Expert opinion and studies show
be used for all. that preterm infants discharged from the hospital at sub-
optimal weight being fed breast milk should continue to be
supplemented to assure adequate nutrient intake.44,45 Some
healthcare professionals suggest adding premature infant
formula or infant formula powder to expressed breast milk to
increase the caloric and nutrient density. There is no evidence
for or against this practice, and there is a great potential for
error. Close medical monitoring is suggested.46

Introducing Complementary Foods amounts of protein, sodium, potassium, and chloride. Milk
to the Infant’s Diet is also limited in EFAs, zinc, and vitamin E. 3
The AAP recommends exclusive breastfeeding for a
minimum of 4 months, but preferably 6 months. There is Foods to Avoid the First Year
no nutrition indication to start complementary foods any Foods that are difficult to chew or can easily choke a child
earlier than 4 to 6 months of age, and starting solids as early or be aspirated should be avoided up to about 4 years of
as 4 months of age has not shown any adverse effects on age. Foods to avoid include, but are not limited to, hotdogs,
growth.3 nuts, grapes, raisins, raw carrots, popcorn, and rounded
Each infant develops at his or her individual rate. An candies. 3
infant is usually ready for solid foods when birth weight has Honey is another food to avoid during the first year of
doubled, there is truncal stability to sit with support, and life. Honey contains a bacteria that results in botulism. The
neuromuscular maturation has been achieved.2 Other signs infant’s developing immune system is not able to adequately
may include frequently putting things in the mouth, leaning protect against the bacteria. Botulism is potentially very
forward and opening the mouth to indicate a desire for serious and can result in death if not diagnosed and treated
food, and consuming more than 32 ounces of human milk properly in the infected infant. 3
or formula each day.2
There is no evidence to support the introduction Toddler Formulas
of foods in any certain order. The general rule is to add 1 Toddlers consuming adequate amounts of nutrients, espe-
“single-ingredient” food at a time and wait about 3 to 5 cially iron, from solid foods do not need formula. Whole
days before introducing a new food, watching for possible cow’s milk is appropriate after 1 year of age. Toddler formulas
intolerances or allergic reactions. 3 Some parents want to (Table 12-13) contain higher amounts of iron, vitamin C,
make their own baby foods. Parents should cook the food and vitamin E than cow’s milk and contain nutrients such
until soft and put it in a baby food grinder or blender until as zinc that cow’s milk does not contain. The calcium and
the desired consistency is reached. For infants just starting phosphorus levels of the toddler formulas are higher than
on solid foods, the consistency should be a smooth puree. infant formulas to match the needs of the growing toddler.
Older infants can tolerate small consistent-sized bits in their Toddler formulas contain DHA and ARA.
food. Parents should avoid adding salt or sugar. 3
A good time to advance textures is when the infant
starts teething. Parents should be aware that “rub on”
teething medications can interfere with chewing and swal-
lowing because muscles in the throat can become numb.
Careful observation is advised.
Juice
After 6 months of age fruit juice can be introduced in a cup
and should be limited to 4 to 6 oz/d. 3 Only 100% fruit juice
should be offered. Fruit juice displaces the more nutrient-
dense human milk or infant formula and therefore should
be used in limited amounts. Infants should not be offered
juice in a bottle or in a cup that can be carried around and
should not consume juice just before bed because of the
increased risk for dental caries. Overconsumption of juice
can lead to osmotic diarrhea due to the high fructose and
sorbitol content. 3
Milk
Milk (whole, 2%, 1%, skim, goat), other than infant formula,
should be avoided during the first year of life. Milk is lower
in iron and has a higher renal solute load due to the higher

Table 12-13 Toddler Formulas (per 100 calories) Standard dilution for these products is 0.67 kcal/mL (20 kcal/oz).
GOOD START® 2.2 (9%) 11.2 (45%) 5.1 (46%) 27 108 190 106 2 265 DHA 0.32%,
Gentle PLUS™ 2 whey protein lactose, corn palm olein, soy oil, ARA 0.64%,
(Nestle/Gerber) concentrate maltodextrin coconut oil, high oleic PRSL 146/L
(from cow’s milk, safflower or sunflower
enzymatically oil
hydrolyzed, reduced
in minerals)
GOOD START® 2.2 (9%) 11.2 (45%) 5.1 (46%) 27 108 190 106 2 265 DHA 0.32%,
Protect PLUS™ 2 whey protein lactose, corn palm olein, soy oil, ARA 0.64%,
(Nestle/Gerber) concentrate maltodextrin coconut oil, high oleic PRSL 146/litre
(from cow’s milk, safflower or sunflower *added probiotics,
enzymatically oil Bifidobacteria
hydrolyzed, reduced lactis
in minerals)
Enfagrow™ 2.6 (10%) 10.5 (42%) 5.3 (48%) 36 130 195 130 2 270 DHA 17 mg,
Premium™ non-fat milk lactose, corn syrup palm olein, soy oil, ARA 34 mg,
Next Step® solids coconut oil, high oleic PRSL 26/100cals
(Mead Johnson) sunflower oils
Similac Go & Grow 2.07 (8%) 10.56 (43%) 5.49 (49%) 24 105 150 81 2 300 DHA 0.15%,
Milk-based non-fat milk, whey lactose high oleic safflower ARA 0.40%,
(Abbott Nutritionals) protein concentrate oil, soy and coconut PRSL 20/100 cals
oils
Bright Beginnings™ 2 2.6 (10%) 10.5 (42%) 5.3 (48%) 36 130 195 130 2 DHA 17 mg,
(PBM Nutritionals) non-fat milk corn syrup solids, vegetable oils ARA 34 mg,
lactose PRSL 26/100cals
Bright Beginnings™ 2 2.6 (10%) 10.5 (42%) 5.3 (48%) 36 130 195 130 2 DHA 17 mg,
with prebiotics non-fat milk corn syrup solids, vegetable oils ARA 34 mg,
(PBM Nutritionals) lactose PRSL 26/100cals
* with added
prebiotic, FOS
Parent’s Choice® 2.6 (10%) 10.5 (42%) 5.3 (48%) 36 130 195 130 2 DHA, ARA
Stage 2 Formula non-fat milk corn syrup solids, palm olein, soy oil,
(PBM Nutritionals) lactose coconut oil, high oleic
safflower oil
GOOD START® Soy 2.8 (11%) 10.9 (44%) 5.0 (45%) 40 116 190 106 2 180 DHA 0.32%,
Plus 2 enzymatically corn maltodextrin, palm olein, soy oil, ARA 0.64%,
(Nestle/Gerber) hydrolyzed soy sucrose coconut oil, high oleic PRSL 175/liter
protein isolate safflower or sunflower
oil
Similac Go & Grow 2.45 (10%) 10.3 (41%) 5.46 (49%) 49 108 150 100 2 200 DHA 0.15%,
Soy-based soy protein isolate, corn syrup solids, high oleic safflower ARA 0.40%,
(Abbott Nutritionals) L-methionine sugar oil, soy oil, coconut oil PRSL 23.7/100 cals
Enfagrow™ Soy 3.3 (13%) 11.8 (47%) 4.4 (40%) 36 120 195 130 2 230 DHA 17 mg,
Next Step® soy protein isolate, corn syrup solids palm olein, soy oil, ARA 34 mg,
(Mead Johnson) L-methionine coconut oil, high oleic PRSL 30/100 cals
sunflower oils

1. Which formula(s) is indicated for transient lactose 2. What is the standard dilution of term infant formulas?
intolerance? A. 15 kcal/oz
A. Enfamil AR LIPIL B. 20 kcal/oz
B. Parent’s Choice Gentle C. 25 kcal/oz
C. Similac Sensitive D. 30 kcal/oz
D. B and C

3. According to the Federal Food, Drug, and Cosmetic 11. Mimouni F, Campaigne B, Naylan M, Tsang RC. Bone
Act, infant formulas that meet a specific medical need mineralization in the first year of life in infants fed human
milk, cow-milk formula or soy-based formula. J Pediatr.
are considered .
1993;122(3):348–354.
A. Exempt 12. Bhatia J, Greer F and the Committee on Nutrition.
B. GRAS (generally recognized as safe) Use of soy-based formulas in infant feeding. Pediatrics.
C. Specialized 2008;121;1062–1068.
D. Medical foods 13. Zeigler RS, Sampson HA, Bock SA, et al. Soy allergy in infant
4. Prebiotics are: and children with IgE-associated cow’s milk allergy. J Pediatr.
1999;134(5):614–622.
A. Oligosaccharides 14. Klemola T, Vanto T, Juntunen-Blackman K, Kalimo K,
B. Complex dietary carbohydrates that are not digest- Korpela R, Verjonen E. Allergy to soy formula and to exten-
ible by humans sively hydrolyzed whey formula in infants with cow’s milk
C. The fuel for beneficial bacteria in the gut allergy: a prospective, randomized study with a follow-up to
D. All of the above the age of 2 years. J Pediatr. 2002;140(2):219–224.
15. Picaud JC, Decullier E, Plan O, et al. Growth and bone miner-
alization in preterm infants fed preterm formula or standard
See p. 487 for answers. term formula after discharge. J Pediatr. 2008;153:616–621.
16. Klein CJ. Nutrient requirements for preterm infant formulas.
References J Nutr. 2002;132(Suppl 16-I):1395S–1577S.
1. World Health Organization. The World Health Organization’s 17. American Academy of Pediatrics Committee on Nutri-
infant feeding recommendation. http://www.who.int/nutrition. Hypoallergenic infant formulas. Pediatrics.
tion/topics/infantfeeding_recommendation/en/. Accessed 2000;106:346–349.
December 15, 2008. 18. Sicherer SH, et al. Hypoallergenicity and efficacy of an amino
2. American Academy of Pediatrics, Section on Breastfeeding. acid-based formula in children with cow’s milk and multiple
Breastfeeding and the use of human milk. Pediatrics. food hypersensitivities. J Pediatr. 2001;138:688–693.
1997;100:1035–1039. 19. Hill DJ, Murch SH, Rafferty K, et al. The efficacy of amino acid-
3. American Academy of Pediatrics, Committee on Nutrition. based formulas in relieving symptoms of cow’s milk allergy: A
Kleinman RE, ed. Pediatric Nutrition Handbook. 6th ed. Elk systematic review. Clin Exp Allergy. 2007;37:808–822.
Grove Village, IL: American Academy of Pediatrics; 2009. 20. Wright EM. Glucose galactose malabsorption. Am J Physiol.
4. Aggett PJ, Agostini C, Goulet O, et al. The nutritional and 1998;275(5):G879–82.
safety assessment of breast milk substitutes and other dietary 21. Joeckel RJ, Phillips SK. Overview of infant and pediatric
products for infants: a commentary by the ESPGHAN formulas. Nutr Clin Prac. 2009;24:356–362.
Committee on Nutrition. J Pediatr Gastroenterol Nutr. 22. Agostoni C, Riva E. Role and function of long-chain poly-
2001;32:256–258. unsaturated fatty acids in infant nutrition. In: Raiha NC,
5. Federal Food, Drug, and Cosmetic Act, § 412, Title 21 Code Rubaltelli FF, eds. Infant Formula: Closer to the Reference.
of Federal Regulations 106, 107. Nestle Nutrition Workshop Series. Pediatric Program. Vol
6. Infant metabolic acidosis and soy-based formula – United 47 Suppl. Philadelphia, PA: Lippincott Williams & Wilkins;
States. MMWR. November 15, 1996:45(45);985–988. http:// 2002.
www.cdc.gov/mmwr/preview/mmwrhtml/00044475.htm. 23. Makrides M, Neumann MA, Simmer K, Gibson RA. Erythro-
Accessed December 1, 2008. cyte fatty acids of term infants fed either breastmilk, standard
7. Klish, WJ. Special infant formulas. Pediatrics in Review. formula, or formula supplemented with long-chain polyun-
1990;12:55–62. saturates. Lipids. 1995;30(10):941–948.
8. VonBerg A, Koletzko S, Filipiak B, et. al. Certain hydro- 24. Martinez M. Tissue levels of polyunsaturated fatty
lyzed formulas reduce the incidence of atopic dermatitis acids during early human development. J Pediatr.
but not that of asthma; three year results of the German 1992;120:S129–S138.
Infant Nutrition Intervention Study. J Allergy Clin Immunol. 25. Berghaus TM, Demmelmair H, Koletzko B. Fatty acid compo-
2007;119(3):7118–7125. sition of lipid classes in maternal and cord plasma at birth. Eur
9. Vanderhoof JA, Moran JR, Harris CL, et.al. Efficacy of a J Pediatr. 1998;157:763–768.
prethickened infant formula: a multicenter double blind, 26. Boza JJ, Martinez-Augustin O. Role and function of nucle-
randomized, placebo controlled parallel group trial in 104 otides in infant nutrition. In: Raiha NC, Rubaltelli FF, eds.
infants with symptomatic gastroesophageal reflux. Clin Infant Formula: Closer to the Reference. Nestle Nutrition Work-
Pediatr. 2003;41:483–495. shop Series. Pediatric Program. Vol 47 (Suppl) Philadelphia,
10. Among healthy 2-month-old infants compared to a standard PA: Lippincott Williams & Wilkins; 2002.
formula. Data on file, AJ68, May 2007. Ross Products Divi- 27. Carver JD. Advances in nutritional modifications of infant
sion, Abbott Laboratories, Columbus, Ohio. formulas. Am J Clin Nutr. 2003;77:1550S–1554S.

28. Koletzko B, Baker S, Cleghorn G, et al. Global standard for 38. Enterobacter sakazakii infections associated with the use of a
the composition of infant formula: recommendations of an powdered infant formula–Tennessee 2001. MMWR Weekly.
ESPGHAN coordinated international expert group. J Pediatr April 12, 2002:51(14);298–300. http://www.cdc.gov/mmwr/
Gastroenterol Nutr. 2005;41:584–599. preview/mmwrhtml/mm5114a1.htm. Accessed March 20,
29. Arslanoglu S, Moro GE, Boehm G. Early supplementation 2009.
of prebiotic oligosaccharides protects formula-fed infants 39. Whaley T, Robbins S. Strategies for Implementing the Guide-
against infections during the first 6 months of life. J Nutr. lines for Handling of Infant Feeding. Building Block for Life.
2007;137:2420–2424. 2004:27(3).
30. Roberfroid M. Prebiotics: the concept revisited. J Nutr. 40. ESPGHAN Committee on Nutrition. Preparation and
2007;137(Suppl 2):830S–837S. handling of powdered infant formula: a commentary by the
31. Kullen MJ, Bettler J. The delivery of probiotics and prebiotics ESPGHAN Committee on Nutrition. J Pediatr Gastroenterol
to infants. Current Pharmaceutical Design. 2005;11:55–74. Nutr. 2004;39(4):320–322.
32. Saavedra JM. Clinical applications of probiotic agents. Am J 41. Mueller C, Nestle M. Regulation of medical foods: toward a
Clin Nutr. 2001;73:1147S–1151S. rational policy. NCP. 1995;10:8–15.
33. Harmsen HJ, Wildeboer-Veloo AC, Raangs GC, et al. Analysis 42. Robbins ST, Beker LT. Infant feedings; Guidelines for prepa-
of intestinal flora development in breast-fed and formula- ration of formula and breastmilk in health care facilities.
fed infants by using molecular identification and detection Chicago, IL: American Dietetic Association; 2004.
methods. J Pediatr Gastroenterol Nutr. 2000;30:61–67. 43. Groh-Wargo S, Sapsford A. Enteral nutrition support of
34. Yoshioka H, Iseki K, Fujita K. Development and differences of the preterm infant in the neonatal intensive care unit. NCP.
intestinal flora in the neonatal period in breast-fed and bottle- 2009;24(3):363–376.
fed infants. Pediatrics. 1983;72:317–321. 44. Aggett PJ, Agostoni C, Axelsson I, et al. Feeding preterm
35. Saavedra JM. Use of probiotics in pediatrics: rationale, infants after hospital discharge: a commentary by the
mechanisms of action, and practical aspects. Nutr Clin Pract. ESPGHAN Committee on Nutrition. J Pediatr Gastroenterol
2007;22:351–365. Nutr. 2006;42(5):596–603.
36. Baldassarre M, Laforgia N, Grosso R, et al. Lactobacillus 45. O’Connor DL, Khan S, Weishuhn K, et al. Growth and
GG improves recovery from cow milk protein allergy colitis nutrient intakes of human milk fed preterm infants provided
compared to extensively hydrolyzed formula alone. Dig Liv with extra energy and nutrients after hospital discharge. Pedi-
Dis. 2008;40:A82. atrics. 2008;121:766–776.
37. Drudy D, Mullane NR, Quinn T, Wall PG, Fanning F. Enter- 46. Academy of Breastfeeding Medicine. Clinical Protocol #12,
obacter sakazakii: an emerging pathogen in powdered infant Transitioning the breastfeeding/breastmilk-fed prema-
formula. Clin Infect Dis. 2006;42:996–1002. ture infant from the neonatal intensive care unit to home.
September 17, 2004. www.bfmed.org. Accessed October 8,
2009.

13
Growth Assessment and Monitoring

Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 143 1. Understand the importance of growth assessment in
Growth Assessment. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 144 pediatrics.
Weight 2. Learn appropriate techniques and parameters for
Height (Length/Stature) assessing growth.
Head Circumference 3. Employ growth charts in the assessment of growth
Weight-for-Length disorders.
Failure to Thrive
Body Mass Index (BMI)
4. Understand limitations of growth charts.
Ideal Body Weight (IBW)
Interpretation of Growth Charts and Percentiles . . . . . . 146 Introduction
Assessing Linear Growth Potential Normal growth and development from infancy through
Limitations of Growth Charts as a Diagnostic Tool. . . . . 147 adolescence to adulthood is the ultimate goal of pediatric
care. Growth is most rapid during infancy, decelerates
during childhood, and has a final increase in velocity during
puberty. The relative protein and energy requirements of
infants, children, and adolescents mirror the growth phase.
Effective nutrition support requires assessment of nutrition
status; protein, energy, fluid, and electrolyte requirements;
and monitoring response to intervention. These objec-
tives are accomplished through careful and repeated
measurements of growth, nutrition status, and biochemical
parameters over time.
The growth parameters most easily obtained are weight
(kg), length/height (cm), head circumference (cm), and
body mass index (BMI) (kg/m 2). Other equally informative
but less frequently obtained parameters include skinfold
measurements, extremity circumferences, and limb lengths.
The Centers for Disease Control and Prevention (CDC) has
published reference charts (www.cdc.gov/growthcharts) for
monitoring growth in North American children aged from
birth to 20 years. In 2006 the World Health Organization
(WHO) published international weight, length/height, and
BMI-for-age growth standards for children aged from birth
143
to 5 years. The data used to derive WHO growth standards Table 13-1. Recommended Time Intervals for Monitoring Short- and
were based on healthy breastfed infants and young children Long-Term Growth in Children3,4,11
representing all continents. Free download of these charts Measurement Age Group Short-Term Long Term
Follow-Up
is available at www.who.int/childgrowth/standard/cht.
Pre-term
Later in 2007 the WHO also published height- and BMI- Daily Weekly
infants
for-age growth charts for children aged 5 to 19 years, and Weight (kg) Birth to 6 mo 1–2 wk 2 mo
weight-for-age growth standards for children aged 5 to 10 6–36 mo 1–4 wk 6 mo
years (http://www.who.int/childgrowth/en/). 2–20 y 2–8 wk 12 mo
After age 2 years the linear growth in most healthy Pre-term
— 4 wk
children stabilizes along a percentile channel that projects infants
Length (cm)
to a final height within 2 standard deviations (SDs) Birth to 6 mo 4 wk 2 mo
6–36 mo 6 mo
(± 8.5 cm) of the calculated mid-parental height.1 Likewise
Height (cm) 2–20 y 3–6 mo 6–12 mo
BMI after age 2 years can now be linked to adolescent and
Head circumference Birth to 6 mo 2 mo
adult BMI, thus providing a window of opportunity for (cm) 6–36 mo 4 wk 6 mo
early intervention to prevent obesity. Thus growth charts BMI (kg/m2) 2–20 y 12 mo
are important road maps for assessing growth status, Soft tissue measurements
response to nutrition intervention, and detection of growth Mid-arm circumference (mm) 4 wk 3–12 mo
disorders. Every pediatric clinician should become familiar Triceps skinfold (mm) 4 wk 1–12 mo
with use and interpretation of childhood growth charts.
The updated 2000 CDC age- and gender-based weight-
Growth Assessment for-age growth reference charts for children aged birth to
Proper instruments, accurate measurement techniques, 36 months and 2 to 20 years should be used (see Chapter
and appropriate reference data are essential for meaningful 33). Individualized weight-for-age percentiles and SD scores
assessment and interpretation of growth status. (z scores) may be computed using the free access CDC Epi
Appropriate time intervals between measurements Info™ nutrition calculator and statistics program. 6 Disease-
should be used when monitoring short- and long-term specific growth charts are available for Down syndrome,7
growth. Weight measurements, which are easy to obtain achrondroplasia, 8 and other genetic disorders. 3
and associated with the least measurement error, should be
made frequently. Length/height increments occur more Height (Length/Stature)
slowly. Length/height is more reliably assessed over longer Linear growth status (cm) is influenced by hereditary
intervals because even with good technique, measurements factors, nutrition, chronic disease, and genetic disorders.
may be associated with an inter-observer measurement error Correct equipment and measuring technique are important
of 0.5 cm.2 Middle upper arm circumference and triceps for obtaining reliable assessments. Accuracy is improved by
skinfold thickness are more difficult to measure reliably and repeating the measurements and obtaining an average. Seri-
reproducibly; however, they correlate well with nutrition ally obtained growth measurements should be plotted on
status.3 See Table 13-1 for suggested time intervals. age- and gender-appropriate CDC growth reference charts.
Pubertal status based on the Tanner system for growth Length (supine) is measured to the nearest 0.1 cm in
of pubic hair in both sexes, breast development in girls, and children younger than 3 years or older children who cannot
genital development in boys should also be assessed for the stand. Length should be assessed using a length board
purposes of interpreting growth velocity during later child- (stadiometer) or firm surface. It requires 2 measurers: one
hood and adolescence. 5 to position the head and the other to stretch and straighten
the legs so that the knees are flat and feet at a 90-degree
Weight angle with the footboard. 3
Infants should be undressed to the diaper and older children Standing height is measured to the nearest 0.1 cm. It is
measured in light clothing using an age-appropriate scale. obtained after age 2 years in children able to support their
Measurements should be in metric units (kg) and rounded weight evenly on both feet. Subjects should stand barefooted
off to 1 decimal point. with heels, buttocks, shoulders, and back of head against the
measuring device and eyes looking straight ahead. 3
The updated 2000 CDC age- and gender-based

GROWTH ASSESSMENT AND MONITORING 145
combined growth reference charts for children aged birth length percentile suggests there is a non-nutrition etiology
to 36 months and 2 to 20 years, respectively, should be used. for impaired linear growth (eg, growth hormone deficiency
Individualized length/height for age percentiles and SD and other endocrine, genetic, and skeletal disorders).
scores (z scores) can be computed using the free access CDC Decreased weight-for-length (< 5th percentile) is consis-
Epi Info™ nutrition calculator and statistics program.6 tent with nutrition failure to thrive (FTT). Impaired growth
Disease-specific growth charts are available for Down in children with nutrition FTT is characterized by weight
syndrome, achondroplasia, and other genetic disorders. 3,7,8 more severely impaired than length and head circumfer-
Tanner-Whitehouse height velocity charts may be used ence. FTT may be secondary to organic factors (ie, illness
to monitor rate of height gain in girls aged 1 to 16 years impairing food intake, digestion, absorption, or utilization).
and boys aged 1 to 19 years.9 Height below the 5th percen- Non-organic FTT refers to factors external to the child (eg,
tile indicates short stature. Height velocity below the 5th food deprivation). Mixed organic and non-organic FTT may
percentile suggests severely stunted growth that warrants occur following infections, gastroenteritis, or any illnesses
assessment of pubertal status, screening for familial short associated with prolonged inadequate calorie intake
stature, constitutional growth delay, and evaluation for secondary to inappropriate food restrictions or behavioral
chronic illness (eg, chronic inflammatory diseases, endo- feeding problems.
crinopathy, and skeletal and genetic disorders).
Children with musculoskeletal deformities (eg, Failure to Thrive
cerebral palsy, spinal kypho-scoliosis, and extremity The term FTT is not a diagnosis or specific disease entity
contractures) that prevent accurate measurement of stature but denotes weight gain or linear growth that is less than
may be assessed using upper-arm and lower-limb lengths. expected for age. FTT may be referred to as wasting when
Obtaining these measurements requires training in anthro- weight is disproportionately affected vs. stunting when
pometry and special instruments (anthropometers). Growth length/height is significantly impaired.
reference charts are available for upper-arm and lower-limb Wasting may occur following an acute illness. The
extremity lengths for girls aged 3 to 16 years and boys aged growth changes are: weight-for-length percentile or BMI
3 to 18 years.10 percentile < 5th percentile (~2 SD) or involuntary lack of
weight gain or loss resulting in dropping below any 2 major
Head Circumference percentile channels (95th, 90th, 75th, 50th, 25th, 10th,
Brain growth occurs most rapidly from birth to age 36 and 5th).
months and thereafter slows down. Head circumference Stunting occurs following chronic inadequate caloric
(cm) must be routinely measured using a non-stretchable intake, disease, or endocrinopathy. The diagnostic growth
measuring tape. Anteriorly the tape is placed just supe- findings are: length or height < 5th percentile (~2 SD) or
rior to the eyebrows and posteriorly it is placed so that the consecutive height measurements dropping below any
maximum circumference is measured. 3 2 major percentile channels.
Impaired brain growth and size is a rare complication Marasmus is moderate-to-severe FTT without edema.
of chronic malnutrition and is not characteristic of primary Kwashiorkor is moderate-to-severe FTT in association with
skeletal disorders. Therefore, children with disproportion- hypoalbuminemia and edema.
ately sized heads should be evaluated for other disorders The WHO classifies FTT as moderate or severe using
impacting brain or skull size. criteria of weight-for-length/height and length/height-for-age
SD scores and presence or absence of edema (Table 13-2).
Weight-for-Length
Weight-for-length percentiles provide a means of assessing Table 13-2 World Health Organization Classification of Malnutrition12
a child’s weight while taking into account his or her length. Classification
They are used to screen overweight and underweight in Moderate Severe
children aged < 36 months. See 2000 CDC weight-for- Yes (Edematous
Edema No
length growth reference charts for children aged birth to malnutrition)
36 months. Weight-for-length
–3 to –2 < –3 (wasting)
z score*
Increased weight-for-length percentile > 90% indi-
Height-for-age z score* –3 to –2 < –3 (stunting)
cates overweight.11 When associated with significantly
*Growth channels of WHO international growth charts are along z scores
decreased length percentile (< 5%), increased weight-for- –3; –2; –1; 0; 1; 2 and 3.

Body Mass Index (BMI) wasting; 70% to 80% moderate wasting; 60% to 70% severe
BMI is a composite index used to relate appropriateness wasting, and < 60% as severe wasting14 approaching incom-
of body weight for height. It is computed by dividing body patibility with survival.15
weight in kilograms by height in meters squared (weight IBW changes more rapidly than BMI. Therefore it may
(kg)/height (m)2). It is very useful for screening and clas- be used to monitor short-term response to nutrition support
sifying overweight and obesity. However, BMI does not or weight reduction therapy.
distinguish between overweight from excess body fat, Computing IBW requires a growth chart and several
increased muscle mass, or even increased weight attrib- steps unlike BMI, which is a simple calculation with known
uted to large bones in tall people. Therefore, additionally cutoff values that correlate with morbidity.
estimating body fat stores by physical exam or measuring
triceps skinfold thickness is essential for interpreting BMI. Interpretation of Growth Charts
The normal range of BMI substantially changes with age and Percentiles
in children. BMI is initially low at birth and then rapidly A percentile value represents the proportion of children at
increases during infancy to peak at age ~1 year. BMI values a given age with growth parameters similar to or less than
then gradually decline, reaching a nadir between ages 2 to 4 the measured value. The most effective way to use growth
years. It then rebounds at age ~7 years as children begin to charts diagnostically is through serial measurements. The
accrue gender unique body fat patterns (adiposity rebound) major percentile channels are labeled lines extending on
and steadily increases throughout puberty and adolescence. the growth chart. They correspond with the 5th, 10th, 25th,
Early occurrence of BMI rebound (before age 5.5 years) is 50th, 75th, 90th, and 95th percentiles.
associated with a longer period of accumulating body fat The 50th percentile corresponds to the median/mean
and thus greater risk for persistent overweight throughout measurement for the growth parameter at a specific age. The
childhood, adolescence, and into adulthood.13 5th and 95th percentiles correspond to ~2 SDs away from
The importance of BMI is its strong correlation with risk mean value. Growth measurements further than 2 SDs
for cardiovascular disease and morbidity. Growth charts from the mean are significantly deviated from normal and
correlating BMI values of children and adolescents with thus require evaluation for disease.
adulthood BMI have been available since 2000. Therefore, Serially obtained growth measurements that rise or
BMI is very useful for screening and monitoring overweight drop below 2 major percentile channels represent accel-
and obesity in children and adolescents. The definition of erated or decelerated growth, respectively. This calls for
overweight is BMI for age ≥ 85th and < 95th percentile. verifying accuracy of the growth plot and in-depth evalua-
The terminology “obesity” denotes excess body fat and the tion if confirmed.
associated health risks. The cutoff for obesity in youth is Growth measurements falling below the 5th percen-
defined as BMI for age ≥ 95th percentile or calculated BMI tile or exceeding the 95th percentile (~±2 SDs) cannot be
≥ 30 kg/m2 , whichever is lower.11 assigned a percentile value. This is because distribution of
BMI for age < 10th percentile may be used to assess measurements above or below the 5th and 95th percentiles
underweight or risk for underweight. However, BMI’s is skewed. Therefore comparison of growth measurements
correlation with risk for morbidity is less sensitive for under- that fall outside the 2-SD range is best assessed by using z
weight patients. scores (SD scores) (Table 13-3). SD scores for any growth
CDC age- and gender-based BMI growth reference measurement can be computed using Web-based Epi-Info
charts for 2000 are available for children and adolescents aged Nutrition anthropometric software (CDC Epi Info™ nutri-
2 to 20 years.6 Computing BMI z score is also available online tion calculator).6
using the free access CDC Epi Info™ nutrition calculator.6
Table 13-3 Comparison of Percentiles and SD Scores (z scores)
Ideal Body Weight (IBW) Percentile Corresponding z score
This is a method to compare the patient’s actual weight with 0.1 –3
the median weight for stature. It is calculated as follows: 3rd –2
[Patient’s measured weight (kg)/50th percentile weight (kg) 16th –1
for patient’s height] × 100. A variation of ±10% is considered 50th 0
within normal. A value > 120% corresponds to significant 84th 1
overweight. The Waterlow criteria classify 80% to 90% mild 97th 2
99.9th 3

GROWTH ASSESSMENT AND MONITORING 147
Assessing Linear Growth Potential 3. The CDC recommends terminology of obesity in chil-
The child’s height percentile before pubertal growth should dren with BMI > 95th percentile.
fall within 2 SDs (±8.5 cm) of the mid-parental height A. True
determined as follows1: B. False
Boys ([Father’s height (cm) + mother’s height (cm) + 4. Diagnosis of FTT or wasting is based on each of the
13 cm]/2) ±8.5 following except:
Girls: ([Father’s height (cm) + mother’s height (cm) – A. Length < 3rd percentile
13 cm]/2) ± 8.5 B. Weight-for-length or BMI < 3rd percentile
Pubertal stage should always be assessed because of its signif- C. Change in weight percentile from 90th to 50th
icant impact on interpretation of weight and height gain in D. Change in weight percentile from 50th to 25th
females > 8 to 9 years and males > 12 to 13 years. Validated 5. The 50th percentile weight, height, or BMI for age
self-assessment figures for pubertal status are available. corresponds with the following z score:
A. 2
Limitations of Growth Charts B. 1
as a Diagnostic Tool C. 0
• The reliability of growth charts as an assessment tool D. –1
depends on accuracy of growth measurements. There- E. –2
fore the nutrition specialist should be trained in proper 6. Which of the following is incompatible with survival?
nutrition assessment technique. A. BMI < 3rd percentile
• The specificity of growth charts in detecting growth B. Change in weight percentile from 75th to 5th
disorders is higher with serially obtained measurements percentile
(longitudinal data). Interpretation of growth disorders C. Height z score –5
should not be based on a single growth measurement. D. ≤ 60% of ideal body weight
• Growth charts are important for detecting extreme devi- 7. Length measurements in an 18-month-old toddler are
ations from normal. Thus milder deviations (< 2 SDs) obtained with the child standing upright.
may be overlooked. A. True
• Growth charts are a screening tool and not diagnostic. B. False
Growth charts do not replace careful history, physical
examination, and diagnostic tests. See p. 487 for answers.
• BMI is a ratio of weight corrected for height. It corre-
lates very well with body fat and risk for cardiovascular References
disease. However, weight is composed of body fat and 1. Tanner JM, Goldstein H, Whitehouse RH. Standards for chil-
fat-free mass (organs, muscle, and bones). Tall and/or dren’s height at ages 2-9 years allowing for heights of parents.
Arch Dis Child. 1970;45(244):755–762.
muscular people tend to have high BMI values unrelated 2. Ulijaszek SJ. Measurement error. In: Ulijaszek SJ, Johnston
to body fat (ie, increased weight attributed to large bones FE, Preece MA, eds. The Cambridge Encyclopedia of Human
and muscle mass). Obesity specifically refers to excess Growth and Development. Cambridge, UK: Cambridge
body fat and the associated medical risks. Therefore BMI University Press; 1998:28.
alone is inadequate for diagnosing obesity. Diagnosis of 3. Zemel BS, Riley EM, Stallings VA. Evaluation of method-
ology for nutritional assessment in children: anthropometry,
obesity additionally requires estimation of excess body
body composition, and energy expenditure. Annu Rev Nutr.
fat by either physical exam or skinfold anthropometry.11 1997;17:211–235.
4. Owen GM. The assessment and recording of measurements
Test Your Knowledge Questions of growth of children: report of a small conference. Pediatrics.
1. BMI at age 18 months is correlated with BMI in 1973;51(3):461–466.
adolescence. 5. Tanner JM. Normal growth and techniques of growth assess-
ment. Clin Endocrinol Metab. 1986;15(3):411–451.
A. True 6. Centers for Disease Control and Prevention. Epi Info™ Down-
B. False loads. http://www.cdc.gov/epiinfo/downloads.htm. Accessed
2. Diagnosis of obesity is based on BMI for age > 85th November 12, 2009.
percentile. 7. Myrelid A, Gustafsson J, Ollars B, Anneren G. Growth charts
A. True for Down’s syndrome from birth to 18 years of age. Arch Dis
Child. 2002;87(2):97–103.
B. False

8. Hoover-Fong JE, McGready J, Schulze KJ, Barnes H, Scott 12. World Health Organization G. The management of severe
CI. Weight for age charts for children with achondroplasia. malnutrition: A manual for physicians and other senior health
Am J Med Genet A. 2007;143A(19):2227–2235. workers. 1999:4–7. http://whqlibdoc.who.int/hq/1999/
9. Tanner JM, Davies PS. Clinical longitudinal standards for a57361.pdf. Accessed November 12, 2009.
height and height velocity for North American children. J 13. Whitaker RC, Pepe MS, Wright JA, Seidel KD, Dietz WH.
Pediatr. 1985;107(3):317–329. Early adiposity rebound and the risk of adult obesity. Pediat-
10. Spender QW, Cronk CE, Charney EB, Stallings VA. Assess- rics. 1998;101(3):E5
ment of linear growth of children with cerebral palsy: use 14. Waterlow JC. Classification and definition of protein-calorie
of alternative measures to height or length. Dev Med Child malnutrition. Br Med J. 1972;3(5826):566–569.
Neurol. 1989;31(2):206–214. 15. Cahill GF Jr. Starvation in man. N Engl J Med.
11. Barlow SE; Expert Committee. Expert committee recommen- 1970;282(12):668–675.
dations regarding the prevention, assessment, and treatment
of child and adolescent overweight and obesity: summary
report. Pediatrics. 2007;120(Suppl 4):S164–S192.

14
Obesity and Metabolic Disorders
Michelle Battista, BS, PhD Candidate and Robert Murray, MD

Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 149 1. Identify the components that comprise the metabolic
What Is the Metabolic Syndrome in Adults? . . . . . . . . . . 150 syndrome diagnosis in the adult population.
2. Describe the most common reasons why the meta-
Metabolic Syndrome Controversies Among Adults . . . . . 150
Cut-points bolic syndrome, as a diagnosable entity, has not been
Etiology accepted in the pediatric population.
Synergistic Risk and Treatment 3. Learn about the Expert Committee Recommendations
What Is the Metabolic Syndrome in Children? . . . . . . . . 151 in pediatric practice.
Select Metabolic Syndrome Controversies in Children
Applying the Metabolic Syndrome Cluster Introduction
to a Pediatric Population . . . . . . . . . . . . . . . . . . . . . . . . . 153 Since the early 1900s evidence has suggested the coexis-
A Clinical Approach to the Identification tence of chronic disorders associated with diabetes mellitus
of the Metabolic Syndrome and Its Attendant and coronary heart disease (CHD).1 It wasn’t until the
Cardiovascular Disease Risks. . . . . . . . . . . . . . . . . . . . . . 153 years between 1980 and 1990 that scientists developed an
Establishing a Risk Factor Profile: Expert Committee understanding of the mechanisms underlying the connec-
Recommendations
Role of Socioeconomic Status and Ethnicity
tion between obesity, hypertension, hyperlipidemia, and
Nutrition and Physical Activity Behaviors type 2 diabetes mellitus and its relationship to increased
Acanthosis Nigricans cardiovascular disease (CVD) risk. Metabolic syndrome
Expert Committee Recommendations . . . . . . . . . . . . . . . 155 was a term first used to describe how environmental and
BMI Percentile genetic factors work together to produce this constellation
The Family Health History of chronic metabolic disorders.1 However, it was the earlier
Behaviors work of Gerald Reaven2 that set the precedent for how the
A Focused Review of Systems and Targeted Physical Examination
metabolic syndrome is applied within the clinical world
Laboratory Analysis
today. In 1988, Reaven’s Banting Lecture described the rela-
The Element of Time. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 156
tionship between hyperinsulinemia, glucose intolerance,
The Role of Weight Reduction, Proper hypertension, and free-fatty acid metabolism and their
Nutrition, and Physical Activity. . . . . . . . . . . . . . . . . . . . . 157
association with CVD. Reaven hypothesized that the state
Summary. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 158 of insulin resistance was the driver for metabolic change and
represented the common pathophysiological link between
these otherwise unrelated metabolic events.2
Through the 1990s, distinct perspectives on the etiology
of metabolic syndrome began to emerge, coupled with
the inclusion of additional biomarkers such as measures
149
of insulin resistance and markers of pro-inflammation to diagnosable entity. The controversy begins with the criteria
augment the original components. This newfound knowl- used. Currently, there are 3 sets of diagnostic criteria widely
edge resulted in several monikers being applied: “syndrome accepted for the metabolic syndrome. These include defini-
X,” “the deadly quartet,” and “the insulin resistance tions from the National Cholesterol Education Program,
syndrome.” However, in 1999 the term metabolic syndrome Adult Treatment Panel III (NCEP-ATP III),6 the World
reappeared, now evolved from a hypothesis to a clinical Health Organization,7 and the International Diabetes
entity. It is an emerging diagnosis applied to the adult popu- Federation (IDF).8 Each of their components, etiological
lation and, to a lesser extent, pediatrics. The diagnosis of perspectives, and intervention strategies can be summa-
metabolic syndrome has been subject to criticism, as much rized (Table 14-1).
remains unknown about the cumulative risk of its compo- Fundamentally, the components that comprise each
nents and the utility of making this diagnosis. 3,4 Despite of the metabolic syndrome definitions are similar. They
these criticisms, identification of metabolic syndrome and feature a measure of body fatness, hypertension, triglycer-
its component disorders among adults or children offers ides, high-density lipoprotein (HDL) cholesterol, and some
useful information about the patient’s metabolic risk, partic- measure of glucose intolerance. Yet, it is important to note
ularly that associated with future cardiovascular morbidity the distinctive arrangement of diagnostic criteria and the
and mortality. 5 management focus of the 3 definitions.
What Is the Metabolic Syndrome in Adults? Metabolic Syndrome Controversies

The early work of Hanefield and Reaven described the meta- Among Adults
bolic syndrome as a constellation of metabolic risk factors Lack of a single set of criteria for the metabolic syndrome
including obesity, hypertension, dyslipidemia, and glucose in adults has created confusion among practitioners. Such
intolerance, all of which are associated with increased cardio- inconsistencies hamper determinations of the specificity
vascular mortality. However, today the metabolic syndrome and sensitivity of the metabolic syndrome diagnosis, as
is no longer viewed as a novel concept, but has surfaced as a well as its prevalence.9 Experts offer several reasons why a
Table 14-1 Etiology and Diagnostic Criteria of the Metabolic Syndrome in Adults
Diagnostic Criteria Etiological Underpinnings Recommendations
National Cholesterol Three or more of the following: The etiological perspective focuses on To control risk, NCEP-ATP III
Education Program, Adult 1) Abdominal Obesity risk for cardiovascular disease which recommends weight control and
Treatment Panel III (NCEP- 2) Elevated Triglycerides is attributed to environmental and physical activity as target therapeutic
ATP III)6 3) Low HDL-Cholesterol genetic causes. interventions.
4) Hypertension
5) Raised Fasting Plasma Glucose
World Health Organization A measure of glucose intolerance The etiological perspective focuses on To control risk, WHO recommends
(WHO)7 characterized by: ameliorating risk for type 2 diabetes weight control, physical activity, and
1) Impaired Glucose Tolerance mellitus which is attributed to the the use of insulin sensitizing agents
2) Impaired Fasting Glucose state of insulin resistance. as target therapeutic interventions.
3) Diabetes
4) Insulin Resistance
Plus 2 or more of the following:
4) Abdominal Obesity
5) Elevated Triglycerides
6) Low HDL- Cholesterol
7) Hypertension
8) Microalbuminuria
International Diabetes A measure of body fatness The etiological perspective focuses Similar to the NCEP-ATP III, IDF
Federation (IDF)8 characterized by: on the need to establish a universally recommends lifestyle changes
1) Abdominal Obesity accepted definition for metabolic including reducing calorie intake,
Plus 2 or more of the following: syndrome in research and clinical increasing physical activity, and
2) Elevated Triglycerides practice. altering dietary habits to mitigate risk.
3) Low HDL-Cholesterol
4) Hypertension
5) Raised Fasting Plasma Glucose

OBESITY AND METABOLIC DISORDERS 151
consensus definition for the metabolic syndrome has not Synergistic Risk and Treatment
been reached. Is the risk of metabolic syndrome greater than the sum of its
parts? In other words, is it truly a syndrome? Even Gerald
Cut-points Reaven challenged the idea that the diagnosis of the meta-
Evidence has failed to identify appropriate cut-point values bolic syndrome was itself a clinical entity of greater value
for any given metabolic component. Worldwide adoption than its individual components. From a clinical standpoint,
of Westernized eating and physical activity behaviors has the influence of the metabolic syndrome suggests to the prac-
resulted in an increased prevalence of obesity, diabetes, titioner the presence of CVD risk and therefore should be
stroke, and heart disease in what were once healthy popula- fully evaluated and aggressively treated.4 Evidence implies
tions. Researchers have learned that the degree of metabolic that after adjusting for each of its individual components, the
risk associated with developing CVD is distinct among metabolic syndrome is no longer associated with early CVD
people with diverse ethnic backgrounds. One good example mortality.18 In an analysis of diabetics and non-diabetics
is the differences of dyslipidemias among various ethnic with the presence or absence of the metabolic syndrome,
groups. In the African American population, the stan- those with diabetes and the metabolic syndrome had the
dard cutoff values for triglycerides and HDL-cholesterol highest prevalence (19.2%) of CHD mortality, followed by
predicted insulin resistance is only 17%.10 Furthermore individuals with metabolic syndrome only (13.9%). Despite
insulin resistance and triglycerides were found to be this significant association of the metabolic syndrome and
inversely correlated (ie, as insulin levels rose with insulin CVD mortality, multivariate analysis confirmed the pres-
resistance, triglycerides fell). In this way markers for dyslip- ence of elevated blood pressure, diabetes, and low HDL
idemia within the range of normal may prove insensitive cholesterol, not the metabolic syndrome, were significant
and fail to identify individuals, particularly African Ameri- predictors for CHD.19 Similarly, the evaluation of metabolic
cans, who are insulin resistant and at risk for cardiovascular syndrome and the 11-year risk of incident CVD confirmed
damage.11 Furthermore, ethnic differences in metabolic risk that when all 5 metabolic syndrome parameters are consid-
have been reported for measures of waist circumference ered, metabolic syndrome as a whole does not incur greater
and hypertension among African Americans, Hispanics, CVD risk when compared with the sum of the individual
Caucasians, Iranians, and Asians.9,12–15 These findings components.20
justify the need to assess the obese patient with a tailored Even though data suggest that the entity of the meta-
approach to capture global metabolic risks. bolic syndrome does not incur risk greater than the sum
of its parts, it has been shown that individuals diagnosed
Etiology with the cluster of disorders that comprise the metabolic
Controversy around the metabolic syndrome has syndrome suffer greater cardiovascular morbidity and
surrounded the criteria utilized to make the diagnosis. mortality when compared with individuals without the
Because the etiological underpinnings of the metabolic syndrome. According to the NCEP-ATP III Framingham
syndrome are substantially altered by ethnic variability Risk Score, approximately one-third of individuals with
it is difficult to build a single, all-inclusive definition.1,4,9 the metabolic syndrome are classified as “high risk.” 21
Since Reaven, the basic connecting point uniting the As demonstrated in the Framingham Offspring and
various components has been insulin resistance. Yet even San Antonio Heart Study, the predicted risk of CHD in
in this there is controversy. Some believe that the primary individuals with the metabolic syndrome was significant
pathway leading to the metabolic syndrome is the result of (11.8% and 9.8%, respectively) when compared with indi-
glucose intolerance and diabetes9 whereas others suggest viduals without the metabolic syndrome (7% and 6.8%,
that glucose has no direct role in the metabolic syndrome respectively). Studies looking at incident CVD mortality
or insulin resistance.16,17 These individuals promote the indicate a twofold increase among individuals having
surprising hypothesis that it is disordered fat metabolism, the metabolic syndrome compared to those without the
not glucose metabolism, which is the etiologic prime mover syndrome.19,20,22
for development of insulin resistance and, as a result, the
metabolic syndrome. Although the current research has not What Is the Metabolic Syndrome in Children?
yet detailed the sequence of events leading to the insulin- Similar to the adult classification of the metabolic syndrome,
resistant state that precedes the metabolic syndrome, no consensus definition in the pediatric population exists,
mounting evidence supports the role of abnormal fat despite begin widely studied among adolescents. This has
metabolism.16,17 created further controversy in the utility of the metabolic

syndrome in children. A recent review23 published in 2008 standardized protocol has been accepted for obtaining its
reported 40 unique definitions characterizing pediatric measurement in clinical practice. 34
metabolic syndrome, most emanating from the NCEP
definition for adults. 23 Depending on the criteria used to Puberty
classify the syndrome, prevalence among obese children Perhaps the greatest confounding factor for the applica-
and adolescents ranges from 26% to 49.7%. 24–26 However, tion of metabolic syndrome in pediatrics is the change of
there are a few fundamental problems with the metabolic the body’s metabolic milieu that occurs during the years of
syndrome in children and adolescents. 27 Lack of consensus puberty. The combined metabolic effects of growth hormone
on etiology, age, and developmentally appropriate cut-point and insulin-like growth factor 1 (IGF-1) are associated with
measures for components of the metabolic syndrome in a normal state of mild insulin resistance, which follows the
children, the effects of growth stage, puberty, and ethnicity onset of puberty. 35 Furthermore, this phenomenon appears
as well as emerging evidence on the role of non-traditional to be independent of body fat. 36 Thus, from the standpoint
risk factors, all need to be considered. This discussion will of the metabolic syndrome, puberty-induced insulin resis-
focus briefly on issues such as cut-points, puberty, and non- tance complicates the task of attributing insulin resistance
traditional risk factors including the pro-inflammatory to the normal pubertal changes versus the metabolic conse-
state and anatomical changes to the vasculature. Brambilla quences of overweight and obesity.
et al 27 offers a more complete review of the major and minor
concerns with the metabolic syndrome in children and Non-Traditional Cardiovascular Risk Factors
adolescents. Furthermore, a scientific statement from the Insults to the cardiovascular system are associated with
American Heart Association (AHA) was released in 2009. obesity and insulin resistance in childhood and adolescence.
In this update to the 2003 report, the AHA provides a more Formation of plaques and fatty streaks, deposited in the
comprehensive synopsis of the current advancements, chal- blood vessel walls, are associated with abnormal lipids and
lenges, and limitations to applying the metabolic syndrome high blood pressure. All of these abnormalities have been
to the child and adolescent populations. 28 found among obese children and adolescents. For example,
excess body weight drives metabolic change resulting in
Select Metabolic Syndrome Controversies in Children insulin resistance and even vascular dysfunction. Over time
anatomical changes to the arterial wall begin to develop and
Cut-point by some are thought to be the earliest indicators of risk for
Pediatric-specific cut-points that are sensitive to age, gender, CVD. 37,38 Further damage to the blood vessel wall compro-
and ethnicity have not been adapted for the majority of the mises arterial distensibility. At this point the ability for the
metabolic syndrome components,27,29,30 thus making it diffi- blood vessel to contract and relax is compromised. Vascular
cult to classify the syndrome as a diagnosable entity in the resistance rises and high blood pressure ensues. 37 Disruption
pediatric population. Wide variations in pediatric-specific of the anatomical and physiological integrity of the vascular
cut-points have been found across studies23 with many system appears to develop silently during childhood, even as
assigning arbitrary threshold values with no proven basis to young as age 5. The persistence of these anatomical vascular
predict future health risk. 31 One example that is subject to changes signifies a new wave of “non-traditional” cardiovas-
much debate is the value of waist circumference to substan- cular risk factors that, like hypertension and dyslipidemia,
tiate metabolic syndrome risk in children. Some argue need to be evaluated and treated aggressively. Happily the
that measurements of visceral fat, when compared with evidence demonstrates that through physical activity and
other measures of body fatness, are the single most predic- proper nutrition these changes can be reversed. 37
tive anthropometric value of the metabolic syndrome. 32 Since Reaven’s lecture in 1988, another major finding
However, in children, percentile values for waist has occurred that has expanded our perspective on the meta-
circumference are poorly established across age groups. bolic syndrome. Chronic inflammation has been found not
Furthermore, the currently established cut-point references only to be closely associated with obesity in adults, children,
for waist circumference in children are not suitable for all and adolescents but also connected with each element of the
ethnic populations, as most guidelines result from studies metabolic syndrome. 39–42 This interconnectedness shapes
conducted in white, European descendents. 33 Even if the the development of CVD. Among a number of actions,
appropriate, age-specific cut-points were established for chronic inflammation, as identified by the biomarker high-
children, the value of waist circumference is arbitrary, as no sensitivity C-reactive protein (hs-CRP), promotes platelet

adhesion, a critical step in the expansion of atherosclerotic more studies are needed to determine the pathophysiology,
plaques. Further, in CVD the atherosclerotic lesion is natural history, and treatment of NAFLD, 55 an expert
expanded and made unstable by the influx of inflamma- committee recognizes that the biomarkers for liver function,
tory cells, resulting in heart disease and stroke.43 This link alanine aminotransferase (ALT) and aspartate aminotrans-
between the immune-inflammatory system and the body’s ferase (AST), are reasonable markers for NAFLD and are
metabolism is a consequence of cytokines secreted from an important part of the laboratory assessment of the obese
excess adipose tissue. child. 56 The Expert Committee recommendations appear
Far from being a passive storage site for triglycerides, later in this chapter (Table 14-2).
the adipocyte produces a vast array of chemokines with
paracrine and endocrine functions.44,45 Among them are Applying the Metabolic Syndrome Cluster
several pro-inflammatory cytokines. Not all adipocytes to a Pediatric Population
are the same. Visceral fat is far more inflammatory than Irrespective of the ability to make a formal diagnosis of the
peripheral fat, explaining why waist circumference, as a metabolic syndrome in the pediatric population, evidence
proxy for visceral fat, is such a key sign when assessing of the clustering of the metabolic syndrome components in
risk in obese patients.46,47 Such adipokines released from children and adolescents suggests (1) that the body’s meta-
metabolically active adipose tissue include tumor necrosis bolic milieu is adapting to the presence of excess body fat,
factor-alpha (TNF-α), C-reactive protein, and interleukin-6 (2) that the clustering of metabolic risk factors infer greater
(IL-6), all of which have been implicated in accelerating the risk for CVD mortality compared with peers who do not
atherosclerotic process.44,45 Obesity and the subsequent present with the metabolic syndrome phenotype, and (3)
pro-inflammatory state are suspected as the underlying that the collective and individual metabolic risks represent
mechanisms responsible for the progression of insulin a high-risk finding among children and adolescents. Devel-
resistance. Consequently, the triad of obesity, inflamma- oping metabolic risk at a young age implies that the health
tion, and insulin resistance is associated with the metabolic burden of cardiovascular damage will be greatly amplified
syndrome in children. Children and adolescents who are by time the child ages into adulthood. The imperative raised
morbidly obese are more insulin resistant and present with in the original concept of the metabolic syndrome remains,
higher levels of inflammatory biomarkers including IL-6, which was to identify insulin-resistant individuals at greatest
intracellular adhesion molecule-1 (ICAM), and E-selectin, risk for CVD and in most urgent need for lifestyle intervention.4
compared to lean counterparts.42,46 In obese children and The overweight pediatric patient represents the leading
adolescents, the presence of traditional metabolic syndrome edge of cardiovascular risk. A comprehensive approach to
components is associated with non-traditional risk factors the assessment of metabolic syndrome and its components
such as CRP and IL-6.47–50 Furthermore, early functional allows the pediatrician to observe the development of meta-
and morphological changes to cardiovascular function, bolic risk at its earliest stages and intervene to arrest the
measured by intima-media thickness and flow-mediated prospect of lifelong CVD risk.
dilation, are present with markers of inflammation and the
metabolic syndrome. 39,43,51 A Clinical Approach to the Identification of
Non-alcoholic fatty liver disease (NAFLD) has also the Metabolic Syndrome and Its Attendant
been implicated as an adverse consequence of carrying Cardiovascular Disease Risks
excess weight in childhood. In general it is estimated
that 38% of obese children have NAFLD. 52 Diagnosis Establishing a Risk Factor Profile: Expert Committee
is confirmed by liver biopsy. The relationship between Recommendations56
NAFLD and the presence or development of the metabolic Essentially, risk is defined as someone or something in a
syndrome is less understood, particularly in the pediatric state of high susceptibility. Factors indicating future risk
population. However, evidence shows a positive correla- for disease are evident at a young age. The clinical utility
tion between increased levels of aminotransferases and of the metabolic syndrome to establish a child’s risk profile
the number of metabolic syndrome risk factors present may be greatly enhanced when combined with other clin-
among children diagnosed with NAFLD. 53 Schwimmer et ical practice tools that help identify disease risk. Family
al54 demonstrated that children with NAFLD have signifi- history, race, socioeconomic status, and eating and physical
cantly more CVD risk factors associated with the metabolic activity behaviors all contribute to the future health risk
syndrome than children without NAFLD. 54 Although of the child. For example, children having a first-degree

relative with type 2 diabetes mellitus double their risk for study looking at Saturday morning TV broadcasts, more
developing the disease. 57 Furthermore, the components of than 50% of the commercials featured promoted food items
the metabolic syndrome are documented to track across and over 90% of these food-oriented commercials featured
generations. In the Northern Manhattan Family Study, 58 high-sugar/salt and high-fat foods.66 As Halford67,68 et al
the heritability of metabolic syndrome components was found, overweight and obese children respond to such
strikingly significant. 58 Among overweight and obese advertisements by consuming more calories and choosing
Hispanic youth, genetic determinants appear to predict the more snack foods after viewing such broadcasts.65,66
components of metabolic syndrome, as 68% and 60% of In light of the sedentary behaviors that children and
children, respectively, reported a family history of diabetes adolescents are displaying today, recent national recom-
and cardiovascular disease. 59 mendations emphasize that children participate in at least
1 hour of moderate to vigorous physical activity each day. 56
Role of Socioeconomic Status and Ethnicity These recommendations are based on evidence from a
Low socioeconomic status is highly associated with the systematic review that highlights the effects of physical
development of overweight and obesity among American activity on health and behavioral outcomes.69 Children
children.60–62 Lower cumulative family income is signifi- who participate in higher levels of physical activity are
cantly associated with the onset of health conditions that leaner. For those children who are overweight and obese,
limit childhood activities and require treatment by a pedia- physical activity has been shown to reduce total body fat
trician.61 However, in other countries lower socioeconomic provided these children are physically active for 30 to 60
class does not necessarily indicate higher prevalence of minutes 3 to 7 days per week. When examining variables of
health risk. In fact, Chinese and Russian children from cardiovascular health, a consistent level of physical activity
upper-level income groups are reported to have a higher improves high-density lipoprotein (HDL) cholesterol and
incidence of overweight and obesity compared with middle triglycerides in high-risk children. Changes to the cardio-
and lower socioeconomic groups, an indication of access to vascular risk profile have been found to occur irrespective
a more Western lifestyle.62 Furthermore, when socioeco- of any significant changes in weight reduction.69
nomic status is a factor along with race/ethnicity, the risk for
obesity is even greater. For example, Hispanic and black chil- Acanthosis Nigricans
dren from lower socioeconomic groups are significantly at Insulin resistance and subsequent hyperinsulinemia initiate
greater risk for obesity than their Caucasian counterparts.63 a series of cascading metabolic events signaling total body
changes in metabolism. Ultimately the clustering of meta-
Nutrition and Physical Activity Behaviors bolic parameters, as seen in the metabolic syndrome, brings
A recent review by the members of the American Dietetic attention to the serious health risks that are associated with
Association examined the relationship between eating and insulin resistance and obesity. Furthermore, such metabolic
sedentary behaviors on the development of overweight and changes identify individuals in most urgent need for lifestyle
obesity in childhood.64 Consuming large amounts of sugar- intervention. Essentially, identifying certain physical signs
sweetened beverages and fruit juices was found to increase may alert clinicians early in the clinical course.
caloric intake and displace more nutritious foods from the Risk associated with family history, socioeconomic
diet. Although at this time evidence is lacking to support status, and nutrition and physical activity behaviors may be
the relationship between sugar-sweetened beverages, fruit effective screening tools for prevention activities. However,
juices, and increased adiposity, epidemiological evidence as evidence suggests, a substantial number of children
has suggested that fruit and vegetable consumption may be and teens already have acquired the first signs of meta-
protective against the development of childhood obesity.64 bolic changes, which will with time place a serious health
Sedentary lifestyle behaviors have also been implicated burden on their cardiovascular system. Unlike family
as a potential cause of pediatric overweight and obesity. A history, ethnicity, lifestyle, behavior, and body mass index
recent study showed that 35% of boys and 25% of girls watch (BMI) that predict future health burdens, the skin sign of
4 or more hours of television (TV) each day.65 Irrespective acanthosis nigricans represents a physical manifestation of
of socioeconomic status and race, children who watch more existing metabolic change.
TV are less physically active and are more overweight.63 Several studies indicate that acanthosis nigricans
Furthermore, TV watching also influences appetite, partic- is relatively common among children and adolescents,
ularly if the child is already overweight or obese. In one particularly those who are obese. In a broad population

the prevalence of acanthosis nigricans among African The Family Health History
American, Hispanic, and Caucasian youth is 19.4%, 23.1%, Family health history is a strong indicator of future health
and 4.9%, respectively.70 However, when overweight and risk for a child, particularly if the risk is identified in a first-
obese sub-populations are examined specifically, rates of degree relative. However, unlike the other health risks,
acanthosis nigricans are much higher. Among an ethnically family health history is not modifiable. It does, however,
diverse sample of obese children, acanthosis nigricans was represent an important context for a discussion about a
seen in 46%. With rates of obesity beyond the 99th percen- child’s risk for chronic diseases that are fueled by excess
tile, children present with acanthosis nigricans 70% of the body weight.
time.70
National directives have recognized acanthosis nigri- Behaviors
cans screening as a non-invasive tool to identify burgeoning A targeted history should capture information about nutri-
changes in metabolism that are associated with numerous tion and physical activity habits of the overweight or obese
risk factors for CVD, including abnormal lipid and glucose child and the family. This information should serve as the
metabolism.71–74 Pediatricians are urged to obtain labora- baseline and basis for prevention and intervention coun-
tory tests on overweight and obese children who present seling directed both at the child and the family.
with acanthosis nigricans including a complete fasting lipid
profile, fasting glucose, and markers of liver function. 56 A Focused Review of Systems and
Targeted Physical Examination
Expert Committee Recommendations56 The focused review of systems and targeted physical exami-
Due to the lack of a standard definition to diagnose the meta- nation of the child should be comprehensive in nature and
bolic syndrome in the adult and pediatric populations, the include, but not be limited to, the presence of anxiety, poly-
best course of treatment for individuals with the syndrome uria/dipsia, headaches, sleep problems, abdominal pain (a
remains to be determined. Experts disagree on whether the focused review of systems); acanthosis nigricans, the pres-
metabolic syndrome should be treated differently from the ence of dysmorphic features, hirsutism and extreme acne,
treatment prescribed for the individual components of the tonsillar hypertrophy, abdominal tenderness, unexpected
syndrome. Some counsel a more comprehensive approach rates of linear growth, and undescended testicles. A crucial
to treatment for patients with the metabolic syndrome. Yet part of the child’s physical exam should be the blood pres-
what we do know is the chronic disease components that sure, but it must be obtained using the correct cuff size at
derive the metabolic syndrome are a direct result of excess rest. The results are then assessed using tables comparing
adiposity and subsequent insulin resistance. Therefore, systolic and diastolic readings against normals for the
national directives established by an expert committee child’s height percentile to ascertain “at risk” values over the
may be used as a guideline to assess overweight and obese 90th percentile and “hypertensive” values above the 95th
children and adolescents for health risks and mediate with percentile.76
the appropriate lifestyle and treatment interventions. These
evidence-supported guidelines were published as a supple- Laboratory Analysis
ment to Pediatrics in December 2007, titled the Expert More invasive testing is required for overweight and obese
Committee Recommendations Regarding the Prevention, children to identify health risks that may be otherwise
Assessment, and Treatment of Child and Adolescent Over- hidden. It is important to note that Expert Committee56
weight and Obesity.56 There are 6 steps to consider when guidelines on further laboratory testing mirror most of
assessing a child’s health risk in a practice-based setting: the components that comprise the metabolic syndrome.
Table 14-2 lists what labs should be drawn at what degree of
BMI Percentile obesity and at what age. The physician also should explore
At least annually, but ideally at each well child visit, the concerns raised during the history and physical exam,
child’s height and weight should be measured and the BMI investigated fully along with the testing recommended for
percentile value should be calculated and plotted on the all overweight children.
growth chart. The pediatrician should be looking for BMI The above have been described by the Expert
percentile trends that show an increasing weight-for-height Committee56 more explicitly and provide the pediatrician
trajectory and classify the child as underweight, normal with practice-ready guidelines to assess the global health
weight, overweight, or obese. 56,75 risk of the overweight or obese child. Furthermore, these

Table 14-2 Laboratory Testing Guidelines Based on Age, BMI Percentile, and Risk Factors Present
Laboratory Testing Fasting Lipid Profile (Cholesterol, Fasting Glucose Hepatic Function (ALT and
Parameters HDL, LDL, and Triglycerides) (Every 2 years) AST; Every 2 years)
Age 2–9 years
BMI %
X
85th–95th (with no additional risk factors*)
BMI %
X
> 85th–95th (with additional risk factors*)
BMI %
X
> 95th–99th (with or without additional risk factors*)
BMI %
X
> 99th (with or without additional risk factors*)
Age 10–18 years
BMI %
X
85th–95th (with no additional risk factors*)
BMI %
X X X
> 85th–95th (with additional risk factors*)
BMI %
X X X
> 95th–99th (with or without additional risk factors*)
BMI %
X X X
> 99th (with or without additional risk factors*)
*Risk factors refer to those risks found during the assessment of family history and physical examination. The laboratory guidelines recommended by the
Expert Committee are merely baseline recommendations. Any concerns found during the assessment of the family history and/or physical examination
should be evaluated and monitored.
recommendations emphasize the need for risk identifica- 1 metabolic abnormality secondary to obesity. In urban
tion to occur sooner in the child’s life, rather than later, Mexico, among obese school-aged children screened for
as identification of these health risks ultimately leads to metabolic syndrome risk, 90% had insulin resistance based
the establishment of an intervention program targeted at on the homeostasis model assessment (HOMA). In addi-
reducing obesity-related comorbidities and controlling tion, 14% of all children screened were at risk for or already
body weight. frankly hypertensive.82 In eastern Kansas, 18% and 37% of
elementary school children had elevated blood pressure or
The Element of Time triglycerides, respectively.83 The most common metabolic
CVD morbidity and mortality is the ultimate outcome of abnormalities among overweight school-aged children from
individuals who carry metabolic risk. The younger the child urban Chicago screening were impaired fasting glucose
is when metabolic risk is acquired, the higher the likeli- (21%), raised triacylglycerols (11%), and elevated blood
hood of tracking these components into adulthood.77–79 For pressure (11%).84
example, if overweight status continues past their first decade Fortunately in pediatrics, the elements of time and
of life, excess body weight tracks into adulthood for 80% of growth are on our side. Yet, time is a double-edged sword for
them.77,80 On examining the metabolic syndrome, metabolic overweight children. Left untreated, the morbidity associ-
predictors also track quite well across childhood, through ated with the array of comorbidities is magnified over time.
young adulthood and into adulthood.78,79 The diagnosis of So, children identified with risk factors in their first decade
the metabolic syndrome in childhood increases the odds will face health challenges even in their young adulthood
of developing the metabolic syndrome and type 2 diabetes and middle age. Yet, data indicate that the cardiovascular
mellitus in adulthood 9-fold and 11-fold, respectively.79 consequences of metabolic dysfunction are reversible if
Examining metabolic changes associated with the detected early and corrected with appropriate management,
metabolic syndrome among elementary age children reveals including a highly nutritious diet and improved fitness. 37
a startling trend. When adult definitions are adjusted to Therefore, the call to healthcare providers is to focus on miti-
reflect the pediatric-specific cut-points, the prevalence of gating risks in very young children, especially because the
metabolic syndrome among pre-pubescent overweight metabolic syndrome is unreliable in the pubescent popula-
and obese children ranges from 39% to 59%.81 Even more tion. Recent national recommendations on lipid screening85
sobering is the number of children who exhibit at least recognized the long-term consequences of obesity on

children in their first decade of life. The committee recom- particularly high-intensity exercise training, show marked
mends screening children with risk factors beginning at the improvement in vascular function.91–93
age of 2 years with close follow-up, particularly where there Mounting evidence in support of optimal nutrition,
is a strong family history.85 physical activity, and weight maintenance to ameliorate
obesity and therefore lessen CVD risk, has prompted
The Role of Weight Reduction, the Expert Committee56 to establish 9 core messages for
Proper Nutrition, and Physical Activity pediatricians to reinforce as preventive and treatment strat-
The underlying driver of metabolic dysfunction is excess egies, applicable both for low-risk and high-risk children.
adipose tissue. Therefore, fundamentally, the initial treat- Evidence-informed prevention and treatment goals should
ment is optimal nutrition, increased physical activity/ focus on:
physical fitness, and weight maintenance. Evidence shows 1) Limiting sugar-sweetened beverages
that for the obese patient a modest reduction in excess 2) Encouraging a healthful diet with at least 9 servings of
body weight of as little as 5% to 7% induces significant fruits and vegetables
health benefits, including a decrease in triglycerides, LDL, 3) Limiting television and screen time to 2 hours a day or
and VLDL cholesterols; raised HDL cholesterol; lowered less
blood pressure; and improvements in insulin action with 4) Eating breakfast daily
improved glucose status.86,87 Optimal nutrition, particu- 5) Limiting eating out away from home
larly a diet rich in fruits, vegetables, and low-fat dairy (as 6) Encouraging family meals
described in the DASH diet) has been shown to prevent 7) Limiting portion sizes
increases in blood pressure during early childhood. 88 The 8) Engaging in 1 hour or more of moderate to vigorous
DASH diet significantly improved measures of systolic physical activity each day
and diastolic blood pressure among adolescents with docu- 9) Breastfeeding exclusively until 6 months of age
mented hypertension.89 For some high-risk children, optimal nutrition,
Physical activity alone is documented to alter CVD physical activity, and weight maintenance efforts are inef-
risk. In the prevention of coronary artery disease, indi- fective at controlling weight and reducing the burden of
viduals who are more physically active cut their risk in comorbidities. A more aggressive intervention is required.
half, compared with sedentary individuals. In adults, Lipid-lowering drug therapies, particularly statins, have
comprehensive lifestyle interventions that include physical been approved for use in children, as young as 8 years of
activity result in modest reductions in body fat, 5% to 7%, age at the highest risk.85 It is important to emphasize that
and demonstrate significant health benefits, starting with pharmacological treatments have demonstrated safety and
a lowered insulin resistance. 86,87 Irrespective of weight effectiveness among high-risk children and adolescents only94
loss, exercise alone still demonstrates improvement of and are not recommended for children presenting with
CVD outcomes. Among individuals with established moderate lab values or risk. Similarly, bariatric weight-loss
CVD, exercise-only interventions significantly reduce surgery has been used in the United States as a treatment
cardiac mortality and total mortality by 31% and 27%, option for morbidly obese adolescents. Bariatric weight loss
respectively.90 in this population is proven to be successful at mitigating the
The physiological and functional changes to the comorbidities of excess body weight.95 However, an expert
vasculature develop silently during childhood and are panel of pediatricians and surgeons has recommended that
fueled by obesity. As mentioned, the damage is amenable candidates demonstrate certain physical and psychological
if detected early and intervention is administered. For readiness before receiving bariatric surgery.95 Therefore,
obese children and adolescents already presenting with whether the treatment for the obese child includes phar-
early CVD risk the use of exercise training has been macological or surgical intervention, it is crucial for the
supported as one management strategy. Irrespective practitioner to assess the risk status of the child. Utilizing
of significant reductions in weight, exercise training practice-ready tools and guidelines provided by the Expert
demonstrates marked improvement in endothelial dysfunc- Committee on the Assessment, Prevention and Treatment
tion. Worsening endothelial dysfunction, measured by of Child and Adolescent Overweight and Obesity56 can
flow-mediated dilation, is a predictor of future adverse assist the practitioner in evaluating risk and making deci-
cardiovascular events and correlates with measures of sions on the appropriate treatment course for the obese
body fatness. Children who perform exercise training, child or adolescent.

Summary Test Your Knowledge Questions

In the decade following Reaven’s Banting Lecture in 1988, 2 1. Which factors are most restrictive in the diagnosis of
the metabolic syndrome evolved from a concept to a diag- the metabolic syndrome in pediatrics?
nosis. Despite providing useful information on metabolic A. Puberty
risk and the susceptibility for developing CVD, the clinical B. Ethnicity
utility of the metabolic syndrome diagnosis remains contro- C. Gender
versial among researchers in adult and pediatric medicine. D. Established cut-points
Among children and adolescents, the lack of consensus on E. Lack of consensus on the clinical component disor-
the definition of the metabolic syndrome is compounded ders of the metabolic syndrome
by (1) the inability to define metabolic thresholds using 2. Which of the following was not an original intention of
pediatric-specific cut-points, (2) the role of natural meta- the metabolic syndrome as a conceptual entity?
bolic changes during puberty, and (3) the application of A. To identify the most at-risk individuals for cardio-
emerging, non-traditional CVD risk factors in the metabolic vascular disease
syndrome definition. But the very presence of the metabolic B. To establish the clinical cluster as a diagnosable
syndrome in the pediatric population suggests that a shift entity
in metabolism fueled by excess body weight is underway. C. To explain the connection between otherwise unre-
Further, the presence of risk factors in early childhood lated metabolic events
means that damage to the cardiovascular system has begun. D. To identify an individual in most urgent need of
When metabolic risk factors present in a cluster, the clinical lifestyle intervention
course and health outcomes for that child are compro- 3. After identifying a 5-year-old child with a body mass
mised, unless interventions are undertaken. The Expert index > the 95th percentile, what would be the most
Committee on the Assessment, Prevention and Treat- inappropriate next steps in the child’s care?
ment of Child and Adolescent Overweight and Obesity56 A. Obtain a detailed family history
underscored the role of the clinician to identify metabolic B. Discuss lifestyle behaviors
risk factors at the earliest stage possible, institute treat- C. Perform a targeted physical exam and review of
ment, and follow up closely. Identification of metabolic risk systems
in a child may prove beneficial for several reasons: (1) the D. Obtain a laboratory analysis
threat of evolving cardiovascular damage throughout the E. Refer to sub-specialty care
lifespan can be reversed, if identified early and coupled with F. Simply monitor the child’s weight over the next 12
aggressive lifestyle changes, and (2) weight management is months
easier due to growth, along with the potential to influence
home and school environments. Practice-ready guidelines See p. 487 for answers.
emphasize a 6-step approach to assessing health risk in prac-
tice. For children at any risk level, the Expert Committee56 References
recommends evidence-based counseling supported by the 1. Leslie BR. Metabolic syndrome: historical perspectives. Am J
9 core messages for prevention and treatment. For children Med Sci. 2005;330:264–268.
2. Reaven GM. Role of insulin resistance in human disease.
presenting with substantial health risks associated with Diabetes. 1988;37:1595–1606.
the metabolic syndrome, pediatricians should focus on a 3. Kahn R, Buse J, Ferrannini E, Stern M. The metabolic
comprehensive intervention strategy, including optimal syndrome: time for a critical appraisal. Diabetologia.
nutrition, physical activity, weight maintenance, and, when 2005;48:1684–1699.
appropriate, pharmacological and/or surgical intervention. 4. Reaven GM. The metabolic syndrome: is this diagnosis neces-
sary? Am J Clin Nutr. 2006;83:1237–1247.
5. Blaha MJ, Bansal S, Rouf R, Golden SH, Blumenthal RS,
DePilippis AP. A practical “ABCDE” approach to the meta-
bolic syndrome. Mayo Clin Proc. 2008;83:932–943.
6. Expert Panel on Detection, Evaluation, and Treatment of
High Blood Cholesterol in Adults. Executive Summary of the
Third Report of the National Cholesterol Education Program
(NCEP) Expert Panel on Detection, Evaluation, and Treat-
ment of High Blood Cholesterol in Adults (Adult Treatment
Panel III). JAMA. 2001;285:2486–2497.

7. Alberti KG, Zimmet PZ. Definition, diagnosis and classifica- 24. Weiss R, Dziura J, Burgert TS, et al. Obesity and the meta-
tion of diabetes mellitus and its complications. Part 1: diagnosis bolic syndrome in children and adolescents. N Engl J Med.
and classification of diabetes mellitus provisional report of a 2004;89:108–113.
WHO consultation. Diabet Med. 1998;15:539–553. 25. Cook S, Weitzman M, Auinger P, Nguyen M, Dietz WH.
8. International Diabetes Federation. The IDF consensus world- Prevalence of metabolic syndrome phenotypes in adoles-
wide definition of the metabolic syndrome. 2006. www.idf. cents: findings from the third national health and nutrition
org/webdata/docs/IDF_Meta_def_final.pdf. examination survey, 1998-1994. Pediatr Adolesc Med.
9. Kahn JM, Beevers DG. Management of hypertension in ethnic 2003;157:821–827.
minorities. Heart. 2005;91:1105–1109. 26. de Ferranti SD, Gauvreau K, Ludwig DS, Neufeld EJ,
10. Sumner AE, Finley KB, Genovese DJ, Criqui MH, Boston Newburger JW, Rifai N. Prevalence of the metabolic
RC. Fasting triglyceride and triglyceride-HDL cholesterol syndrome in American adolescents: findings from the third
ratio are not markers of insulin resistance in African Ameri- national health and nutrition examination survey. Circulation.
cans. Arch Intern Med. 2005:165:1395–1400. 2004;110:2494–2497.
11. Sumner AE, Cowie CC. Ethnic differences in the ability of 27. Brambilla P, Lissau I, Flodmark CE, et al. Metabolic risk factor
triglyceride levels to identify insulin resistance. Atheroscle- clustering estimation in children: to draw a line across pedi-
rosis. 2008;196:696–703. atric metabolic syndrome. Int J Obes. 2007;31:591–600.
12. Zhu S, Heymsfield SB, Toyoshima H, Wang Z, Piertrobelli A, 28. Steinberger J, Daniels SR, Eckel RH, et al. Progress and
Heshka S. Race-ethnicity-specific waist circumference cutoffs Challenges in Metabolic Syndrome in Children and Adoles-
for identifying cardiovascular disease risk factors. Am J Clin cents: A Scientific Statement From the American Heart
Nutr. 2005;81:409–415. Association Atherosclerosis, Hypertension, and Obesity in
13. Esteghamati A, Ashraf H, Rashidi A, Meysamie A. Waist the Young Committee of the Council on Cardiovascular
circumference cut-off points for the diagnosis of meta- Disease in the Young; Council on Nursing; and Council on
bolic syndrome in Iranian adults. Diabetes Res Clin Prac. Nutrition, Physical Activity, and Metabolism. Circulation.
2008;82:104–107. 2009;119:628–647.
14. Oka R, Kobayashi J, Yagi K, et al. Reassessment of the cutoff 29. Huang TT. Finding thresholds of risk for components of the
values of waist circumference and visceral fat area for identi- pediatric metabolic syndrome. J Pediatr. 2008;152:158–159.
fying Japanese subjects at risk for the metabolic syndrome. 30. Zimmet P, Alberti KG, Kaufman F, et al; IDF Consensus
Diabetes Res Clin Pract. 2008;79:474–481. Group. The metabolic syndrome in children and adolescents:
15. Ferdinand KC, Saunders E. Hypertension related morbidity an IDF consensus report. Pediatr Diabetes. 2007; 8:299–306.
and mortality in African Americans—why we need to do 31. Joliffe CJ, Janssen I. Development of age specific adolescent
better. J Clin Hypertens. 2006;8: 21–31. metabolic syndrome criteria that are linked to the Adult Treat-
16. Unger J. Reinventing Type 2 diabetes: pathogenesis, treatment Panel III and International Diabetes Federation criteria.
ment, and prevention. JAMA. 2008;299:1185–1187. J Am Coll Cardiol. 2007;27:891–898.
17. Lewis GF, Carpentier A, Adeli K, Giacca A. Disordered fat 32. Moreno LA, Pineda I, Rodriquez G, Fleta J, Sarria A, Bueno M.
storage and mobilization in the pathogenesis of insulin resis- Waist circumference for the screening of metabolic syndrome
tance and type 2 diabetes. Endocr Rev. 2002;23:201–229. in children. Acta Pediatr. 2002;91:1307–1312.
18. Iribarren C, Go AS, Husson G, et al. Metabolic syndrome and 33. Seidell JC, Perusse L, Despres JP, Bouchard C. Waist and
early-onset coronary artery disease: is the whole greater than hip circumference have independent and opposite effects on
its parts? J Am Coll Cardiol. 2006;48:1800–1807. cardiovascular disease risk factors: the Quebec family study.
19. Alexander CM, Landsman PB, Teutsch SM, Haffner SM. Am J Clin Nutr. 2001;74:315–321.
NCEP-defined metabolic syndrome, diabetes, and prevalence 34. Moreno LA, Joyanes M, Mesana MI, et al; AVENA Study
of coronary heart disease among NHANES III participants Group. Harmonization of anthropometric measurements for
age 50 years and older. Diabetes. 2003;52:1210–1214. a multicenter nutrition survey in Spanish adolescents. Nutri-
20. McNeill AM, Rosamond WD, Girman CJ, et al. The meta- tion. 2003;19:481–486.
bolic syndrome and 11 year risk of incident cardiovascular 35. Moran A, Jacobs DR Jr, Steinberger J, et al. Association
disease in the atherosclerosis risk in communities. Diabetes between the insulin resistance of puberty and the insulin-like
Care. 2005;28: 385–390. growth factor/growth hormone axis. J Clin Endocrinol Metab.
21. Hoang KC, Ghanderhari H, Lopez VA, Barboza MG, Wong 2002;87:4817–4820.
ND. Global coronary heart disease assessment of individ- 36. Hannon TS, Janosky J, Arslanian SA. Longitudinal study
uals with the metabolic syndrome in the U.S. Diabetes Care. of physiological insulin resistance and metabolic changes of
2008;31:1405–1409. puberty. Pediatr Res. 2006;60:759–763.
22. Tong W, Lai H, Yang C, Ren S, Dai S, Lai S. Age, gender, and 37. Groner JA, Joshi M, Bauer JA. Pediatric precursors of adult
metabolic syndrome related coronary heart disease in U.S. cardiovascular disease: noninvasive assessment of early
adults. Int J Cardiol. 2005;104:288–291. vascular changes in children and adolescents. Pediatrics.
23. Ford ES, Li C. Defining the metabolic syndrome in children 2006;118(4):1683–1691.
and adolescents: will the real definition please stand up? J 38. Woo KS, Chook P, Yu CW, et al. Overweight in children is asso-
Pediatr. 2008;152:160–164. ciated with arterial endothelial dysfunction and intima-media
thickness. Int J Obes Relat Metab Disord. 2004;28:852–857.

39. Ferri C, Croce G, Confini V, et al. C-reactive protein: interac- 54. Schwimmer JB, Pardee PE, Lavine JE, Blumkin AK, Cook
tion with the vascular endothelium and possible role in human S. Cardiovascular risk factors and the metabolic syndrome
atherosclerosis. Curr Pharm Des. 2007;13:1631–1645. in pediatric non-alcoholic fatty liver disease. Circulation.
40. Valle M, Maros R, Gascon F, Canete R, Zafra MA, Morales R. 2008;15:277–283.
Low-grade systemic inflammation, hypoadiponectinemia and 55. Barshop NJ, Sirlin CB, Schwimmer JB, Lavine JE. Review
a high concentration of leptin are present in very young obese article: epidemiology, pathogenesis and potential treatment of
children, and correlate with metabolic syndrome. Diabetes paediatric non-alcoholic fatty liver disease. Aliment Pharmacol
Metab. 2005; 3:55–62. Ther. 2008;28:13–24.
41. Soriano-Guillen L, Hernandez-Garcia B, Pita J, 56. Barlow SE; Expert Committee. Expert committee recommen-
Dominguez-Garrido N, Del Rio-Camacho G, Rovira A. dations regarding the prevention, assessment, and treatment
High-sensitivity C-reactive protein is a good marker of of child and adolescent overweight and obesity: summary
cardiovascular risk in obese children and adolescents. Eur J report. Pediatrics. 2007;120:S164–S192.
Endocrinol. 2008;159:R1–R4. 57. Dallo FJ, Weller SC. Effectiveness of diabetes mellitus
42. Poirier P, Giles TD, Bray GA, et al. Obesity and cardiovascular screening recommendations. Proc Natl Acad Sci.
disease: pathophysiology, evaluation and effect of weight loss. 2003;100:10574–10579.
Arterioscler Thromb Vasc Biol. 2006;26:968–976. 58. Lin HF, Boden-Albala B, Juo SH, Park N, Rundek T, Sacco
43. Pai JK, Pischon T, Ma J, et al. Inflammatory markers and the RL. Heritabilities of the metabolic syndrome and its compo-
risk of coronary heart disease in men and women. N Engl J nents in the Northern Manhattan study. Diabetologia.
Med. 2004;351:2599–2610. 2005;48:2006-2012.
44. Wozniak SE, Gee LL, Wachtel MS, Frezza EE. Adipose tissue: 59. Butte NF, Comuzzie AG, Cole SA, et al. Quantitative genetic
the new endocrine organ? A review article. Dig Dis Sci. 2009 analysis of the metabolic syndrome in Hispanic children.
Sep;54(9):1847-56. Epub 2008 Dec 4. Pediatr Res. 2005;58:1243–1248.
45. Antuna-Puente B, Feve B, Fellahi S, Bastard JP. Adipokines: 60. Goodman E. The role of socioeconomic status gradients in
the missing link between insulin resistance and obesity. explaining differences in US adolescents health. Am J Public
Diabetes Metab. 2008;34:2–11. Health. 1999;89:1522–1528.
46. Fox CS, Massaro JM, Hoffmann U, et al. Abdominal visceral 61. Chen E, Martin AD, Matthews KA. Trajectories of socio-
and subcutaneous adipose tissue compartments: association economic status across children’s lifetime predict health.
with metabolic risk factors in the Framingham Heart Study. Pediatrics. 2007;120:e297–e303. doi:10.1542/peds.2006-
Circulation. 2007;116:39–48. 3098.
47. Pou KM, Massaro JM, Hoffmann U, et al. Visceral and 62. Wang Y. Cross national comparison of childhood obesity: The
subcutaneous adipose tissue volumes are cross-sectionally epidemic and the relationship between obesity and socioeco-
related to markers of inflammation and oxidative stress: the nomic status. Int J Epidemiol. 2001;30:1129–1136.
Framingham Heart Study. Circulation. 2007;116:1234–1241. 63. Singh SG, Kogan MD, Van Dyck PC, Siahpush M. Racial/
48. Lee S, Bacha F, Gungor N, Arslanian S. Comparison of ethnic, socioeconomic, and behavioral determinants of
different definitions of pediatric metabolic syndrome: rela- childhood and adolescent obesity in the United States:
tion to abdominal adiposity, insulin resistance, adiponectin, analyzing independent and joint associations. Ann Epidemiol.
and inflammatory biomarkers. J Pediatr. 2008;152:177–184. 2008;18:682–695.
49. Retnakaran R, Zinman B, Connelly PW, Harris SB, Hanley 64. American Dietetic Association. Factors associated with child-
AJG. Nontraditional risk factors in pediatric metabolic hood overweight. http://www.adaevidencelibrary.com/topic.
syndrome. J Pediatr. 2006;148:176–182. cfm?cat=2792. Accessed December 3, 2008.
50. Langenberg C, Bergstrom J, Scheidt-Nave C, Pfeilschifter J, 65. Marshall SJ, Gorely T, Biddle SJH. A descriptive epidemiology
Barrett-Connor E. Cardiovascular death and the metabolic of screen-based media use in youth: a review and critique. J
syndrome: role of adiposity signaling hormones and inflam- Adolesc. 2006;29:333–349.
matory markers. Diabetes Care. 2006;29:1363–1369. 66. Kotz K, Story M. Food advertisements during children’s
51. Kapiotis S, Holzer G, Schaller G, et al. A pro-inflammatory Saturday morning television programming: are they consis-
state is detectable in obese children and is accompanied by tent with dietary recommendations? J Am Diet Assoc.
functional and morphological vascular changes. Arterioscler 1994;29:1296–1300.
Thromb Vasc Biol. 2006;26:2541–2546. 67. Halford JC, Gillespie J, Brown V, Pontin EE, Dovey TM. Effect
52. Schwimmer JB, Deutsch R, Kahen T, Lavine JE, Stanley C, of television advertisements of foods on food consumption in
Behling C. Prevalence of fatty liver in children and adoles- children. Appetite. 2004;42:221–225.
cents. Pediatrics. 2006;118:1388–1393. 68. Halford JC, Boyland EJ, Hughes GM, Stacey L, McKean S,
53. Manco M, Marcellini M, Devito R, Comparcola D, Sartorelli Dovey TM. Beyond brand-effect of television food advertise-
MR, Nobili V. Metabolic syndrome and liver histology ments on food choice in children: the effects of weight status.
in paediatric non-alcoholic steatohepatitis. Int J Obes. Public Health Nutr. 2008;11:897–904.
2008;32:381–387. 69. Strong WB et al. Evidence based physical activity for school-
age youth. J Pediatr. 2005;146:732–737.

70. Nguyen TT, Keil MF, Russell DL, et al. Relation of acanthosis 85. Daniels SR, Greer FR, and the Committee on Nutrition. Lipid
nigricans to hyperinsulinemia and insulin sensitivity in screening and cardiovascular health in childhood. Pediatrics.
overweight African American and white children. J Pediatr. 2008;122:198–208.
2001;138(4)474–480. 86. McBride PE, Einerson JA, Grant H, et al. Putting the diabetes
71. Mukhtar Q , Cleverley G, Voorhees RE, McGrath JW. prevention program into practice: a program for weight
Prevalence of acanthosis nigricans and its association with loss and cardiovascular disease reduction with metabolic
hyperinsulinemia in New Mexico adolescents. J Adoles Health. syndrome or type 2 diabetes mellitus. J Nutr Health Aging.
2001;28:372–376. 2008;12:745s–749s.
72. Sinha S, Schwartz RA. Juvenile acanthosis nigricans. J Am 87. Racette SB, Weiss EP, Hickner RC, Holloszy JO. Modest
Acad of Dermatol. 2007;57:502–508. weight loss improves insulin action in African Americans.
73. Ice CL, Murphy E, Minor VE, Neal WA. Metabolic syndrome Metabolism. 2005;54:960–965.
in fifth grade children with acanthosis nigricans: results from 88. Moore LL, Singer MR, Bradlee ML, et al. Intake of fruits,
the CARDIAC project. World J Pediatr. 2009;5:23–30. vegetables and dairy products in early childhood and subse-
74. Guran T, Turan S, Akcay T, Bereket A. Significance of acan- quent blood pressure changes. Epidemiol. 2005;16:4–11.
thosis nigricans in childhood obesity. J Paediatr and Child 89. Couch SC, Saelens BE, Levin L, Dart K, Falciglia G, Daniels
Health. 2008;44:338–341. S. The efficacy of a clinic based behavioral nutrition inter-
75. Murray R, Battista M. Managing the risk of childhood over- vention emphasizing a DASH-type diet for adolescents with
weight and obesity in primary care practice. Curr Probl Pediatr elevated blood pressure. J Pediatr. 2008;152:494–502.
Adoles Health Care. 2009;39:145–166. 90. Thompson PD, Buchner D, Pina IL, et al. American Heart
76. National High Blood Pressure Education Program Working Association Council on Clinical Cardiology Subcommittee
Group on High Blood Pressure in Children and Adolescents. on Exercise, Rehabilitation, and Prevention; American
The fourth report on the diagnosis, evaluation, and treatment Heart Association Council on Nutrition, Physical Activity,
of high blood pressure in children and adolescents. Pediatrics. and Metabolism Subcommittee on Physical Activity. Exer-
2004;114(suppl):555–576. cise and Physical Activity in the Prevention and Treatment
77. Freedman DS, Khan LK, Serdula MK, Dietz WH, Srinivasan of Atherosclerotic Cardiovascular Disease: A Statement
SR, Berenson GS. Racial differences in the tracking of child- from the Council of Clinical Cardiology and the Counsel
hood BMI to adulthood. Obes Res. 2005;13:928–935. on Nutrition, Physical Activity and Metabolism. Circulation.
78. Katzmarzyk PT, Pérusse L, Malina RM, Bergeron J, Després 2003;24:3109–3116.
JP, Bouchard C. Stability indicators of the metabolic syndrome 91. Hopkins ND, Stratton G, Tinken TM, et al. Relationships
from childhood and adolescence to young adulthood: the between measures of physical fitness, physical activity, body
Quebec family study. J Clin Epidemiol. 2001;54:190–195. composition, and vascular function in children. Atheroscle-
79. Morrison JA, Fredman LA, Wang P, Glueck CJ. Metabolic rosis. 2009; 204:244–249.
syndrome in childhood predicts adult metabolic syndrome 92. Meyer AA, Kundt G, Lenschow U, Schuff-Werner P, Kienast
and type 2 diabetes mellitus 25-30 years later. J Pediatr. W. Improvement of early vascular changes and cardiovas-
2008;152:201–206. cular risk factors in obese children after a six-month exercise
80. Whitaker RC, Wright JA, Pepe MS, Seidel KD, Dietz WH. program. J Am Coll Cardiol. 2006;7:1865–1870.
Predicting obesity in young adulthood from childhood and 93. Watts K, Beye P, Siafarikas A, et al. Exercise training normal-
parental obesity. N Engl J Med. 1997;337:869–873. izes vascular dysfunction and improves central adiposity in
81. Golley RK, Magarey AM, Steinveck KS, Baur LA, Daniels obese adolescents. J Am Coll Cardiol. 2004;19:1823–1827.
LA. Comparison of metabolic syndrome prevalence using 94. McCrindle BW, Urbina EM, Dennison BA, et al. American
six different definitions in overweight pre-pubertal chil- Heart Association Atherosclerosis, Hypertension, and
dren enrolled in a weight management study. Int J Obes. Obesity in Youth Committee; American Heart Association
2006;30:853–860. Council of Cardiovascular Disease in the Young; American
82. Perichart-Perera O, Balas-Nakash M, Schiffman-Selechnik Heart Association Council on Cardiovascular Nursing.
E, Barbato-Dosal A, Vadillo-Ortega F. Obesity increases Drug therapy of high-risk lipid abnormalities in children and
metabolic syndrome risk factors in school-aged children adolescents: a scientific statement from the American Heart
from an urban school in Mexico City. J Am Diet Assoc. Association Atherosclerosis, Hypertension, and Obesity in
2007;107:81–91. Youth Committee, Council of Cardiovascular Disease in the
83. Dubois, K et al. Prevalence of the metabolic syndrome Young, with the Council on Cardiovascular Nursing. Circula-
in elementary school children. Acta Paediatrica. tion. 2007;115:1948–1967.
2006;95:1005–1011. 95. Spear BA, Barlow SE, Ervin C, et al. Recommendations for
84. Braunschweig CL, Gomez S, Liang H, et al. Obesity and risk treatment in children and adolescents with overweight or
factors for the metabolic syndrome among low-income, urban, obesity. Pediatrics. 2007;120:S254–S288.
African American schoolchildren: the rule rather than the
exception? Am J Clin Nutr. 2005;81:970–975.

15
Lipid Disorders
Shirley Huang, MD, and Melanie Katrinak, RD, CSP, LDN

Background . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 162 1. Understand cardiovascular disease risk and the etiolo-
Types of Lipid Disorders. . . . . . . . . . . . . . . . . . . . . . . . . . . 163 gies of lipid disorders.
Genetic 2. Describe how to screen for lipid disorders and interpret
Polygenic lab results.
Other 3. Discuss the role of dietary factors and physical activity
Screening and Lab Interpretation. . . . . . . . . . . . . . . . . . . 163 in treating lipid disorders.
Dietary Cholesterol
Dietary Fats Background
Simple Carbohydrates
Fiber
Cardiovascular disease (CVD) remains the leading cause
Plant Sterols/Stanols of death and morbidity in the United States.1 Risk factors
Omega-3 Fatty Acids for CVD include family history of early heart disease,
Soy Protein abnormal serum cholesterol levels, high blood pressure,
Garlic insulin resistance, diabetes mellitus, physical inactivity,
Antioxidants
obesity, cigarette smoking, and certain medications. The
Physical Activity
specific abnormal serum cholesterol levels include a high
Pharmacologic Intervention . . . . . . . . . . . . . . . . . . . . . . . 167
concentration of low-density lipoprotein (LDL) choles-
terol, a low concentration of high-density lipoprotein
(HDL) cholesterol, and high triglycerides. While CVD is
considered an adult disease, research has shown that the
process of arthrosclerotic CVD begins early in life and is
progressive throughout the lifespan.2–4 High cholesterol in
childhood accelerates the atherosclerotic process and places
the child at risk for CVD as an adult. Children with high
LDL cholesterol are also likely to have high levels as adults. 5
With increasing rates of obesity in children over the past 3
decades, the rates of obesity-related lipid disorders have also
risen.6,7 Nutrition intervention during childhood plays a
critical role in CVD prevention and dyslipidemia treatment
to reduce the risk of CVD.
162
LIPID DISORDERS 163
Types of Lipid Disorders triglyceride levels, low HDL levels, abdominal obesity, high
blood pressure, insulin resistance, and fatty liver increases
Genetic the risk of CVD and diabetes mellitus.6,9,10 In children who
Two of the most common genetic lipid disorders will be are obese with a body mass index ≥ 95th percentile for age
described. These disorders are unique and require an indi- and gender, 52% have high triglycerides, and 50% have low
vidualized diet and treatment plan with a lipid specialist HDL levels.6 Children with polygenic hypercholesterolemia
and registered dietitian or other skilled clinician. often respond well to nutrition and lifestyle behavioral
interventions.
Familial Hypercholesterolemia
There are 2 types of familial hypercholesterolemia (FH): Other
homozygous FH and heterozygous FH. Homozygous Other causes of lipid disorders include medications and
FH is rare, with an occurrence of approximately 1 in 1 certain disease states. Medications such as progestins,
million, with total cholesterol levels ranging from 600 to anabolic steroids, glucocorticoids, psychotherapeutic
1000 mg/dL. Skin xanthomas (cholesterol plaques) may drugs, and retinoic acid acne treatment can cause abnormal
also be found in these patients at birth or before 6 years of lipid levels. In addition, diseases such as untreated hypo-
age. Angina pectoris and myocardial infarction can occur thyroidism, renal disease, polycystic ovarian syndrome
before 6 years of age. Heterozygous FH has an occurrence (PCOS), or liver disease may also cause dyslipidemias.11
from 1 in 200 to 1 in 500, with total cholesterol levels
exceeding 230 mg/dL and LDL cholesterol exceeding Screening and Lab Interpretation
160 mg/dL. No other clinical symptoms are present in Tables 15-1 and 15-2 indicate who should be screened for
the first decade of life, but by the second decade, tendon lipid disorders and the screening procedure. Interpreta-
xanthomas of the hands may be found in 10% to 15% of the tion of the resultant fasting lipid profile is delineated in
children.8 Nearly all patients with FH require medications Table 15-3.
in addition to lifestyle behavior interventions to normalize,
or at least improve, their LDL levels.1 Table 15-11
Who to screen?
Lipoprotein Lipase Deficiency Any patient > 2 years of age with any of the following CVD risk factors:
Lipoprotein lipase (LPL) deficiency results in high levels  A parent, grandparent, aunt, or uncle with cardiovascular disease
of triglycerides, which presents in infancy with abdominal < 55 years (male) or < 65 years (female). Cardiovascular disease
pain and hypertriglyceridemia.8 Because LPL deficiency includes: myocardial infarction, sudden cardiac death, coronary
bypass surgery, balloon angioplasty, angina pectoris, coronary
involves a specific metabolic abnormality or defect, dietary atherosclerosis, peripheral vascular disease, or stroke or
intervention requires only restriction in fat and not simple  A parent with a total cholesterol > 240 mg/dL or
carbohydrates (compared to polygenic hypertriglyceridemia  A family history that is not available (adopted child) or
which responds to a restriction of simple carbohydrates).  Other cardiovascular risk factors: obesity (BMI > 95th percentile),
Treatment requires long-term weight control and a diet sedentary lifestyle, smoking, hypertension, diabetes, congenital
of ≤ 20 g of fat daily. The diet can be supplemented with heart disease, renal disease or
medium-chain triglycerides (MCTs), which will not  Treatment with retinoid acid, anticonvulsants, or oral contraceptives
increase triglyceride levels, to provide another source of fat
and calories. Table 15-21
How to screen?
Polygenic  After a 9-12 hour fast, obtain a fasting lipid profile that includes:
Of all types of lipid disorders, polygenic hypercholester- ■ Total cholesterol (TC)
olemia (nonfamilial) is the most common. Lifestyle factors ■ High-density lipoprotein cholesterol (HDL)
■ Triglycerides (TG)
such as diet, weight, and physical inactivity combined ■ Low-density lipoprotein cholesterol (LDL), calculated*
with a genetic susceptibility are the cause of this form of  If TG > 400 mg/dL, a Direct LDL needs to be ordered
dyslipidemia. High triglycerides and low HDL levels are * Calculated LDL = TC–(HDL-TG/5) (if TG < 400 mg/dL)
often seen with obesity and/or a diet with food and drinks
high in simple carbohydrates. In the metabolic syndrome
(Chapter 14), a constellation of findings including high

Figure 15-1
*A more conservative HDL cut-point is chosen here. HDL > 40 mg/dL is a cut-point used in pediatric and adult
metabolic syndrome.1,6 The American Heart Assocation recommends HDL > 35 mg/dL in pediatrics.20
Adapted from The Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood
Cholesterol in Adults (Adult Treatment Panel III).1
Nutrition Management Dietary Cholesterol

The emphasis on a healthy diet and lifestyle is key in the Dietary cholesterol is found in animal-based foods and
prevention of CVD and treatment of abnormal lipid levels.12 can be reduced by limiting foods such as butter, egg yolk,
To prevent CVD in all children ≥ 2 years old, recommenda- high-fat meat, beef, poultry with skin, and whole milk dairy
tions include a daily diet with total fat < 30% total calories, products. Although limiting dietary cholesterol has less of a
saturated fat < 10% of total calories, trans fat < 1% of total serum lipid lowering effect and has a more variable response
calories, and dietary cholesterol < 300 mg.1 Furthermore, among individuals than limiting saturated and trans fats, it
CVD prevention also includes increasing consumption of is still important because cholesterol and saturated fat are
fruits, vegetables, fish, whole grains, and reduced-fat dairy found together in most foods.9,14 In general, LDL may be
products while reducing the intake of fruit juice, sugar- decreased by 3% to 5% if dietary cholesterol is restricted
sweetened beverages and foods, and salt.13 For children ≥ 2 to < 200 mg daily. In addition, an increase of 100 mg/d of
years old at risk for CVD, the daily diet should be further dietary cholesterol increases total serum cholesterol by 2 to
restricted to saturated fat < 7% of total calories and dietary 3 mg/dL.
cholesterol to < 200 mg.1 For children between 12 months
and 2 years of age who are overweight, obese, or have a Dietary Fats
family history of obesity, dyslipidemia, or CVD, reduced
fat milk is now considered safe and appropriate.1 Additional Saturated Fats
dietary management for high-risk patients should always be Limiting saturated fats can help to lower LDL levels.14 Satu-
tailored based on individual lipid profile and involve coun- rated fat is found more in animal- than plant-based foods.
seling with a lipid specialist and registered dietitian or other A major source of saturated fat is red meat, but dairy prod-
skilled clinician to ensure effective nutrition intervention ucts are also commonly overlooked as a source of saturated
while maintaining appropriate growth and development. fat in children’s diets. Plant-based sources of saturated fat

LIPID DISORDERS 165
are mainly found in tropical oils (coconut, palm, and palm hypertriglyceridemia, other than LPL deficiency, primarily
kernel), which are often used in commercially baked goods. need to limit their intake of simple carbohydrates. Simple
To reduce saturated fat intake, whole milk dairy products sugars and carbohydrates, found in foods such as sweetened
may be replaced with low-fat or non-fat (“skim”) dairy prod- beverages, desserts, snacks, and white breads and other
ucts, and leaner cuts of meat may be recommended. Low-fat, refined starches, raise triglycerides more than saturated and
reduced fat, and baked cookies, crackers, and other baked trans fats. For children who are overweight or obese with
goods should be consumed instead of full-fat versions. Using high triglycerides, limiting dietary fat, especially saturated
additional saturated fat in the cooking process should be and trans fats, and increasing physical activity should also be
limited. Low-fat cooking methods such as broiling, grilling, recommended in addition to limiting simple carbohydrates
steaming, microwaving, poaching, or baking are preferable because obesity will have a direct effect on triglyceride
to frying. Saturated fats should be limited to < 7% total calo- levels.13
ries in children with high cholesterol.
Fiber
Trans Fats Fiber combined with a low-fat diet may help to improve
Trans fats, or hydrogenated fats, are produced when fat is cholesterol levels further. Soluble fiber such as oat bran,
hydrogenated to make it solid at room temperature. In psyllium, pectin, and guar gum decreases LDL choles-
the process of hydrogenation, bonds in the cis position are terol primarily, and has some effect on increasing HDL
switched to the trans position, which has been shown to cholesterol.17 An increase in soluble fiber of 5 to 10 g/d may
increase LDL and decrease HDL cholesterol. Trans fats reduce LDL by 3% to 5%.9 One study found that children
are found mostly in stick margarine, high-fat baked goods, who consumed 6.4 g of soluble fiber as psyllium decreased
shortening, commercial frying oils, and fried snack foods. their LDL by 7%.18 Fiber binds to bile acids and decreases
Examples of these foods are doughnuts, pastries, crackers, cholesterol absorption. Specific guidelines for the suggested
cookies, potato and tortilla chips, french fries, and other amount of fiber intake for children with dyslipidemia
bakery and snack foods. Trans fats should be limited to currently do not exist, and remain controversial. However,
< 1% of total calories for all children ≥ 2 years old.1 Nutri- general guidelines for estimating adequate fiber intake in
tion labels are allowed to list zero grams of fat per serving if children are found in the dietary reference intake (DRI)
the product contains less than 0.5 g of trans fat per serving. and are generally much higher than most children and
Therefore, to ensure a food is completely free of trans fat, it adolescents consume.19 Another commonly used method
is important to check the ingredients for hydrogenated and/ is adding 5 to the child’s age to obtain the recommended
or partially hydrogenated oils. daily intake of fiber in grams, up to 20 g/d (for example,
a 6-year-old child should consume approximately 11 g of
Monounsaturated and Polyunsaturated Fats fiber), although there is limited supporting evidence for this
Children with dyslipidemia are encouraged to replace satu- calculation.17,20
rated and trans fats with the healthier monounsaturated and
polyunsaturated fats, which decrease LDL cholesterol.1,15 Plant Sterols/Stanols
Monounsaturated fats are found in avocados, many nuts Plant sterols and stanols are essential components of cell
and seeds, and vegetable oils such as olive, canola, peanut, membranes in plants that are structurally similar to choles-
and sesame oil.13 Polyunsaturated fats are found in most terol. Plant stanols are saturated sterols and have no double
nuts and seeds, fatty fish (salmon, tuna, mackerel, herring, bonds. Their action is to inhibit absorption of dietary
and trout) and vegetable oils like soybean, corn, safflower, cholesterol and to decrease re-absorption of cholesterol
and sunflower oils.16 It is important to note that while these from bile. Plant sterols or stanol esters have been incorpo-
fats are healthy, they are still calorically dense and should rated into margarine/butter spreads, granola bars, yogurt
be limited as recommended by the Dietary Guidelines for drinks, oatmeal, cereal, and some other foods and are also
Americans,13 especially for weight maintenance or loss. available in caplets. A randomized control study in children
using 2 g of plant sterol in margarine per day decreased LDL
Simple Carbohydrates by 8%.21 Plant sterols are considered safe for children at
For the general population, current recommendations recommended doses of 2 g/d to lower LDL levels. However,
encourage choosing mostly complex carbohydrates with they may theoretically have the potential to decrease levels
a limited intake of simple carbohydrates.13 Patients with of fat-soluble vitamins such as vitamin A (beta carotene)

or vitamin E (alpha tocopherol), which can typically be benefits of soy remain controversial, soy can provide polyun-
prevented by increasing intake of food sources of both. A saturated fatty acids, fiber, vitamins, and minerals beneficial
multivitamin may be considered if additional risk factors for for cardiovascular and overall health.17
vitamin deficiency are present. 21
Garlic
Omega-3 Fatty Acids Garlic may have beneficial cardiovascular effects such
The omega-3 fatty acids, docosahexaenoic acid (DHA) as lowering LDL cholesterol, lowering blood pressure,
and eicosapentaenoic acid (EPA), are found in fish oils and reducing platelet aggregation, and acting as an antioxidant
ocean fish (herring, mackerel, salmon, and sardines), and and anti-inflammatory agent.24 However, the mechanism
lower triglycerides by inhibiting very low-density lipo- of garlic’s actions are unclear. Other studies have shown no
protein (VLDL) and apolipoprotein B (apoB) synthesis. 22 cardiovascular effect in children.20 At this time, there are no
While fish intake has been shown to be cardioprotective, recommendations regarding the use of garlic for lowering
it has no effect on total cholesterol, LDL, or HDL and has cholesterol in children.
only been shown to lower triglycerides. Still, the American
Heart Association (AHA) and American Academy of Antioxidants
Pediatrics (AAP) recommend increasing fish consump- Antioxidants have been raised as a possible treatment for
tion for CVD prevention; no specific guidelines exist for high cholesterol because oxidized LDL is implicated in
pediatrics, but the recommendation for adults is 2 servings plaque development. Although daily supplementation of
per week.23 DHA and EPA may be synthesized from alpha- vitamins C and E may improve endothelial function, large-
linolenic acid, which is found in flaxseed oil, canola oil, soy scale clinical trials have not shown any benefit related to the
oil, and walnuts. A total of 2 to 4 g of DHA/EPA may be primary or secondary prevention of CVD. 24,27 Studies in chil-
recommended for triglycerides > 500 mg/dL.24,25 This level dren are limited, and antioxidant vitamin supplementation
of intake, in general, cannot be achieved by seafood intake is not currently recommended to manage dyslipidemia.27
alone and requires supplementation or medication. It should
be noted that over-the-counter fish oil supplements are Physical Activity
often dosed with the total grams of fish oil, but one should Physical activity is beneficial for children and adolescents
pay attention to total grams of combined DHA and EPA, with dyslipidemia, due to its effects on raising HDL and
and not total grams of fish oil, in dosing supplements for the decreasing triglyceride levels. Improvement of LDL levels
treatment of high triglycerides. and insulin resistance have also been documented.28,29 In
addition, physical activity plays a critical role in maintaining
Soy Protein an appropriate weight, which also affects cholesterol levels.
The effect of soy on lowering cholesterol remains controver- Physical activity should be encouraged in all patients with
sial. While some studies show soy isoflavones can decrease dyslipidemia unless another medical condition contraindi-
LDL and triglycerides and increase HDL, others show little cates this. New physical activity guidelines recommend that
or no effect. Although a daily intake of 25 g of soy in adults children have at least 60 minutes of moderate to vigorous
may decrease total and LDL cholesterol from 1.5% to 4.5%, physical activity daily, including vigorous physical activity
this may be related more to the use of soy as a substitute for at least 3 days per week. 30
foods high in saturated fat.22,24,26 No recommendations have Nutrition and physical activity recommendations for
been made for children. While the cholesterol-lowering specific lipid abnormalities are summarized in Table 15-3.
TABLE 15-3 Summary of Nutrition and Physical Activity Recommendations for Specific Lipid Abnormalities
Lipid Abnormality Fiber Simple Dietary Trans Fat Saturated Fat Omega-3 Fats Physical
Carbohydrates Cholesterol Activity
High LDL Increase DGA < 200 mg < 1% total kcal < 7% total kcal DGA Increase
High TG DGA Decrease < 200 mg < 1% total kcal < 7% total kcal Increase Increase
Low HDL DGA DGA < 200 mg < 1% total kcal < 7% total kcal DGA Increase
DGA = Dietary Guidelines for Americans 2005.

LIPID DISORDERS 167
Pharmacologic Intervention References

Medications may be considered in conjunction with nutri- 1. Daniels SR, Greer FR; Committee on Nutrition. Lipid
tion and physical activity interventions for patients 8 years screening and cardiovascular health in childhood. Pediatrics.
2008;122:198–208.
and older with an LDL ≥ 190 mg/dL (or ≥ 160 mg/dL with 2. Newman WP III, Freedman DS, Voors AW, et al. Relation of
a family history of early heart disease or ≥ 2 additional risk serum lipoprotein levels and systolic blood pressure to early
factors present, or ≥ 130 mg/dL or > 100 mg/dL depending atherosclerosis: the Bogalusa Heart Study. N Engl J Med.
if Type 1 diabetes mellitus or other high-risk conditions 1986;314(3):138–144.
exist).1,31 HMG CoA-reductase inhibitors, or statins, are the 3. Berenson GS, Srinivasan SR, Bao W, Newman WP III,
Tracy RE, Wattigney WA. Association between multiple
recommended class of medications to lower LDL levels in
cardiovascular risk factors and the early development of
pediatrics. Statins have been shown to be safe and effective atherosclerosis. The Bogalusa Heart Study. N Engl J Med.
in lowering cholesterol in a number of clinical trials, though 1998;338(23):1650–1656.
they have generally been short-term. 32–36 Patients, however, 4. McGill HC Jr, McMahan CA, Malcom GT, Oalmann MC,
need to be monitored closely for liver and muscle side Strong JP; for the PDAY Research Group. Effects of serum
effects. Niacin and bile acid-binding resins are other classes lipoproteins and smoking on atherosclerosis in young men
and women. Aterioscler Thromb Vasc Biol. 1997:17(1):95–106.
of cholesterol-lowering medications but are not routinely 5. Webber LS, Osganian V, Luepker RV, et al. Cardiovascular
recommended in pediatrics due to limited effectiveness and risk factors among third grade children in four regions of
poor compliance. Cholesterol-absorption inhibitors are the the United States. The CATCH Study: Child and Adoles-
newest class that are often combined with other medications cent Trial for Cardiovascular Health. Am J Epidemiol.
such as statins, but have not yet been extensively studied in 1995;141(5):428–439.
6. Cook S, Weitzman M, Auinger P, Nguyen M, Dietz WH.
children.
Prevalence of a metabolic syndrome phenotype in adoles-
cents: findings from the third National Health and Nutrition
Test Your Knowledge Questions Examination Survey, 1988-1994. Arch Pediatr Adolesc Med.
1. Which of the following values is least important in 2003;157:821–827.
assessing a fasting lipid profile? 7. Ogden CL, Carroll MD, Flegal KM. High body mass index for
A. Triglycerides age among US children and adolescents, 2003-2004. JAMA.
2008;299(20):2401–2405.
B. Total cholesterol 8. Kwiterovich PO. Diagnosis and management of familial
C. LDL dyslipidemia in children and adolescents. Pediatr Clin North
D. HDL Am. 1990;37:1489–1523.
2. What percentage of trans fats is recommended by the 9. Expert Panel on Detection, Evaluation, and Treatment of
American Heart Association? High Blood Cholesterol in Adults. Executive Summary of the
Third Report of the National Cholesterol Education Program
A. < 5% total calories/day
(NCEP) Expert Panel on Detection, Evaluation, and Treat-
B. < 10% total calories/day ment of High Blood Cholesterol in Adults (Adult Treatment
C. < 30% total calories/day Panel III). JAMA. 2001;285:2486–2497.
D. < 1% total calories/day 10. Schwimmer JB, et al. Cardiovascular risk factors and the meta-
3. In which lipid profile would omega-3 fats be beneficial bolic syndrome in pediatric nonalcoholic fatty liver disease.
for a pediatric patient? Circulation. 2008;118:277–283.
11. Kwiterovich PO. Recognition and management of dyslipi-
A. LDL 200 mg/dL, triglycerides 80 mg/dL, HDL 50 demia in children and adolescents. J Clin Endocrinol Metab.
mg/dL 2008;93(11):4200-4209.
B. LDL 110 mg/dL, triglycerides 550 mg/dL, HDL 25 12. Rose G. Sick individuals and sick populations. Int J Epidemiol.
mg/dL 1985;14(1):32–38.
C. LDL 120 mg/dL, triglycerides 150 mg/dL, HDL 25 13. US Department of Health and Human Services. 2005 dietary
guidelines for Americans. http://www.healthierus.gov/
mg/dL
dietaryguidelines. Accessed November 12, 2009.
D. LDL 180 mg/dL, triglycerides 100 mg/dL, HDL 30 14. Howell WH, McNamara DJ, Tosca MA, Smith BT, Gaines
mg/dL JA. Plasma lipid and lipoprotein responses to dietary
fat and cholesterol: a meta-analysis. Am J Clin Nutr.
See p. 487 for answers. 1997;65:1747–1764.
15. American Academy of Pediatrics Policy Statement. Choles-
terol in Childhood. (RE9805) Pediatrics. 1998;101:141–147.

16. American Heart Association. Face the Fats. http://www. 28. Maron BJ, Chaitman BR, Ackerman MJ, et al. Recommenda-
americanheart.org/presenter.jhtml?identifier=3046074 tions for physical activity and recreational sports participation
Accessed November 12, 2009. for young patients with genetic cardiovascular diseases. Circu-
17. Dalidowitz C. Nutrition management of dyslipoproteinemia. lation. 2004;109(22):2807–2816.
In: Nevin-Folino NL, ed. Pediatric Manual of Clinical 29. Strong WB, Malina RM, Blimkie CJ, et al. Evidence-
Dietetics. 2nd ed. Chicago, IL: American Dietetic Association; based physical activity for school-age youth. J Pediatr.
2003:319–340. 2005;146(6):732–737.
18. Davidson MH, Dugan LD, Burns JH, Sugimoto D, Story K, 30. US Department of Health and Human Services. 2008 physical
Drennan K. A psyllium enriched cereal for the treatment of activity guidelines for Americans. http://www.health.gov/
hypercholesterolemia in children: a controlled, double-blind, paguidelines. Accessed November 12, 2009.
cross-over study. Amer J Clin Nutr. 1996;63:96–102. 31. Kavey R, Aladda V, et al. Cardiovascular Risk Reduction
19. Food and Nutrition Board, Institute of Medicine. Dietary in High-Risk Patients: A Scientific Statement From the
Reference Intakes for Energy, Carbohydrate, Fiber, Fat, Fatty American Heart Association Expert Panel on Population
Acids, Cholesterol, Protein, and Amino Acids (Macronutrients). and Prevention Science; the Councils on Cardiovascular
Washington DC: National Academy Press; 2005. Disease in the Young, Epidemiology and Prevention, Nutri-
20. Kavey RE, Daniels SR, Lauer RM, et al. American
��
Heart Asso- tion, Physical Activity and Metabolism, High Blood Pressure
ciation guidelines for primary prevention of atherosclerotic Research, Cardiovascular Nursing, and the Kidney in Heart
cardiovascular disease beginning in childhood. Circula- Disease; and the Interdisciplinary Working Group on Quality
tion. 2003;107(11):1562–1566; copublished in J Pediatr. of Care and Outcomes Research: Endorsed by the American
2003;142(4):368–372. Academy of Pediatrics. Circulation. 2006;114 :2710–2738.
21. Tammi A, Ronnemaa T, Miettinen TA, et al. Effects of gender, 32. de Jongh S, Ose L, Szamosi T, et al. Efficacy and safety of
apolipoproteína E phenotype and cholesterol-lowering by statin therapy in children with familial hypercholesterolemia:
plant stanol esters in children: the STRIP study. Special Turku a randomized double-blind, placebo-controlled trial with
Coronary Risk Factor Intervention Project. Acta Paediatr. simvastatin. Circulation. 2002;106(17):2231–2237.
2002;91(11):1155–1162. 33. Lambert M, Lupien PJ, Gagne C, et al. Treatment of familial
22. Krummel D. Nutrition in cardiovascular disease. In: Mahan hypercholesterolemia in children and adults: effect of
LK, Escott-Stump S, eds. Krause’s Food, Nutrition, and lovastatin. Canadian Lovastatin in Children Study Group.
Diet Therapy. 10th ed. Philadelphia, PA: WB Saunders Co; Pediatrics. 1996;97(5):619–628.
2000:571. 34. McCrindle BW, Ose L, Marais AD. Efficacy and safety
23. Nutrition Committee of the American Heart Association. of atorvastatin in children and adolescents with familial
AHA Dietary Guidelines. Circulation. 2000:2296. hypercholesterolemia or severe hyperlipidemia: a multi-
24. Fletcher B, Berra K, Ades P, et al. Managing abnormal center, randomized, placebo-controlled trial. J Pediatr.
blood lipids: a collaborative approach. Circulation. 2003;143(1):74–80.
2005;112:3184–3209. 35. de Jongh S, Lilien MR, op’t Roodt J, et al. Early statin therapy
25. Kris-Etherton PM, Harris WS, Appel LJ; American Heart restores endothelial function in children with familial hyper
Association Nutrition Committee. Fish consumption, fish oil, cholesterolemia. J Am Coll Cardiol. 2002;40(12):2117–2121.
omega-3 fatty acids, and cardiovascular disease. Circulation. 36. Wiegman A, Hutten BA, de Groot E, et al. Efficacy and safety of
2002;106:2747–2757. statin therapy in children with familial hypercholesterolemia:
26. Erdman JW Jr. AHA Science Advisory. Soy protein and a randomized controlled trial. JAMA. 2004;292(3):331–337.
cardiovascular disease: a statement for healthcare profes-
sionals from the Nutrition Committee of the AHA.
Circulation. 2000;102:2555–2559.
27. Engler MM, Engler MB, Malloy MJ, et al. Antioxidants vita-
mins C and E improve endothelial function in children with
hyperlipidemia: Endothelial Assessment of Risk From Lipids
in Youth (EARLY) Trial. Circulation. 2003;108:1059–1063.

16
Use of Popular and Fad Diets
Catherine Christie, PhD, RD, Julia A. Watkins, PhD, MPH, and Judith C. Rodriguez, PhD, RD

Background . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 169 1. Describe the importance of weight maintenance versus
Clinical Approach to the Overweight/Obese Child or weight loss recommendations when working with
Adolescent . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 170 children and adolescents.
Use of Fad and Popular Diets . . . . . . . . . . . . . . . . . . . . . . 170 2. Critique one of the discussed popular/fad diets for use
with children.
Lifelong Weight Management. . . . . . . . . . . . . . . . . . . . . . 171
3. Critique another popular/fad diet discussed for use with
Types of Fad and Popular Diets. . . . . . . . . . . . . . . . . . . . . 171
adolescents.
Behavioral Weight-Loss Plans
Food-Focused Weight Loss Plans 4. Assess the efficacy of a balanced macronutrient
Reduced Macronutrient Content Plans low-kilocalorie diet for use with children.
Food Group Guides/Exchange Systems
Food Timing/Meals and Snacks Combinations Background
Commercial Meal/Snack Replacements The incidence and prevalence of childhood overweight and
Other Plans
obesity is increasing worldwide.1 This increase is associated
Diets Designed for Use with Children. . . . . . . . . . . . . . . . 174 with multiple health risks and adverse effects in childhood as
Balanced Macronutrient Low-Kilocalorie Diets
Traffic Light Diet™
well as later in life such as sleep problems, endocrine disorders,
Food Guide Pyramid respiratory problems, gastrointestinal problems, skin condi-
Multidisciplinary Behavior Change Programs tions, orthopedic disorders, and cardiovascular risk factors.2
Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 175 Dietary intake data are also of concern. Less than 40%
of U.S. youth meet the U.S. Dietary Guidelines for saturated
fat, which is related to risk for heart disease and diabetes.3
According to the Youth Risk Behavior Surveillance (YRBS)
survey, 80% of adolescents do not eat fruits and vegetables 5
or more times per day, which impacts on the findings that only
39% of youth 2 to 17 years meet the U.S. Department of Agri-
culture’s recommendations for fiber.4,5
There is a need for successful, scientifically sound weight-
loss measures with dietary, physical activity, and social support
components to assist youth. According to the YRBS survey, a
large number of adolescents use unhealthy methods to lose or
maintain weight, evidenced by the finding that during the 30
days preceding the survey, 12.3% of students went without
eating for 24 hours or more, 4.5% had vomited or taken
169
laxatives; and 6.3% had taken diet pills, powders, or liquids Clinical Approach to the Overweight/Obese
without a doctor’s advice.4 Child or Adolescent
Systematic reviews of childhood obesity and expert The American Dietetic Association evidence-based analysis
committee recommendations have emerged over the last of pediatric overweight literature on intervention programs
several years6–9 and all agree that child and adolescent reported positive effects from 2 specific kinds of inter-
obesity treatment should: ventions: (1) multi-component, family-based programs
• be directed at motivated families in which the child for children between the ages of 5 and 12 and (2) multi-
and/or parents perceive obesity to be a problem and component school-based programs for adolescents. The
appear willing to make lifestyle changes components included were behavioral counseling, promo-
• be directed at the entire family rather than just the tion of physical activity, parent training/modeling, dietary
overweight/obese child counseling, and nutrition education.10
• aim for weight maintenance unless body mass index Interventions should be based on the family’s readiness
(BMI) is > 99th percentile to change and include the following recommendations9:
• be more intensive than has been the norm • consumption of ≥ 5 servings of fruits and vegetables per
• combine changes in diet plus changes in physical day
activity and/or reduction in sedentary behavior • minimization or elimination of sugar-sweetened
The current definitions state that if BMI is greater than beverages
or equal to the 95th percentile, the child is “obese,” and if • limits of ≤ 2 hours of screen time per day, no television
BMI is between the 85th and 94th percentiles, the child is in the room where the child sleeps, and no television if
“overweight” (Table 16-1). the child is < 2 years of age
• ≥ 1 hour of physical activity per day
Table 16-1 Weight Recommendations According to Age and BMI Percentile9
In addition, parents and family members should be coun-
Age Target
seled to facilitate the following eating behaviors:
2–5 years • eating breakfast daily
BMI of 85th to Weight maintenance until BMI of < 85th percentile
94th percentile or slowing of weight gain, as indicated by • limiting meals outside the home, including at fast-food
downward deflection of BMI curve. venues and other restaurants
BMI of ≥ 95th Weight maintenance until BMI of < 85th • eating family meals at least 5 or 6 times per week
percentile percentile; however, if weight loss occurs with • allowing the child to self-regulate his or her meals and
healthy, adequate energy diet, then it should
not exceed 1 lb/mo. If greater loss is noted, avoiding overly restrictive behaviors
then patient should be monitored for causes of
excessive weight loss. Use of Fad and Popular Diets
6–11 years Parents of overweight or obese children may be overweight
94th percentile or slowing of weight gain, as indicated by themselves and often look to popular diets as a means of
downward deflection of BMI curve. losing weight. Because these diets are often adopted by the
BMI of 95th to Weight maintenance until BMI of < 85th percentile family and modified for children or adolescents, a discussion
98th percentile or gradual weight loss of ~1 lb/mo. If greater loss of the use of popular diets for pediatric patients is warranted.
is noted, then patient should be monitored for
causes of excessive weight loss. Family-friendly popular diets include elements of
BMI of ≥ 99th Weight loss not to exceed average of 2 lb/wk. healthy eating that are applicable or can be easily modified
percentile If greater loss is noted, then patient should be to safely include children. Popular diets can be categorized
monitored for causes of excessive weight loss. into 7 major types: behavioral, food-focused, reduced
12–18 years
macronutrient content, food group guides or exchange
94th percentile or slowing of weight gain, as indicated by systems, food timing or specific combinations of meals and
downward deflection of BMI curve. snacks, commercial meal or snack replacements, and an
BMI of 95th to Weight loss until BMI of < 85th percentile, no “other” category for plans that do fit in any previous cate-
98th percentile more than average of 2 lb/wk. If greater loss
is noted, then patient should be monitored for gory.11 Within each category of weight-loss diets, many are
causes of excessive weight loss. effective in reducing weight because regardless of the plan
BMI of ≥ 99th Weight loss not to exceed average of 2 lb/wk. or claim, they principally lower caloric intake by prescribing
percentile If greater loss is noted, then patient should be limits on food intake. However, the scientific evidence
monitored for causes of excessive weight loss.
consistently concludes that successful weight loss should be
Reproduced with permission from Pediatrics, Vol. 120, page 254, copyright
© 2007 by the American Academy of Pediatrics.

USE OF POPULAR AND FAD DIETS 171
coupled with a plan that enables the dieter to manage weight Lifelong Weight Management
over a lifetime.11 The more extreme the plan, the more diffi- The following 5 steps to lifelong weight management are
cult it is to follow over the long term. The key for lifelong helpful for families who are considering a change in their
weight management is following a plan individualized to diet for weight loss of any family member11:
each person’s needs. Kilocalorie- and portion-controlled 1. Eat food in appropriate portion sizes.
diets seem to be more conducive to long-term compliance A. Meat, poultry, and fish servings should be the size of
than fat- and carbohydrate-restricted diets.12 a deck of cards or a bar of soap.
According to the Weight Control Registry,13 adults who B. Pasta, rice, and other grains should not be larger
are successful at losing weight and keeping it off individu- than the size of a tennis ball.
alize their changes in lifestyle to include eating and exercise C. Legumes should be about half the size of a tennis
behaviors that they can sustain for a lifetime. Therefore, ball.
when considering any diet plan individuals should consider D. A piece of cheese should be about the size of four dice.
nutrition, food variety, moderate intake, food portions, rate 2. Focus on slow, gradual weight loss or weight mainte-
of including these into their lifestyle, ways to continue them nance in children through regular eating and physical
for an extended time, and how to add physical activity. For activity. Skipping meals has not been shown to help
many, the term “diet” evokes thoughts of something tempo- weight loss. Breakfast is particularly important for chil-
rary. The resultant “on-off” mindset produces short-term dren and adolescents.
change only and does not address the underlying behaviors 3. Eat a variety of foods with an emphasis on whole grains,
that created the need to diet in the first place. fruits, vegetables, low-fat dairy products, lean meats,
Successful weight-reduction programs reduce body poultry, fish, legumes, nuts, and seeds.
weight and body fat gradually by decreasing caloric intake 4. Drink water and avoid sweetened caloric beverages.
and increasing caloric expenditure. An increase in physical 5. Limit fats, added sugars, and refined foods.
activity builds or maintains muscle mass and, together
with aerobic activity, determines the utilization of body Types of Fad and Popular Diets
fat reserves and thus the metabolic rate or the rate of kilo- Although there are a myriad of fad and popular diets, most
calories being burned. Diets that promise immediate or fast share some common claims or principles that enable them
weight loss are not recommended as they defy the scientific to be grouped into a few categories.
basis for metabolism, particularly in children as normal
growth may be inhibited. Such claims are at best misleading Behavioral Weight-Loss Plans
and at worst, potentially harmful. The calculation of A recent example of a behavioral weight-loss plan is the
energy balance reveals that fat loss occurs at the rate of 1 French Women Don’t Get Fat15 diet. This diet makes the
to 2 pounds per week, even when a person severely restricts following basic recommendations:
caloric intake. To lose 1 pound of body fat per week, a nega- • Avoid the extremes of either going hungry or
tive caloric deficit of 3500 kilocalories or 500 kilocalories feeling stuffed.
for 7 days must occur. Weight loss greater than the recom- • Avoid obsessing about eating and dieting.
mended 1 to 2 pounds per week can only occur by losing • Do not skip meals or induce feelings of deprivation.
muscle and water in addition to fat.14 • Eat nuts as snacks or sprinkled over foods.
It is important for families to set a reasonable and • Eat the real thing in moderation instead of using
reachable goal for weight loss with their physician and a substitutes.
registered dietitian before undertaking a diet. When plan- • Eat 3 daily meals that include carbohydrates, proteins,
ning a change in diet for the family, the plan should first be and fats.
evaluated to see if it is compatible with their lifestyle and • Do not replace regular meals with beverages such as
health needs. It should be a plan that the family can foresee shakes or smoothies.
continuing indefinitely. A lifestyle change is required to • Eat yogurt with active cultures.
prevent periods of on and off dieting and regression to the • Eat without stuffing yourself or feeling guilty.
previous habits which initially caused weight gain. On and • Enjoy high-quality bread and chocolate in moderate
off dieting results in weight regain, which could negatively amounts.
impact health and affect disease progression. • Enjoy fresh foods and flavorful fruits and vegetables in
season.

• Enjoy different seasonings by using either fresh or dried most recent Atkins diet promotes 5 nutrition rules: a high
herbs and spices. consumption of protein and fiber, substantial vitamin and
• Focus on small portions of high-quality foods. mineral intake, low amounts of sugar, and the elimination
• If you relapse, simply get back on track. of trans fats. Although physical activity is encouraged with
• Make physical activity an integral part of your day. the diet plan, the main focus is on high-protein, low-carbo-
• Plan what to eat in advance. hydrate eating. Short-term research studies tracking the
• Savor meals, slow down, relax, and stop what you are progress of adults on the diet have reported high levels of
doing to eat. satiety, a temporary improvement in blood lipids and glucose
• Take pleasure in eating and focus on the “good” not levels, some loss of body fat, and the sparing of muscle
“bad” things to eat. protein.18,19 In a recent 2-year trial, researchers concluded
While not exclusive to this diet, behavioral approaches to Mediterranean-style diets that are not necessarily lower
weight loss that include portion control, regular physical fat but focus on healthier fats and low-carbohydrate diets
activity, self-efficacy and self-regulation, and the monitoring may be effective alternatives to low-fat diets. The more posi-
of eating and weight have been shown to be effective for tive effects on lipids with the low-carbohydrate diet and on
successful long-term weight management in adults.12 These glycemic control with the Mediterranean-style diet indicate
principles are also recommended for children and adoles- that diets should be tailored to individual preferences and
cents.9 Behavioral strategies to help overweight children and health risks.20 Whereas reducing intake of simple sugars
their families include establishing a regular meal and snack may be appropriate for children and adolescents, low-
pattern; eating smaller portions at meals and snacks; limiting carbohydrate plans should not be recommended due to the
second helpings to fresh fruit and non-starchy vegetables; potential low intake of fiber, nutrients, and kilocalories to
selecting lower-fat dairy products; eating more foods that are support growth and development.
baked, broiled, grilled, or boiled instead of fried; selecting The South Beach Diet17 is a variation on the carbohy-
healthful snacks that include low-fat protein along with fresh drate-restricted diet divided into 3 phases. Phase I allows
fruit, vegetables, or whole grain bread and cereals; and when lean meats, chicken, egg or egg substitutes, fish, olive oil,
eating out, selecting more healthful options or splitting larger vegetables, salads, nuts, and some low-fat milk. Phase II
servings to share with other family members or peers.8 introduces lower glycemic-index carbohydrates in limited
amounts. Fruits are recommended for lunch or dinner,
Food-Focused Weight Loss Plans but not breakfast. Whole grain bread, sweet potatoes, and
One of the oldest and most well-known examples of a food- brown or wild rice in modest portions replace white bread,
focused weight-loss plan is the grapefruit diet. Although white potatoes, and white rice. Mashed, steamed cauliflower
grapefruit is credited with containing a special fat-burning replaces mashed potatoes. Sandwiches are replaced by fill-
enzyme, no scientific evidence exists to substantiate that ings in lettuce wraps. This phase lasts for 2 weeks or until
claim. Weight loss is achieved through limited food selec- the desired weight is lost. If overindulgence occurs during
tion, reduced caloric intake, and loss of fluid. Complex this phase, the recommendation is to return to Phase I for
carbohydrates and snacks between meals are forbidden, 1 week. Phase III is the lifelong maintenance phase where
while most vegetables and all meat and fish are allowed. the emphasis is on the “good” carbohydrates and fats with
Meals comprise eggs, meat or fish, salads, vegetables, skim restriction of the “bad” carbohydrates and fats. This low-
milk, tomato juice, and unlimited amounts of black coffee kilocalorie, high-protein, lower-carbohydrate plan allows
or tea. Each meal is accompanied by half a grapefruit or half healthy fats, high-fiber foods, and selected carbohydrates
a cup of unsweetened grapefruit juice. If no behavioral or in moderate amounts. The evidence suggests that moderate
lifestyle changes are instituted, it is likely that weight lost intake of carbohydrates, proteins, and healthy fats facili-
will be regained over time.11 This type of plan would not tates weight management in adults.10 This plan is adaptable
be recommended for children or adolescents due to the for use with children particularly in Phase III. However,
potential for nutrient deficiencies, severely restricted caloric the entire family should be committed to focusing on > 5
intake, and excessive weight loss. fruits and vegetables per day, minimizing sweetened bever-
ages, increasing physical activity, and reducing sedentary
Reduced Macronutrient Content Plans behaviors as well as eating breakfast daily, limiting meals
The best known of the low-carbohydrate plans may be outside the home including at fast-food venues and other
the Atkins Diet16 followed by the South Beach Diet.17 The restaurants, eating family meals at least 5 or 6 times per

week, allowing the child to self-regulate his or her meals, and managing cues to overeating, stress management, and
and avoiding overly restrictive behaviors.9 making a plan to handle setbacks. There are no forbidden
The Pritikin Diet21 and the Dean Ornish Diet22 are the foods and treats are allowed as long as the predominant
most well-known of the low-fat diets. Both diets were origi- eating style is low-kilocalorie density. There is strong scien-
nally developed for the prevention and treatment of heart tific evidence that reducing caloric intake combined with
disease and also became popular as weight-loss diets. The exercise and behavior management produces weight loss in
Pritikin plan comprises a total caloric breakdown of 10% adults.12 There are no studies that have evaluated the use of
fat, 10% to 15% protein, and 75% to 80% carbohydrates with this diet in children or adolescents however it does contain
35 g of fiber, less than 100 mg of cholesterol, and 600 mg of many of the elements recommended (eg, focusing on > 5
sodium. Exercise and stress management are integral to the fruits and vegetables per day, minimizing sweetened bever-
plan. Encouraged as a life-long commitment, this restric- ages, increasing physical activity and reducing sedentary
tive, very low-fat, high-fiber plan requires extensive menu behaviors as well as eating breakfast daily, limiting meals
planning and may be difficult to implement as it entails outside the home including at fast-food venues and other
careful label reading and product comparison.11 In addition, restaurants, and allowing the child to self-regulate his or her
there are no studies that have evaluated the use of this diet meals and avoiding overly restrictive behaviors).9
in children or adolescents.
Like the Pritikin plan, the Dean Ornish Diet22 allows Food Timing/Meals and Snacks Combinations
only 10% of kilocalories from fat. It also limits sugar and A recent example of this category is the Suzanne Somers
honey. The restriction on fat and simple sugars prevents Diet.24 According to this diet, eating fat does not cause
individuals from consuming excess kilocalories and the weight gain, sugar is more fattening than fat, and carbohy-
high-fiber content contributes to a feeling of fullness. In drates are not essential in the diet. According to Ms. Somers,
addition, the diet promotes whole foods and a high intake weight gain is caused by hormonal imbalances and successful
of phytochemicals from vegetarian-based foods and forbids weight loss depends on keeping insulin stable following
meat, nuts, seeds, avocados, white flour, white rice, and fried digestion. This is achieved by eating certain foods in specific
foods. The diet also advocates a comprehensive lifestyle combinations, cutting carbohydrate intake, and eliminating
change including stress management training, smoking sugars and refined carbohydrates, starchy foods, white flour,
cessation, meditation, and moderate exercise. There is caffeine, and “funky” foods. Meals should not be skipped and
strong scientific evidence to support the plan’s claim to after eating fruit, the dieter should wait 20 minutes before
reverse the risk of heart disease in adults, and the resulting consuming other foods. There are 2 levels to this diet. Level
weight loss is due to the caloric restriction.22 However, there 1 is the most restrictive and is designed to initiate weight
are no studies that have evaluated the use of this diet in chil- loss. Level 2 is the maintenance phase and introduces some
dren or adolescents. protein, fat, and carbohydrate combinations. The rationale
for the diet’s effectiveness is not substantiated by scientific
Food Group Guides/Exchange Systems data; however weight loss may be achieved due to the many
One example of a food group or exchange plan is the Volu- food restrictions and the total caloric intake of the structured
metrics Weight-Control Plan.23 Food choices are based on meals.11 This type of plan would not be recommended for
kilocalorie density. Fat, fiber, protein, and water content children or adolescents due to the lack of scientific validity
of foods all affect energy or kilocalorie density. By eating in the premise, the potential for nutrient deficiencies, and
predominantly filling, low-kilocalorie, dense foods, smaller severely restricted caloric intake.
portions of a few high-kilocalorie, dense foods can be
included and the person will still lose weight due to the Commercial Meal/Snack Replacements
overall kilocalorie restriction. Low-energy, dense foods One of the largest commercial weight-loss programs is
include fruits and vegetables, skim milk, broth-based soups, WeightWatchers®.25 WeightWatchers, International, Inc.
fat-free salad dressings, pasta, cooked high-fiber grains, has more than 1.5 million members attending one of its
potatoes, legumes, low-fat meats, salads, low-fat soups, 50,000 weekly meetings around the world. WeightWatchers
low-fat cheeses, cottage cheese, frozen yogurt, and non- was one of the first to incorporate a walking program and
kilocalorie beverages. This diet is complemented by regular emphasize physical activity as a necessary part of dieting.
exercise and behavior management, which includes keeping The POINTS® Weight-Loss System assigns a point value to
a food and exercise log, not skipping meals, identifying activities and food which is determined by the number of

kilocalories, total fat, and dietary fiber in a defined serving. and reducing health risks in the environment are integrated
Each person is given a daily POINTS target that will lead to into each plan. However, there is no scientific validity to the
a caloric deficit that translates into 1 to 2 pounds per week idea that diet should be defined by blood type. By limiting
weight loss. A second plan called the Core Plan® focuses specific foods and sometimes food groups, those who follow
on choosing foods with low energy density. By routinely the diet can lose weight, but the elimination of specific foods
monitoring hunger cues and with an allowance for periodic and groups is based on a premise without adequate scientific
“indulgences,” the Core Plan® has been shown to produce evidence.11 This diet plan is not recommended for children
weight losses equal to the POINTS® system. There is strong or adolescents.
evidence to support a lifestyle plan that includes regular
monitoring and support systems using commonly avail- Diets Designed for Use with Children
able foods. The emphasis on portion control and low energy
density foods can be translated to many food settings, Balanced Macronutrient Low-Kilocalorie Diets
and the recipes help teach dieters to prepare dishes lower Evidence does suggest that short- and long-term reduced
in kilocalories. Members do pay a fee for the weight-loss energy (less than 1200 kcal) may be an effective part of a
services including those on the Internet and for Weight- multi-component weight-management program in children
Watchers-branded food items.11 WeightWatchers does not 6 to 12 years of age.29 In the adolescent population, the use
recommend its plan for children and instead discusses chil- of reduced energy (not less than 1200 kcal) is generally
dren’s needs in terms of 2 goals: ensuring the child grows effective for short-term weight loss but without continuing
and develops normally and helping the child reach a healthy dietary intervention, weight is regained. 29
weight. Weight maintenance strategies are recommended
for children as young as 3 years of age26 and weight gain in Traffic Light Diet™
overweight young children should be limited to 2 pounds The Traffic Light Diet™ was designed to promote weight
for every inch of growth.25 Over age 4, it is recommended loss, provide adequate kilocalories and nutrients for growth
that the child maintain weight until the BMI drops down and development, and be easy to follow. 30 The diet divides
into the normal range, below the 85th percentile. 27 foods into 11 categories, with the foods in each category
then separated into 3 color groups: green, yellow, and red.
Other Plans These colors correspond to the colors of a traffic light and
Eat Right for Your Type28 was on the New York Times best- signify GO (green), eat as much as you like; approach with
seller list and remains a popular diet plan today. The book CAUTION (yellow), eat in moderate amounts; and STOP
provides 4 diets based on the Blood Types O, A, B, and AB. (red), do not eat. Green foods are those foods that contain
People with Type O blood are described as hunters, who less than 20 kcal per average serving and are found only in
need a diet with high protein, lean, chemical-free meat, the vegetable and free foods categories. Yellow foods are
poultry, and fish with limited grains, beans, and legumes. foods that are within 20 kcal per average serving of the
Those with type A blood, the cultivators, need to eat predom- caloric value of the average food within that food group.
inantly vegetarian with fish and an emphasis on vegetables, Yellow foods are items from the 4 basic food groups, which
tofu, grains, beans, legumes, and fruit. Type B, the nomads, a child should eat in recommended amounts in order to
should eat meat (no chicken), dairy, grains, beans, legumes, obtain adequate nutrition. Red foods are foods that exceed
vegetables, and fruit. Type AB, the enigma, can eat a mixed the caloric value of a yellow food, thereby lowering the
diet in moderation including meat, seafood, dairy, tofu, nutrient density of the food. In addition, red foods include
beans, legumes, grains, vegetables, and fruit. Each blood any food that is made to resemble red food, as low-kilo-
type has a long list of forbidden foods including specific calorie lasagna, which might not be a red food in terms of
meats and poultry, seafood, dairy, eggs, oils and fats, nuts kilocalories, but is labeled a red food because a person will
and seeds, beans, legumes, cereals, breads, muffins, grains, not break the habit of eating lasagna if often substituting
pasta, vegetables, fruit, juices, fluids, spices, condiments, low- for high-kilocalorie lasagna. Participants are limited to
herbal teas, and other beverages. 4 red foods per week.
Each of the blood-type diets consists of whole, unpro- Results showed a clear superiority of the parent and
cessed foods and all recommend the consumption of child intervention including diet and self-monitoring by
vegetables, which provide fiber, health-promoting nutrients, both parent and child (Group I) over diet and self-moni-
and phytochemicals. Physical activity, stress management, toring by the child alone (Group II) and the control group

with no diet or self-monitoring (Group III). After 8 months kids together about healthy eating for weight loss, sepa-
and 21 months of treatment, the results for children in rate meetings for adults and children with a mental health
the 3 treatment groups were similar. Children’s weight professional to learn to change habits and behaviors and
decreased by 16.6%, 18.6%, and 16.1% in Groups I, II, and receive group support, and meetings for adults to discuss
III, respectively. However, after 5 years, the children in their specific questions while kids participate in 30 minutes
Group I maintained their relative weight change (-13.6%), of aerobic exercise; during 2 weeks adults and kids exer-
while children in Group II were at baseline (+3.3%) and the cise together. 35 Program effectiveness was evaluated in
children in Group III were heavier (+7%). 31 a study of 1,022 families from 24 community-based and
hospital-based sites in Pennsylvania and California from
Food Guide Pyramid 2004 through 2006. Food records, activity logs, program
The Food Guide Pyramid was designed as a general guide for questionnaires, and participant BMIs were obtained at the
diet and exercise in adults; however it was used as a dietary beginning and the end of the program. Statistically signifi-
component in childhood weight management in one study cant improvements in BMI, eating, physical activity, and
of adolescents. The results found that the adolescents using self-esteem were reported. 36 A follow-up study looked at a
the Food Guide Pyramid actually gained weight over the convenience sample of 86 children at 3 months, 88 children
course of the study compared with adolescents who ate a at 6 months, 30 children at 12 months, and 15 children at 18
balanced macronutrient low-kilocalorie diet. 32 to 24 months after completion of the KidShape® program.
Graduates of the program maintained a significant change
Multidisciplinary Behavior Change Programs in BMI up to 24 months after the program and reported
Two examples of multidisciplinary behavior change continued improvement in eating and physical activity. 37
programs for overweight children and their families are
SHAPEDOWN® and Kidshape®. Both were developed in Conclusion
academic medical centers and are offered in community There are many diets that will result in weight loss or weight
settings such as hospitals or clinics with interdisciplinary maintenance in adults and children because they control
teams of health professionals. They often include the disci- and lower caloric intake. The scientific evidence is strong
plines of nutrition, exercise physiology, endocrinology, that a successful weight-loss or weight-maintenance plan
psychology, family therapy, adolescent medicine, family for children and adolescents should include reduced kilo-
medicine, and/or behavioral and developmental pediatrics. calorie intake though consumption of ≥ 5 servings of fruits
SHAPEDOWN® incorporates behavioral techniques and vegetables per day and minimization or elimination
to address underlying issues of the child’s or adolescent’s of sugar-sweetened beverages (which are both present in
weight. Included are problem solving, communication, and a balanced macronutrient reduced kilocalorie diet and the
parenting skills (eg, limit setting and nurturing). In addi- Traffic Light Diet™) as well as the behavioral components
tion, cognitive therapy, stress management techniques, (eg, eating breakfast daily, limiting meals outside the home
and body image therapies are used. 33 SHAPEDOWN® including at fast-food venues and other restaurants, eating
was shown to produce significant long-term outcomes in a family meals at least 5 or 6 times per week, allowing the child
controlled study of 66 adolescents followed for 15 months to self-regulate his or her meals and avoiding overly restric-
who were randomly assigned to experimental or control tive behaviors). Long-term weight management happens
groups. There were no significant differences between when a plan is individualized to a family’s needs and prefer-
groups in any of the variables studied at the beginning of ences. Kilocalorie- and portion-controlled diets such as the
the study. The SHAPEDOWN® group at the end of the balanced macronutrient low-calorie diets and the Traffic
treatment (3 months) and at 1 year follow-up (15 months) Light Diet have been studied over time and may be more
significantly decreased relative weight and significantly conducive to long-term compliance in families than fat- and
improved weight-related behavior, self-esteem, depression, carbohydrate-restricted diets.
and knowledge. The control group made no significant Reviewing the various categories of popular and fad diets
improvement in any of these variables except self-esteem. 34 indicates that all have strengths and weaknesses and have the
KidShape® is a 9-week comprehensive family-based potential to result in weight loss in adults. However, for chil-
pediatric weight management program for overweight children and adolescents, these diets have not been studied due
dren and their families. Classes are divided into 3 major to potential risks for growing children and adolescents from
parts including a registered dietitian teaching adults and elimination of key food groups, greater-than-recommended

caloric restriction, adverse behavioral patterns of eating, and/ B. Greater than recommended caloric restriction
or lack of scientific evidence for the basis of the diet’s recom- C. Promotion of an adverse eating pattern
mendations. The key requirement for dietary treatment of D. Adequate scientific data for use in children for the
overweight children and adolescents is to initiate and main- diet/plan
tain lifelong healthy eating habits that focus on unhealthy
weight in the short term and foster improved health outcomes See p. 487 for answers.
in the long term. Family involvement, and particularly
parental involvement in weight control, weight maintenance, References
and weight-loss interventions, is associated with weight loss 1. World Health Organization. Diet, Nutrition and the Prevention
in children, and the use of behavior change techniques as an of Chronic Diseases. WHO TRS 916. Geneva: WHO/FAO;
2003.
integral part of the program improves weight outcomes for 2. Weiss R, Dziurra J, Burgert TS, et al. Obesity and the meta-
both children and parents.38 bolic syndrome in children and adolescents. N Engl J Med.
2004;350:2362–2374.
3. US Department of Agriculture. Continuing Survey of Food
Test Your Knowledge Questions Intakes by Individuals 1994–96. US Dept. of Agriculture, Agri-
cultural Research Service; 1998.
1. According to the American Dietetic Association
4. Centers for Disease Control and Prevention. Youth Risk
Evidence Analysis Library, which of the following clinical Behavior Surveillance—United States, 2005. Morbidity &
approaches had positive effects when working with over- Mortality Weekly Rep. 2006;55(SS-5):1–108.
weight/obese children ages 5 to 12? 5. Lin BH, Guthrie J, Frazao E. American children’s diets not
A. Multi-component, school-based making the grade. Food Rev. 2001;24(2):8–17.
B. Behavioral, family-based 6. Washington, R. Overview of the expert recommendations for
the assessment, prevention, and treatment of child and adoles-
C. Multi-component, family-based cent overweight and obesity. Obes Manage. 2008;2:20-23.
D. Diet, family-based 7. Barlow SE and the Expert Committee. Expert committee
2. The parents of an 8-year-old child have decided to imple- recommendations on the assessment, prevention, and
ment changes that will promote healthier lifestyle habits treatment of child and adolescent overweight and obesity.
among all the family members. Which of the following Pediatrics. 2007;120 (suppl4):S163–S288.
8. Kirk S, Scott BJ, Daniels SR. Pediatric obesity epidemic: treat-
changes is in line with changes recommended when there
ment options. J Am Diet Assoc. 2005;105:S44–S51.
is readiness to change? 9. Spear BA, Barlow SE, Ervin C, et al. Recommendations for
A. Adding a salad or vegetable to lunch and dinner meals treatment of child and adolescent overweight and obesity.
B. Substituting the dinner soda with a caffeine free Pediatrics. 2007;120;S254–S288.
beverage 10. Position of the American Dietetic Association: individual-,
C. Limiting family television viewing time to 3 hours family-, school-, and community-based interventions for pedi-
atric overweight. J Am Diet Assoc. 2006;106:925–945.
a day 11. Rodriguez J. The Diet Selector. Philadelphia, PA: Running
D. Taking the family for a 30-minute walk after dinner Press; 2007.
3. Diets that have been studied for use with children or 12. American Dietetic Association. Adult Weight Management
adolescents include: Evidence Based Nutrition Practice Guideline. ADA Evidence
A. The Food Guide Pyramid and The (Children’s) Atkins Library. 2008. http://www.adaevidencelibrary.com/topic.
cfm?cat=2798. Accessed July 28, 2008.
Plan
13. National Weight Control Registry. http://www.nwcr.ws/
B. The Traffic Light Diet and the Food Guide Pyramid Research/default.htm. Accessed May 27, 2008.
C. The Traffic Light Diet and the Pritikin Plan 14. Evans SA, Parsons AD, Overton JM. Homeostatic responses
D. The Volumetrics and the Exchange Plans to caloric restriction: influence of background metabolic rate.
4. Many of the popular/fad diets commonly used by adults J Appl Physiol. 2005;99(4):1336–1342.
are generally not recommended for children for all of the 15. Guiliano M. French Women Don’t Get Fat. New York, NY:
Random House; 2005.
following reasons except: 16. Atkins RC. Atkins New Diet Revolution. New York, NY: M.
A. Their potential negative risks to a growing child Evans & Co; 2002.
related to the elimination or decrease of a key food 17. Agatson A. The South Beach Diet. New York, NY: Random
group House; 2003.

18. Sharman MJ, Gomez AL, Kraemer WJ, Volek JS. Very 30. Epstein LH, Valoski A, Wing RR, McCurley J. Ten-year
low-carbohydrate and low-fat diets affect fasting lipids and follow-up of behavioral, family based treatment for obese chil-
postprandial lipemia differently in overweight men. J. Nutr. dren. JAMA. 1990;264:2519–2523.
2004;134:880–885. 31. Epstein LH, Valoski A, Wing RR, McCurley J. Ten-year
19. Brehm BJ, Seeley RJ, Daniels SR, et al. A random- outcomes of behavioral family-based treatment for childhood
ized trial comparing a very low carbohydrate diet and a obesity. Health Psychol. 1994;13:373–383.
kilocalorie-restricted low fat diet on body weight and cardio- 32. Saelens BE, Sallis WF, Wilfley DE, Patrick K, Cella JA, Buchta,
vascular risk factors in healthy women. J Clin Endocrinol R. Behavioral weight control for overweight adolescents initi-
Metab. 2003;88(4):1617–1623. ated in primary care. Obes Res. 2002;10:22-32.
20. Shai I, Schwarzfuchs D, Henkin Y, et al. Weight loss with a 33. SHAPEDOWN® information and description. http://www.
low-carbohydrate, Mediterranean, or low-fat diet. N Engl J shapedown.com/SD_About.html. Accessed August 4, 2009.
Med. 2008;359:229–241. 34. Mellin LM, Slinkard LA, Irwin CE Jr. Adolescent obesity
21. Pritikin R. The New Pritikin Program. New York, NY: Simon intervention: validation of the SHAPEDOWN program. J Am
& Schuster; 2000. Diet Assoc. 1987;87:333–338.
22. Ornish D. Eat More Weight Less. New York, NY: Harper 35. KidShape® information and description. http://www.
Collins; 1993. kidshape.com/. Accessed August 7, 2009.
23. Rolls B, Barnett RA. The Volumetrics Eating Plan. New York, 36. Rivard CW, Neufeld N. A comprehensive outcome analysis of
NY: Harper Collins; 2005. a multi-site, multi state family-based pediatric weight manage-
24. Somers S. Eat Great, Lose Weight. New York, NY: Random ment program. J Am Diet Assoc. 2007;107(8):A-11.
House; 1999. 37. Rivard CW, Neufeld N. A long-term comprehensive evalua-
25. WeightWatchers®. www.weightwatchers.com. Accessed tion of a family based pediatric weight management program
December 10, 2008. implemented in multiple community based and hospital based
26. Barlow S, Dietz W. Obesity evaluation and treatment: expert sites. J Am Diet Assoc. 2008;109(9):A-94.
committee recommendations. Pediatrics. 1998;102(3). 38. McLean N, Griffin L, Toney K, Hardeman W. Family involve-
27. Daniels SR, Arnett DK, Eckel RH, et al. Overweight in ment in weight control, weight maintenance and weight-loss
children and adolescents: pathophysiology, consequences, interventions: a systematic review of randomized trials. Int J
prevention and treatment. Circulation. 2005;111:1999–2012. Obesity. 2003;27:987–1005.
28. D’Adamo P, Whitney C. Eat Right for Your Type. New York,
NY: GP Putnam & Sons; 1996.
29. American Dietetic Association. Pediatric Weight Manage-
ment Evidence Based Nutrition Practice Guidelines. ADA
Evidence Library. www.adaevidenceanalysislibrary.com.
Accessed December 10, 2008.

17
Sports Nutrition
Jackie Buell, PhD, RD, LD, ATC, LAT and Diane L. Habash, PhD, RD, LD

Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 178 1. Outline the distribution and quantity of macronutrients
Carbohydrates in the diet of the child/adolescent athlete, and with
Protein attention to timing around sport.
Fat. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 181 2. Discuss differences in adult and youth heat dissipation,
Hydration . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 181 and suggest fluid intake to help protect the young
Vitamins and Minerals. . . . . . . . . . . . . . . . . . . . . . . . . . . . 182 athlete from heat injury and poor performance due to
dehydration.
Timing to Sport. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 182
3. Describe to young athletes how to think about fueling
Recovery Nutrition. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 183
(food) relative to the timing of sport to maximize muscle
Bedtime Nutrition. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 183 glycogen (pre-event) and encourage muscle growth/
Nutrition Challenges . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 183 strength (post-event).
Nutrition Resources. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 183 4. Provide young athletes and their supporters with educa-
tional Web sites and professional organizations to locate
current information and resources.
Introduction
The drive to improve and perfect performance is not new to
athletes of any age. As a result of the desire to excel, athletes
train harder and longer, and may look for dietary supple-
ments or other nutrition advantages. Depending on the
sport, athletes perceive that they can gain a further edge over
competitors by changing their body weight or composition.
Young athletes who are highly motivated in their sport and
performance may not be well educated about the potential
impact of proper nutrition or dietary supplements. Research
suggests they obtain most of their information from teachers
and parents, followed by trainers, friends, and Web sites.1
These athletes are ripe for information in this teaching oppor-
tunity for the healthcare professional, and the following
conversation points2 may make the greatest impact:
• tips focused on sports performance with some attention
to body image and weight issues since these are likely
significant motivators for the athlete;
178
SPORTS NUTRITION 179
• a positive approach and reinforcement counseling with 4500 calories daily. Estimating energy needs and moni-
goal setting; toring for desirable changes is necessary to confirm the
• inclusion of the family when appropriate; accuracy of the energy prescription.
• suggestions for recipes, shopping, and cooking tips
when family is included; Carbohydrates
• encouragement for the athlete to take responsibility for The most obvious dietary need within the calories allotted
food choices, eating behaviors, and some preparation for the young athlete should be carbohydrate to fuel the
and packing of foods; and muscle. It has long been accepted that carbohydrate is
• involvement of the athlete in diet evaluation and subse- the primary fuel for human muscle as intensity of activity
quent goal determinations and goal evaluations. increases, and this is well confirmed in adult athletes. It is
The spectrum of young athletes, from child through young suggested that children may be able to use even more carbo-
adult, undoubtedly differs from other groups—including hydrate as substrate than adults5; thus, fueling the muscle
those of different ages, less active peers, and adults—in to at least the adult mass-dependent recommendation is
terms of nutrition needs. Research on this young cohort prudent. In adults, carbohydrate has been demonstrated
spectrum is sparse. Working to evaluate or improve the diet to be supportive before, during, and after endurance exer-
of a young athlete likely involves using the (non-athletic) cise when enough calories are consumed overall. 6 Ensuring
life-stage dietary reference intake (DRI) peer standards 5 g of carbohydrate per kilogram body weight is the basic
with extrapolation on how exercise, motion inefficiency, starting point for all athletes.7,8 The need for carbohydrate
or growth/development might influence the standards. increases as the time and intensity of activity increases. The
In addition to the life-stage DRI energy (kilocalories) more serious athlete who practices daily for 1 to 2 hours
and protein recommendations to support growth, young might increase this fueling to 7 g/kg up through 11 to 12
athletes need to consume enough additional calories to g/kg for 3 to 4 hours of intense exercise per day.7,8 It is not
cover the needs of sport if the desire is to remain in energy as simple as asking the frequency and length of practices;
balance and fuel the muscle for growth and performance. to apply these guidelines it is important to gauge the actual
Because more research exists for adult populations, it is time spent in high-intensity activity. Most sport practice
tempting to apply adult recommendations to identify sports sessions include periods of inactivity and rest. Including the
nutrition goals for young individuals. It is wise to remember downtime of sessions would overestimate fueling needs.
that children and youth are different, such as their degree Consuming too much simple carbohydrate may increase
of motion inefficiency, 3 and this may invalidate the adult- dental caries—especially when the choices include sticky
to-child extrapolation. Nonetheless, due to a lack of data on and fermentable sources—and there is a high degree of
broad groups of child or adolescent athletes, this chapter will variability in how humans tolerate high carbohydrate. It is
extrapolate from peer and adult cohort recommendations. prudent to consider the athlete’s preferences, tolerance, and
Achieving the desired caloric balance is the starting performance enhancement when fine-tuning the carbohy-
nutrition consideration and calculation for athletes of all drate in the diet.
ages. Athletes with significant caloric imbalances may Awareness of the underlying health benefits of the
demonstrate undesired weight gain or weight loss, and this source of carbohydrate should also be emphasized in this
is the usual reason for nutrition intervention with a young cohort as a strategy to encourage lifelong healthy habits.
athlete. The best starting number is to use the life-stage Carbohydrate in the diet comes mostly from the grains,
energy needs as outlined in the current DRIs according to fruit, and milk food groups with smaller contributions
activity level.4 Be aware that many child/adolescent athletes from the vegetable group. Overall encouragement to use
may exceed the very active physical activity category within whole grains over refined products will improve the fiber
the DRI, and consider increasing the estimated calories content and nutrient density of the diet and may confer
accordingly to achieve the desired weight maintenance or long-term health benefits. The value of fruit in the diet is
gain goals. This is particularly true with adolescents during uncontested, and the child or adolescent athlete needs 4
the growth spurt engaged in high-intensity sports (eg, servings of milk/dairy daily for skeletal health. Even though
basketball, soccer, lacrosse, etc.) who usually desire to gain vegetables provide a minimal contribution, promoting
lean mass. Such athletes may need upwards of 6000 calories them for carbohydrate advantages may encourage better
daily to tip the energy balance to favor muscle mass accre- consumption in this young population. Another potential
tion, and these same athletes would lose weight consuming advantage of encouraging healthier carbohydrate sources

in this population is the carryover it might extend to the Table 17-1 Translation of Gram Recommendations to Foods
athlete’s family unit. The use of high-carbohydrate recom- Grams
Primary Foods Portion Per
mendations for individuals who do not tolerate carbohydrate Portion
well due to allergies or metabolic issues (such as diabetes) Carbohydrates Grains 1 oz equivalent, ½ cup 15
should be approached with caution and attention to toler- (4 kcal/g) starchy beans
ance. In general, there is very little nutrition value in the use Fruits 1 medium fruit 15
of sugar-sweetened beverages, and the evaluating clinician Milk 8 oz milk, 6 oz yogurt 12
should be vigilant for overuse of these products and the Vegetables 1/2 cup cooked, 1 cup raw 5
Protein Meat 1 oz equivalent 7
amount of sugar and empty calories they contribute to the (4 kcal/g) Milk 8 oz milk, 6 oz yogurt, 8
overall diet. The current DRI would accept up to 25% of the 1 oz cheese
diet in simple sugars.4 An exception where consumption Beans 1/2 cup starchy 7
of sugar-sweetened drinks may actually be desirable and Peanut Butter 1 TBSP counts as 1 fat 7
helpful is the appropriate use of commercial sports drinks and 1 protein
Fats saturated 1 tsp equivalent of animal 5
designed to help the athlete maintain hydration and blood (9 kcal/g) fat (butter, bacon, cream,
glucose levels with timing around and during practice shortening, sour cream)
or events.9 polyunsaturated 1 tsp plant oil (corn, 5
safflower, soy)
Practical application: Athlete’s weight ÷ 2.2 = kg body weight, 1 TBSP regular salad
multiply by 5 g/kg to recommend minimal daily carbohydrate intake. dressing
Consuming 0.5 to 1 g/kg within the hour prior to exercise, with a (2 TBSP reduced fat)
predilection for liquid sources for those “unable to eat right before” 1 tsp mayonnaise
practice or events, may better prepare the muscle for high-intensity (1 TBSP reduced fat)
work. For events lasting longer than 90 minutes, consumption of a 1 TBSP sunflower seeds
formulated glucose-electrolyte solution may help maintain blood monounsaturated 1 tsp oil (canola, olive, 5
glucose and glycogen stores to delay fatigue. Recovery nutrition peanut)
would also include 1 g/kg taken immediately after exercise if the next
2 TBSP or 1/6 medium
meal is not immediately available. Note the fraction of the total daily
avocado, 8 large black
carbohydrate that is suggested to surround the competition to keep
olives or 10 green
the muscle fueled. This nutrient timing is novel to many athletes and
is simply a snack-planning issue for desired results. See Table 17-1 to 6 nuts of most nuts
help translate the grams to actual foods. 1 TBSP sesame seeds
Protein development needs in addition to the usual lean mass goals. It

Protein is not typically viewed as energy for sport, but is has become an easy-to-remember recommendation for adult
critical for growth and development. The amount of protein athletes to consume 1 g/lb (2.2 g/kg) of body weight, and this
needed in the athlete’s diet remains controversial in all would likely be an appropriate recommendation for youth as
populations.10,11 The DRI for protein, without consideration well when it is desirable to assure that the athlete has more than
of athletic activity, ranges from the adult recommended adequate protein for lean mass accretion and muscle metabo-
dietary allowance (RDA) of 0.8 g/kg/d to the child adoles- lism. Phillips’ article is helpful in understanding the argument
cent recommendation of 1.05 g/kg/d,4 and this current over adequate (required) versus advantageous protein, and
protein DRI excludes additional protein possibly available addresses the potential fat loss associated with high-protein
for muscle fueling or metabolism. It is well-documented diets as well as the metabolic inefficiency of using protein for
that adult athletes are able to utilize more than these DRI- energy.11 It should be emphasized that consuming more than
recommended amounts to support the muscle protein about 2 g/kg/d is not necessary for muscle growth and may
turnover and energy demands of varying activities.12 In actually suppress muscle protein synthesis.15 Protein conversa-
general, nutrition recommendations for adult athletes tions often include debates around the safety of high-protein
encompass a range of about 1 to 1.7 g/kg/d.13 Bulk-seeking diets, but examination of the literature finds little evidence of
strength athletes top the recommendation chart at 1.7 g/ liver or kidney function issues in healthy adult athletes.16 There
kg/d as the extrapolated upper threshold that nitrogen is no research on high-protein diets in child, preadolescent, or
balance studies have demonstrated can physiologically be adolescent athletes, but error on the side of safety where the
used for lean mass accretion.14 It is intuitive that the upper ceiling is defined as 2.2 g/kg would be prudent. High-protein
threshold for the child or adolescent athlete may be slightly diets will displace carbohydrate from the diet and that is not in
higher than these adult values due to compounded growth and the best interest of performance.

The quality of protein in the athlete’s diet should also be Practical application: Fat should provide 20% to 35% of daily
assessed. The protein in animal products should contain all the energy. The total energy recommendation multiplied by 0.2 and 0.35
essential amino acids, and the essential amino acids have been will yield a range of calories of fat, and dividing the calories by 9
calories per gram will calculate the grams of fat desired. It is standard
demonstrated most important to the muscle during and after to derive the needed protein and carbohydrate first, then ensure the
exercise.17 Athletes who rely on plant proteins need to ensure suggested fat is within this caloric range for the athlete.
a wide variety and adequate amount of plant protein sources
to provide sufficient essential amino acids consumed over the
course of a day.18 The use of processed protein supplements, Hydration
especially among males, is quite popular in the form of whey- Ensuring adequate hydration is a safety concern as well as a
based protein powders, shakes, and energy bars. Reminding performance advantage.23–25 Dehydration may contribute to a
the athlete that there is no formal (ie, Food and Drug Admin- decrement in aerobic performance at as little as 2% per body
istration) oversight for these “food” products to ensure label weight in adults, and may be life-threatening to adults at levels
accuracy, purity, and lack of adulteration should be part of the of 7% to 8% per body weight depending on the athlete.25 Chil-
educational conversation. The protein literature demonstrates dren do not adapt as well as adults to heat extremes or thirst
that strength19 and endurance20 athletes can easily consume mechanism, and differ from adults in production of metabolic
this higher level of protein within the habitual diet without heat and sweat capacity26 demonstrating the likely difference
using supplements. It is critical to remember that high-protein in heat balance at any given intensity or environment. Research
diets will unduly tax the unhealthy liver and kidneys, but is not in young male populations by the Bar-Or group demonstrates
proven to be an issue for healthy livers or kidneys in adults.16 reduced aerobic capacity and increased core temperature at 1%
dehydration.26 Additionally, the American Academy of Pedi-
Practical application: Athlete’s body weight in pounds is equal atrics outlines the physiological differences in sweating and
to grams of total protein for maximal muscle support such as heavy
endurance exercise or muscle-building training phases. Athletes not heat dissipation in children and adolescents.23 The research on
engaged in endurance exercise or muscle-building phases of training youth hydration and physiology convince the sports nutrition
would likely fare well with 1.1 to 1.4 g/kg. The growth phase of the practitioner to ensure hydration awareness in young athletes.
athlete must always be taken into consideration for protein needs
where periods of increased growth place the athlete at a higher protein Young athletes have been demonstrated to be less aware of
need. For best muscle recovery, athletes should strive to consume fluid needs (thirst) and need strong encouragement and guid-
about 15 g of good-quality protein (along with adequate carbohydrate) ance from the parent, coach, and/or athletic trainer to consume
immediately after exercise to support a positive growth environment.
See Table 17-1 to help translate the grams to actual foods.
fluids as often as the weather and activity dictate.9 Professional
organization guidance statements (Table 17-2) call for ensured
pre-hydration, evaluation of the practice environment (heat,
Fat humidity, available shade, clothing modifications), adequate
The ideal amount and type of fat in the diet remains as contro- fluid breaks every 15 to 20 minutes during activity, and inten-
versial for athletes as it is in general. The current acceptable tional rehydration after activity.
macronutrient distribution range from the DRIs calls for 20%
to 35% of the calories be taken as fat. Prudent heart health Table 17-2 Professional Organization Guidance Statements on Hydration
recommendations encourage incorporation of mono- and American Academy of Athlete should begin “well-hydrated.
Pediatrics (2000)23 During activity, periodic drinking should
polyunsaturated fats to displace many of the typical satu- be enforced” with 5 oz of water or salted
rated fats in the Western diet.21 When athletes are struggling beverage for 88-lb child or 9 oz for
to maintain body mass during the competitive season, it is 132-lb adolescent (with inferred volume
imperative to encourage calorie-dense foods which typically adjustment for body size differences).
include a higher fat proportion. The hormonal milieu in the National Athletic Trainers’ Pre-hydrate 3–4 hr before with
Association (2000)24 17–20 oz, then 7–10 oz 10–20 minutes
body is undoubtedly supported by an adequate fat intake and immediately before; consume 7–10 oz
calorie balance. Recent literature has addressed “fat loading” during activity; post-exercise hydration
as a method of supporting fueling for sub-maximal endurance aims to provide 125%–150% losses.
exercise, but the studies thus far demonstrate a loss of “high American College of Sports Slowly consume 5–7 mL/kg at least 4 hr
gear” or reduced ability to reach or sustain high intensity,22 and Medicine (2007)25 prior; if urine is concentrated consume
3–5 mL/kg 2 hours before; event
there is no research on how these diets may influence body hydration focuses on individual sweat
composition or cardiovascular health (in child athletes). rate and tolerance.

The recommendation for consumption of plain water Overdrinking can lead to hyponatremia, but this is usually
versus commercially prepared sports drinks containing limited to smaller athletes who drink large amounts of
carbohydrate, sodium, and/or potassium likely depends water (hypotonic) over a period of hours while engaged
on voluntary fluid consumption, the length of the athletic in endurance exercise. Use of a sports drink for activities
session, pre-event carbohydrate status, and the sodium loss lasting longer than 60 to 90 minutes may help avoid this
of the individual. Athletes who sweat profusely and lose a life-threatening condition. Teaching children and adoles-
lot of sodium are best to also be aware of their sodium needs cents to drink an appropriate amount is an important task
alongside fluid needs. Bar-Or has demonstrated the flavor for safe participation and good health.
and sodium content of a drink to be important to volun-
tary consumption by young athletes. 27,28 Foods helpful Vitamins and Minerals
in replacing sodium include soup, pretzels, or liberal salt Athletes or their parents often ask if a vitamin-mineral
shaker use. The use of sugar-flavored milk products has supplement is necessary or protective. Athletes consuming
become common in recovery nutrition,29 and it is notable at least 1800 calories per day within a diet that includes a
that an 8 oz glass of milk typically contains 120 to 170 mg of wide variety of foods from all food groups do not likely need
sodium (depending on brand and type), which would also to supplement the vitamins and minerals. Athletes who
contribute to fluid balance.29–31 Shirreffs and Maughan have restrict food choices like red meat (iron), milk (calcium),
nicely demonstrated the value of sodium in the rehydration and carbohydrates (B vitamins) from the diet may benefit
plan. 32 When discussing additional sodium intake, advice from supplementation. The inclusion of a generalized multi-
should be tailored to the likely salt loss of the athlete. vitamin where the label reflects 100% to 200% Daily Value
for most contained nutrients is likely harmless when the
Heavy sodium loss indicators: Eyes burn when sweat gets in them,
workout shirts appear to have rings of salt around sweat areas, granular
supplement is a known and reputable brand. There is no
feeling to skin after workout at the side of face where sideburns would be. evidence that consuming supplements containing large
amounts of antioxidants protects the body. In fact, there
If the practitioner is able to estimate energy expenditure, it is is evidence in adults that this sort of therapy may actually
relatively simple to suggest a daily drinking plan to provide oppose the goals of the supplement. 34 In general, a “one-a-
1 mL/kcal of fluid as a starting point. It is common practice day” style vitamin-mineral supplement should not be seen
to screen for dehydration risks by weighing athletes before as a substitution for a balanced and variety-filled diet, but
and after practice, and to encourage consumption of 150% may be a low-risk answer for parents or athletes worried
of the fluids (weight) lost (approximately 3 cups or 24 oz per about dietary adequacy.
pound lost). Evaluation of urine osmolality, refractometry,
and bioelectrical impedance are among the current trends Timing to Sport
for evaluation of hydration status, 33 but likely the most prac- A common pattern seen in some young athletes is to eat
tical to teach is evaluation of urine color. For athletes with sparse calories early in the day with the bulk of energy
significant sweat losses and muscle-cramping issues, it is consumption later in the day. It is a positive health habit
helpful to calculate a personalized sweat rate to formulate to distribute energy consumption throughout the day, and
the strongest hydration plan. this habit has the added benefit for athletes of providing the
muscle with more consistent access to storage fuels as well.
Practical application: Hydration should be a continuous process Athletes who wait to eat most of their calories late in the
throughout the athlete’s day, but routine hydration with respect to day are usually so hungry that it is hard to make positive
exercise should also be habit. Athletes should ensure pre-hydration
with 5 to 7 mL/kg of fluids at least 4 hours before events; this leaves
decisions about which foods to eat and how much should be
enough time for the body and kidneys to produce urine for evaluation consumed. It may be better for hunger levels, metabolism,
of hydration status. If urine is still concentrated (color and smell), body composition, and muscle fueling to eat multiple small
consume an additional 3 to 5 mL/kg 2 hours prior. Fluid breaks every meals throughout the day (every 2 to 4 hours) to achieve
15 to 20 minutes during activity should provide about 5 oz for the
smaller child (88 lb) and 9 oz for the adolescent (132 lb). Rehydration energy balance instead of imploding the body with too
is best achieved with consuming fluid equal to 150% of the weight lost many calories late in the day.
during activity. This means drinking about 24 oz of fluid per pound lost. An athlete cannot underestimate the importance of
Co-ingestion of sodium will help replenish lost sodium, which is critical
to maintaining hydration. breakfast on a daily basis. On non-competition days, a
mixed breakfast supplying ample carbohydrate and about
25% of the daily calories will refuel the muscle and liver

from the overnight fast and should be consumed before fat any differently than other eating throughout the day
practices. On competition days when breakfast is the assuming the calorie consumption matches calories needed.
pre-event meal, the athlete should consider that the carbo- It is the overall calorie balance that is important. As long
hydrate will pre-fuel the muscle while the protein and fat as the nighttime snack is within the daily calorie needs of
of the meal will determine the satiety during competi- the individual, the timing is not important. It is common
tion. Finding the timing of consumption and mixture of to suggest the use of dairy products (eg, low-fat milk or
foods to promote high-intensity competition along with a yogurt) late in the evening for the possible positive influ-
comfortable gastrointestinal system is the task to practice ence on fat metabolism38 and continued anabolic support to
and master during non-competition sessions. Most athletes the muscle.
do well with a fairly high carbohydrate meal (at least 1 g/
kg body weight (BW)) and about 3 oz of lean protein with Nutrition Challenges
1 or 2 fat portions (Table 17-3) 2 to 3 hours (no more than Common nutrition-related issues that young athletes may
about 4 hours) before competition. Some athletes perform experience are listed in Table 17-5. Young athletes are often
well when they further top off the muscle carbohydrate by serious about their bodies and sports, and a healthcare
consuming 40 to 60 g of carbohydrate within 1 hour of practitioner’s respect and guidance can help them through
competition. An athlete needs to experiment with various nutrition-related challenges.
foods to know what works best; some athletes will prefer
fluid sources of carbohydrate for gut comfort this close to Nutrition Resources
intense exercise. Consumption of high-fiber, high-fat, or Many resources are available that can provide greater depth
high-sugar foods can cause abdominal distress in some across the field of sports nutrition. In a field that is subject to
individuals resulting in abdominal cramping, gas, and/or popular opinion and media-sensitized measures of perfor-
diarrhea. Table 17-4 provides examples of fueling ideas for mance, the information given to athletes, caregivers, and
the day of the competition. coaches should be grounded in and supported by evidence-
based science. See Table 17-6 for resources suggested by the
Recovery Nutrition authors. (All Web sites accessed January 20, 2009.)
Recovery nutrition has become one of the hottest recom-
mendation topics in recent years of sports nutrition.17,35
Consuming an appropriate recovery snack immediately
after exercise should become habit for athletes who do not
have at least 24 hours to recover the muscle nutritionally.
A recovery snack should be a priority for multiple-event
athletes or when the daily routine demands multiple prac-
tices close together. An appropriate recovery snack for
adult athletes suggests 40 to 60 g of carbohydrate and 15 to
20 g of good-quality protein to provide the essential amino
acids. The carbohydrate for recovery has demonstrated a
more rapid period of glycogen restoration, and the addi-
tional calories in protein stimulate the muscle to set up an
anabolic environment.15,36 The current research supports
essential amino acids as the stimulus for this anabolic
change and leucine (a branched-chain essential amino acid)
is likely important to the response. 37
Bedtime Nutrition
Bedtime nutrition is another recommendation that serious
athletes should consider. Concerns about eating after a
certain time of the evening and if a protein supplement
should be taken are commonplace in adult populations.
Bedtime snacking does not necessarily convert to body

Table 17-3 Examples of Meals and Snacks Used With Timing Around Sport
Description kcal g CHO g pro g fat
Pre-game
Target is high carbohydrate within mixed diet
(3–4 hr prior)
2 cups whole wheat pasta with 1 cup sauce and 3 oz lean meat, 1
Pasta meal 797 120 54 18
cup of salad, 1 piece garlic bread, and 1 cup 2% milk
Fast food Wendy’s® grilled chicken with baked potato with broccoli cheese sauce 780 117 44 16
Larger athletes might add a small Frosty™ to above to bring total to 1080 143 59 31
Pre-event
Target is well-tolerated carbohydrates kcal g CHO g pro g fat
(20–60 min prior)
12 oz sweet tea with 1 oz animal crackers 231 48 2 4
20 oz sports drink 160 40 0 0
2 oz pretzels with water 200 47 6 0
During event
Sports drink only warranted if longer than 90 minutes of intense
(4–8 oz every kcal g CHO Na (mg) K (mg)
activity (otherwise water is great)
15–20 min)
Per 8 oz Gatorade® G™ 50 14 110 30
Gatorade® G2™ series 25 7 110 30
Powerade® 60 17 55 30
Powerade® Zero 0 0 55 33
Accelerade® (incl 4 g protein) 80 15 120 15
kcal g CHO g pro g fat
Recovery Target Target Target
Target is intentional mix of carbohydrate and good-quality protein Target low
(within 45 min) 200–300 40–60 10–15
1 cup ready-to-eat cereal (eg, multi-grain Cheerios®) with 1 cup
250 50 11 1.5
skim milk and 1 medium banana
Peanut butter (1 TBSP) and jelly (1 TBSP) sandwich on 2 slices
368 52 20 10
whole wheat bread with 1 cup milk
Turkey sandwich with 2 slices bread and about 2 oz turkey with 12
300 50 18 3
oz sports drink
1 cup lowfat chocolate milk with 1 oz pretzels 259 50 11 2.5
1 mozzarella string cheese stick, 1 cup green grapes, 1 medium
215 44 10 2
orange with water
PowerBar® and water 247 48 10 2
kcal = calories, g CHO = grams of carbohydrate, g pro = grams of protein, g fat = grams fat, Na = sodium, K = potassium
Table 17-4 Fueling Ideas for the Day of Competition

Timing Nutrition Goals Example (always relative to athlete size and energy needs)
Breakfast at least 3–4 hr from event Balanced meal heavy on Whole grain or fruit pancakes with syrup, 8 oz milk, side of fresh fruit,
carbohydrate 2 oz lean meat, 16 oz water after meal will begin hydration on right path
Pre-event snack 1–2 hr before High carbohydrate 12 oz sports drink, piece of fruit or pretzels; if urine is strong, more water
During event if high intensity lasts Liquid carbohydrate 30–60 g/hr 4–8 oz of sports drink every 15–20 minutes
longer than 90 minutes
After event within 45 minutes if Carbohydrate and good-quality 8 oz chocolate milk with peanut butter (limit to 1 TBSP)
multiple events (“Recovery” snack) protein (3:1 or 4:1 ratio of and jelly sandwich on whole grain bread
carbohydrate to protein)
Snacks between meals not as close Carbohydrate with little protein Trail mix with 2 TBSP dried cranberries or raisins, 1 tsp peanuts,
to event and little fat and 1 oz mozzarella cheese stick
-OR-
Turkey or ham sandwich with 2 oz meat, 2 slices whole grain bread,
tomato/lettuce as tolerated, with glass of water
Meals not close to time of event Balanced with carbohydrate, Plate surface divided as 1/4 meat, 1/4 whole grain, 1/2 brightly colored
adequate protein, and fat fruits and vegetables with glass of milk

Table 17-5 Common Issues for Athlete Nutrition

Issue Possible Indicators and Concerns Solutions
Limited nutrition • Cannot describe desirable pre-game meals or • Provide reputable Web sites
knowledge recovery eating • Suggest easy-to-read books
related to sports • Has
no hydration plan • Stress planning and organization for having foods and beverages available
performance • Practice having all the foods and beverages needed for sport
• Note timing of events and fuel/hydrate accordingly
• Note travel impact on eating and hydrating opportunities and on performance
• Identify community partners (eg, a Certified Specialist in Sports Dietetics (CSSD))
Picky eater • Low variety in habitual diet • Educate on advantages of diet with varied food groups to include performance
• “Does
not like” entire food groups advantages of carbohydrate foods
• Encourage athlete to bring foods that she or he likes so the athlete is at
least fueling
• Encourage practice for fuel/hydration
Eating on a budget • Eating 1 or 2 meals per day • Discuss planning strategies for foods typically afforded
or low income • Eating little meat and lots of bread and pasta • Buy in bulk and separate/store in pantry/freezer
• Help athlete understand correct amount of protein to prevent
undernutrition or overspending
• Cook in bulk and freeze for later access
• Buy generic for most foods
• Buy fruits and vegetables in season
• Ensure family is not eligible for federal food assistance program
Male athlete • Questions about how much protein needed or what • Stress that normal physical activity and adequate nutrition optimize growth
with high growth supplements will “work” • Educate that growth has genetic and environmental components
expectations • Usually
overt in desire to be bigger • Consider that intense exercise may be associated with delayed growth
• Check and reinforce appropriate athlete vs parent expectations of lean
mass accretion; use growth charts
Weight control • Secondary sex characteristics not desirable to • Explain puberty progression and risks of stifling puberty
expectations some female athletes • When in doubt, suggest evaluation by psychological professional and dietitian
(typically females) • Underfueling to avoid gaining weight; poor • Early intervention may avoid Female Athlete Triad outcome (see below)
performance and health detriments may result
• Poor
self-esteem and/or self-image
• Overt comments about not liking body parts
(eg, belly or thighs)
• Unhealthy control methods (eg, diet pills,
smoking, vomiting, laxatives, or starvation)
Vegetarianism • Often occurs in young females who want to lose • Educate about optimal protein-alternative foods (dairy, legumes) or how to
weight combine foods to ensure complete proteins
• Can be due to perceptions that meat has too much • Alert athlete to consume adequate nutrients such as iron, calcium, and zinc
fat and calories • Inquire about why this lifestyle is appealing to the athlete to ensure answer
is consistent with balanced decision
The Female Athlete • A combination of 3 disorders (or spectrums) that • Encourage eating a diet with a wide variety of foods that will fuel the muscle
Triad includes low energy availability (ie, expend more for optimal performance
calories than consume), amenorrhea, and low • When in doubt, suggest evaluation by psychological professional and dietitian
bone density • Intervene early to increase chances for recovery
• May be related to disordered eating, poor body
image, unrealistic body weight goals, and weight-
loss expectations
• Often undetectable or not considered until stress
fracture occurs
• Exists in all sports but especially in those with
weight or appearance requirements
• Critical read for this area of evaluation is ACSM
Position Statement39
Use of • May be related to athlete’s desire to excel but • There are no pediatric evidence-based clinical trials on the use or the adverse
performance- often not supported by evidence effects of some supplements (herbals, ergogenic aids, etc.)
enhancing • Often used by athlete as a substitute for • Recent review of supplement studies shows anabolic steroid use ranges from 1%
supplements (legal adequate nutrition to 11.1% of adolescents surveyed and creatine use in reviewed studies ranged
and illegal) • Could be related to peer pressure and media from 5.6% to 30%40
influences • Supplements sought frequently for improving speed, decreasing weight, or
increasing size/bulk of athlete
• Use of one multivitamin/mineral supplement daily has been suggested for all
individuals, not just athletes
• Seek advice of certified sports dietitian (CSSD)

Table 17-6 Additional Exercise and Nutrition Resources

Topic Resources
To find a Registered Dietitian (RD) • American Dietetic Association (ADA) list of RDs
certified to work with athletes; www.eatright.org
known as a Certified Specialist in • ADA Dietetic Practice Group for Sports, Cardiovascular, and Wellness Nutritionists (SCAN) list of CSSD RDs
Sports Dietetics (CSSD) www.scandpg.org
General Sports Nutrition Information Position Papers:
• American Dietetic Association41
www.eatright.org
• American College of Sports Medicine25,41
www.acsm.org
• National Athletic Trainers’ Association
www.nata.org/statements/
Books/Web sites:
• Sports Nutrition; A Practice Manual for Professionals. 4th ed. Chicago, IL: American Dietetic Association; 2006
http://www.scandpg.org/cssd_promotion.php
General Exercise Physiology • Gatorade Sports Science Institute*
Information www.gssiweb.com
• American College of Sports Medicine
www.acsm.org
• NISMAT Exercise Physiology Corner*
www.nismat.org/physcor/index.html
Supplement Information • Australian Institute of Sport*
www.ausport.gov.au/ais/nutrition
• Gatorade Sports Science Institute*
www.gssiweb.com
• Drug Free Sport*
www.drugfreesport.com/
• IBIDS database
ods.od.nih.gov/Health_INformation/IBIDS.aspx
• Natural Medicines Database
www.naturaldatabase.com
• Consumer Labs third party quality testing
www.ConsumerLabs.com
Digital Athlete Resources *Many of the above Web sites have companion athlete links or at an appropriate level for athletes.
Test Your Knowledge Questions 3. How much fluid should an athlete who requires 3500
1. How much carbohydrate as a minimum should the kcal/d be aiming to consume?
young athlete include in the daily diet? A. 3.5 L along with evaluation of urine color for
A. This is not important. It is the overall calories that hydration
count. B. Athletes should let thirst be their guide.
B. 5 g/kg body weight C. Athletes need 8 to 10 glasses of water per day.
C. 15 g/kg body weight D. All athletes should consume an electrolyte sports
D. Athletes only need about 35% of their diet as drink during activities in the heat.
carbohydrate. 4. Which of the following are included spectrums of the
2. When, relative to a strength-training session, is the female athlete triad?
timing and amount of protein intake the most impor- A. Amenorrhea or delayed menarche
tant for a young athlete trying to gain lean mass? B. Poor bone mineral acquisition compared with age
A. Protein should be the primary focus. cohort
B. Carbohydrate only; no protein needed C. Low energy availability
C. 3:1 or 4:1 ratio of carbohydrate to protein D. All of the above
D. Athletes should not eat within 30 to 45 minutes of
exercise. See p. 487 for answers.

19. Phillips SM. Protein requirements and supplementation in

References strength sports. Nutrition. 2004;20(7-8):689–695.
1. Hoffman JR, Faigenbaum AD, Ratamess NA, Ross R,
20. Tarnopolsky M. Protein requirements for endurance athletes.
Kang J, Tenenbaum G. Nutritional supplementation and
Nutrition. 2004;20(7-8):662–668.
anabolic steroid use in adolescents. Med Sci Sports Exerc.
21. Position of the American Dietetic Association and Dieti-
2007;40(1):15–24.
tians of Canada: Dietary fatty acids. J Am Diet Assoc.
2. Andrew K. Practice tips (in children and young athletes). In:
2007;107(9):1599–1611.
L. Burke, V. Deakin, eds. Clinical Sports Nutrition. 3rd ed.
22. Stellingwerff T, Spriet LL, Watt MJ, et al. Decreased PDH
Sydney: McGraw Hill; 2006:620.
activation and glycogenolysis during exercise following fat
3. Walker JL. The energy cost of horizontal walking and running
adaptation with carbohydrate restoration. Am J Physiol Endo-
in adolescents. Med Sci Sports Exerc. 1999;31(2):311.
crinol Metab. 2006;290(2):380–388.
4. Food and Nutrition Board, Institute of Medicine. Dietary
23. American Academy of Pediatrics: Climatic heat stress and the
Reference Intakes for Energy, Carbohydrate, Fiber, Fat, Fatty
exercising child and adolescent. Committee on Sports Medi-
Acids, Cholesterol, Protein, and Amino Acids (Macronutrients).
cine and Fitness. Pediatrics. 2000;106(1):158–159.
Washington, DC: National Academy Press; 2005:12.
24. Casa DJ, Armstrong LE, Hillman SK, et al. National Athletic
5. Bass S, Inge K. Nutrition for special populations: children
Trainers’ Association position statement: Fluid replacement
and young athletes. In: L. Burke, V. Deakin, ed. Clinical Sports
for athletes. J Athl Train. 2000;35(2):212.
Nutrition. 3rd ed. Sydney: McGraw Hill; 2006:605.
25. American College of Sports Medicine. American College of
6. Jacobs K, Sherman W. The efficacy of carbohydrate supple-
Sports Medicine position stand. Exercise and fluid replace-
mentation and chronic high carbohydrate diets for improving
ment. Med & Sci Sports & Exerc. 2007;39(2):377–390.
endurance performance. Int J Sports Nutr. 1999;9:92–115.
26. Bar-Or O. Temperature regulation during exercise in children
7. Burke L, Cox G, Cummings N, Desbrow B. Guidelines for
and adolescents. In: C. Gisolfi, DR Lamb, eds. Perspectives in
daily carbohydrate intake: Do athletes achieve them? Sports
Exercise Sciences and Sports Medicine. Indianapolis, IN: Bench-
Med. 2001;31:267–299.
mark Press; 1989:335–367.
8. Dunford M. Sports Nutrition: A Practice Manual for Profes-
27. Wilk B, Bar-Or O. Effect of drink flavor and NaCl on volun-
sionals. 4th ed. Chicago, IL: American Dietetic Association;
tary drinking and hydration in boys exercising in the heat. J
2006:547.
Appl Physiol. 1996;80(4):1112–1117.
9. Ali A, Williams C, Nicholas CW, Foskett A. The influence
28. Wilk B, Kriemler S, Keller H, Bar-Or O. Consistency in
of carbohydrate-electrolyte ingestion on soccer skill perfor-
preventing voluntary dehydration in boys who drink a flavored
mance. Med Sci Sports Exerc. 2007;39(11):1969–1976.
carbohydrate-NaCl beverage during exercise in the heat. Int J
10. Tipton KD, Witard OC. Protein requirements and
Sport Nutr. 1998;8(1):1–9.
recommendations for athletes: relevance of ivory tower
29. Karp JR, Johnston JD, Tecklenburg S, Mickleborough TD,
arguments for practical recommendations. Clin Sports Med.
Fly AD, Stager JM. Chocolate milk as a post-exercise recovery
2007;26(1):17–36.
aid. Int J Sport Nutr Exerc Metab. 2006;16(1):78–91.
11. Phillips SM. Dietary protein for athletes: from require-
30. Bauman DE, Mather IH, Wall RJ, Lock AL. Major advances
ments to metabolic advantage. Appl Physiol Nutr Metab.
associated with the biosynthesis of milk. J Dairy Sci.
2006;31(6):647–654.
2006;89(4):1235–1243.
12. Lemon PW. Beyond the zone: protein needs of active indi-
31. Roy BD. Milk: The new sports drink? A review. J Int Soc Sports
viduals. J Am Coll Nutr. 2000;19(5):513S–521S.
Nutr. 2008;5:15.
13. Tarnopolsky MA. Protein and amino acid needs for training
32. Merson SJ, Maughan RJ, Shirreffs SM. Rehydration with
and bulking up. In: L. Burke, V. Deakin, eds. Clinical Sports
drinks differing in sodium concentration and recovery from
Nutrition. 3rd ed. Sydney: McGraw Hill; 2006:95.
moderate exercise-induced hypohydration in man. Eur J Appl
14. Lemon PW. Effects of exercise on dietary protein require-
Physiol. 2008;103(5):585–594.
ments. Int J Sport Nutr. 1998;8(4):426–447.
33. Stuempfle KJ, Drury DG. Comparison of 3 methods to assess
15. Bolster DR, Pikosky MA, Gaine PC, et al. Dietary protein
urine specific gravity in collegiate wrestlers. J Athl Train.
intake impacts human skeletal muscle protein fractional
2003;38(4):315–319.
synthetic rates after endurance exercise. Am J Physiol Endo-
34. Knez WL, Jenkins DG, Coombes JS. Oxidative stress in
crinol Metab. 2005;289(4):E678–E683.
half and full Ironman triathletes. Med Sci Sports Exerc.
16. Martin WF, Cerundolo LH, Pikosky MA, et al. Effects of
2007;39:283–288.
dietary protein intake on indexes of hydration. J Am Diet
35. Baty JJ, Hwang H, Ding Z, et al. The effect of a carbohydrate
Assoc. 2006;106(4):587–589.
and protein supplement on resistance exercise performance,
17. Borsheim E, Tipton KD, Wolf SE, Wolfe RR. Essential amino
hormonal response, and muscle damage. J Strength Cond Res.
acids and muscle protein recovery from resistance exercise.
2007;21(2):321–329.
Am J Physiol Endocrinol Metab. 2002;283(4):E648–E657.
36. Ivy JL, Goforth HWJ, Damon BM, McCauley TR, Parsons
18. American Dietetic Association, Dietitians of Canada. Position
EC, Price TB. Early postexercise muscle glycogen recovery
of the American Dietetic Association and Dietitians of Canada:
is enhanced with a carbohydrate-protein supplement. J Appl
vegetarian diets. J Am Diet Assoc. 2003;103(6):748–765.
Physiol. 2002;93(4):1337–1344.

37. Tipton K, Sharp C. The response of intracellular signaling and 40. Castillo EM, Comstock RD. Prevalence of use of performance-
muscle-protein metabolism to nutrition and exercise. Eur J enhancing substances among United States adolescents.
Sport Sci. 2005;5(3):107–121. Pediatr Clin N Am. 2007;54:663–675.
38. Zemel MB, Donnelly JE, Smith BK, et al. Effects of dairy 41. American Dietetic Association; Dietitians of Canada; Amer-
intake on weight maintenance. Nutr & Metab. 2008;5:28. ican College of Sports Medicine, Rodriguez NR, Di Marco
39. Nattiv A, Loucks AB, Manore MM, et al. American College of NM, Langley S. American College of Sports Medicine posi-
Sports Medicine position stand. The female athlete triad. Med tion stand. Nutrition and athletic performance. Med Sci Sports
Sci Sports Exerc. 2007;39(10):1867–1882. Exerc. 2009;41(3):709–731.

PART III
DISEASE STATES AND

NUTRITION
18. Developmental Delay. . . . . . . . . . . . . . . . . . . . . . . 191 27. Intestinal Failure . . . . . . . . . . . . . . . . . . . . . . . . . . 311

Kathleen J. Motil, MD, PhD Robert H. Squires, Jr., MD
19. Eating Disorders . . . . . . . . . . . . . . . . . . . . . . . . . . 204 28. Pulmonary Disorders . . . . . . . . . . . . . . . . . . . . . . . 323
Christina Fitzgerald, MS, RD, LDN Allison Mallowe, RD, LDN
Betsy Hjelmgren, MS, RD, LDN, CSP Suzanne Michel, MPH, RD, LDN
20. Food Allergies. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 213 Maria Mascarenhas, MBBS
Mary Beth Feuling, MS, RD, CD, CNSD 29. Organ Transplantation. . . . . . . . . . . . . . . . . . . . . . 337
Michael B. Levy, MD Anita Nucci, PhD, RD, LD
Praveen S. Goday, MBBS, CNSP Sharon Strohm, MBA, RD, LDN
21. Diabetes Mellitus and Neelam Katyal, MS, RD, LDN
Other Endocrine Disorders. . . . . . . . . . . . . . . . . . . 226 Beth Lytle, RD, LDN
Diane Olson, RD, CNSD, CSP, LD 30. Oncology, Hematopoietic Transplant,
W. Frederick Schwenk II, MD and Survivorship. . . . . . . . . . . . . . . . . . . . . . . . . . . 349
22. Inborn Errors of Metabolism . . . . . . . . . . . . . . . . . 232 Nancy Sacks, MS, RD, LDN
Bridget Reineking, MS, RD, CD Elizabeth Wallace, RD, CNSC, LDN
Sandy van Calcar, PhD, RD, CD Seema Desai, MS, RD, LDN, CNSD
Vinod K. Prasad, MD, MRCP (London)
23. Cardiac Disease. . . . . . . . . . . . . . . . . . . . . . . . . . . 247 David Henry, MS, BCOP
Anupama Chawla, DCH(UK), MD, CNSP Virginia Guzikowski, MSN, CRNP
Janice Antino, RD, MS, CNSD, CSP Liesje Nieman Carney, RD, CNSD, LDN
Mindy Freudenberg, RD, MS, CNSD Beth Bogucki Wright, MS, RD, CSP, LDN
Susan Rheingold, MD
24. Renal Disease. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 256
Christina L. Nelms, MS, RD, CSP, CNSC, LD 31. Trauma and Burns . . . . . . . . . . . . . . . . . . . . . . . . . 378
Marisa Juarez, MPH, RD, LD Arlet G. Kurkchubasche, MD
32. Surgery. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 387
25. Gastrointestinal Disease. . . . . . . . . . . . . . . . . . . . 283 Arlet G. Kurkchubasche, MD
Donald George, MD
Elizabeth Bobo, MS, RD, LDN, CNSD
26. Hepatic Disease. . . . . . . . . . . . . . . . . . . . . . . . . . . 302
Samuel A. Kocoshis, MD
Renee A Wieman, RD, CSP, LD, CNSD
18
Developmental Delay
Kathleen J. Motil, MD, PhD

Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 191 1. Identify the nutrition problems frequently diagnosed in
Nutrition Problems. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 192 children with developmental delay.
Undernutrition, Growth Failure, and Overweight 2. Assess the nutrition status of the child with develop-
Micronutrient Deficiencies mental delay.
Osteopenia 3. Understand the approach to provide oral and enteral
Nutrition Assessment. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 194 support to the child with developmental delay.
Medical History
Growth and Anthropometric Measurements Introduction
Physical Examination
Meal Observation
Undernutrition, growth failure, overweight, micronutrient
Diagnostic Studies deficiencies, and osteopenia are nutrition comorbidities
Nutrition Support. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 196 that affect the child with developmental delay regardless
Nutrition Requirements of the specific neurological disability. The epidemiology,
Positioning and Oral Feeding pathogenesis, assessment, and treatment of these disorders
Behavioral Modification in neurologically impaired children have been reviewed
Enteral Tube Feeding elsewhere.1–3 This chapter examines further the principles
Feeding Intolerance
and practices associated with the nutrition management of
Ethical Considerations
children with developmental disabilities that are character-
Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 199
ized primarily by gross and fine motor dysfunction and with
or without cognitive or speech delay.
Early involvement by a multidisciplinary team of
physicians, nurses, dietitians, feeding therapists, psycholo-
gists, and social workers is essential to prevent the adverse
outcomes associated with poor nutrition status in the child
with developmental delay. Undernutrition and overweight
lead to more frequent hospital admissions and physician
visits and diminished participation in home and school
activities.4 Adequate nutrition support may restore linear
and ponderal growth, improve health and quality of life,
reduce the frequency of hospitalization, enhance neurolog-
ical function and developmental progress, support wound
healing and peripheral circulation, decrease the frequency
of aspiration, and ameliorate gastroesophageal reflux in
191
these children. 5–9 Careful evaluation and monitoring of Inappropriate dietary intake
children with severe disabilities is warranted because of the Inappropriate dietary energy intake is the primary cause of
risk of nutrition-related morbidity and mortality.10 undernutrition, growth failure, and overweight in the neuro-
logically impaired child.24–28 Children with cerebral palsy
Nutrition Problems and myelomeningocele consume less dietary energy and
nutrients than unaffected children. They may be unable to
Undernutrition, Growth Failure, and Overweight communicate hunger, food preferences, and satiety, leaving
caretakers responsible for regulating their dietary intake.
Prevalence Caretakers often overestimate the child’s energy intake and
The true prevalence of undernutrition, growth failure, underestimate the time spent feeding the child.26,29 Because
and overweight in children with developmental delay is the task of feeding may be difficult and time-consuming,
unknown. Estimates are limited to disorders such as cerebral the amount of food provided may be insufficient to meet
palsy, myelodysplasia, spina bifida, spinal cord injury, and the child’s growth needs. When adequate dietary energy is
Rett syndrome.11–20 Undernutrition, based on weight-for- provided by enteral tube feedings, nutritional therapy leads
height and triceps skinfold thickness, has been documented to weight gain and linear growth.22 Careful monitoring may
in 29% to 46%, linear stunting in 23%, and overweight in be necessary to avoid overfeeding, and consequently over-
8% to 40% of individuals with these disorders. The preva- weight, in these children. 30
lence of undernutrition increases with increasing age,
lower intelligence, and increased severity of neurological Oral motor dysfunction
impairment.17 Feeding problems associated with oral motor dysfunction
occur frequently in children with developmental delay.12,29
Pathophysiology In one study, 90% of preschool children with cerebral palsy
Non-nutrition factors including the type and severity of had oral motor dysfunction during the first year of life; 57%
neurological disability, ambulatory status, and cogni- had sucking problems, 38% had swallowing problems, and
tive ability contribute to growth failure in children with 80% were fed non-orally at least once as infants. Severe
developmental delay.21 Children with seizures or spastic feeding difficulties preceded the diagnosis of cerebral palsy
quadriplegia and those who are non-ambulatory have lower in as much as 60% of patients. Poor suck, difficulty breast-
height z scores than children who lack these disabilities.18 feeding, problems with the introduction of solid foods,
Children with spastic hemiplegia have smaller measures difficulty drinking liquids, difficulty biting or chewing
of breadth and length on the affected side, suggesting that solids, and coughing and choking with meals were common
neurological impairment influences growth.21 Inherent parental complaints.
genetic factors may be associated with permanent linear Dependency on a caretaker and the inefficiency of the
stunting.22 Height-for-age z scores may decrease with feeding process, including the amount of food spilled and
advancing age independently of weight-for-age z scores in the time required for feeding, influence the child’s nutrition
individuals affected with scoliosis or contractures.18 status.12,16,29 Children with cerebral palsy take 2 to 12 times
Nutrition factors contribute to growth failure in longer to swallow pureed food and up to 15 times longer
children with developmental delay based on correlations to chew and swallow solids than unaffected children. 31
between height and weight z score deficits.23 Nutrition In one report, 28% of parents required more than 3 hours
status explains 10% to 15% of the variability of linear daily to feed their child and 3% required more than 6 hours
growth in children with cerebral palsy. 23 Nutrition status daily. 32 Longer mealtimes may not compensate for feeding
has a stronger effect on linear growth in younger than in inefficiency. 31 Parents may perceive mealtime as a stressful,
older children, attesting to the irreversible effects of long- unpleasant experience. 32 Parents’ perceptions of mealtime
term undernutrition on growth. Inappropriate dietary are important because 60% of children with cerebral palsy
intake relative to nutrient needs, oral motor dysfunction, are totally dependent on a caretaker for feeding.29
increased nutrient losses, and altered energy expenditure Oral motor dysfunction usually correlates with the
may account for the poor nutrition status of children with severity of motor impairment.16,33–35 Children may present
developmental delay. with inadequate lip closure, drooling, and persistent tongue
thrust, resulting in food loss through spillage. Bolus forma-
tion may be difficult to accomplish because of abnormal

DEVELOPMENTAL DELAY 193
oral sensation, uncoordinated or involuntary tongue move- clinical features. Altered body composition and reduced
ments, or delayed development of age-appropriate oral motor physical activity make formulas used to calculate energy
skills. Initiation of the swallowing reflex may be delayed, needs in healthy children invalid for children with develop-
resulting in food accumulation in the vallecula or pyriform mental delay.
sinuses and subsequent aspiration. Neurologically impaired
children with these findings have lower height-, weight-, and Clinical Features
weight-for-height z scores, body fat, and arm muscle area Height-for-age and weight-for-age growth standards of chil-
than unaffected children.16,34,35 Children with more severe dren with developmental delay are lower than those of the
impairment who are unable to lift their heads or feed them- reference population.11,12,23,46–48 The median height-for-age
selves have a higher risk of aspiration. 36 Early, persistent, and weight-for-age for children with spastic quadriplegic
and severe feeding difficulties are markers of subsequent cerebral palsy and Rett syndrome range between the 5th and
poor health, nutrition status, and growth and identify chil- 10th percentiles for the National Center for Health Statis-
dren who may benefit from gastrostomy feedings. 35,37 tics (NCHS) reference population. The differences between
the observed growth pattern of children with spastic quad-
Increased nutrient losses riplegic cerebral palsy or Rett syndrome and the NCHS
Children with developmental delay who feed themselves reference population become greater with increasing age.
may have poor hand-to-mouth coordination, leading to Developmental impairment may adversely affect linear
loss of nutrients as a result of excessive spillage. The use of growth even in the absence of undernutrition because of the
adaptive utensils may enhance movement performance and underlying genetic or medical condition. As a consequence,
minimize food spillage in these individuals. 38 Gastroesoph- growth failure may not be corrected completely by nutri-
ageal reflux, which affects 75% of developmentally impaired tional therapy.22
children, and delayed gastric emptying may result in a loss Children with developmental delay may have progres-
of nutrients because of frequent emesis. sive weight deficits due to fat loss, while muscle and visceral
proteins are maintained. Some children lack weight gain in
Abnormal energy expenditure the presence of linear growth, while others have progressive
Children with spastic quadriplegic cerebral palsy and muscle atrophy unresponsive to nutritional intervention.
myelodysplasia may grow adequately with average energy Although children with developmental delay may be shorter
intakes as low as 50% to 61% of the dietary reference intake and weigh less than unaffected children, others may be
(DRI) for age and gender because their lean body mass, overweight based on weight-for-height, triceps skinfold
and hence resting energy expenditure (REE), is lower thickness, or underwater weighing11–13 or have features
than that of unaffected children.14,26,39,40 REE in children consistent with the metabolic syndrome (Chapter 14).19 The
with myelomeningocele is 96% of predicted, but total daily prevalence of overweight may be underestimated because
energy expenditure is lower than predicted because of a weight-for-height gains are overlooked in the presence
reduction in physical activity.41,42 Children with diplegia, of a small body size or an aberrant distribution of body
hemiplegia, and spina bifida have higher rates of energy fat. Weight-for-height comparisons may be monitored
expenditure while walking compared with unaffected chil- less frequently than weight alone because of the difficulty
dren.43 Dietary energy needs of children with cerebral palsy obtaining accurate height measurements.
who ambulate or have athetosis are higher than those who
do not.44 REE correlates poorly with body cell mass in some Micronutrient Deficiencies
developmentally impaired children, suggesting that central Vitamin, trace element, and essential fatty acid (EFA)
nervous system injury may affect energy regulation. 39 REE deficiencies have been documented in children with devel-
in well-nourished, non-ambulatory children with cerebral opmental delay who have reduced dietary intakes.49–51
palsy is lower than that predicted from equations based on Iron, selenium, zinc, EFAs, and vitamins C, D, and E were
age, gender, and weight in healthy children. 39,45 The DRI reported to be deficient in 15% to 50% of the children.49–52
for energy in healthy children overestimates the energy Some may develop nutrient deficiencies because enteral
needs of children with spastic quadriplegic cerebral palsy in formulas provide adequate amounts of micronutrients only
whom a value of REE × 1.1 may be sufficient.26 The ability when volumes that meet their age-related DRI for energy are
to estimate dietary energy needs of children with develop- consumed. 53 Because many children with developmental
mental delay is difficult because of the heterogeneity in their delay require lower energy intakes, their micronutrient

intakes are correspondingly lower. Replacement therapy itself may remain stable, manifestations of the disorder may
reverses these abnormalities. change over time and require periodic reassessment.
Complementary and alternative medicine is admin-
istered frequently to children with chronic medical Medications
conditions. 54 The use of dietary supplements, including A review of medications is important because drugs
vitamins, minerals, herbs, or other botanicals, was reported prescribed for gastroesophageal reflux, drooling, consti-
by 6% of families with children who have cerebral palsy. 55 pation, seizures, and spasticity may influence the child’s
Concerns have been raised because of potential interactions eating pattern. Gastric acid inhibitors and laxatives often
between complementary or alternative medicines and anti- minimize gastrointestinal discomfort and reverse feeding
epileptic drugs and consequently modification of seizure refusal. Valproic acid, gabapentin, topiramate, zonisamide,
risk. 56 and felbamate may affect appetite and result in weight gain
or loss. Many anticonvulsants impact the level of conscious-
Osteopenia ness, thereby reducing oral motor skills and airway
Osteopenia is prevalent in developmentally impaired chil- protection. Glycopyrrolate may reduce pooling of oral
dren. 52,57–59 Weight z score is the best correlate of bone secretions, but may aggravate constipation. Baclofen and
mineral density z score in children with developmental trihexyphenidyl may reduce spasticity, and consequently,
delay. 58 Dietary calcium, vitamin D, and phosphorus intakes energy expenditure.
are lower than the DRI in 50% to 80% of these children. 24,60
Non-ambulatory children have lower bone mineral content Review of Systems
than those who ambulate independently. 58 Limited ambu- The review of systems identifies clinical problems that may
lation, increased duration of anticonvulsant therapy, and influence the type of nutritional intervention prescribed.
reduced sun exposure contribute to the pathogenesis of Respiratory and gastrointestinal problems impact all
osteopenia. 57–60 Osteopenia is associated with an increased aspects of nutrition support. Emesis, food refusal, anemia,
fracture risk in developmentally impaired children. 57–59 and intestinal blood loss suggest gastroesophageal reflux
Supplemental calcium improves bone mineral density by and esophagitis. Acid reflux tends to be more frequent in
5% over 4 years in healthy children, but the effect of dietary children with severe disabilities and those with scoliosis.
calcium in children with developmental delay is unknown.61 Irritability, infrequent bowel movements, and abdominal
The use of bisphosphonates increased bone mineral density distention suggest constipation. Chronic cough, poorly
by 89% over 18 months in children with cerebral palsy. 62 controlled asthma, or recurrent pneumonia raises the possi-
However, the relation between bisphosphonate use and bility of aspiration.
fracture risk or frequency in these children is unknown. The
use of bisphosphonates is limited because their indications Growth History
in childhood diseases are not well defined and their long- Birth weight and length and previous weight and length
term effects on bone remodeling in children are unknown. measurements, when recorded on NCHS growth charts,
may be compared with the reference population to deter-
Nutrition Assessment mine if growth faltering or abnormal weight gain or loss has
Nutrition assessment of the child with developmental occurred. Height measurements may be erroneous if the
delay includes a thorough medical history, accurate growth child has difficulty standing. The heights of the biological
and anthropometric measurements, a complete physical parents may provide insight regarding the child’s genetic
examination, meal observation and food record review, and growth potential.
selected diagnostic studies.
Social History
Medical History The child with developmental delay requires a considerable
The medical history includes information about the amount of care, a factor that impacts the parent’s ability to
etiology, duration, and severity of neurological impairment work and the family’s social activities. Scheduled activi-
and its expected course. These factors correlate with the ties, such as school or physical therapy, and the siblings’
risk of undernutrition and may affect the type of nutritional school and parents’ work schedules require consideration
intervention required. Although the neurological condition when planning nutritional interventions. Financial issues,

medical insurance, and the availability of home care require The BMI-for-age may be used to screen children with
exploration. All individuals involved in the care and feeding neurological disabilities for underweight and overweight.
of the child and all settings in which feeding occurs require Children are classified as underweight if their BMI-for-age
consideration to ensure that nutritional interventions can is less than the 5th percentile, overweight if their BMI-for-
be integrated into the family or institutional routines. age is between the 85th and 95th percentile, and obese if
their BMI-for-age is greater than the 95th percentile. The
Growth and Anthropometric Measurements use of BMI-for-age may be problematic because of decreased
Growth measures reflect the child’s nutrition status.17 muscle mass, increased regional and total body fat, and/or
Accurate measures of height, length, or a proxy if these skeletal deformities in children with neurological disabili-
measurements are not reliable, and weight are obtained, ties. Nevertheless, an estimate of the BMI-for-age serves as
using standardized techniques and equipment, at every a useful guide for the approach to nutritional intervention.
medical encounter. Length is obtained supine in children Thus, nasogastric or gastrostomy tube feedings may be indi-
less than age 2 years or in older children unable to stand. cated if the BMI-for-age is less than 11 to 13 kg/m 2 because
Alternative measures such as upper arm length (UAL) or of the increased morbidity and mortality associated with
lower leg length (LLL) may be used to estimate body length these values.65 Conversely, an energy-deficit diet may be
in children who have contractures or scoliosis. Reference implemented if the BMI-for-age is greater than 30 kg/m 2 ,
standards are available for UAL and LLL in children age whereas a more restrictive diet such as a protein-sparing
2 years and older.63 Standing height, without shoes and modified fast may be necessary for a BMI-for-age greater
braces, is obtained in all other children. Weight is measured than 40 kg/m 2 .66 Body fat and arm muscle area can be
with the child wearing little or no clothing. Children with estimated from mid-upper arm circumference and triceps
severe disabilities may be weighed while being held by a skinfold thickness.11 Reliability is improved when the same
parent, while seated in a wheelchair, or on a table scale. Body observer obtains the measurements. The values for triceps
mass index (BMI) can be calculated from height and weight skinfold thickness and arm muscle area may be compared to
measurements of children age 2 years and older. Although reference standards.67 Body fat usually is reduced at all sites,
the inability to measure standing height theoretically with the triceps being affected more than the subscapular
invalidates the calculation of BMI, estimates derived from skinfold thickness in children with developmental delay.11,23
LLL serve as a practical alternative in the clinical setting. Measures of triceps skinfold thickness rather than weight-
Weight-for-length is determined for children less than age for-height percentiles may better identify those children
2 years. Head circumference may be of limited use in the with undernutrition. Decreased triceps skinfold thickness
presence of microcephaly. Height (length), weight, BMI, identifies 96% of children with depleted fat stores, while
and weight-for-length, when properly measured and plotted weight-for-height less than the 10th percentile identifies
on gender- and age-appropriate growth charts (http://www. only 55%.46 Waist circumference may serve as an alternative
cdc.gov/growthcharts), can be compared with previous indicator of adiposity because this measure correlates well
measures and the reference population. Condition-specific with truncal fat.19
growth charts may be available, but often have limited
use because of small data sets that contributed to their Physical Examination
formation. Physical examination focuses on signs of undernutrition,
Any height or weight measurement that falls below the linear stunting, overweight, and specific nutrient deficien-
5th percentile, is greater than the 95th percentile, or crosses cies. Muscle tone, activity level, and the presence of athetoid
2 growth channels is considered to represent an abnormal movement are relevant because they influence dietary
growth pattern. Serial measurements are obtained to energy needs. Contractures and scoliosis are noteworthy
determine if the growth pattern is truly abnormal or if for positioning during meals. Abnormal breath sounds may
these findings represent constitutional short stature or be suggestive of chronic respiratory problems associated
the re-channeling of the genetic growth potential in chil- with aspiration. Abdominal distention in conjunction with
dren with neurological disabilities. Radiographic studies palpable masses suggests constipation. Examination of the
of bone age may help to clarify the presence of abnormal skin may reveal the presence of decubitus ulcers. Pallor,
growth patterns because chronic undernutrition is one of skin rashes, smooth tongue, gingival bleeding, petechiae,
the causes of delayed bone maturation, and hence, delayed bone deformities, or pedal edema may suggest other micro-
linear growth.64 nutrient deficiencies.

Meal Observation aspiration in the absence of choking and coughing during

A 24-hour recall of habitual food intake or a 3-day record meals. Assessment of swallowing function at the end of a
of food consumption reflects the adequacy of dietary meal is informative because feeding fatigue may lead to
energy and nutrient intake. 34 Meal observation, with aspiration. A swallowing function study may provide guid-
emphasis on the child’s ability to feed independently and ance for appropriate food textures and therapeutic feeding
the efficiency of the feeding process, may reveal a reason techniques.
for poor weight gain.12,16,29,30 An evaluation of oral motor Gastroesophageal reflux may be apparent based on
skills, including inadequate lip closure, drooling, a persis- symptoms of vomiting, chest or abdominal pain, feeding
tent extrusion reflex, gagging and delayed swallowing, or refusal, or irritability. A 24-hour esophageal pH probe study
coughing and choking during meals reflects poor feeding may be helpful if the diagnosis of acid reflux is not obvious. A
capabilities. Limited texture tolerance may indicate poor gastric emptying scan may detect delayed gastric emptying
oral ability to manage food, resulting in self-restricted which indirectly may contribute to gastroesophageal reflux
eating patterns, reduced nutrient intake, and poor weight and aspiration. An upper gastrointestinal series may detect
gain.68,69 Consumption of inappropriate food textures may gastroesophageal dysmotility or superior mesenteric artery
result in aspiration. Fatigue and lethargy during meals may syndrome, both of which may interfere with feeding.
suggest hypoxemia.70 Meal observation shows that children Episodic reflux occurring during the study may not be diag-
with developmental delay may be offered less, consume less, nostic of acid reflux disease. An abnormal location of the
and spill more food than unaffected children. Classifica- stomach in the thorax of children with severe scoliosis may
tion systems based on measures of growth and patterns of influence the type of intervention used for enteral access.
food consumption, such as eating efficiency and oral motor The child with symptoms suggestive of chronic aspi-
feeding skills, may be helpful to assess the effectiveness of ration may require a chest x-ray and an evaluation by a
oral feeding interventions.71,72 pulmonologist, especially if surgical intervention for enteral
access is considered. Monitoring O2 saturation during a meal
Diagnostic Studies may be important because children with developmental
Although isolated nutrient deficiencies may be present in delay may have hypoxemia with feedings.70 Modifying food
children with developmental delay, extensive laboratory textures and liquid consistencies with thickening agents
evaluation is not necessary.49–51 A complete blood count and may help to reduce aspiration risk.
serum ferritin may document anemia or iron deficiency.
Serum electrolytes and blood urea nitrogen (BUN) reflect Nutrition Support
hydration status; however, BUN may be low because of Nutrition support is provided enterally rather than paren-
poor protein intake and low muscle mass. Serum albumin terally, assuming competency of the gastrointestinal tract.
and prealbumin, factors that correlate strongly with the Enteral tube feedings are essential in children who cannot
risk of morbidity and mortality, are less reliable indicators meet their energy and nutrient needs orally.75 Evidence of
of nutrition status.73 Abnormal serum phosphorus, alkaline oral motor feeding difficulties, undernutrition (weight-for-
phosphatase, and 25-hydroxyvitamin D levels may coincide height < 80% of expected, BMI < 5th percentile), growth
with poor bone mineral status. Bone densitometry may be failure (height-for-age < 90% of expected), overweight
considered in children who have pathologic fractures. Bone (BMI > 85th percentile), and individual nutrient deficien-
quantitative ultrasonography may be more easily performed cies indicate the need for nutritional intervention.1
than bone densitometry; however, normative data for chil-
dren are not yet available.74 Nutrition Requirements
Additional diagnostic studies may be helpful, depending Energy requirements of children with developmental delay
on the child’s symptoms and the need for permanent enteral vary with the severity of their neurological disability, their
access. A videofluoroscopic assessment of chewing and mobility, the presence of feeding difficulties, altered body
swallowing function, using different food and beverage composition, and the need for weight gain or loss and catch-
textures, determines the degree of oral motor dysfunction up growth. Dietary energy needs for the maintenance of
and risk of aspiration. Positioning the child during the body weight may be estimated from either the DRI stan-
evaluation is important because some children may not dards for basal energy expenditure (http://www.nal.usda.
aspirate when placed upright, but do so in a reclined posi- gov/fnic/etext/000105.html), indirect calorimetry,76 or
tion. A swallowing function study may demonstrate silent height77 (Table 18-1). Dietary energy needs for catch-up

growth may approximate the DRI for basal energy expen- of the neck, has been used; however, improved feeding
diture × 1.5. Monitoring the rate of weight gain or loss and efficiency in children has not been documented. 80 Periodic
change in BMI is the best way to determine the adequacy of reassessment of oral feeding skills is important to deter-
diet in the child with developmental delay. Adequate provi- mine the potential for continued oral feeding.
sion of dietary protein, vitamins, and minerals is mandatory
when energy intakes are modified to obtain the desired rate Behavioral Modification
of weight change. In the absence of evidence-based nutrient Behavioral therapy initiated by a skilled child psychologist
allowances for children with developmental delay, the may improve the quantity of food consumed, the feeding
DRIs for protein, vitamins, and minerals in healthy chil- efficiency, and the range of textures accepted, as well as the
dren are recommended (http://www.nal.usda.gov/fnic/ quality of feeding interactions between the caretaker and
etext/000105.html). Multivitamin and mineral supple- the child.81
ments may be prudent for children with developmental
delay who rely primarily on table foods and beverages to Enteral Tube Feeding
meet their nutrient needs, particularly in relation to the Oral feedings can be maintained in children with adequate
need for improved vitamin D status.78 oral motor skills who have a low risk of aspiration. Adequate
positioning and adjustment of food and beverage consis-
Table 18-1. Methods to Determine Dietary Energy Needs in Neurologically tency with thickening agents may improve feeding
Impaired Children
efficiency. Increasing the energy density of food maximizes
Dietary Reference Intake Standards for Basal Energy Expenditure energy intake. If oral intake is insufficient to promote
(http://www.nal.usda.gov/fnic/etext/000105.html)
weight gain, linear growth, and adequate hydration, if the
Energy intake (kcal/d) = Basal Energy Expenditure (BEE) x 1.1
amount of time to feed the child is excessive because of
Age (y) Basal Energy Expenditure (kcal/d) chewing and swallowing dysfunction, or if aspiration is a
Boys Girls
risk, enteral tube feedings may be considered. The type of
3–8 1035 1004
enteral access selected will depend upon the nutritional and
9–13 1320 1186
14–18 1729 1361
clinical status of the child and the anticipated duration of
Indirect Calorimetry76
enteral feedings. Parents will be concerned about the child’s
Energy intake (kcal/d) loss of oral feeding skills, the risks and benefits of enteral
= [basal energy expenditure (BMR) x muscle tone x activity] + growth tube feeding, and the manner in which alternative feeding
where: methods fit the family’s lifestyle. Enteral feeding regimens
■ BMR (kcal/d) = body surface area (m2) x metabolic rate (kcal/m2/h) that preserve oral feeding skills while providing adequate
x 24 h
nutrient intakes facilitate the transition back to oral feeds
■ Muscle tone = 0.9 if decreased, 1 if normal, and 1.1 if increased
■ Activity = 1.1 if bedridden, 1.2 if wheelchair dependent or crawling,
when safe or after catch-up growth has been achieved.
and 1.3 if ambulatory
■ Growth = 5 kcal/g of desired weight gain (normal and catch-up Enteral Access
growth) Nasogastric or nasojejunal tube feedings are minimally
Height77 invasive methods that may be used for short-term nutri-
■ 15 kcal/cm in children without motor dysfunction tion support in undernourished children or in those with
■ 14 kcal/cm in children with motor dysfunction who are ambulatory acid reflux or aspiration who are awaiting gastrostomy
■ 11 kcal/cm in children who are non-ambulatory
placement. Nasogastric or nasojejunal tubes are not used
long-term because they may be dislodged easily, may stiffen
Positioning and Oral Feeding and cause intestinal perforation, or may result in nasal
The feeding therapist can assist with oral motor skills, congestion, sinusitis, otitis media, and skin and mucosal
correct positioning of the child, and the use of appro- irritation. Bedside placement of nasojejunal tubes can be
priate chairs and adapted utensils during meals. Therapy achieved by allowing the tube to migrate spontaneously
to improve oral motor skills may be attempted, especially or in conjunction with a prokinetic drug. 82–84 Newer tech-
before age 5 years. Oral feeding interventions may enhance niques such as pH-assisted tube placement are available. 85
oral motor function, but are not effective in promoting Fluoroscopic or endoscopic tube placement may be required
feeding efficiency and weight gain.79 VitalStim®, a device if these approaches are unsuccessful.
that administers electrical stimulation to the musculature Gastrostomy feedings provide an option for children

with severe feeding problems who have poor weight gain, developmental delay.95,98,99 Retching may be a disturbing
although evidence-based practice guidelines with atten- symptom after a fundoplication, but generally can be con-
dant risks and benefits are lacking.6,7 A gastrostomy tube trolled by slowing the rate of formula administration.100
or “button” device is recommended for long-term enteral Surgical gastrojejunostomy or jejunostomy tube place-
nutrition (EN) because it is more comfortable for the child ment may be required in children who do not tolerate
and is less easily dislodged than a nasogastric tube. Gastros- gastric feeds, have severe gastroesophageal reflux, are at
tomy feedings may promote weight gain, improve the child’s risk for aspiration, are poor candidates for fundoplication,
health, and reduce the time spent feeding the child.6–8,22 The or are high-risk for failure of a second anti-reflux procedure.
best clinical response is seen in children with the shortest A surgical or laparoscopic loop or Roux-en-Y jejunostomy is
time between the neurological insult and gastrostomy reserved for selected children in whom other options have
placement. Children who have a gastrostomy placed within failed.101
the first year of life are more likely to exceed the 5th percen- Image-guided, retrograde or antegrade, percutaneous
tile for height and weight. Gastrostomy feedings initiated placement of gastrostomy or gastrojejunostomy tubes is
within 1 year of the neurological insult are associated with an alternative, minimally invasive fluoroscopic method for
improved weight-for-age, weight-for-length, and length- enteral feeding.102 The retrograde percutaneous technique
for-age. Nutritional intervention initiated 8 years after has a higher rate of successful placement than the PEG
the neurological insult does not normalize length-for-age, method and has a lower rate of major complications than
despite improvement in weight-for-age. 86 PEG or surgical gastrostomy placement.
Percutaneous endoscopic gastrostomy (PEG) place-
ment, a minimally invasive non-surgical procedure, involves Formula Administration
little discomfort and the feeding device can be used within a The choice of enteral formula depends on the child’s
few hours of installation. 87 The higher death rate in children age, medical condition, energy requirement, and mode of
fed by gastrostomy may reflect the severity of their neuro- enteral access. Standard, age-appropriate, infant or pedi-
logical disability compared with those fed orally.7,88 The risk atric, casein-based formulas are administered routinely.
of acid reflux or esophagitis after PEG placement in devel- Whey-based formulas may be better tolerated because
opmentally impaired children without previous symptoms they enhance gastric emptying.103 Children who manifest
is increased.89–93 Medical therapy for pre-existing acid reflux symptoms associated with cow’s milk protein sensitivity
often will be required after PEG placement. 88 An evaluation may require a protein hydrolysate or amino acid formula.
for acid reflux before PEG placement may be warranted Nutrient deficiencies may occur as a consequence of enteral
because 5% of developmentally impaired children who have feedings.2,6,17 Adult formulas may prevent hypoalbumin-
a normal pH probe study eventually require an anti-reflux emia during periods of catch-up growth, but care should
procedure compared with 29% to 58% of those who have be taken to avoid iron, vitamin D, calcium, and phosphorus
an abnormal pH probe study.88,89 Acid reflux may improve deficiency.24 If high energy density (1.5 or 2 kcal/mL)
in some children after PEG placement and nutritional reha- formulas are used, monitoring hydration status and protein
bilitation. Further evaluation with upper endoscopy and and micronutrient intake is necessary. A fiber-containing
esophageal biopsy does not predict clinical outcome after formula may ameliorate constipation, but may aggravate
PEG placement in children.94 intestinal gas bloating if the volume is increased rapidly.
Surgical gastrostomy placement is a safe alternative to Bolus formula feedings are preferred in children who
enteral access in the child with developmental delay. Lap- do not have acid reflux or delayed gastric emptying because
aroscopic gastrostomy placement is associated with less they mimic the physiologic responses associated with meals,
morbidity, permits earlier EN, and has a cost advantage allow a more flexible feeding schedule, and are more conve-
compared with the open technique. Laparoscopic or open nient in ambulatory children. Continuous formula infusions
surgical fundoplication may be required in as much as 25% may be used throughout the day or night in children who
of neurologically impaired children.88,89,93,95,96 Although py- do not tolerate bolus feeds or have formula administered
loroplasty improves gastric emptying, dumping syndrome directly into the jejunum. When large volumes are required,
may occur and require long-term continuous infusions bolus feeds can be combined with continuous nocturnal
until bolus feeds are tolerated.97,98 The risk of feeding diffi- infusions of formula. Continuous nocturnal infusions avoid
culty, gas bloat, or dumping syndrome, and recurrence of interruptions during daytime activities, but may interfere
acid reflux after a fundoplication, varies in children with with sleep.104

Feeding Intolerance Acknowledgments

Feeding intolerance may be associated with recurrent The authors thank V. Moore for secretarial support. This
acid or non-acid reflux, delayed gastric emptying, diar- chapter is a publication of the USDA/ARS Children’s Nutri-
rhea, or constipation.105 In the absence of progression of tion Research Center, Department of Pediatrics, Baylor
the neurological disorder, intercurrent infection, or intes- College of Medicine, Houston, TX, and has been funded
tinal obstruction, the quality and quantity of the feeding in part with federal funds from the U.S. Department of
regimen requires periodic re-evaluation. Changing the Agriculture, Agricultural Research Service, under Coop-
feeding schedule from bolus to continuous infusion, erative Agreement Number 58-6250-1-003. The contents
decreasing the rate of infusion, concentrating the formula herein do not necessarily reflect the views or policies of
to decrease the volume of feeds, or selecting an alternative the U.S. Department of Agriculture, nor does mention of
formula may ameliorate symptoms. If symptoms persist, trade names, commercial products, or organizations imply
medical treatment of acid reflux or delayed gastric emptying endorsement by the U.S. government.
may be instituted before exploring laparoscopic or surgical
procedures. Medical management of acid reflux and delayed Test Your Knowledge Questions
gastric emptying consists of using whey hydrolysate 1. Which anthropometric measurements are most useful
formulas and medications that promote acid suppres- to determine nutrition status of the child with develop-
sion (histamine antagonists, proton pump inhibitors) and mental delay?
motility (bethanechol, metoclopramide, erythromycin, A. Height, length, and triceps skinfold
cisapride). Although the availability of cisapride is restricted B. Weight, head circumference, and arm circumference
because of safety concerns, its use in neurological disorders C. Head circumference, body mass index, and triceps
associated with QT wave abnormalities (eg, Rett syndrome) skinfold thickness
is cautioned. Medical management of constipation consists D. BMI, weight, and height
of single or multiple laxative agents with stool-softening 2. What are the most common reasons for poor weight
and stimulatory effects (polyethylene glycol-electrolyte gain in the child with developmental delay?
solution, magnesium hydroxide, senna extract, lactulose, A. Inadequate dietary intake and constipation
bisacodyl). Rectal inertia may require local treatment with B. Increased basal metabolic rate
suppositories (bisacodyl) or enemas.106 C. Chewing and swallowing dysfunction and inad-
equate dietary intake
Ethical Considerations D. Athetoid or repetitive motor movements and
Many families find the idea of a feeding gastrostomy diffi- aspiration
cult to accept.107 Caregivers believe that they have failed 3. The best way to determine the adequacy of the diet for
to adequately care for the child when physicians insist on children with developmental delay is to:
gastrostomy placement. Starvation, quality of life, prolon- A. Calculate dietary energy needs based on the DRI
gation of life, and meaningful family interrelationships standards for basal energy expenditure.
constitute a framework for discussion. Although medical B. Monitor the rate of weight gain or loss and change
opinions generally prevail, parental wishes should be in BMI.
considered and respected. C. Measure hemoglobin concentration and serum
albumin levels.
Conclusion D. Provide a protein hydrolysate or amino acid formula
Nutrition support is essential for the care of the child with as the main source of nutrients.
developmental delay. After a thorough evaluation, an indi-
vidualized intervention plan that accounts for the child’s See p. 487 for answers.
nutrition status, feeding ability, and medical condition may
be determined. Nutrition assessments may be performed References
at least annually in the older child and more frequently in 1. Motil KJ. Enteral nutrition in the neurologically impaired
the infant and toddler to document adequate growth and child. In: Baker SB, Baker RD Jr, Davis A, eds. Pediatric Enteral
Nutrition. New York, NY: Chapman & Hall; 1994:217–237.
nutrient intakes. The goal of nutrition assessment and inter- 2. Thomas AG, Akobeng AK. Technical aspects of feeding
vention is to optimize the child’s health, functional status, the disabled child. Curr Opin Clin Nutr Metab Care.
and quality of life, while maintaining adequate growth and 2000;3(3):221–225.
nutrition status.

3. Marchand V, Motil KJ, NASPGHAN Committee on Nutri- 22. Motil KJ, Morrissey M, Caeg E, Barrish JO, Glaze DG. Gastros-
tion. Nutrition support for neurologically impaired children: tomy placement improves height and weight in girls with Rett
a clinical report of the North American Society for Pedi- syndrome. J Pediatr Gastroenterol Nutr. 2009;49:237–242.
atric Gastroenterology, Hepatology, and Nutrition. J Pediatr 23. Stallings VA, Charney EB, Davies JC, Cronk CE. Nutrition-
Gastroenterol Nutr. 2006;43(1):123–135. related growth failure of children with quadriplegic cerebral
4. Samson-Fang L, Fung E, Stallings VA, et al. Relationship of palsy. Dev Med Child Neurol. 1993;35(2):126–138.
nutritional status to health and societal participation in chil- 24. Fried MD, Pencharz PB. Energy and nutrient in-
dren with cerebral palsy. J Pediatr. 2002;141(5):637–643. takes of children with spastic quadriplegia. J Pediatr.
5. Rogers B. Feeding method and health outcomes of children 1991;119(6):947–949.
with cerebral palsy. J Pediatr. 2004;145(2 Suppl):S28–S32. 25. Reilly S, Skuse D. Characteristics and management of
6. Sleigh G, Brocklehurst P. Gastrostomy feeding in cerebral pal- feeding problems of young children with cerebral palsy. Dev
sy: a systematic review. Arch Dis Child. 2004;89(6):534–539. Med Child Neurol. 1992;34(5):379–388.
7. Samson-Fang L, Butler C, O’Donnell M. Effects of gastros- 26. Stallings VA, Zemel BS, Davies JC, Cronk CE, Charney
tomy feeding in children with cerebral palsy: an AACPDM EB. Energy expenditure of children and adolescents with
evidence report. Dev Med Child Neurol. 2003;45(6):415–426. severe disabilities: a cerebral palsy model. Am J Clin Nutr.
8. Sullivan PB, Juszczak E, Bachlet AM, et al. Gastrostomy tube 1996;64(4):627–634.
feeding in children with cerebral palsy: a prospective, longitu- 27. Hillesund E, Skranes J, Trygg KU, Bohmer T. Micronu-
dinal study. Dev Med Child Neurol. 2005; 47(2):77–85. trient status in children with cerebral palsy. Acta Paediatr.
9. Craig GM, Carr LJ, Cass H, et al. Medical, surgical, and health 2007;96(8):1195–1198.
outcomes of gastrostomy feeding. Dev Med Child Neurol. 28. Mathisen BA, Shepherd K. Oral-motor dysfunction and
2006;48(5):353–360. feeding problems in infants with myelodysplasia. Pediatr
10. Strauss D, Kastner T, Ashwal S, White J. Tubefeeding and Rehabil. 1997;1:117–122.
mortality in children with severe disabilities and mental retar- 29. Reilly S, Skuse D, Poblete X. Prevalence of feeding problems
dation. Pediatrics. 1997;99(3):358–362. and oral motor dysfunction in children with cerebral palsy: a
11. Stallings VA, Charney EB, Davies JC, Cronk CE. Nutritional community survey. J Pediatr. 1996;129(6):877–882.
status and growth of children with diplegic or hemiplegic 30. Sullivan PB, Alder N, Allison ME, et al. Gastrostomy feeding
cerebral palsy. Dev Med Child Neurol. 1993;35(11):997–1006. in cerebral palsy: too much of a good thing? Dev Med Child
12. Dahl M, Thommessen M, Rasmussen M, Selberg T. Feeding Neurol. 2006;48(11):877–882.
and nutritional characteristics in children with moderate or 31. Gisel EG, Patrick J. Identification of children with cerebral
severe cerebral palsy. Acta Paediatr. 1996;85(6):697–701. palsy unable to maintain a normal nutritional state. Lancet.
13. Mita K, Akataki K, Ono Y, Ishida N, Oki T. Assessment of 1988;1(8580):283–286.
obesity of children with spina bifida. Dev Med Child Neurol. 32. Sullivan PB, Lambert B, Rose M, Ford-Adams M, Johnson A,
1993;35:305–311. Griffiths P. Prevalence and severity of feeding and nutritional
14. Bandini LG, Schoeller DA, Fukagawa NK, Wykes LJ, Dietz problems in children with neurological impairment: Oxford
WH. Body composition and energy expenditure in adoles- Feeding Study. Dev Med Child Neurol. 2000;42(10):674–680.
cents with cerebral palsy or myelodysplasia. Pediatr Res. 33. Thommessen M, Heiberg A, Kase BF, Llarson S, Riis G.
1991;29(1):70–71. Feeding problems, height and weight in different groups of
15. Schultz R, Glaze DG, Motil KJ, et al. The pattern of growth fail- disabled children. Acta Paediatr Scand. 1991;80(5):527–533.
ure in Rett syndrome. Am J Dis Child. 1993;147(6):633–637. 34. Sullivan PB, Juszczak E, Lambert BR, et al. Impact of feeding
16. Troughton KE, Hill AE. Relation between objectively problems on nutritional intake and growth: Oxford Feeding
measured feeding competence and nutrition in children with Study II. Dev Med Child Neurol. 2002;44:461–467.
cerebral palsy. Dev Med Child Neurol. 2001;43(3):187–190. 35. Fung EB, Samson-Fang L, Stallings VA, Rose M, Ford-Adams
17. Sanchez-Lastres J, Eiris-Punal J, Otero-Cepeda JL, Pavon- ME, Johnson A. Feeding dysfunction is associated with poor
Belinchon P, Castro-Gago M. Nutritional status of mentally growth and health status in children with cerebral palsy. J Am
retarded children in north-west Spain. I. Anthropometric Diet Assoc. 2002;102(3):361–368.
indicators. Acta Paediatr. 2003;92(6):747–753. 36. Strauss D, Ashwal S, Shavelle R, Eyman RK. Prognosis for
18. Stevenson RD, Hayes RP, Cater LV, Blackman JA. Clinical survival and improvement in function in children with severe
correlates of linear growth in children with cerebral palsy. Dev developmental disabilities. J Pediatr. 1997;131(5):712–717.
Med Child Neurol. 1994;36(2):135–142. 37. Motion S, Northstone K, Emond A, Stucke S, Golding J. Early
19. Nelson MD, Widman LM, Abresch RT, et al. Metabolic feeding problems in children with cerebral palsy: weight
syndrome in adolescents with spinal cord dysfunction. J Spinal and neurodevelopmental outcomes. Dev Med Child Neurol.
Cord Med. 2007;30(Suppl 1):S127–S139. 2002;44(1):40–43.
20. Fiore P, Picco P, Castagnola E, et al. Nutritional survey of 38. Van Roon D, Steenbergen B. The use of ergonomic
children and adolescents with myelomeningocele (MMC): spoons by people with cerebral palsy: effects of food
overweight associated with reduced energy intake. Eur J spilling and movement kinematics. Dev Med Child Neurol.
Pediatr Surg. 1998;8(Suppl 1):34–36. 2006;48(11):888–891.
21. Stevenson RD, Roberts CD, Vogtle L. The effects of non- 39. Azcue MP, Zello GA, Levy LD, Pencharz PB. Energy
nutritional factors on growth in cerebral palsy. Dev Med Child expenditure and body composition in children with spastic
Neurol. 1995;37(2):124–130. quadriplegic cerebral palsy. J Pediatr. 1996;129(6):870–876.

40. Grogan CB, Ekvall SM. Body composition of children 56. Kaiboriboon K, Guevara M, Alldredge BK. Understanding
with myelomeningocele, determined by 40K, urinary herb and dietary supplement use in patients with epilepsy.
creatinine and anthropometric measures. Am J Coll Nutr. Epilepsia. 2009;50(8):1927–1932.
1999;18:316–323. 57. Chad KE, McKay HA, Zello GA, Bailey DA, Faulkner RA,
41. Littlewood RA, Trocki O, Shepherd RW, Shepherd K, Davies Snyder RE. Body composition in nutritionally adequate
PS. Resting energy expenditure and body composition in chil- ambulatory and non-ambulatory children with cerebral
dren with myelomeningocele. Pediatr Rehabil. 2003;6:31–37. palsy and a healthy reference group. Dev Med Child Neurol.
42. van den Berg-Emons HJ, Bussmann JB, Brobbel AS, 2000;42(5):334–339.
Roebroeck ME, van Meeteren J, Stam HJ. Everyday physical 58. Henderson RC, Kairalla J, Abbas A, Stevenson RD.
activity in adolescents and young adults with meningomy- Predicting low bone density in children and young adults
elocele as measured with a novel activity monitor. J Pediatr. with quadriplegic cerebral palsy. Dev Med Child Neurol.
2001;139:880–886. 2004;46(6):416–419.
43. Duffy CM, Hill AE, Cosgrove AP, Corry IS, Graham HK. 59. Motil KJ, Ellis KJ, Barrish JO, Caeg E, Glaze DG. Bone
Energy consumption in children with spina bifida and mineral content and bone mineral density are lower in older
cerebral palsy: a comparative study. Dev Med Child Neurol. than in younger females with Rett syndrome. Pediatr Res.
1996;38(3)238–243. 2008; 64(4):435–439.
44. Rose J, Medeiros JM, Parker R. Energy cost index as an 60. Baer MT, Kozlowski BW, Blyler EM, Trahms CM, Taylor ML,
estimate of energy expenditure of cerebral-palsied chil- Hogan MP. Vitamin D, calcium, and bone status in children
dren during assisted ambulation. Dev Med Child Neurol. with developmental delay in relation to anticonvulsant use and
1985;27(4):485–490. ambulatory status. Am J Clin Nutr. 1997;65(4):1042–1051.
45. Bandini LG, Puelzl-Quinn H, Morelli JA, Fukagawa NK. 61. Matkovic V, Goel PK, Badenhop-Stevens NE, et al. Calcium
Estimation of energy requirements in persons with severe supplementation and bone mineral density in females from
central nervous system impairment. J Pediatr. 1995;126(5 Pt childhood to young adulthood: a randomized controlled trial.
1):828–832. Am J Clin Nutr. 2005;81(1):175–188.
46. Samson-Fang LJ, Stevenson RD. Identification of malnutrition 62. Henderson RC, Lark RK, Kecskemethy HH, Miller
in children with cerebral palsy: poor performance of weight for F, Harcke HT, Bachrach SJ. Bisphosphonates to treat
height centiles. Dev Med Child Neurol. 2000;42(3):162–168. osteopenia in children with quadriplegic cerebral palsy:
47. Stallings VA, Cronk CE, Zemel BS, Charney EB. Body compo- a randomized, placebo-controlled clinical trial. J Pediatr.
sition in children with spastic quadriplegic cerebral palsy. J 2002;141(5):644–651.
Pediatr. 1995;126(5 Pt 1):833–839. 63. Spender QW, Cronk CE, Charney EB, Stallings VA. Assess-
48. Tarquinio D, Motil K, Hou W, et al. Growth charts for Rett ment of linear growth of children with cerebral palsy: use
syndrome: Birth to 18 years of age. Neurology. 2009;72 (Suppl of alternative measures to height or length. Dev Med Child
3):A427–A428. Platform presentation American Academy Neurol. 1989;31(2):206–214.
of Neurology annual meeting, Seattle, WA. April, 2009. ID: 64. Greulich WW, Pyle SI. Radiographic Atlas of Skeletal Develop-
2740AAN09D1. ment of the Hand and Wrist. 2nd ed. Stanford, CA: Stanford
49. Hals J, Ek J, Svalastog AG, Nilsen H. Studies on nutrition in University Press, 1959.
severely neurologically disabled children in an institution. 65. Collins S. The limits of human adaptation to starvation. Nat
Acta Paediatr. 1996;85(12):1469–1475. Med. 1995;1(8):810–814.
50. Jones M, Campbell KA, Duggan C, et al. Multiple micronu- 66. Figueroa-Colon R, Franklin FA, Lee JY, von Almen TK,
trient deficiencies in a child fed an elemental formula. J Pediatr Suskind RM. Feasibility of a clinic-based hypocaloric dietary
Gastroenterol Nutr. 2001;33(5):602–605. intervention implemented in a school setting for obese chil-
51. Hals J, Bjerve KS, Nilsen H, Svalastog AG, Ek J. Essential fatty dren. Obes Res. 1996;4(5):419–429.
acids in the nutrition of severely neurologically disabled chil- 67. Frisancho AR. New norms of upper limb fat and muscle
dren. Br J Nutr. 2000;83(3):219–225. areas for assessment of nutritional status. Am J Clin Nutr.
52. Henderson RC, Lark RK, Gurka MJ, et al. Bone density and 1981;34(11):2540–2545.
metabolism in children and adolescents with moderate to 68. Isaacs JS, Murdock M, Lane J, Percy AK. Eating difficulties in
severe cerebral palsy. Pediatrics. 2002;110 (1 Pt 1):e51. girls with Rett syndrome compared with other developmental
53. Piccoli R, Gelio S, Fratucello A, Valletta E. ��
Risk of low micro- disabilities. J Am Diet Assoc. 2003;103(2):224–230.
nutrient intake in neurologically disabled children artificially 69. Gisel EG, Alphonce E. Classification of eating impairments
fed. J Pediatr Gastroenterol Nutr. 2002;35(4):583–584. based on eating efficiency in children with cerebral palsy.
54. Samdup DZ, Smith RG, Il Song S. The use of complementary Dysphagia. 1995;10(4):268–274.
and alternative medicine in children with chronic medical 70. Rogers BT, Arvedson J, Msall M, Demerath RR. Hypoxemia
conditions. Am J Phys Med Rehabil. 2006;85(10):842–846. during oral feedings of children with severe cerebral palsy.
55. Hurvitz EA, Leonard C, Ayyangar R, Nelson VS. Comple- Dev Med Child Neurol. 1993;35(1):3–10.
mentary and alternative medicine use in families of children 71. Gisel EG, Alphonce E, Ramsay M. Assessment of ingestive
with cerebral palsy. Dev Med Child Neurol. 2003;45:364–370. and oral praxis skills: children with cerebral palsy vs. controls.
Dysphagia. 2000;15(4):236–244.

72. Gisel EG. Effect of oral sensorimotor treatment on 89. Sulaeman E, Udall JN, Brown RF, et al. Gastroesophageal
measures of growth and efficiency of eating in the moder- reflux and Nissen fundoplication following percutaneous
ately eating-impaired child with cerebral palsy. Dysphagia. endoscopic gastrostomy in children. J Pediatr Gastroenterol
1996;11(1):48–58. Nutr. 1998;26(3):269–273.
73. Fuhrman MP, Charney P, Mueller CM. Hepatic 90. Khattak IU, Kimber C, Kiely EM, Spitz L. Percutaneous
proteins and nutritional assessment. J Am Diet Assoc. endoscopic gastrostomy in paediatric practice: complications
2004;104(8):1258–1264. and outcome. J Pediatr Surg. 1998;33(1):67–72.
74. Hartman C, Brik R, Tamir A, Merrick J, Shamir R. Bone 91. Behrens R, Lang T, Muschweck H, Richter T, Hofbeck M.
quantitative ultrasound and nutritional status in severely Percutaneous endoscopic gastrostomy in children and adoles-
handicapped institutionalized children and adolescents. Clin cents. J Pediatr Gastroenterol Nutr. 1997;25(5):487–491.
Nutr. 2004; 23(1):89–98. 92. Grunow JE, al-Hafidh A, Tunell WP. Gastroesophageal reflux
75. Axelrod D, Kazmerski K, Iyer K. Pediatric enteral nutrition. J following percutaneous endoscopic gastrostomy in children.
Parenter Enteral Nutr. 2006;30(1 Suppl):S21–S26. J Pediatr Surg. 1989;24(1):42–44.
76. Krick J, Murphy PE, Markham JF, Shapiro BK. A proposed 93. Isch JA, Rescorla FJ, Scherer LR 3rd, West KW, Gros-
formula for calculating energy needs of children with cerebral feld JL. The development of gastroesophageal reflux after
palsy. Dev Med Child Neurol. 1992;34(6):481–487. percutaneous endoscopic gastrostomy. J Pediatr Surg.
77. Culley WJ, Middleton TO. Caloric requirements of mentally 1997;32(2):321–322.
retarded children with and without motor dysfunction. J 94. Heikenen JB, Werlin SL. Esophageal biopsy does not predict
Pediatr. 1969;75(3):380–384. clinical outcome after percutaneous endoscopic gastrostomy
78. Misra M, Pacaud D, Petryk A, Collett-Solberg PF, Kappy M. in children. Dysphagia. 2000;15(3):167–169.
Vitamin D deficiency in children and its management: review 95. Cameron BH, Blair GK, Murphy JJ 3rd, Fraser GC. Morbidity
of current knowledge and recommendations. Pediatrics. in neurologically impaired children after percutaneous
2008;122(2):398–417. endoscopic versus Stamm gastrostomy. Gastrointest Endosc.
79. Gisel EG, Applegate-Ferrante T, Benson JE, Bosma JF. Effect 1995;42(1):41–44.
of oral sensorimotor treatment on measures of growth, eating 96. Heine RG, Reddihough DS, Catto-Smith AG. Gastro-
efficiency and aspiration in the dysphagic child with cerebral oesophageal reflux and feeding problems after gastrostomy in
palsy. Dev Med Child Neurol. 1995;37(6):528–543. children with severe neurological impairment. Dev Med Child
80. Chetney R, Waro K. A new home health approach to swal- Neurol. 1995;37(4):320–329.
lowing disorders. Home Health Nurse. 2004;22(10):703–707. 97. Farrell TM, Richardson WS, Halkar R, et al. Nissen fundopli-
81. Linscheid TR. Behavioral treatments for pediatric feeding cation improves gastric motility in patients with delayed
disorders. Behav Modif. 2006;30(1):6–23. gastric emptying. Surg Endosc. 2001;15(3):271-274.
82. Kalliafas S, Choban PS, Ziegler D, Drago S, Flancbaum 98. Bufler P, Ehringhaus C, Koletzko S. Dumping syndrome: a
L. Erythromycin facilitates postpyloric placement of common problem following Nissen fundoplication in young
nasoduodenal feeding tubes in intensive care unit patients: children. Pediatr Surg Int. 2001;17(5–6):351–355.
randomized, double-blinded, placebo-controlled trial. J 99. Pimpalwar A, Najmaldin A. Results of laparoscopic antire-
Parenter Enteral Nutr. 1996;20(6):385–388. flux procedures in neurologically impaired children. Semin
83. Kittinger JW, Sandler RS, Heizer WD. Efficacy of metoclo- Laparosc Surg. 2002;9(3):190–196.
pramide as an adjunct to duodenal placement of small-bore 100. Friedman JN, Ahmed S, Connolly B, Chait P, Mahant
feeding tubes: a randomized, placebo-controlled, double- S. Complications associated with image-guided gastros-
blind study. J Parenter Enteral Nutr. 1987;11(1):33–37. tomy and gastrojejunostomy tubes in children. Pediatrics.
84. Davies AR, Bellomo R. Establishment of enteral nutrition: 2004;114(2):458–461.
prokinetic agents and small bowel feeding tubes. Curr Opin 101. Richards CA, Milla PJ, Andrews PL, Spitz L. Retching and
Crit Care. 2004;10(2):156–161. vomiting in neurologically impaired children after fundopli-
85. Krafte-Jacobs B, Persinger M, Carver J, Moore L, Brilli R. cation: predictive preoperative factors. J Pediatr Surg.
Rapid placement of transpyloric feeding tubes: a comparison 2001;36(9):1401–1404.
of pH-assisted and standard insertion techniques in children. 102. Neuman HB, Phillips JD. Laparoscopic Roux-en-Y feeding
Pediatrics. 1996;98(2 Pt 1):242–248. jejunostomy: a new minimally invasive surgical procedure for
86. Sanders KD, Cox K, Cannon R, et al. Growth response to permanent feeding access in children with gastric dysfunc-
enteral feeding by children with cerebral palsy. J Parenter tion. J Laparoendosc Adv Surg Tech A. 2005;15(1):71–74.
Enteral Nutr. 1990;14(1):23–26. 103. Fried MD, Khoshoo V, Secker DJ, Gilday DL, Ash JM,
87. Gauderer MW. Percutaneous endoscopic gastrostomy: Pencharz PB. Decrease in gastric emptying time and episodes
a 10-year experience with 220 children. J Pediatr Surg. of regurgitation in children with spastic quadriplegia fed a
1991;26(3):288–292. whey-based formula. J Pediatr. 1992;120(4 Pt 1):569–572.
88. Catto-Smith AG, Jimenez S. Morbidity and mortality 104. Holden CE, Puntis JW, Charlton CP, Booth IW. Nasogastric
after percutaneous endoscopic gastrostomy in children feeding at home: acceptability and safety. Arch Dis Child.
with neurological disability. J Gastroenterol Hepatol. 1991;66(1):148–151.
2006;21(4):734–738.

105. Del Buono R, Wenzl TG, Rawat D, Thomson M. Acid

and nonacid gastro-oesophageal reflux in neurologically
impaired children: investigation with the multiple intralu-
minal impedance procedure. J Pediatr Gastroenterol Nutr.
2006;43(3):331–335.
106. Leibold S, Eckmark E, Adams RC. Decision-making for a
successful bowel continence program. Eur J Pediatr Surg.
2000;10(Suppl. 1):26–30.
107. Isaacs D, Kilham HA, Somerville HM, O’Loughlin EV,
Tobin B. Nutrition in cerebral palsy. J Paediatr Child Health.
2004;40(5–6):308–310.

19
Eating Disorders
Christina Fitzgerald, MS, RD, LDN and Betsy Hjelmgren, MS, RD, LDN, CSP

Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 204 1. Discuss the basic macro- and micronutrient needs in
Classification and Diagnosis of Eating Disorders. . . . . . 205 the eating-disordered patient.
Physical Presentation 2. Summarize the rationale for providing oral nutri-
Etiology of Eating Disorders tion versus enteral nutrition or parenteral nutrition in
Nutrition in Eating Disorders. . . . . . . . . . . . . . . . . . . . . . . 206 patients with eating disorders.
Nutrition Requirements 3. Identify patients at risk for refeeding syndrome and
Laboratory Assessment identify key monitoring parameters in its prevention
Nutrition Support in Eating Disorders . . . . . . . . . . . . . . . 208 and treatment.
Oral Nutrition and Meal-Planning Guidelines
Enteral Nutrition Support and Route of Feeding Introduction
Parenteral Nutrition
Monitoring Nutrition Interventions
An eating disorder is an elusive disease that afflicts many
adolescents and young adults. It can be difficult to detect and
Refeeding Syndrome . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 209
Definition and Incidence
can go undiagnosed for extended periods while wreaking
Pathophysiology and Characteristics of Starvation and Refeeding havoc on the young growing body. Unfortunately, eating
Prevention and Therapy disorders, specifically anorexia nervosa, have the highest
premature fatality rate of all mental illnesses.1 In the United
States alone, more than 10 million females and 1 million
males are battling an eating disorder such as anorexia
nervosa or bulimia nervosa. Of those females afflicted,
approximately 5 million are American girls.2 However, this
disease is not specific to the female gender; approximately
10% of those afflicted are males. Once thought of as a
“white upper-class” disease, eating disorders are seen across
all cultures and all socioeconomic classes. Robinson et al
found that among the leanest 25% of sixth- and seventh-
grade girls, Hispanics and Asians reported significantly
more body dissatisfaction than did Caucasians. 3
This chapter reviews the classification, diagnosis, and
etiology of eating disorders; describes nutrition therapy and
monitoring of interventions for eating disorders; defines
and describes the pathogenesis of refeeding syndrome; and
discusses prevention and treatment of refeeding syndrome.
204
EATING DISORDERS 205
Classification and Diagnosis of Eating is the most common comorbid disease among persons with
Disorders anorexia nervosa7 and substance abuse prevalence is esti-
Anorexia nervosa, bulimia nervosa, binge-eating disorder, mated at 30% to 70% in persons with bulimia. 8 It is often
and eating disorder not otherwise specified are eating these psychiatric comorbidities or other medical problems,
disorders with the commonalities of extreme emotion and such as continued dizziness or fatigue, that are presented to
behaviors around food and body image. The American the physician prior to the eating disorder detection.
Psychiatric Association recommends using a multiaxial
system in assessing and diagnosing mental disorders and Physical Presentation
now lists the subcategories Anorexia Nervosa, Bulimia Physical presentation of a person with anorexia nervosa
Nervosa, Binge-Eating Disorder, and Eating Disorder Not includes lanugo-type hair, muscle wasting, dry skin,
Otherwise Specified in its Diagnostic and Statistical Manual cyanosis of extremities, bradycardia less than 60 beats/min,
of Mental Disorders (DSM) (Figures 19-1–19-4). These and cachexia. When anorexia develops in childhood, the
subcategories are diagnosed and classified on Axis 1 of the first clinical sign may be failure to make weight gains while
multiaxial system.4 Of note, amenorrhea (ie, the absence continuing to grow in height as opposed to documented
of at least 3 consecutive menstrual cycles) is one of the weight loss. Growth charts should be evaluated for typical
diagnostic criteria for anorexia nervosa listed in the DSM. growth patterns of the individual.9
However, this may not be useful in the assessment of adoles- Physical signs and symptoms of a person with bulimia
cent patients as healthy adolescent females may normally nervosa are more difficult to detect but may include parotid
have episodes of amenorrhea during the first 1 to 2 years gland enlargement, scarring of the hand used to stimulate
after the onset of menarche. 5 gag reflux (referred to as Russell’s sign), erosion of dental
Psychiatric comorbidities, such as obsessive-compul- enamel with increased dental caries, and sore red throat
sive disorder and affective disorder, are common and should
be treated alongside the eating disorder.6 Major depression
Figure 19-2 American Psychiatric Association Diagnostic Criteria for
307.51 Bulimia Nervosa
Figure 19-1 American Psychiatric Association Diagnostic Criteria for A. Recurrent episodes of binge eating. An episode of binge eating is
307.1 Anorexia Nervosa characterized by both of the following:
1. Eating, in a discrete period of time (ie, within any 2-hour period),
A. Refusal to maintain body weight at or above a minimally normal
an amount of food that is definitely larger than most people
weight for age and height (ie, weight loss leading to maintenance
would eat during a similar period of time and under similar
of body weight less than 85% of that expected; or failure to make
circumstances;
expected weight gain during period of growth, leading to body
weight less than 85% of that expected). 2. A sense of lack of control over eating during the episode (ie, a
feeling that one cannot stop eating or control what or how much
B. Intense fear of gaining weight or becoming fat, even though
one is eating).
underweight.
B. Recurrent inappropriate compensatory behavior in order to prevent
C. Disturbance in the way in which one’s body weight or shape is
weight gain, such as self-induced vomiting; misuse of laxatives,
experienced, undue influence of body weight or shape on self-
diuretics, enemas, or other medications; fasting; or excessive
evaluation, or denial of the seriousness of the current low body
exercise.
weight.
C. The binge eating and inappropriate compensatory behaviors both
D. In postmenarcheal females, amenorrhea, ie, the absence of at least
occur, on average, at least twice a week for 3 months.
three consecutive menstrual cycles. (A woman is considered to
have amenorrhea if her periods occur only following hormone, eg, D. Self-evaluation is unduly influenced by body shape and weight.
estrogen, administration.) E. The disturbance does not occur exclusively during episodes of
Restricting Type: During the current episode of anorexia nervosa, the anorexia nervosa.
person has not regularly engaged in binge-eating or purging behavior Purging Type: During the current episode of bulimia nervosa, the
(ie, self-induced vomiting or the misuse of laxatives, diuretics, or person has regularly engaged in self-induced vomiting or the misuse of
enemas). laxatives, diuretics, or enemas.
Binge-Eating/Purging Type: During the current episode of anorexia Nonpurging Type: During the current episode of bulimia nervosa, the
nervosa, the person has regularly engaged in binge-eating or purging person has used other inappropriate compensatory behaviors, such
behavior (ie, self-induced vomiting or the misuse of laxatives, diuretics, as fasting or excessive exercise, but has not regularly engaged in self-
or enemas). induced vomiting or the misuse of laxatives, diuretics, or enemas.
Reprinted with permission from: American Psychiatric Association. Diagnostic Reprinted with permission from: American Psychiatric Association. Diagnostic
and Statistical Manual of Mental Disorders. 4th ed. Washington, DC: American and Statistical Manual of Mental Disorders. 4th ed. Washington, DC: American
Psychiatric Association; 2000. Psychiatric Association; 2000.

secondary to excessive purging.10 Dependent on the degree Nutrition in Eating Disorders

of purging, and if any restriction is utilized, the patient with Although nutritional rehabilitation and weight stabilization
bulimia nervosa may meet all expected weight gains and are essential components in the treatment of and recovery
track normally along the growth chart percentiles. from eating disorders, research continues to be limited in
this population. The following recommendations should be
Etiology of Eating Disorders used as guidelines and not definitive treatment.
The etiology of eating disorders is complex but appears
to originate from not only predisposed genetic factors Nutrition Requirements
but also serotonin dysfunction and psychological factors
surrounding childhood abuse and/or trauma.11 A 17-year Macronutrients
longitudinal study of 800 children found that eating
conflicts, struggles with food, and unpleasant meals were Energy Requirements
additional risk factors for the development of an eating Initial energy requirements for anorexia nervosa are 30
disorder in this population.12 The role of heredity is still to 40 kcal/kg of current body weight.4 An elevated diet-
unclear, as twin studies, often utilized to differentiate induced thermogenesis (DIT) has been reported in anorexia
between genetic factors and environment in familial studies, nervosa.14 In patients with an elevated DIT or patients who
have reported mixed data, with some demonstrating a are extremely anxious, energy requirements may be as high
strong correlation while others little correlation.13 as 80 to 100 kcal/kg before weight gain can be achieved.4 If
higher energy needs are required in a patient with anorexia
Figure 19-3 Research Criteria for Binge-Eating Disorder nervosa due to poor weight gain, the patient should be eval-
uated for manipulation of intake. In patients with bulimia
A. Recurrent episodes of binge eating. An episode of binge eating is
characterized by both of the following: nervosa or binge-eating disorder, initial energy require-
1. Eating, in a discrete period of time (ie, within any 2-hour ments for weight maintenance may start at 1.2 to 1.3 ×
period), an amount of food that is definitely larger than most measured resting energy expenditure (REE) for sedentary
people would eat in a similar period of time under similar activity.15 It is recommended to avoid caloric levels that
circumstances;
promote weight loss until an eating pattern is stabilized,
2. A sense of lack of control over eating during the episode (ie, a
feeling that one cannot stop eating or control what or how much
because a restriction in calories in such a patient may trigger
one is eating). a binging episode.
B. The binge-eating episodes are associated with three (or more) of
the following:
1. Eating much more rapidly than normal, Figure 19-4 American Psychiatric Association Diagnostic Criteria for
2. Eating until feeling uncomfortably full, 307.50 Eating Disorder Not Otherwise Specified
3. Eating large amounts of food when not feeling physically hungry, A. For females, all of the criteria for anorexia nervosa are met except
4. Eating alone because of being embarrassed by how much one that the individual has regular menses.
is eating, B. All the criteria for anorexia nervosa are met except that, despite
5. Feeling disgusted with oneself, depressed, or very guilty after significant weight loss, the individual’s current weight is in the
overeating. normal range.
C. Marked distress regarding binge eating is present. C. All of the criteria for bulimia nervosa are met except that the binge
eating and inappropriate compensatory mechanisms occur at a
D. The binge eating occurs, on average, at least 2 days a week for frequency of less than twice a week or for duration of less than 3
6 months. months.
Note: The method of determining frequency differs from that used D. The regular use of inappropriate compensatory behavior by an
for bulimia nervosa; future research should address whether the individual of normal body weight after eating small amounts of food
preferred method of setting a frequency threshold is counting the (ie, self-induced vomiting after the consumption of two cookies).
number of days on which binges occur or counting the number of
episodes of binge eating. E. Repeatedly chewing and spitting out, but not swallowing, large
amounts of food.
E. The binge eating is not associated with the regular use of
inappropriate compensatory behaviors (ie, purging, fasting, F. Binge-eating disorder: recurrent episodes of binge eating in the
excessive exercise) and does not occur exclusively during the course absence of the regular use of inappropriate compensatory behaviors
of anorexia nervosa or bulimia nervosa. characteristic of bulimia nervosa.
Reprinted with permission from: American Psychiatric Association. Diagnostic Reprinted with permission from: American Psychiatric Association. Diagnostic
and Statistical Manual of Mental Disorders. 4th ed. Washington, DC: American and Statistical Manual of Mental Disorders. 4th ed. Washington, DC: American
Psychiatric Association; 2000. Psychiatric Association; 2000.

Protein Requirements anorectic patients with thiamin and magnesium in addi-

Recommended protein intake is the recommended dietary tion to addressing any other found deficiencies.17 At onset
allowance (RDA) in g/kg ideal body weight for age (0.8–1.5 of intervention, provide a 100% RDA multivitamin with
g/kg) or 15% to 20% of total calories from a high biologic minerals.15
value source.4,15
Laboratory Assessment
Fat Requirements A detailed laboratory assessment is recommended at time of
Recommended fat intake is 25% to 30% of total daily calo- initial assessment. Although a complete blood count (CBC)
ries from fat, with appropriate sources of essential fatty and chemistry profile is recommended, these traditional
acids.4,15 tests are typically normal and may underestimate the phys-
ical damage and degree of malnutrition. More targeted and
Micronutrients sensitive tests are recommended, including zinc, iron, preal-
A number of micronutrient deficiencies occur in patients bumin, transferrin, ferritin, 25-OH vitamin D, thiamin,
with eating disorders. In both anorexia nervosa and bulimia and complement 3 (C3) level.18 Refer to Figure 19-5 for a
nervosa, zinc deficiency is common and documented as complete recommendation of laboratory tests.
resultant from suboptimal intake attributed to severe Despite these normal CBC panels, elevated serum
caloric restriction, avoidance of red meat, and/or the adop- cholesterol and abnormal lipoprotein profiles are often
tion of an inadequate vegetarian lifestyle.16 Additionally, found in an anorectic patient regardless of consumption
riboflavin, thiamin, calcium, B-vitamin, and magnesium of extremely low-fat and low-cholesterol diets. Arden et al
deficiencies are well documented and are of concern in postulates that mild hepatic dysfunction, decreased bile
both anorexia nervosa and bulimia nervosa.11 It is recom- acid secretion, and/or hypothalamic dysfunction may
mended to routinely screen and subsequently supplement contribute to these abnormalities.19
Figure 19-5 Recommended Laboratory Tests
Standard
Complete Blood Count (CBC) with differential
Urinalysis
Complete Metabolic Profile: Sodium, Chloride, Potassium, Glucose, Blood Urea Nitrogen, Creatinine, Total Protein,
Albumin, Globulin, Calcium, Carbon Dioxide, AST, Alkaline Phosphates, Total Bilirubin
Serum magnesium
Thyroid Screen (T3, T4, TSH)
Electrocardiogram (ECG)
Special Circumstances
15% or more below ideal body weight (IBW)
Chest X-Ray
Complement 3 (C3)
24 Creatinine Clearance
Uric Acid
20% or more below IBW or any neurological sign
Brain Scan
20% or more below IBW or sign of mitral valve prolapse
Echocardiogram
30% or more below IBW
Skin Testing for Immune Functioning
Weight loss 15% or more below IBW lasting 6 months or longer at any time during course of eating disorder
Dual Energy X-Ray Absorptiometry (DEXA) to assess bone mineral density
Estradiol Level (or testosterone in males)
Adapted from http://www.nationaleatingdisorders.org/p.asp?WebPage_ID=758#Table1. Accessed January 2, 2009.

Copyright © 2008 National Eating Disorders Association. www.nationaleatingdisorders.org.

Nutrition Support in Eating Disorders easily purged.15 For the anorectic patient, several options are
appropriate: bolus feed appropriate supplemental calories
Oral Nutrition and Meal-Planning Guidelines only at mealtimes, bolus feed only uneaten calories to meet
In all eating disorders, the ultimate nutrition treatment goals mealtime goal, or nighttime continuous feed of uneaten or
include non-restrictive eating that incorporates variety and excessive calories.20
nutritional adequacy, and absence of purging behaviors.20 When EN is utilized, an isotonic, fiber-containing, poly-
In bulimia, purging efforts are utilized in attempts to lose meric formula is usually sufficient for nutritional repletion,
weight, and patients will often request assistance during unless impaired digestion or absorption indicates use of an
treatment in achieving this goal. For patients suffering from elemental- or peptide-based product. Due to the high risk
either bulimia or binge-eating disorder, although long- of refeeding syndrome (discussed below) in an anorectic
term weight loss may be reasonable and/or recommended, patient, the initial infusion should not exceed 25 to 50 mL/h
the immediate goal should be interruption of the binge or and should be gradually increased 10 to 25 mL every 8 to 24
binge-purge cycle with stabilization of weight.9 hours as tolerated until goal feeds are achieved.20
For all eating disorder types, plan 4 to 6 eating opportu- Manipulation behaviors may arise when utilizing EN
nities per day. Allow no more than 4 hours between eating in the eating-disordered individual. Precautions need to be
opportunities in order to prevent hypoglycemia, extreme taken. Sample behaviors used in tube feeding manipulation
hunger, and/or the temptation to binge.20 Each meal and include18:
snack should contain a balance of sufficient carbohydrates • lowering the delivery rate on the feeding pump;
to prevent craving, and adequate protein and fat to promote • using sharp objects to poke holes in the feeding tube;
satiety.9 • filing the tube to reduce thickness, then bending the
For patients with binge-eating disorder or bulimia, tube at that point to spill the feeding;
the initial meal plan should not include any foods that • removing the feeding bag from its hanging pole and
the patient is unwilling or unable to keep from vomiting. swinging it to create air pockets to clog the tube;
Provide support to the patient during and after meals while • purging through the surgical opening of a percutaneous
encouraging expression of feelings. Additionally, encourage endoscopic gastrostomy tube; and
the patient to remain out of the bathroom for up to an hour • placing the nasogastric tube in another place (in a plant,
after meal consumption.20 out the window, in the mattress).
Enteral Nutrition Support and Route of Feeding Parenteral Nutrition

The decision to initiate enteral nutrition (EN) in a person Parenteral nutrition (PN) is only indicated in cases of diges-
with an eating disorder is a complex one and should take tive inability as it leads to a continued loss of hunger cues in
into account not only the patient’s immediate physical the eating-disordered individual. 20 When PN is initiated in
health but also his or her psychological health. EN support is severely malnourished patients, caution needs to be taken
indicated if a patient is refusing any oral intake, rapid weight due to the possibility that refeeding syndrome might occur.
loss continues despite improved oral intake, or the patient Refer to the Refeeding Syndrome section in this chapter for
is hypermetabolic and unable to meet nutritional needs definitions and guidelines.
orally. When choosing a route for EN, the nasogastric route
is preferred for the relative ease of administration; however, Monitoring Nutrition Interventions
a nasojejunal placement may alleviate discomfort from The anthropometric status of patients with eating disorders
delayed gastric emptying.15 If long-term enteral support is should be assessed and monitored regularly. Rehydration
needed, it is recommended that the tube ending be placed and replenished glycogen stores contribute to weight gain
in the duodenum to avoid problems with gastric reflux and during the initial refeeding; thereafter, weight gain results
purging by the patient.18 from increased lean and fat stores.9 In hospitalized patients
When utilizing EN in an eating-disordered patient, it in whom weight restoration is a goal, 2 to 3 pounds per week
is encouraged to provide the supplementation in a manner is reasonable.9
that will continue to promote the person’s ability to identify The hospitalized individual should be weighed daily,
natural hunger cues. In a patient with bulimia nervosa, a gowned, preprandial and postvoid. Baseline height and
continuous drip tube feeding is often recommended because growth history should be obtained and monitored every
a bolus feeding may cause involuntary vomiting and is more 1 to 2 months in patients who still have growth potential.

Baseline anthropometric measurements (skinfolds, midarm fluid shifts from extracellular to intracellular spaces.21 In
circumference, and midarm muscle circumference) should addition, because electrolytes, especially phosphorus, play
be obtained at onset of intervention and monitored as medi- a major role in glucose metabolism, electrolyte demands are
cally indicated.9,15 diminished during ketosis and starvation.28
As nutrition is reintroduced to the body, a rapid spike
Refeeding Syndrome of insulin accompanies the introduction of carbohydrate,
which seems to be the driving force of refeeding syndrome.1
Definition and Incidence Insulin promotes the uptake of glucose, water, and elec-
Refeeding syndrome can be described as a cascade of trolytes by the cells, and thus glycogen, protein, and fat
potentially fatal complications caused by shifts in fluid synthesis resume. Water and sodium are retained causing
and electrolytes as nutrition is reintroduced into the body, extracellular fluid overload, which can lead to pulmonary
taxing wasted and weakened tissues and demanding more edema and cardiac decompensation.22 Hyperglycemia
nutrients than are readily available.21,22 It is manifested in may result from excess carbohydrate administration and
an assemblage of symptoms that result from rapidly and inadequate insulin output. Hyperglycemic complications
inappropriately refeeding (via oral, enteral, or parenteral include osmotic diuresis, dehydration, metabolic acidosis,
route) individuals who have been malnourished or starved and ketoacidosis.21 Anabolism is triggered by macronu-
for a period of time, usually exceeding 7 to 10 days. 23 trient intake and places demands on the body for a myriad
Other symptoms of refeeding syndrome include cardiac of other nutrients including phosphorus, potassium,
dysfunction, edema, and neurological changes.24 Hypo- magnesium, and water-soluble vitamins. These nutrients
phosphatemia is the hallmark clinical sign of refeeding are now in short supply due to their depletion during the
syndrome, but hypomagnesemia and hypokalemia are also prolonged period of fasting, and the body’s remaining
common indicators. Glucose intolerance and thiamin defi- stores are exhausted quickly.21 Thus, hypophosphatemia,
ciency are often present as well.25 hypokalemia, hypomagnesemia, and thiamin deficiency
The exact incidence of refeeding syndrome is unknown, may clinically present.
due in part to the lack of a universal definition 21 and also Phosphorous is involved in the intracellular processes
poor recognition of the condition. It is known that 30% to and structural integrity of all the cells.21 It is also required
38% of previously unfed patients receiving PN containing for the production of energy in the form of adenosine
phosphorus experience hypophosphatemia, 26 and 100% of triphosphate (ATP), and is a structural component of
these patients develop hypophosphatemia when no phos- 2,3-diphosphoglycerate (2,3-DPG).25 Hypophosphatemia
phorus has been added to the PN solution. It has also been may cause clinical symptoms when serum levels reach 1.5
documented that when patients were vigorously refed, mg/dL, and severe hypophosphatemia (≤ 1 mg/dL) can
80% experienced hypokalemia, hypomagnesemia, and/or have devastating effects on multiple systems.22 Serum phos-
hypophosphatemia.27 phorus levels typically reach a nadir around 2 to 3 days of
refeeding.1 Cardiovascularly, ATP depletion and cardiac
Pathophysiology and Characteristics of atrophy contribute to hypocontractility and ventricular
Starvation and Refeeding arrhythmia, which is complicated by volume overload.
In a normal, fed state, glucose and fatty acids are the preferred Skeletal muscle weakness and sarcolema disruption lead
energy substrates for the human body. During periods of to rhabdomyolysis. Myopathy causes difficulty with ambu-
starvation exceeding 3 to 5 days, the body shifts glucose lation and may additionally contribute to respiratory
metabolism to fat and protein metabolism and enters a state dysfunction due to accessory muscle and diaphragmatic
of ketosis. The brain switches from glucose to ketones as weakness/catabolism. Hypophosphatemia affects the
an energy source. The liver visceral protein stores and vital hemo-immunologic system by inducing bone marrow
organs, adipose tissue, and fluids also become depleted. The dysfunction, which can lead to decreased immune func-
wasting of muscle affects vital organ function, including tion evidenced by hemolytic anemia, thrombocytopenia,
both respiratory capacity and cardiac mass and output.21,24 hemolysis, and decreased oxygen delivery to peripheral
During starvation, the kidneys’ role is to decrease the tissue. Hypophosphatemia influences the nervous system
excretion of minerals as the body’s stores become depleted. via inadequate 2,3-DPG and/or ATP deficiency, which may
Serum electrolyte levels are maintained by decreased excre- contribute to the incidence of delirium, coma, hallucina-
tion through the kidneys and by volume constriction as tions, seizures, tetany, weakness, and parasthesias. 25

Hypokalemia may result as anabolism resumes and 70% ideal body weight are at the greatest risk.22 Catego-
cells take up potassium during fluid and electrolyte shifts. ries of patients who may meet these criteria include those
Serum potassium levels < 2.5 mg/dL may cause devastating with anorexia nervosa, alcoholism, cancer, uncontrolled
paralysis, respiratory dysfunction, rhabdomyolysis, muscle diabetes, marasmus, malabsorptive syndrome (eg, pancrea-
necrosis, and changes in myocardial contraction and signal titis, cystic fibrosis, short bowel), prolonged fasting, morbid
conduction.22 Serum magnesium levels < 1 mg/dL can obesity with profound weight loss, prolonged antacid use
cause electrocardiographic changes, tetany, convulsions, (due to binding of phosphorus), and long-term diuretic use
and seizures.29 Patients experiencing refeeding syndrome (due to electrolyte losses), as well as postoperative patients,
may present with hypophosphatemia, hypokalemia, and/or the elderly, and patients allowed nothing by mouth for
hypomagnesemia, thus illustrating the importance of close greater than 5 to 7 days.21
electrolyte monitoring. If a patient meets the preceding high-risk criteria
All vitamins may be deficient as a result of long-term for refeeding syndrome, there are several acceptable
inadequate nutritional intake. However, due to its role in approaches for preventing or treating refeeding (Table
carbohydrate metabolism, thiamin is of particular impor- 19-1). Importantly, baseline electrolytes (including potas-
tance. Thiamin (vitamin B1) is a structural component of sium, phosphorus, magnesium, and calcium) should be
nervous system membranes30 and thus its deficiency may obtained and corrected if low prior to the initiation of feeds.1
present with symptoms of beriberi such as parasthesia, Electrolyte monitoring should continue 1 to 4 times per day
hypoesthesia, anesthesia, and lower extremity weakness,4 or depending upon the severity of malnutrition, for the first 3
as Wernicke’s encephalopathy (ocular abnormalities, ataxia, days.24 During this time, calories may be introduced at 50%
confusion, hypothermia, coma) or Korsakoff’s psychosis of goal, not to exceed 20 to 25 kcal/kg/d.1,21,22,24 Macro-
(retrograde and anterograde amnesia, confabulation). 31 nutrient distribution should limit carbohydrate intake to
2 to 3 g/kg/d based on actual body weight. No restriction
Prevention and Therapy is necessary for protein or fat intake, and common recom-
Prevention of refeeding syndrome is the most effective mendations for each are 1 to 1.5 g/kg/d1,22,24 and 1 g/kg/d,
factor in its management, therefore an awareness and ability respectively.1 Fluid should be restricted to 800 to 1000
to identify high-risk patients is key.22 Patients with a weight mL/d due to the potential risk of fluid overload and cardiac
loss of ≥ 10% within 2 to 3 months or those at or below decompensation.22,24
TABLE 19-1 Timeline for Prevention and Therapy of Refeeding Syndrome1,21,22,24,25,32,33

Days 1–3 Days 4–7 Days 8–14
Calories 50% of goal, or 15–20 kcal/kg/d Advance by 200–300 kcal if Advance every 3 days by 200–300
electrolytes stable kcal if electrolytes remain stable
Carbohydrate 2–3 g/kg/d Advance to meet daily calorie Advance to meet daily calorie
adjustments adjustments
Protein 1–1.5 g/kg/d 1–1.5 g/kg/d 1–1.5 g/kg/d
Fat 1 g/kg/d 1 g/kg/d 1 g/kg/d
Fluid 800–1000 mL/d Advance with calories if electrolytes Advance with calories if electrolytes
stable and no clinical signs of fluid stable and no clinical signs of fluid
overload overload
Phosphorus 0.3–0.6 mmol/kg/d for normal 0.3–0.6 mmol/kg/d. Continue 0.3–0.6 mmol/kg/d. Continue
serum levels. Correct low serum to correct low serum levels as to correct low serum levels as
levels aggressively with 9–18 mmol necessary necessary
over 2–12 hours as indicated
Potassium 2–4 mmol/kg/d. Correct low 2–4 mmol/kg/d. Correct low 2–4 mmol/kg/d. Correct low
serum levels as necessary serum levels as necessary serum levels as necessary
Magnesium 0.2 mmol/kg/d. Correct 0.2 mmol/kg/d if stable. 0.25 0.2 mmol/kg/d
moderately low serum levels with mmol/kg/d for patients who have
0.5 mmol/kg x 24 hours. Correct been hypomagnesemic
severely low levels with 24 mmol
over 6 hours
Thiamin 200–300 mg daily 200–300 mg daily 200–300 mg daily until day 10
Other vitamins/minerals Multivitamin/mineral supplement Multivitamin/mineral supplement Multivitamin/mineral supplement
daily daily daily

During these first few days of renourishment, electro- 2. In an eating-disordered individual, parenteral nutrition
lytes, if low, should be corrected aggressively. Potassium is only indicated
phosphate preferably, or sodium phosphate in the presence A. If the person is unwilling to consume food orally
of normal serum potassium, can be given intravenously for B. In cases of digestive inability
moderate to severe hypophosphatemia.25 Different refer- C. If the person is < 75% of ideal body weight
ences recommend infusing 9 to 18 mmol over anywhere D. If the person is manipulating the enteral tube
from 2 to 12 hours.21,25,32 For orally fed patients with mild 3. Persons at greatest risk for refeeding syndrome
to moderate hypophosphatemia, cow’s milk is an excellent include:
source of both phosphorus and potassium,25 and can be used A. Weight loss ≥ 10% within 2 to 3 months or those at
to treat mild electrolyte derangements. Oral sodium phos- or below 70% ideal body weight
phate can also be used, at 500 mg 4 times per day until serum B. Weight loss ≥ 10% within 6 to 8 months or those at
phosphorus is stable, then decreased to 250 mg 3 times per or below 70% ideal body weight
day for maintenance.22 Mild to moderate hypomagnesemia C. Weight loss ≥ 7% within 2 to 3 months or those at or
can be treated with an initial dose of 0.5 mmol/kg over a below 75% ideal body weight
24-hour infusion, then maintained at 0.25 mmol/kg/d for D. Weight loss ≥ 7% within 2 to 3 months or those at or
the next 5 days to maintain serum levels.21 For severe hypo- below 70% ideal body weight
magnesemia, infuse 24 mmol over 6 hours, then follow with
0.25 mmol/kg/d for the next 5 days as above.21 See p. 487 for answers.
In addition to the attention paid to macronutrients and
electrolytes, patients at risk of refeeding should receive a References
daily multivitamin/mineral supplement. Any signs or symp- 1. Skipper A, ed. Dietitian’s Handbook of Enteral and Parenteral
toms of thiamin deficiency can be treated with 200 to 300 Nutrition. 2nd ed. Gaithersburg, MD: American Society for
Parenteral and Enteral Nutrition; 1998.
mg of oral thiamin daily for 10 days to correct deficiency. 21 2. Crowther JH, Wolf EM, Sherwook N. Epidemiology of
After electrolytes have stabilized and the patient has bulimia nervosa. In: Crowther M, Tannenbaum DL, Hobfoll
received ≥ 72 hours of nutrition at 50% of goal, calories can SE, Stephens MAP, eds. The Etiology of Bulimia Nervosa: The
gradually be increased every 3 days by 200 to 300 kcal. 22,24,33 Individual and Familial Context. Washington, DC: Taylor +
Continue to monitor and correct electrolytes as feedings Francis; 1992:1–26.
3. Robinson T, Killen J, Litt I, et al. Ethnicity and body dissat-
progress for the duration of the first 2 weeks of feeding. 21
isfaction: are Hispanic and Asian girls at increased risk for
With awareness and proper monitoring, refeeding eating disorders? J Adolesc Health. 1996;19(6):384–393.
syndrome can be prevented or managed appropriately to 4. American Psychiatric Association. Practice Guideline for the
prevent serious complications and the potential of death. Treatment of Patients with Eating Disorders. 2nd ed. Wash-
Monitoring and correction of electrolytes, supplemen- ington, DC: APA Press; 2000b.
tation of nutrients, and conservative administration of 5. Fischer M, Golden NH, Katzman DK, et al. Eating disor-
ders in adolescents: a background paper. J Adolesc Health.
carbohydrate and fluid can save lives of those at highest risk 1995;16:420–437.
for refeeding. 6. Carney CP, Andersen AE. Eating disorders. Guide to medical
evaluation and complications. Psychiatr Clin North Am.
1996;19:657–679.
Test Your Knowledge Questions 7. Herzog DB, Nussbaum KM, Marmor AK. Comorbidity
and outcome in eating disorders. Psychiatr Clin North Am.
1. The following are common physical signs and symp-
1996;19:843–859.
toms of anorexia nervosa: 8. Vastag B. What’s the connection? No easy answers for
A. Lanugo-type hair, cyanosis of the extremities, and people with eating disorders and drug abuse. JAMA.
erosion of the dental enamel 2001;285:1006–1007.
B. Cyanosis of the extremities, erosion of the dental 9. Mahan LK, Escott-Stump S. Krause’s Food, Nutrition, & Diet
enamel, and Russell’s sign Therapy. 11th ed. Philadelphia: WB Saunders Co; 2004.
10. Russell GFM. The changing nature of anorexia nervosa. J
C. Cachexia, cyanosis of the extremities, and muscle Psychiatr Res. 1985;19:101–109.
wasting 11. Patrick L. Eating disorders: a review of the literature with
D. Cachexia, Russell’s sign, and sore red throat emphasis on medical complications and clinical nutrition —
Eating Disorders. Alternative Med Rev. FindArticles.com Web
site. http://findarticles.com/p/articles/mi_m0FDN/is_3_7/
ai_88823869/pg_3/ Accessed January 3, 2009.

12. Kotler LA, Cohen P, Davies M, Pine DS, Walsh BT. Longi- 22. Tresley J, Sheean PM. Refeeding syndrome: recognition
tudinal relationships between childhood, adolescent, and is the key to prevention and management. J Am Diet Assoc.
adult eating disorders. J Am Acad Child Adolesc Psychiatry. 2008;108:2105–2108.
2001;40(12):1434–1440. 23. Lagua RT, Claudio VS. Nutrition and Diet Therapy Reference
13. Fairburn CG, Cowen PJ, Harrison PJ. Twin studies Dictionary. 4th ed. New York, NY: Chapman and Hall; 1996.
and the etiology of eating disorders. Int J Eat Disord. 24. McCray S, Walker S, Parrish CR. Much ado about refeeding.
1999;26:349–358. Practical Gastroenterology. 2005;23:26–44.
14. de Zwaan M, Aslam Z, Mitchell JE. Research on energy 25. Marinella MA. The refeeding syndrome and hypophos-
expenditure in individuals with eating disorders: a review. Int phatemia. Nutr Rev. 2003;61:320–323.
J Eating Disord. 2002;32:127–134. 26. Sacks GS, Walker J, Dickerson RN, et al. Observations of
15. The Royal College of Psychiatrists. Guidelines for the nutri- hypophosphatemia and its management in nutrition support.
tional management of anorexia nervosa. http://www.rcpsych. Nutr Clin Pract. 1994;9:105–108.
ac.uk/files/pdfversion/cr130.pdf. Accessed December 15, 27. Yantis M, Velander R. How to recognize and respond to
2008. refeeding syndrome. Nursing. 2008;38:34–39.
16. Bakan R, Birmingman CL, Aeberhardt L, Goldner EM. 28. Brody T. Nutritional Biochemistry. San Diego, CA: Academic
Dietary zinc intake of vegetarian and nonvegetarian patients Press; 1994.
with anorexia nervosa. Int J Eating Disord. 1993;13:229–233. 29. Kraft MD, Btaiche IF, Sacks GS. Review of the refeeding
17. Winston AP, Jamieson CP, Madira W, et al. Prevalence of syndrome. Nutr Clin Prac. 2005;20:625–633.
thiamin deficiency in anorexia nervosa. Int J Eat Disord. 30. Itokaiva Y, Schulz RA, Cooper JR. Thiamine in nerve
2000;28:451–454. membranes. Biochem Biophys Acta. 1972;266:293–299.
18. Woosley M. Eating Disorders: A Clinical Guide to Counseling 31. Reuler JB, Girard DE, Cooney TG. Wernicke’s encephalop-
and Treatment. Chicago, IL: American Dietetic Association; athy. N Engl J Med. 1985;312:1035–1039.
2002. 32. Dwyer K, Barone JE, Rogers JF. Severe hypophosphatemia in
19. Arden MR, Weiselberg EC, Nussbaum MP, et al. Effect of postoperative patients. Nutr Clin Pract. 1992;7:279–283.
weight restoration on the dyslipoproteinemia of anorexia 33. Klein CJ, Stanek GS, Wiles CE. Overfeeding macronutrients
nervosa. J Adolesc Health. 1990;11:199–202. to critically ill adults — metabolic complications. J Am Diet
20. Setnick JS. The Eating Disorders Clinical Pocket Guide: Quick Assoc. 1998;98:795–806.
Reference for Healthcare Professionals. Snack Time Press;
2005.
21. Mehanna HM, Moledina J, Travis J. Refeeding syndrome:
What it is, and how to prevent and treat it. BMJ.
2008;336:1495–1498.

20
Food Allergies
Mary Beth Feuling, MS, RD, CD, CNSD, Michael B. Levy, MD, and Praveen S. Goday, MBBS, CNSP

Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 213 1. Understand the epidemiology, pathophysiology,
Definitions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 213 clinical presentation, and recognition of pediatric food
allergies.
Epidemiology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 214
2. Describe the nutrition assessment of children with food
Pathophysiology. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 215
allergies.
Major Food Allergens. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 215 3. Summarize the nutrition management of children with
Clinical Presentation. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 215 food allergies.
IgE-Mediated Diseases 4. Understand the food and non-food allergy issues that
Mixed IgE and Non-IgE Mediated Diseases
may impact the provision of nutrition support.
Non-IgE Mediated Disease
Allergy Testing . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 216 Introduction
Management. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 216 Adverse reactions to foods are a growing public health
Clinical and Laboratory Assessment
concern in the Western world. Food allergies are a greater
Nutrition Intervention
Nutritionally Complete Formulas problem in children than in adults, with significant food
Milk Substitutes allergies being associated with poorer nutrition outcomes
Dietary Allowance Versus Dietary Restrictions in children. This chapter discusses the epidemiology,
Micronutrient Supplementation . . . . . . . . . . . . . . . . . . . . 221 pathophysiology, clinical presentation, management, and
Two Special Scenarios prognosis of children with food allergies.
Prognosis and Follow-Up
Food Allergies and Nutrition Support. . . . . . . . . . . . . . . . 223 Definitions
Enteral Nutrition Several terms may be used when defining adverse reac-
Parenteral Nutrition tions to foods. An abnormal response to a food may include
“allergy,” “hypersensitivity,” or “intolerance.” Tolerance
usually refers to the ability to consume a food that may have
the potential for allergy or a food that previously caused
allergy and is now consumed without sequelae.
Adverse reactions to foods may occur within a spec-
trum of reactions ranging from immunoglobulin E (IgE)
to non-IgE mechanisms. Generally speaking, allergy or
hypersensitivity refers to IgE-mediated events and intoler-
ance refers to non-IgE events. Other important definitions
that will be used in this chapter are outlined in Table 20-1.
213
Table 20-1 Definitions of Common Terms That Are Frequently Used in Association with Food Allergies
Term Definition
Adverse food reaction Any undesired response to a food regardless of mechanism.
Allergen Substance foreign to the body that, on interaction with the immune system, causes an allergic reaction.
Anaphylaxis An acute, often severe, and sometimes fatal immune response that may affect one or more organ systems.
Antibodies Immunoglobulins produced in response to an antigen or allergen.
Antigen Any substance (as a toxin or enzyme) that stimulates an immune response in the body (especially the production of
antibodies).
Atopic dermatitis (eczema) A disease characterized by chronic inflammation of the skin which is atopic, hereditary, and non-contagious.
Atopy Tendency toward the development of allergic diseases, determined genetically.
Elimination diet An eating plan that omits one or more foods suspected to cause an adverse food reaction.
Food allergy An adverse food reaction that is mediated by an immunologic mechanism; the reaction occurs consistently after
(hypersensitivity) consumption of a particular food and causes functional changes in target organs; IgE-mediated food hypersensitivity,
gluten sensitivity.
Food challenge Administration of a food in increasing amounts performed in order to establish whether a patient is orally tolerant. This
may be performed in an open, single-blind, or double-blind fashion.
Food and symptom diary A subjective tool for recording food and drink consumed and onset, intensity, and duration of symptoms.
Food intolerance An adverse reaction to a food caused by toxic, pharmacologic, metabolic, or idiosyncratic reactions to the food or
chemical substances in the food.
Mast cells Tissue cells that release histamine and other mediators that cause allergic symptoms.
Skin prick test A test in which an antigen is applied directly to the skin and is pricked with a specifically designed device. The localized
histamine and mediator release correlates to the presence of specific IgE.
Tolerance Ability to consume a food that may have the potential for allergy or a food that previously caused allergy and is now
consumed without sequelae.
For many clinicians, defining a food reaction as “IgE-medi- Gastrointestinal diseases related to foods also may be
ated” or “non-IgE mediated” has great utility. IgE reactions caused by IgE and non-IgE mechanisms. Some diseases
have been well understood and chemically described as a such as eosinophilic esophagitis may have both an IgE and
cascade of events which involves a process that results from a non-IgE component. These diseases are characterized in
mast cell or basophil degranulation at mucosal surfaces Table 20-2.
or the skin. Because IgE can be quantitatively measured,
levels of food-specific IgE may aid in the diagnosis of IgE- Epidemiology
mediated food allergy and serial food-specific IgE levels Adverse reactions to foods have been reported in up to
may be followed to help determine the development of 15% to 20% of the population with the highest prevalence
clinical tolerance. in infancy and childhood. In 2007, the Centers for Disease
Non-IgE food intolerance may include immunologic Control and Prevention (CDC) reported that an estimated
and non-immunologic reactions due to the effects of other 3 million children under age 18 years (3.9%) had a reported
components within food (eg, lactose, seafood toxins, or food allergy. Higher rates were seen in children under age
naturally occurring pharmacologically active compounds 5, as compared with children 5 to 17 years of age with boys
such as tyramine). These substances may cause an adverse and girls showing similar rates of food allergy. Interestingly,
reaction, but are differentiated from true food allergy Hispanic children had lower rates than non-Hispanic black
because they do not involve the IgE cascade. or non-Hispanic white children.1
Table 20-2 Clinical Food Allergy Syndromes Associated with IgE or Non-IgE Mechanisms
IgE-Mediated Syndromes Mixed IgE & Non-IgE-Mediated Syndromes Non-IgE-Mediated Syndromes
Oral allergy syndrome Eosinophilic esophagitis Protein-induced enterocolitis
Anaphylaxis Eosinophilic gastritis Protein-induced enteropathy
Urticaria Eosinophilic gastroenteritis Food protein-induced enterocolitis syndrome (FPIES)
Angioedema Atopic dermatitis Dermatitis herpetiformis, gluten enteropathy

FOOD ALLERGIES 215
There has been a significant rise in atopic conditions ingestion, inhalation of airborne residue (eg, steam droplets
in westernized countries over the past 20 years. Results carrying antigen), or by skin contact. The allergenic prop-
from the third National Health and Nutrition Examination erties of foods may be affected by product processing (eg,
Survey (NHANES III), which measured the prevalence of heating or enzymatic digestion), which may affect changes
positive skin prick test responses to common allergens in in the antigenic epitope conformation. This may render a
the U.S. population from 1988–1994, showed a significant food more or less allergenic. The allergen threshold dose,
rise in allergy skin prick test reactivity from the NHANES which is the dose that triggers a systemic allergic reaction
II study of 1976–1980.2 In 2007, the reported food allergy in the host, involves many factors and is an area of current
rate among all children younger than 18 years was 18% research interest.
higher than in 1997. During the 10-year period of 1997 to IgE-mediated degranulation of effector cells occurs
2006, food allergy rates increased significantly among both after the food allergen contacts the food-specific IgE anti-
preschoolers and older children. In addition, from 2004 to bodies. Cross-linking of the IgE antibodies present on the
2006, there were approximately 9,500 hospital discharges surface of these cells results in mediator release of hista-
per year with a diagnosis related to food allergy among chil- mine, leukotrienes, and prostaglandins. These mediators
dren under age 18 years.1 cause the clinical manifestations of immediate hypersensi-
Most studies suggest that 6% to 8% of the pediatric tivity reactions including pruritus, vasodilatation, smooth
population and up to 1% to 3% of adults may have true food muscle contraction, mucus production, and inflammatory
allergy based on skin prick tests. The true prevalence in the cell recruitment to tissues.6
population is probably lower because of false-positive skin
prick tests and this fact has also been noted using random Major Food Allergens
telephone surveys. 3 Sicherer et al determined the preva- Almost every major food allergen identified is a protein or
lence of peanut and tree nut allergy to be 0.7% adults and glycoprotein. They tend to resist denaturation by heat or acid
0.4% children in a New York telephone survey. 3,4 and may be more or less common depending on the society
Children with food allergies are more likely to have or ethnicity of the population observed. In the United States,
other allergic conditions including asthma and atopic milk, soy, egg, wheat, peanut, tree nut, fish, and seafood are
dermatitis when compared to children without food aller- the most common allergens noted. However, other legumes,
gies. Asthma has been reported in 29% of children with food sesame, poppy seed, sunflower seed, pine nuts, and spices
allergies (12% in children without food allergies); respira- are allergens of increasing importance.
tory allergy is noted in over 30% versus 9% without food
allergies while eczema is seen in 27% as compared with 8% Clinical Presentation
of children without food allergies.2 Patients with a peanut
allergy have asthma and atopic dermatitis prevalence rates IgE-Mediated Diseases
of 46% and 50%, respectively. 5 The major IgE-mediated allergic diseases are oral allergy
syndrome, anaphylaxis, urticaria, and angioedema.
Pathophysiology The pollen-associated oral allergy syndrome presents
The production of IgE antibody may develop in the geneti- with pruritus of the lips, palate, tongue, and oropharynx
cally predisposed individual through mechanisms that following oral mucosal contact with fresh fruits and vege-
involve multiple factors. Once allergen-specific IgE is tables. The reaction usually does not occur following a
produced, binding to the high-affinity IgE receptor which cooking process because the cross-reactive allergen is very
is present on mast cells and basophils occurs. Low-affinity heat sensitive. These symptoms usually resolve without
IgE receptors are present on eosinophils, monocytes, and treatment and generally do not progress to cause more
macrophages.6 systemic involvement. Cross-reactivity between plant
There are multiple host, antigen, and allergen factors pollens and fruits is responsible for the clinical syndrome.
that may be involved in the IgE-sensitization cascade which Specifically, patients with ragweed sensitivity may have
may result in the subsequent development of clinical allergy. these symptoms after ingesting watermelon, cantaloupe,
These factors include the genetics of the host, immunologic banana, or honeydew while patients sensitive to birch
competence at the mucosal level, and allergen presenta- pollen may notice symptoms with apple, pear, celery,
tion by intact antigen-processing cells, as well as the route carrot, or peach.
of exposure to the allergen. Sensitization may occur via Food-induced anaphylaxis is the most severe form of

immediate hypersensitivity reaction. Symptoms may include on the clinical history and presentation, and removal of the
hypotension, urticaria, angioedema, respiratory compromise offending food serves as a simple and effective therapy. The
including laryngeal edema, and gastrointestinal symptoms age at which oral tolerance develops varies.
of pain, vomiting, and diarrhea; although, food-induced
anaphylaxis can occur without any skin manifestations. Allergy Testing
Near-fatal and fatal reactions often occur in the teenage to Allergy skin prick testing is commonly used by the prac-
35-year age range and are associated with a patient history of ticing allergist-immunologist to determine the presence
asthma, an accidental ingestion of a known allergen, and the of IgE to specific foods. Clinical correlation of the patient
delayed administration of epinephrine. The foods implicated history to the testing results is important. The skin prick
are usually peanut, tree nut, or seafood.7 technique is highly reproducible and extracts for these
tests are commercially available for hundreds of airborne
Mixed IgE and Non-IgE Mediated Diseases and food allergens. These tests are performed by applying
The gastrointestinal eosinophilic disorders listed in Table the extracts by a prick or puncture technique to the palmar
20-2 have features that may best be described as mixed surface of the forearm or upper back. The allergy prick test
IgE and non-IgE disorders. There may be evidence of IgE is actually a localized mediator-release phenomenon which
present (eg, positive skin prick tests or serologic in vitro occurs following allergen presentation to skin mast cells.
IgE to the offending food) but other mechanisms may be The reaction is a nearly immediate wheal and flare reac-
involved. These disorders are characterized by eosinophilic tion characteristic of IgE-mediated allergy. The test is read
infiltration of the esophageal, gastric, or intestinal mucosa. within 20 minutes and correlates closely with the presence
These patients often present with vomiting, abdominal of specific IgE to the suspected allergen. Positive tests indi-
pain, weight loss, or failure to thrive. Diagnosis is confirmed cate the presence of IgE but not clinical reactivity with an
with endoscopic examination and biopsy. Eosinophilic estimated false positive rate of approximately 50%. A nega-
esophagitis is discussed later in this chapter. tive test has high negative predicted value of nearly 95%,
thus excluding the role of IgE.13
Non-IgE Mediated Disease In-vitro radioallergosorbent tests (RAST) are blood
Efforts to define the mechanisms underlying the non-IgE tests that are available for the determination of serum-
mediated diseases listed in Table 20-2 have shown varying specific IgE with close correlation to skin prick testing
results. These conditions are thought to be caused by other results. The Pharmacia ImmunoCAP™ system has been
immunologic mechanisms not involving IgE. Typical studied with food challenge results showing a greater than
symptoms may include recurrent vomiting or diarrhea. In 95% predictive value for reactions to peanut, egg, and milk.
infancy, this is most commonly related to cow’s milk or soy There are a small number of false negative ImmunoCAP
protein. This condition is discussed in detail below. tests for peanuts. The established values can be utilized by
Food protein-induced enterocolitis syndrome clinicians to determine when a food challenge may be safe
(FPIES) is classified as a non-IgE mediated allergic disorder, to perform in the patient with IgE-mediated food allergy.14
triggered by the ingestion of certain food proteins.8 Children
usually present at less than 12 months of age with vomiting Management
and/or diarrhea within hours of ingestion of the causative There is currently no cure available for the food allergic
food. The symptoms should mimic IgE-mediated anaphy- individual. Strict avoidance of the allergy-causing food is
laxis, however the clinical picture lacks the usual cutaneous the only way to prevent a reaction. Future treatment hori-
signs of urticaria, angioedema, or respiratory compromise. zons may include anti-IgE monoclonal antibody which has
Some children present in a moribund state, with shock and already been trialed in peanut allergy, as well as newer forms
metabolic acidosis.9 Typically, the offending food is either of allergen immunotherapy.15 Trials in oral desensitization
cow’s milk or soy10,11 although meats, vegetables, and grains have been recently published and have shown efficacy in
have also been implicated.9 Tests for food-specific IgE by inducing tolerance.16
either skin prick testing or serologic in-vitro methods are Exclusion of foods may lead to nutrition problems that
negative.12 Awareness of the entity is important as the clin- require the expertise of a qualified dietitian. All patients
ical presentation can be confused with other life-threatening with anaphylaxis to foods (or other allergens) and patients
conditions. Multiple presentations before the true diagnosis with severe food allergies should be educated regarding the
is established are the norm. Early diagnosis should be based use of injectable epinephrine, which may be lifesaving in the

FOOD ALLERGIES 217
event of accidental exposure. Practically, all children with disorders. There should be ongoing care by both the allergist
multiple food allergies should be co-managed by an allergist who periodically determines whether the child has developed
and a dietitian. tolerance to any of the offending foods and the dietitian who
Because avoidance is the only proven treatment,17 chil- continues to monitor the nutrition status and growth of the
dren with food allergies need to avoid the foods to which they child. An algorithm for the management of the food-allergic
are allergic. The goals of the dietitian are twofold: to provide child is proposed in Figure 20-1.
families and patients with guidelines, education, and sugges-
tions for avoiding the allergenic foods and to monitor the Nutrition Assessment
child to ensure a nutritionally adequate diet that will promote Restriction of a child’s diet due to the diagnosis of food aller-
appropriate weight gain and growth. There must be a multi- gies may have a severe impact on his or her nutrition intake.
disciplinary approach that is adopted in conjunction with the This section provides a practical approach to identifying the
allergist with accurate diagnosis of causative foods, assess- risk factors that can lead to nutrition deficiencies, undernu-
ment of nutrition status, institution of a diet that eliminates trition, and poor growth while providing guidelines for a
the offending foods (elimination diet), prevention of adverse comprehensive nutrition assessment.
reactions, development of proper emergency treatment with Because strict avoidance of the causative food is neces-
an “action plan” in place, and treatment of associated atopic sary, it is critical to clearly define the avoidance list. The
Figure 20-1: Algorithm for the Evaluation of Suspected Food Reactions

nutrition risk increases as the number of foods avoided requirements for healthy children. Occasionally they will
increases. This compounds the challenge for providing a require increased caloric intake to provide catch-up growth
nutritionally complete diet. Any additional problems asso- due to poor growth often associated with allergen restric-
ciated with feeding further compound the risk. It is crucial tion. In addition, children with moderate to severe atopic
to collaborate with the allergist and the family to clearly dermatitis may have higher caloric and protein needs based
define the foods to be avoided and prevent any unnecessary on the degree of skin involvement. The more medically
restrictions. The degree of nutrition risk can be ascertained complex allergic child may have other nutrition needs due to
by methods outlined in Table 20-3. his or her other medical diagnoses and these are discussed
elsewhere in this book.
Table 20-3 Questions That Need To Be Asked To Determine the Degree of
Nutrition Risk in Children with Food Allergies Clinical and Laboratory Assessment
How many foods need to be avoided? Nutrient intake and growth are affected in children with
Risk increases with more foods being/needing to be avoided food allergies. Children with greater than 2 food allergies
What is the impact on nutrients? have a lower height, weight, and body mass index (BMI)
Risk increases with more of the following nutrients being impacted than those with 1 food allergy.19 Diagnosis of food aller-
or fewer nutrients being severely impacted
Calories gies often results in poor growth due to lack of caregiver
Protein knowledge, inadequate intake due to lack of guidance for
Fat substitutions to meet nutrition needs, and increased anxiety
Micronutrients
associated with feeding. Failure to achieve normal growth
Are there other concerns about food intake?
rates or growth velocity definitely suggests the need for
Risk increases with other medical and psychological diagnoses
affecting intake
medical nutrition therapy but a multidisciplinary approach
Swallowing/chewing difficulties involving a dietitian at the time of diagnosis of food allergy
Psychological diagnoses affecting intake may be able to prevent or attenuate problems associated with
Feeding disorder growth. Accurate anthropometric data and use of growth
charts is critical to the evaluation of these children.
When a diagnosis of food allergy has been made, Based on the diet and feeding history, the clinician
medical nutrition therapy with scheduled follow-up visits must review the risk of micronutrient deficiency. Table 20-5
can provide a way to monitor the overall health effects of summarizes the micronutrients provided by the top 8 aller-
food elimination. Identifying individuals at risk may protect gens and provides the most common food alternatives that
and possibly improve the patient’s nutrition and overall can be used when these foods need to be avoided.
health status. Medical nutrition therapy with appropriate Many children with multiple food allergies are at high
food substitution(s) provides the tools necessary, giving the risk for inadequate essential amino acids and essential fatty
food-allergic patient the specific focus needed for improved acids. Refer to Chapter 3 (Carbohydrates) and Chapter 4
nutrition self-care and food allergen avoidance.18 (Fats) for a complete discussion of the goals for the pediatric
Table 20-4 provides a case scenario where 3 toddler population. Often protein hydrolysate-based and/or amino
diets are presented. The first diet is a typical unrestricted acid-based formulas can be used to supplement the diet to
diet. Once the toddler is diagnosed with food allergies to meet these nutrition needs. Patients who present after being
milk, egg, and peanut, the second diet that needs to be on prolonged significantly restricted diets without concom-
followed puts him at a high risk for malnutrition and micro- itant multivitamin-multimineral use and patients who
nutrient deficiencies. The third diet provides the vital food present with significant malnutrition should be considered
substitutions (for the foods that the child must avoid) to for laboratory tests of micronutrient adequacy. The clinical
ensure adequate nutrition. scenario should guide which laboratory tests are obtained
Nutrient intake needs change over time throughout (eg, a vegetarian child who is sustained on rice milk should
the life cycle. This includes all of the macronutrient, microbe tested for anemia, zinc deficiency, essential fatty acid
nutrient, and fluid needs, all of which play a key role in a deficiency, and vitamin D deficiency). Most patients in
developing child. These intake guidelines can be found the United States with minimal dietary restrictions can be
in other chapters of this book. Nutrient requirements for managed through judicious use of a multivitamin-multi-
infants and children with food allergies are the same as the mineral supplement and without laboratory testing.

FOOD ALLERGIES 219
Table 20-4 Case Scenario

Diet 1 Diet 2 Diet 3
Breakfast Lunch Dinner Breakfast Lunch Dinner Breakfast Lunch Dinner
Whole milk Whole milk Whole milk Whole milk Whole milk Whole milk Enriched Enriched Enriched
soy milk soy milk soy milk
Cereal Peanut Meatloaf Cereal Peanut Meatloaf Cereal Soynut butter Milk-free,
butter & jelly butter & jelly and jelly egg-free
sandwich sandwich sandwich meatloaf
Banana Cooked Peas Banana Cooked Peas Banana Cooked Peas
carrots with carrots carrots with
butter with butter milk-free
margarine
Strawberries Mashed Strawberries Mashed Strawberries Mashed
potatoes potatoes potatoes
made with
chicken broth
Roll with Roll with Milk-free roll
butter butter with milk-free
margarine
SNACK SNACK SNACK SNACK SNACK SNACK SNACK SNACK SNACK
Granola bar Yogurt drink Ice cream Granola bar Yogurt drink Ice cream Teddy Soy yogurt Soy ice cream
Grahams®
Juice Oatmeal Juice Oatmeal Juice FAAN Oatmeal
cookie cookie cookie*
*Food Allergy and Anaphylaxis Network recipe
(can be found at http://www.foodallergy.org/recipes.html)
Nutrition Analysis of Diet 1 Nutrition Analysis of Diet 2 Nutrition Analysis of Diet 3

Nutrient % Goal** Nutrient % Goal** Nutrient % Goal**
Calories 1490 kcal > 100 Calories 305 kcal 25 Calories 1360 kcal > 100
Protein 47 g 360 Protein 5g 41 Protein 42 g 321
Fat 55 g 33% of Fat 2g 6% of Fat 49 g 32% of
total kcal total kcal total kcal
Calcium 1100 mg 221 Calcium 98 mg 20 Calcium 754 mg 151
Vitamin D 203 IU 101 Vitamin D 20 IU 10 Vitamin D 285 IU 285
Iron 9.9 mg 141 Iron 4 mg 59 Iron 10 mg 147
Zinc 8.9 mg 297 Zinc 2.6 mg 87 Zinc 6 mg 201
**Based on DRI for age.20
iet 1: Sample menu for an 18-month-old child prior to diagnosis of food allergy.
Legend: D
Diet 2: Nutritionally depleted sample menu for the same child who has been diagnosed with milk, egg, and peanut allergy.
Diet 3: Revised nutritionally adequate menu for the child with acceptable food substitutions.
Table 20-5 Key Micronutrients Provided by the Most Common Food Allergens and Alternative Food Sources That Can Serve as Food Substitutes for the
Allergenic Foods
Allergenic Foods Micronutrients Provided Appropriate Food Substitutes
Milk vitamin A, vitamin D, riboflavin, pantothenic acid, vitamin meats, legumes, whole grains, nuts, fortified foods/
B12, calcium, phosphorus beverages (with B vitamins, calcium, and vitamin D)
Egg vitamin B12, riboflavin, pantothenic acid, biotin, selenium meats, legumes, whole grains
Soy thiamin, riboflavin, pyridoxine, folate, calcium, phosphorus, meats, legumes
magnesium, iron, zinc
Wheat thiamin, riboflavin, niacin, iron, folate if fortified alternative fortified grains (barley, rice, oat, corn, rye, quinoa,
soy) and potatoes
Peanut/Tree nut vitamin E, niacin, magnesium, manganese, chromium whole grains, vegetable oils
Fish/Shellfish vitamin B6, vitamin E, niacin, phosphorus, selenium, whole grains, meats, oils, soybean, flaxseed, nuts
omega-3 fatty acids, folate, copper, zinc, potassium

Nutrition Intervention the small fraction of children who are also allergic to the
Education provides a family and patient the pathway for protein hydrolysates. Both of these types of formulas are
success with an elimination diet. This includes education generally less palatable than standard formulas and are
regarding dietary avoidance and consideration of nutrition considerably more expensive. Significant advances in the
deficiencies that may result. In addition, they must receive flavor and acceptability of the formulas have been made
education regarding the nutrition goals for the patient in order which has improved the adherence to incorporating these
to avoid nutrition consequences of food allergies. They must formulas as supplemental nutrition. The major categories
also be educated about resources for obtaining additional of formulas are enumerated in Table 20-7.
information regarding living with food allergies (eg, support
groups, local retail establishments that sell allergen-free Table 20-7 Major Pediatric Formulas
foods, cookbooks, and other helpful tips for the elimination Formula Protein Examples
diet). A list of food allergy resources is provided in Table 20-6. Cow’s Milk Casein, whey Infant formulas
Each food-allergic child/family must be given a list of substi- Similac® Advance® Early Shield™
Enfamil® Premium™
tutions in order to be successful with strict avoidance of the
Formulas for older children
food allergens. In addition, a nutritionally complete formula PediaSure®
or beverage, if possible, should be encouraged. This type of Lactose-free Infant formulas
information assists the patient and family in living a normal Similac Sensitive®
and well-nourished life despite having food allergies. Without Formulas for older children
PediaSure®
education, the recommendation of an elimination diet can be
Soy Soy Infant formulas
overwhelming and unsuccessful as families struggle to find Enfamil® ProSobee®
accurate and useful information. Similac® Isomil® Advance®
Formulas for older children
Bright Beginnings™ Soy Pediatric Drink
Table 20-6 Food Allergy Resources
Hydrolysate Peptides, Infant formulas
Resource Website amino acids Nutramigen®
Food Allergy & Anaphylaxis Network http://www.foodallergy.org Similac® Alimentum®
American Academy of Allergy, http://www.aaaai.org Formulas for older children
Asthma & Immunology Vital jr™
American Dietetic Association http://www.eatright.org Peptamen Jr®
Asthma and Allergy Foundation http://www.aafa.org Elemental Amino acids Infant formulas
of America Neocate®
EleCare®
American Partnership For http://www.apfed.org Nutramigen® AA™
Eosinophilic Disorders
older children (ELEMENTAL)
American College of Allergy, http://www.acaai.org Neocate® Jr
Asthma & Immunology EleCare®
EO28 Splash®
Nutritionally Complete Formulas
Identification of formulas is dependent upon the known Most children with food allergies can be managed
food allergens. Most standard formulas are free of wheat, through judicious food substitutions. When faced with an
egg, peanut, tree nut, fish, and shellfish. It is common extensive array of food allergies that span multiple food
to substitute a soy protein-based formula for the cow’s groups, protein hydrolysate and elemental formulas become
milk protein-allergic patient. In patients who are allergic the primary option. Infants under the age of 4 to 6 months
to both cow’s milk and soy, a protein hydrolysate or usually accept these less-palatable formulas without diffi-
elemental formula is recommended. These formulas culty but with increasing age acceptability of these formulas
exploit the concept that intact proteins are allergenic and becomes a problem. In toddlers or preschool children, when
with increasing breakdown of the intact protein, the aller- elemental formulas are the sole or major source of nutrition
genicity can be reduced. Protein hydrolysates are made and the patient will not consume enough to sustain nutri-
by hydrolysis of proteins into mostly di- and tri-peptides tion, tube feeding may become necessary.
and can be tolerated by the vast majority (80% – 90%) of Patients who are extremely malnourished at presenta-
patients with allergies to milk and soy. Elemental formulas tion may need to be admitted to the hospital to monitor for
are made up of individual amino acids and are tolerated by refeeding syndrome (Chapter 19); otherwise, most patients

FOOD ALLERGIES 221
with food allergies can be managed in the outpatient supplements, medications, bath products, lotions, pet foods,
setting. and cosmetics as young children may accidentally or volun-
tarily consume these products.
Milk Substitutes The Food Allergen and Consumer Protection Act
Milk substitutes must be used in combination with nutri- (FALCPA), which became effective in January 2006,
tion assessment and monitoring. There are many different mandates that foods (including spices and flavorings)
“milk” products in the marketplace that continue to identify the 8 major allergens on the food label. Voluntary
provide alternatives for the allergic patient. However, each allergen advisories or “may contain” statements are also
product should only be used with careful consideration of appearing on an increasing number of products. 22 These
the nutritional quality of the milk product. Many provide statements are voluntary; companies elect when to use the
adequate micronutrients such as vitamin D, calcium, and B statements and what language to use. The statements are
vitamins; however most provide minimal fat and protein. used by some companies to indicate there may be a risk of
Children under the age of 2 are at high risk for malnutrition cross-contact with an allergen in another product. Recent
if one of the incomplete milk substitutes is used in place of efforts to increase public awareness and strides made in
whole cow’s milk. See Table 20-8 for a list of the nutritional labeling of food products are encouraging. However, there
constituents of various milk substitutes. is also a concern that food companies may choose to make
voluntary statements regarding cross-contamination in an
Dietary Allowance Versus Dietary Restrictions attempt to avoid accidental exposures to allergens. If this
The diagnosis of food allergy impacts the patient and family practice does occur, it may decrease food choices for patients
in many different ways including grocery shopping, cooking, with food allergies. Table 20-9 provides some examples of
socializing, travel/vacations, eating out, and family rela- “hidden” food allergens in common foods.
tionships. It is essential to provide education regarding all
of these topics. One of the cornerstones of management is Micronutrient Supplementation
education about reading food labels.21 Labels must be read The benefit of early intervention is to avoid micronutrient
every time a food product is purchased as the ingredients deficiency by recommending adequate substitutions and
may change without warning. Labels must also be read for supplementation. The DRIs20 for vitamins, minerals, and
Table 20-8 Nutrition Comparisons of Various Milk Substitutes with Whole Milk
Nutrient per 8 oz. Rice Milk, Rice Milk, Soy Milk, Whole Milk PediaSure® Almond Hazelnut Oat Milk Multigrain
Non-Enriched Enriched, Enriched Milk Milk Milk
Refrigerated
Calories 120 120 130 150 237 70 110 130 160
Protein (g) 1 1 7 8 7.1 2 2 4 5
Carbohydrate (g) 25 25 17 11 26 11 18 24 30
Fat (g) 2 2 4 8 11.8 2.5 3.5 2.5 2
Unsaturated fat (g) 2 2 3.5 3 7.4 2.5 3.5 2.5 2
Saturated fat (g) 0 0 0.5 5 3.1 0 0 0 0
Calcium (mg) 20 300 300 294 230 300 300 300 300
Iron (mg) NS NS 1.8 0.1 3.3 0.36 0.36 0.36 1.08
Zinc (mg) 0.29 0.29 0.6 1 2.8 — — — —
Selenium (mcg) NS NS — 9 5.4 — — — —
Thiamin-B1 (mg) NS 0.12 0.15 0.107 0.64 NS — — —
Riboflavin-B2 (mg) NS — 0.07 0.447 0.5 0.5 0.5 0.5 0.5
Niacin-B3 (mg) 0.8 0.8 0.8 0.261 4 NS — — —
Pantothenic acid-B5 (mg) NS 0.23 0.4 0.883 2.4 NS — — —
Folate (mcg) 1.5 — 60 12 88 NS — — —
Vitamin B12 (mcg) 1.5 1.5 3 1.07 1.4 NS — — —
Vitamin A ( IU) NS 500 500 300 610 500 500 500 500
Vitamin D (IU) NS 100 100 100 120 100 100 100 100
NS — Not a significant source
Legend: These are typical nutrition values for various milk substitutes. Individual brands may have varying amounts of nutrients.

Table 20-9 Common Sources of Hidden Food Allergens

Egg Milk Nuts Soy Wheat Rice
Pasta Bread/bread crumbs Breakfast cereals/ Bread/bread crumbs Cereals Baby food
granola bars
Bread/bread crumbs Breakfast cereals Egg rolls Waffles Gluten-free products Bread/bread crumbs
Egg Beaters® Frozen desserts Cakes/cookies Crackers Chicken hot dogs/ Cake/muffin mixes
low-fat beef franks
Candy/chocolate Candy/chocolate Frozen desserts Chicken hot dogs/ Soy sauce Waffles
low-fat beef franks
Marshmallows Canned tuna Nut butters Cakes/muffins Barbecue-flavored Soups
potato chips
Waffles Processed meats Sauces/chili Bouillon cubes Modified food starch
trace elements can be used for children with food aller- and respiratory symptoms (allergic rhinoconjunctivitis,
gies because the vast majority of these children are normal asthma).24 This condition can also develop when an infant is
except for their food allergies and atopic problems. Chapter exclusively breastfed, through the passage of the offending
6 (Minerals), Chapter 7 (Water-Soluble Essential Micronu- antigens from food consumed by the mother through the
trients), and Chapter 8 (Fat-Soluble Vitamins) discuss these breast milk.
topics. Recommendations for supplementations should be The diagnosis is usually made through the history of
made based on foods that need to be eliminated and the clinical symptoms in young infants that develop soon after
patient’s nutrition status. There are several hypo-allergenic birth or shortly after starting cow’s milk-based formula in
multivitamin-multimineral supplements that are appro- an infant with a family history of atopy. If the reaction is
priate for children with food allergies (Table 20-10). IgE-mediated, then the specific IgE levels may be elevated.
Up to 80% to 90% of these infants will do well with a
Table 20-10 Allergen-Free Multivitamins protein hydrolysate and the rest will require an elemental
All of these products are free of milk, soy, egg, wheat, peanut, formula.25 In breastfed infants, the mother should initially
tree nut, fish, and shellfish. avoid cow’s milk; if there is no improvement, she may also
One-A-Day® Kids Scooby-Doo! Complete Multivitamin need to exclude some of the other common food allergens.
One-A-Day® Bugs Bunny Complete Multivitamin These children, particularly infants with gastrointes-
Flintstones™ Complete-Children’s Chewable Multivitamin tinal symptoms, have a good prognosis. Approximately 50%
NanoVM® (1–3 yrs and 4–8 yrs)*# Multivitamin
of infants are able to tolerate cow’s milk by the age of 1 year
Nature’s Plus Animal Parade Children’s Chewable Multivitamin
and the vast majority remits by the age of 3 years.23
*This product is only available online.
# This is the only allergen-free vitamin that contains selenium. Eosinophilic esophagitis
Note: Products can change at any time and labels should be read Eosinophilic esophagitis (EE) is a disorder of the esophagus
before use.
characterized by upper gastrointestinal tract symptoms in
association with esophageal mucosal eosinophilia. 26 EE
Two Special Scenarios tends to be a chronic disease with persistent or relapsing
symptoms and appears to be becoming more prevalent.
Cow’s Milk-Protein Allergy Children under the age of 5 years commonly present
Cow’s milk-protein allergy (CMPA) is the most common with food refusal, regurgitation, and emesis. Abdominal
food allergy in early childhood with an incidence of 2% pain and failure to thrive may also be seen. Dysphagia
to 3% in the first year of life.23 Most infants with CMPA and food impaction tend to be increasingly common with
develop symptoms before 1 month of age, often within a age. There is a strong association between EE and allergic
week after introduction of cow’s milk-based formula. The rhinitis, asthma, and eczema as well as food allergies. All
majority have 2 or more symptoms with symptoms from patients with EE must be managed with coordinated care
2 or more organ systems: cutaneous symptoms (urticarial between a gastroenterologist, allergist, and dietitian.
rash, atopic eczema), gastrointestinal symptoms (blood in Systemic and topical corticosteroids effectively resolve
the stool, diarrhea, vomiting, protein-losing enteropathy), acute features of EE; however, when discontinued, the

FOOD ALLERGIES 223
disease generally recurs. Three types of nutrition interven- commencement of nutrition support.
tion have met with varying degrees of success in EE. First,
specific food elimination can be based on allergy testing Enteral Nutrition
and clinical history.27 Even when allergy testing does not Enteral nutrition support of children presenting with food
reveal specific food allergens, elimination diets can be used. allergies can be straightforward. Because most enteral
Simply removing the 8 most common allergenic foods (milk, formulas contain cow’s milk protein, children with cow’s
soy, egg, wheat, peanut, tree nut, fish, and seafood) from milk protein allergies can be managed with soy-based,
the diet has significant efficacy.28 Finally, a 100% amino protein hydrolysate, or elemental formula using the prin-
acid-based formula diet can be utilized, thus removing all ciples outlined earlier in this chapter.
potential food allergens; this approach has been extremely Some of the formula intolerances that occur in young
effective.29,30 children receiving nutrition support are probably secondary
Hence, medical nutrition therapy should be considered to food allergies and are usually not recognized at the first
as an effective treatment in all children diagnosed with EE. instance. Since one of the management strategies for formula
When deciding on the use of a specific nutrition therapy, intolerances during nutrition support includes a transi-
the patient’s lifestyle and family resources also need to be tion to a protein hydrolysate/elemental formula, the acute
considered. This requires comprehensive education and situation usually resolves. Often, food allergy is diagnosed
nutrition monitoring by a dietitian. retrospectively when the child cannot be transitioned back
to a more standard formula.
Prognosis and Follow-Up
There is a good possibility that many young children diag- Parenteral Nutrition
nosed with allergies to foods such as milk, egg, wheat, and There are minimal data on PN support in children with
soybeans will outgrow the sensitivity after several years. 31 documented allergies to foods. Egg allergy can be a cause
There is a trend for non-IgE-mediated milk allergy to be for concern because these proteins can be found in intrave-
outgrown more quickly than IgE-mediated allergy with nous lipid solutions. In patients with documented allergies
both forms of the allergy having a good prognosis. 31 Chil- to eggs, 3 options could be considered—consultation with
dren who develop a food allergy after 3 years of age are less an allergist who may or may not do a skin prick test, lipid-
likely to lose the food reactions over a several-year period. 25 free PN, or the use of Liposyn® II. 32 There is a theoretical
Peanut allergy is a lifelong disorder for most but not all risk with extremely soy-allergic patients needing PN. Most
patients. 31 Individuals with allergies to foods such as tree of these patients probably tolerate intravenous lipid, but the
nuts, fish, and seafood seem likely to retain their allergic first 2 options outlined above should be considered.
sensitivity for a lifetime. 31 A variety of allergies to PN have been described
Follow-up visits with the allergist-immunologist are through case reports in the literature. 32–38 As with other
important for the management of food allergies. Because allergies, they appear to be more common in children. 36–38
pediatric patients have the potential for outgrowing a food Skin rashes appear to be the most common manifestation.
allergy, the follow-up visits can re-assess the allergic status However, they can present with dyspnea, cyanosis, nausea,
and determine if any food allergens may be re-introduced. vomiting, headache, flushing, fever, and chest pain. Anaphy-
Re-introduction of a food allergen should only be consid- laxis can occur. 37–39 All of these reactions can occur at the
ered if managed and directed by the allergist. Introduction first administration, after several days of administration, or
of previously avoided allergens may increase food options, after reinstitution following a hiatus.
decrease cost if the patient is drinking a specialty formula These reactions have been attributed to intravenous
and/or eating specialty allergen-free foods, and decrease lipid preparations, 32,34 crystalline amino acid solutions, 37
the stress around preparing meals for the child. and multivitamin mixtures (either due to stabilizers and
emulsifiers in the M.V.I. Pediatric® or due to vitamin
Food Allergies and Nutrition Support K). 35–37,39
There are two possible scenarios wherein food allergies When these reactions occur, PN needs to be stopped and
are associated with nutrition support. The first is when a appropriate drug treatment for the allergic reaction started.
child with known food allergies requires nutrition support If the reaction is severe and the patient is going to continue
and the second is where allergies to formula or parenteral to require PN, a multidisciplinary approach utilizing an
nutrition (PN) components become apparent only after the allergist, pharmacist, nutrition-support physician, and/

or dietitian should be pursued. Two approaches may be does not drink a milk substitute. All of the following
considered when the reaction is mild and resolves after must be done or considered at this visit EXCEPT:
PN is discontinued. The first is to have skin prick testing A. Assessment of growth and nutrient intake
of the lipid, multivitamin, and amino acid components and B. Suggesting an age-appropriate beverage
removal of the offending agent(s) before PN is restarted. C. Recommending follow-up with allergist as patient
The other approach has been to identify the offending agent is tolerating milk and soy
through trial and error. D. Suggesting food challenge of peanut butter at home
One micronutrient that may be added to PN solutions 4. A 6-month-old breastfed infant has significant
and cause significant allergic reactions is intravenous iron. vomiting and diarrhea within hours of being given a
All 3 parenteral iron compounds—iron dextran, sodium bottle of cow’s milk-based formula. His mother reports
ferric gluconate complex in sucrose, and iron sucrose— that this has happened each time he has been fed the
can be associated with allergic reactions.40,41 It appears that formula. She denies any skin rashes. RAST testing for
iron sucrose is associated with the lowest risk of allergy.41 IgE directed against cow’s milk protein is negative. All
Iron dextran is the least expensive preparation, and a test of the following are true about this child EXCEPT:
dose should always be given with the thought of routinely A. This is consistent with IgE-mediated anaphylaxis.
pre-treating patients with diphenhydramine and acet- B. This is most likely food protein-induced entero-
aminophen to minimize adverse events. Both sodium colitis syndrome.
ferric gluconate and iron sucrose offer safe alternatives to C. Cow’s milk protein must be eliminated from the
patients intolerant of iron dextran but at a higher cost.40,41 child’s diet.
Iron dextran-sensitive patients and patients with multiple D. In addition to breastfeeding, a protein hydrolysate
allergies who receive one of the newer preparations should formula may be appropriate.
receive test doses prior to therapy.
1. A 7-year-old boy with an enterocutaneous fistula References
develops an urticarial rash the day that he is started on 1. Branum AM, Lukacs SL. Food allergy among U.S. children:
parenteral nutrition. All of the following constituents of trends in prevalence and hospitalizations. NCHS data brief, no
10. Hyattsville, MD: National Center for Health Statistics;
his parenteral nutrition could cause the rash EXCEPT: 2008.
A. Intravenous lipid 2. Arbes SJ Jr, Gergen PJ, Elliott L, Zeldin DC. Prevalences
B. Amino acid solution of positive skin test responses to 10 common allergens in
C. Pediatric multivitamin solution the US population: results from the third National Health
D. Dextrose and Nutrition Examination Survey. J Allergy Clin Immunol.
2005;116(2):377–383.
2. An 18-month-old vegetarian girl with presumed
3. Sicherer SH, Muñoz-Furlong A, Burks AW, Sampson HA.
milk and soy protein allergy is drinking 32 ounces of Prevalence of peanut and tree nut allergy in the US deter-
enriched rice milk per day. She also eats rice, wheat, mined by a random digit dial telephone survey. J Allergy Clin
corn, fruits, and vegetables but does not consume any Immunol. 1999;103(4):559–562.
egg or meat products. She does not receive any vitamin 4. Sicherer SH, Muñoz-Furlong A, Sampson HA. Preva-
or mineral supplementation. You are concerned about lence of seafood allergy in the United States determined
by a random telephone survey. J Allergy Clin Immunol.
her intake of all of the following EXCEPT: 2004;114(1):159–165.
A. Fat 5. Sicherer SH, Furlong TJ, Burks AW, Sampson HA. A
B. Vitamin D voluntary registry for peanut and tree nut allergy: charac-
C. Energy teristics of the first 5149 registrants. J Allergy Clin Immunol.
D. Zinc 2001;108(1):128–132.
6. Sampson HA, Burks AW. Mechanisms of food allergy. Annu
3. A 6-year-old Asian boy is seen by a dietitian for follow-
Rev Nutr. 1996;16:161–177.
up nutrition assessment and education. His parents 7. Bock SA, Muñoz-Furlong A, Sampson HA. Fatalities due
report he is allergic to milk, soy, and peanuts. He has to anaphylactic reactions to foods. J Allergy Clin Immunol.
a history of anaphylaxis while eating peanut butter one 2001;107(1):101–103.
year ago. His current intake includes tofu stir-fry and 8. Sicherer SH. Food protein-induced enterocolitis syndrome:
milk chocolate candy bars. Parents report he eats these clinical perspectives. J Pediatr Gastroenterol Nutr. 2000;30
Suppl:S45–49.
foods at least once a week without any problems. He

FOOD ALLERGIES 225
9. Sicherer SH, Eigenmann PA, Sampson HA. Clinical features 27. Spergel JM, Andrews T, Brown-Whitehorn TF, Beausoleil
of food protein-induced enterocolitis syndrome. J Pediatr. JL, Liacouras CA. Treatment of eosinophilic esophagitis
1998;133(2):214–219. with specific food elimination diet directed by a combination
10. Powell GK. Milk- and soy-induced enterocolitis of infancy. of skin prick and patch tests. Ann Allergy Asthma Immunol.
Clinical features and standardization of challenge. J Pediatr. 2005;95(4):336–343.
1978;93(4):553–560. 28. Kagalwalla AF, Sentongo TA, Ritz S et al. Effect of six-
11. Burks AW, Casteel HB, Fiedorek SC, Williams LW, Pumphrey food elimination diet on clinical and histologic outcomes
CL. Prospective oral food challenge study of two soybean in eosinophilic esophagitis. Clin Gastroenterol Hepatol.
protein isolates in patients with possible milk or soy protein 2006;4(9):1097–1102.
enterocolitis. Pediatr Allergy Immunol. 1994;5(1):40–45. 29. Kelly KJ, Lazenby AJ, Rowe PC, Yardley JH, Perman JA,
12. Nowak-Wegrzyn A, Sampson HA, Wood RA, Sicherer SH. Sampson HA. Eosinophilic esophagitis attributed to gastroe-
Food protein-induced enterocolitis syndrome caused by solid sophageal reflux: improvement with an amino acid-based
food proteins. Pediatrics. 2003;111(4)Pt 1:829–835. formula. Gastroenterology. 1995;109(5):1503–1512.
13. Bock SA, Lee WY, Remigio L, Holst A, May CD. Appraisal of 30. Markowitz JE, Spergel JM, Ruchelli E, Liacouras CA.
skin tests with food extracts for diagnosis of food hypersensi- Elemental diet is an effective treatment for eosinophilic
tivity. Clin Allergy. 1978;8(6):559–564. esophagitis in children and adolescents. Am J Gastroenterol.
14. Sampson HA. Utility of food specific IgE concentrations in 2003;98(4):777–782.
predicting symptomatic food allergy. J Allergy Clin Immunol. 31. Wood RA. The natural history of food allergy. Pediatrics.
2001;107(5):891–896. 2003;111(6):1631–1637.
15. Burks W, Bannon G, Lehrer SB. Classic specific immuno- 32. Buchman AL, Ament ME. Comparative hypersensitivity
therapy and new perspectives in specific immunotherapy for in intravenous lipid emulsions. J Parenter Enteral Nutr.
food allergy. Allergy. 2001;56(Suppl 67):121–124. 1991;15(3):345–346.
16. Jones SM, Pons L, Roberts JL, et al. Clinical efficacy and 33. Nagata MJ. Hypersensitivity reactions associated with paren-
immune regulation with oral peanut immunotherapy. J teral nutrition: case report and review of the literature. Ann
Allergy Clin Immunol. 2009;124:292–230. Pharmacother. 1993;27(2):174–177.
17. Sicherer SH. Diagnosis and management of childhood food 34. Weidmann B, Lepique C, Heider A, Schmitz A, Niederle
allergy. Curr Probl Pediatr. 2001;31(2):35–57. N. Hypersensitivity reactions to parenteral lipid solutions.
18. Hubbard S. Nutrition and food allergies: the dietitian’s role. Support Care Cancer. 1997;5(6):504–505.
Ann Allergy Asthma Immunol. 2003;90(6 Suppl 3):115–116. 35. Scolapio JS, Ferrone M, Gillham RA. ��
Urticaria associ-
19. Christie L, Hine RJ, Parker JG, Burks W. Food allergies in ated with parenteral nutrition. J Parenter Enteral Nutr.
children affect nutrient intake and growth. J Am Diet Assoc. 2005;29(6):451–453.
2002;102(11):1648–1651. 36. Bullock L, Etchason E, Fitzgerald JF, McGuire WA. Case
20. Food and Nutrition Board, Institute of Medicine. Dietary report of an allergic reaction to parenteral nutrition in a pedi-
reference intakes: recommended intakes for individuals; 2009 atric patient. J Parenter Enteral Nutr. 1990;14(1):98–100.
(2/5):7. http://iom.edu/en/Global/News%20Announce- 37. Pomeranz S, Gimmon Z, Ben Zvi A, Katz S. Parenteral
ments/~/media/Files/Activity%20Files/Nutrition/DRIs/ nutrition-induced anaphylaxis. J Parenter Enteral Nutr.
DRISummaryListing2.ashx. Accessed November 23, 2009. 1987;11(3):314–315.
21. Joshi P, Mofidi S, Sicherer SH. Interpretation of commercial 38. Market AD, Lew DB, Schropp KP, Hak EB. Parenteral nutri-
food ingredient labels by parents of food-allergic children. J tion-associated anaphylaxis in a 4-year-old child. J Pediatr
Allergy Clin Immunol. 2002;109(6):920–922. Gastroenterol Nutr. 1998;26(2):229–231.
22. Food Allergy Issues Alliance. Food Allergen Labeling Guide- 39. Andersen HL, Nissen I. Presumed anaphylactic shock after infu-
lines. Washington, DC: National Food Processors Association; sion of Lipofundin. Ugeskr Laeger. 1993;155(28):2210–2211.
2001. 40. Silverstein SB, Rodgers GM. Parenteral iron therapy options.
23. Høst A. Frequency of cow’s milk allergy in childhood. Ann Am J Hematol. 2004;76(1):74–78.
Allergy Asthma lmmunol. 2002;89(Suppl):33–37. 41. Bailie GR, Clark JA, Lane CE, Lane PL. Hypersensitivity
24. Høst A. Cow’s milk protein allergy and intolerance in infancy. reactions and deaths associated with intravenous iron prepa-
Some clinical, epidemiological and immunological aspects. rations. Nephrol Dial Transplant. 2005;20(7):1443–1449.
Pediatr Allergy Immunol. 1994;5(Suppl):1–36.
25. Atkins D. Food allergy: diagnosis and management. Prim
Care. 2008;35(1):119–140.
26. Furuta GT, Liacouras CA, Collins MH et al. First ��
Interna-
tional Gastrointestinal Eosinophil Research Symposium
(FIGERS) Subcommittees. Eosinophilic esophagitis in
children and adults: a systematic review and consensus
recommendations for diagnosis and treatment. Gastroenter-
ology. 2007;133(4):1342–1363.

21
Diabetes Mellitus and
Other Endocrine Disorders
Diane Olson, RD, CNSD, CSP, LD and W. Frederick Schwenk II, MD

Diabetes Mellitus. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 226 1. Define the different types of diabetes mellitus that
Definitions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 226 occur in childhood.
Type 1 Diabetes Mellitus 2. Relate how to create a parenteral formulation or choose
Type 2 Diabetes Mellitus an enteral formula in a child with diabetes mellitus
CF-Related Diabetes Mellitus receiving nutrition support.
Consequences of Hyper/Hypoglycemia 3. Report the optimal way to administer insulin in a
in the Critically Ill Child. . . . . . . . . . . . . . . . . . . . . . . . . . . 227 child with diabetes on parenteral or enteral nutrition
Glucose Control in Healthy Children with Diabetes. . . . .228 support.
Short-Term Implications 4. State how to prevent hypo- or hypernatremia in a child
Long-Term Complications with central diabetes insipidus on nutrition support.
Glucose Control in Children with Diabetes
Mellitus on Parenteral Nutrition. . . . . . . . . . . . . . . . . . . . 228 Diabetes Mellitus
Choice of Dextrose Solution
Use of an Insulin Infusion
Diabetes mellitus is one of the most common chronic
Addition of Insulin to Parenteral Nutrition Solutions illnesses in the pediatric-aged population. It results from an
Glucose Control in Children with Diabetes absolute or relative lack of insulin, with or without insulin
Mellitus on Enteral Nutrition. . . . . . . . . . . . . . . . . . . . . . . 229 resistance. While there are a number of different causes
Choice of Formula of diabetes in children, all untreated forms of diabetes
Administration of Insulin mellitus are associated with elevated plasma glucose and
Nutrition Support in CF-Related Diabetes . . . . . . . . . . . . 229 lipid concentrations.
Choice of Formula
Control of Blood Glucose Definitions
Nutrition Support in Other Endocrine Conditions . . . . . . 229
Central Diabetes Insipidus Type 1 Diabetes Mellitus
Panhypopituitarism
The most common form of diabetes in children remains
Future Research. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 230 type 1 diabetes mellitus. This disorder is usually an autoim-
mune destruction of the beta cells of the pancreas, resulting
in an absolute deficiency of insulin.1–4 Incidence of type 1
diabetes mellitus in the United States and other western
countries has been increasing. In the United States, the
prevalence of type 1 diabetes mellitus at 18 years of age is 2
to 3 per 1000.1 The incidence of type 1 diabetes mellitus is
about 1.5 times greater in the American non-Hispanic white
226
DIABETES MELLITUS AND OTHER ENDOCRINE DISORDERS 227
population than in African Americans or Hispanic Ameri- in almost 90% of the patients sometime during the admis-
cans. Children with type 1 diabetes mellitus are at risk for sion.16 In a second retrospective study, almost 70% of 192
developing ketoacidosis and require insulin to prevent critically ill children had blood glucose concentrations
hyperglycemia.2 Because of a risk for developing low blood greater than 120 mg/dL within 24 hours of admission to a
glucose concentrations, current recommendations from the pediatric ICU.17
American Diabetes Association (ADA) are to keep target Hyperglycemia has been linked to poor outcome. In
blood glucose goal ranges in children somewhat higher than a study of 184 children less than 1 year of age who had
what is recommended for adults.2,4 undergone cardiac surgery, hyperglycemia in the postop-
erative period was associated with increased mortality and
Type 2 Diabetes Mellitus morbidity.18 However, in a fourth retrospective study of
In the last 20 years, there has been an epidemic of child- 1094 admissions to a pediatric intensive care unit, the risk of
hood obesity in developed countries. 5 Associated with this having a blood glucose value over 200 mg/dL was less than
increase in childhood obesity has been a marked increase in the risk of having a blood glucose value less than 65 mg/dL.18
the incidence of children with type 2 diabetes mellitus. 6–9 Furthermore, the risk of dying was 6 times greater if the child
The etiology of type 2 diabetes remains to be established, had a blood glucose less than 110 mg/dL than if all blood
but appears to be caused not only by a relative insufficiency glucose values were greater than 110 mg/dL.19
of insulin secretion by the pancreas but also by insulin resis- There are many reasons why hyperglycemia might affect
tance. In the United States, depending upon the geographic mortality and morbidity in critically ill patients. In vitro, high
location, between 8% and 43% of new-onset cases of diabetes glucose concentrations have been shown to cause abnor-
are type 2 diabetes mellitus. Children with type 2 diabetes malities in several aspects of immune function, including
mellitus rarely develop ketoacidosis.8 Optimal treatment intracellular killing, complement function, granulocyte
of children with type 2 diabetes mellitus remains contro- adhesion, chemotaxis, phagocytosis, and respiratory burst
versial.9 The incidence of type 2 diabetes mellitus varies by function.20 Glucose attaches itself to the third component of
ethnic group, with higher rates (in order) in Native Ameri- complement, affecting this component’s ability to attach itself
cans, African Americans, Hispanic Americans, and Pacific to microbes and impairing opsonization of the microbe.21
Islanders/Asian children.9 On the other hand, it is not difficult to understand why low
blood sugars might affect mortality and morbidity in criti-
CF-Related Diabetes Mellitus cally ill children. More than 60% of the basal metabolic rate
Children with cystic fibrosis (CF) and pancreatic insuf- in an infant is estimated to be related to brain metabolism,
ficiency are at increased risk of developing CF-related compared with less than 30% in an adult.22
diabetes.10–13 The prevalence of this condition in children Numerous studies in adult patients with diabetes have
with CF and pancreatic insufficiency less than 18 years of shown increased morbidity and mortality associated with
age has been reported to be between 5% and 15%, while in hyperglycemia.23,24 These studies formed the backdrop for
similar adults the prevalence may be as high as 50%.12,13 a large retrospective study in surgical patients showing that
These children do not typically develop ketoacidosis and intensive insulin therapy reduced in-hospital mortality rates
may have increased insulin resistance, particularly at by 34% and had a profound effect on a variety of morbidities.21
time of intercurrent illness.10,14 Children with CF-related A similar retrospective study in non-surgical patients also
diabetes may not exhibit the classic symptoms of polyuria showed reductions in mortality and morbidity, although the
and polydipsia associated with other types of diabetes results were not as striking.25 These reports led many inten-
mellitus.15 sive care units to modify their management of hyperglycemia
in diabetic and non-diabetic patients. Since those initial
Consequences of Hyper/Hypoglycemia in the studies, there have been a plethora of additional reports, with
Critically Ill Child varying conclusions.26,27 Additional studies have focused on
Hyperglycemia appears to be common in pediatric inten- the increased morbidity and morality associated with hypo-
sive care units (ICUs) regardless of whether the child has glycemia in adult hospitalized patients,28,29 consistent with
known diabetes mellitus.16–19 In one retrospective study the findings in children.
involving 152 children in a pediatric ICU, blood glucose The optimal control of blood glucose in the adult hospi-
concentrations greater than 125 mg/dL were observed in talized patient with or without diabetes remains controversial.
over half of the patients within 24 hours of admission and There are very limited data in children. While one recent

randomized, prospective study of intensive insulin therapy Glucose Control in Children with Diabetes
in critically ill children did show improved morbidity and Mellitus on Parenteral Nutrition
mortality in a subgroup of patients,30,31 near normal plasma
glucose concentrations, regardless of whether the child has Choice of Dextrose Solution
pre-existing diabetes, are not set as goals by many pediatric There are no data to suggest that children with diabetes
practitioners. require a special formulation for parenteral nutrition (PN).
The composition of the PN solution should be determined
Glucose Control in Healthy Children with independent of whether the patient has diabetes. This includes
Diabetes the choice of the final concentration of dextrose. However,
it should be noted that many children with diabetes have
Short-Term Implications hyperlipidemia,4 so that the triglyceride levels in children
The current recommendations of the ADA are that target with diabetes on PN need to be monitored carefully.
blood glucose concentrations be individualized for each
child with diabetes.4 In general, children less than the age Use of an Insulin Infusion
of 7 years often have a form of hypoglycemic unawareness When an infusion containing a high concentration of
due to limited cognitive ability and immature counter- dextrose is given intravenously in a child (or adult) with
regulation, making them more susceptible to severe diabetes, blood glucose concentrations are most safely
hypoglycemia.4 Children less than 5 years of age appear to be controlled using a separate intravenous (IV) insulin infu-
at risk for permanent cognitive impairment after episodes of sion.43 If insulin is given intravenously, the infusion can
severe hypoglycemia. 32–34 In addition, severe hypoglycemia easily be changed if the rate of IV glucose administration
occurs in younger children most frequently during sleep. 35 is changed. In adults, insulin is often directly added to the
Consequently, blood glucose targets for younger children PN, beginning with a dose of 0.1 units of regular insulin
are usually higher than for adolescents or adults.2,4,36 While per gram of dextrose in the infusate (eg, 10 units/L of
ketoacidosis continues to be a concern in undiagnosed chil- 10% dextrose; 20 units/L of 20% dextrose).43 Additional
dren with type 1 diabetes mellitus, it is rarely a problem subcutaneous regular insulin or an IV insulin infusion may
in children known to have type 1 diabetes mellitus unless be needed to supplement the insulin in the PN. This ratio
inadequate or no insulin is given.4 Overall, the incidence of of insulin to dextrose is unlikely to cause hypoglycemia
short-term adverse events in children, such as hospitaliza- and minimizes the need to discard a bag of PN because it
tion and severe hypoglycemia, is high. 37 contains too much insulin.43
While a similar protocol may be used in children, a
Long-Term Complications strong case can be made to control blood glucose concen-
In contrast to some older children with type 2 diabetes, trations using a separate infusion of insulin. Using a syringe
children with type 1 diabetes rarely have complications at pump, the insulin infusion can be directly “piggy-backed”
the time of diagnosis.38 A large prospective, randomized into the IV line. A reasonable rate to begin such an infusion
study called the Diabetes Control and Complications Trial would be 0.05 units of regular insulin per kilogram body
(DCCT) established that the major risk factor for microvas- weight per hour. The rate of insulin administration can be
cular complications is glycemic control.39–41 What appears to changed to optimize blood glucose control.
be important is the exposure to elevated glucose concentra- As mentioned previously, there is no consensus as to
tions over time.38 However, despite marked improvement in how tightly to control the plasma glucose concentration in
treatment options, 12 years after diagnosis more than 50% of a critically ill child, with or without a previous diagnosis of
patients with type 1 diabetes had developed complications or diabetes. However, most practitioners would suggest that
comorbities.39,42 Persistently high blood glucoses over time blood glucose concentrations between 100 mg/dL and
also appear to increase the risk of macrovascular complica- 200 mg/dL might be a reasonable goal, preventing both
tions, but these rarely occur in childhood. hypoglycemia and ketoacidosis.
Whatever method is chosen to administer the IV
insulin, blood glucose concentrations need to be checked
frequently. This is often done at least hourly in children on
an insulin infusion until there appears to be stability in the
blood glucose concentrations. Blood glucose concentrations

are easiest to control if the PN is given as a continuous infu- in adults that patients who develop CF-related diabetes
sion, rather than being cycled. It should also be mentioned have lower body mass indices and are more likely to require
that even if the IV infusion of dextrose is stopped, patients enteral feedings from 2 years prior to diagnosis compared to
with type 1 diabetes mellitus will continue to need some adults who do not develop CF-related diabetes.48
insulin to inhibit hepatic gluconeogenesis and prevent the
child from developing ketoacidosis. Control of Blood Glucose
Blood glucose concentrations in children with CF and
Addition of Insulin to Parenteral Nutrition Solutions CF-related diabetes receiving EN support can usually be
If a separate IV insulin infusion is used to control blood managed with subcutaneous insulin.10–13 However, with
glucose concentrations and both the rate of insulin infusion intercurrent illness, children with CF have increased insulin
and blood glucose concentrations have remained stable over resistance, requiring larger doses than the typical 1 unit of
24 hours, the separate insulin infusion can be discontinued insulin per kilogram body weight per day requirements of
and insulin added directly to the PN. In such cases, one can children with type 1 diabetes mellitus.10,14
easily calculate the amount of insulin that is required to
control blood glucose concentrations during the adminis- Nutrition Support in Other Endocrine
tration of the PN by totaling the amount of insulin infused Conditions
with the separate infusion. Previously, albumin was also
added to the PN to prevent the insulin from binding to the Central Diabetes Insipidus
bag and tubing being used to administer the PN. However, Central or neurogenic diabetes insipidus is a relatively rare
adequate blood glucose control can be obtained without condition in children resulting from an inability to secrete
such an addition.44 active vasopressin from the posterior pituitary gland.49
While genetic defects in vasopressin synthesis have been
Glucose Control in Children with Diabetes described, the usual etiology of this condition is a hypo-
Mellitus on Enteral Nutrition thalamic or posterior pituitary lesion.49 There are multiple
causes of this condition including tumors, inflammatory
Choice of Formula lesions, vascular diseases, and cranial malformations.49
The use of enteral formulas designed for patients with Outpatient treatment for this condition in children
diabetes has not been studied in children with diabetes. with intact thirst sensation involves giving an analogue of
Therefore, the current recommendations are to use a stan- vasopressin either orally or intranasally. Such children are
dard age-appropriate formula.45 allowed to drink to thirst. Fluid intake in children without
an intact thirst mechanism must be monitored carefully to
Administration of Insulin prevent hypo- or hypernatremia.
Blood glucose concentrations in children with diabetes on There do not appear to be any published guidelines as
enteral nutrition (EN) support can usually be adequately to how to manage a child with central diabetes insipidus
controlled by using subcutaneous injections of insulin. who might require PN or EN. Because of the large volumes
Guidelines for adults have been published for the adminis- of fluid associated with such therapy, the child is at risk for
tration of insulin at the initiation of tube feedings, as the rate both hypo- and hypernatremia.
of tube feedings increases, and for continuous intermittent One option for managing such a patient is to use a
and nocturnal feeding schedules.44 By dosing the insulin on low-dose IV infusion of aqueous vasopressin, as has been
a per kilogram body weight basis, these recommendations described for use in children who are receiving additional
can also be utilized in children. Of course, careful moni- fluid as part of a chemotherapy regimen. 50 To maintain
toring of blood glucose concentrations is required. adequate hydration and serum sodium concentrations, a
dilute infusion of aqueous vasopressin is given at a starting
Nutrition Support in CF-Related Diabetes rate of 0.08 to 1 mU/kg/h. During the infusion, fluid intake,
urine output, body weight, urine specific gravity, and serum
Choice of Formula electrolyte concentrations are monitored carefully.
PN support is rarely required in children with CF.46 If EN
support is being considered, no evidence suggests that one
enteral formulation is superior to another.47 There are data

Panhypopituitarism 4. Serum sodium concentrations can be safely maintained in

Another relatively uncommon endocrine condition that a child with diabetes insipidus on EN or PN support by:
might affect nutrition support is panhypopituitarism. Again, A. Limiting oral fluids
no guidelines exist for how to manage nutrition support in B. Administering a vasopressin analogue orally
such patients. Children with panhypopituitarism are unable C. Doubling the patient’s usual dose of a vasopressin
to secrete a number of anterior pituitary hormones, including analogue
growth hormone and corticotropin. This condition can be D. Using an intravenous drip of aqueous vasopressin
the result of intracranial surgery, but can also be idiopathic.
Children with this condition often present with hypo- See p. 487 for answers.
glycemia and are at continuing risk for low blood sugars. The
hypoglycemia is due to an inability to counterregulate. 51 To References
prevent hypoglycemia in a critically ill child with this condi- 1. Cooke DW, Plotnick L. Type 1 diabetes mellitus in pediatrics.
tion, additional glucocorticoids are administered. In such Pediatr Rev. 2008;29:374 –385.
2. Silverstein J, Klingensmith G, Copeland K, et al. Care of children
patients, a strong case can also be made for administering and adolescents with Type 1 diabetes: a statement of the Amer-
nutrition support as a constant infusion, rather than giving ican Diabetes Association. Diabetes Care. 2005;28(1):186–212.
enteral feeds as boluses or cycled PN. 3. American Diabetes Association. Diagnosis and classification of
diabetes. Diabetes Care. 2006;20(suppl 1):S4–S25.
Future Research 4. American Diabetes Association. Clinical Practice Recommen-
dations 2009. Diabetes Care. 2009;32(suppl 1):S13–S61.
Research in children is difficult, not only because they
5. American Academy of Pediatrics, Committee on Nutrition.
cannot give informed consent but also because mortality Pediatric obesity. In: Kleinman RE, ed. Pediatric Nutrition
is quite low, requiring large numbers of patients to do Handbook. 6th ed. Elk Grove Village, IL: American Academy
outcome studies. Consequently, many of the above recom- of Pediatrics; 2009:733–782.
mendations are extrapolated from adult recommendations. 6. American Academy of Pediatrics, Committee on Nutrition.
Future studies will hopefully answer what is the optimal Pediatric dietary management of diabetes mellitus in chil-
dren. In: Kleinman RE, ed. Pediatric Nutrition Handbook. 6th
blood glucose concentration for a critically ill child. It is also ed. Elk Grove Village, IL: American Academy of Pediatrics;
hoped that new strategies will be developed to help children 2009:673–697.
with diabetes mellitus achieve improved blood glucose 7. Sinha R, Fisch G, Teague B, et al. Prevalence of impaired glucose
control when they are receiving PN or EN. tolerance among children and adolescents with marked obesity.
N Engl J Med. 2002;346(22):802–810.
8. American Diabetes Association. Type 2 diabetes in children
Test Your Knowledge Questions and adolescents. Diabetes Care. 2000; 23(3):381–389.
1. When creating a parenteral formulation to use in a child with 9. Kaufman F. Type 2 diabetes in youth: rate, antecedents, treat-
diabetes mellitus, the dextrose concentration should be: ment, problems and prevention. Pediatr Diabetes. 2007:8(suppl
A. Kept to a minimum 9):4–6.
B. No greater than 15% 10. Moran A, Hardin D, Rodman, et al. Diagnosis, screening
C. At least 20% and management of cystic fibrosis related diabetes mellitus:
a consensus conference report. Diabetes Res Clin Pract.
D. Chosen without regard to whether the child has 1999;45(1):61–73.
diabetes mellitus 11. Hardin DS, Moran A. Diabetes mellitus in cystic fibrosis. Endo-
2. To prevent hyperglycemia, hospitalized children with crinol & Metab Clin North Am. 1999;28(4):787–800.
CF-related diabetes mellitus and acute infections may 12. Solomon MP, Wilson DC, Corey M, et al. Glucose intolerance
require: in children with cystic fibrosis. J Pediatr. 2003;142(2):128–132.
13. Moran A, Doherty L, Wang X, Thomas W. Abnormal glucose
A. An increased amount of insulin
metabolism in cystic fibrosis. J Pediatr. 1998;133(1):10–17.
B. A decreased amount of insulin 14. Brennan AL, Geddes DM, Gyi KM, Baker EH. Clinical
C. Their usual doses of insulin importance of cystic fibrosis-related diabetes. J Cyst Fibros.
D. Frequent doses of short-acting insulin 2004;3(4):209–222.
3. In children with diabetes mellitus on EN, insulin should 15. American Academy of Pediatrics, Committee on Nutrition.
usually be: Nutrition in cystic fibrosis. In: Kleinman RE, ed. Pediatric
Nutrition Handbook. 6th ed. Elk Grove Village, IL: American
A. Discontinued Academy of Pediatrics; 2009:1001–1020.
B. Given parenterally
C. Given subcutaneously
D. Given enterally

16. Srinivasan V, Spinella PC, Drott HR, Roth CL, Helfaer MA, 34. Bjorgaas M, Gimse R, Vik T, Sand T. Cognitive function in type
Nadkarni V. Association of timing, duration, and intensity of 1 diabetic children with and without episodes of sever hypogly-
hyperglycemia with intensive care unit mortality in critically ill caemia. Acta Paediatr. 1997;86(2):148–153.
children. Pediatr Crit Care Med. 2004;5(4):329–336. 35. Ryan C, Gurtunca N, Becker N. Hypoglycemia: a complica-
17. Faustino EV, Apkon M. Persistent hyperglycemia in critically ill tion of diabetes therapy in children. Pediatr. Clin North Am.
children. J Pediatr. 2005;146(1):5–7. 2005;52(6):1705–1733.
18. Yates AR, Dyke PC 2nd, Taeed R, et al. Hyperglycemia is a 36. Ryan CM, Becker DJ. Hypoglycemia in children with type 1
marker for poor outcome in the postoperative pediatric cardiac diabetes mellitus. Pediatr Endocrinol. 1999;28(4):883–900.
patient. Pediatr Crit Care Med. 2006;7(4):351–355. 37. Levine B, Anderson BJ, Butler DA, et al. Predictors of glycemic
19. Wintergerst KA, Buckingham B, Gandrud L, Wong BJ, Kache S, control and short-term adverse outcomes in youth with type 1
Wilson DM. Association of hypoglycemia, hyperglycemia, and diabetes. J Pediatr. 2002;139(2):197–203.
glucose variability with morbidity and death in the pediatric 38. Gallego PH, Wiltshire E, Donaghue KC. Identifying children
intensive care unit. Pediatrics. 2006;118(1):173–179. at particular risk of long-term diabetes complications. Pediatric
20. Van den Berghe G, Wouters P, Weeker F, et al. Intensive Diabetes. 2007;8(suppl 6):40–48.
insulin therapy in the critically ill patients. N Engl J Med. 39. The Diabetes Control and Complications Trial Research Group.
2001;345(19):1359–1367. The effect of intensive treatment of diabetes on the development
21. McMahon MM, Bistrian BR. Host defenses and susceptibility and progression of long-term complications in insulin-depen-
to infection in patients with diabetes mellitus. Infect Dis Clin dent diabetes mellitus. N Engl J Med. 1993;329(14):977–986.
North Am. 1995;9(1):1–9. 40. Diabetes Control and Complications Trial Research Group.
22. Haliday MA. Metabolic rate and organ size during growth from Effect of intensive therapy on the microvascular complication
infancy to maturity and during late gestation and early infancy. of type 1 diabetes mellitus. JAMA. 2002;287(19):2563–2569.
Pediatrics. 1971;47(1):167–179. 41. Writing Team for the DCCT and EDIC Research
23. Capes SE, Hunt D, Malmberg K, Gerstein HC. Stress hyper Group. Sustained effect of intensive treatment of type
glycemia and increased risk of death after myocardial infarction 1 diabetes mellitus on development and progression of
in patients with and without diabetes: a systematic overview. diabetic nephropathy: the Epidemiology of Diabetes
Lancet. 2000:355(9206):773–778. Interventions and Complications (EDIC) study. JAMA.
24. Capes SE, Hunt D, Malmberg K, Pathak P. Stress 2003;290(16):2159–2167.
hyperglycemia and prognosis of stroke in nondiabetic 42. Danne T, Kordonouri O. Current challenges in children with
and diabetic patients: a systematic overview. Stroke. type 1 diabetes. Pediatr Diabetes. 2007;8(Suppl 6):3–5.
2001;32(10):2426–2432. 43. McMahon MM. Diabetes mellitus. In: Merritt T, ed. A.S.P.E.N.
25. Van den Berghe G, Wilmer A, Hermans C, et al. Inten- Nutrition Support Practice Manual. 2nd ed. Silver Spring,
sive insulin therapy in the medical ICU. N Engl J Med. MD: American Society for Parenteral and Enteral Nutrition.
2006;345(5):449–461. 2005:317–323.
26. Inzucchi Se, Slegel MD. Glucose control in the ICU—how tight 44. Weber SS, Wood WA, Jackson EA. Availability of insulin
is too tight? N Engl J Med. 2009;360(13):1346–1349. from parenteral nutrient solutions. Am J Hosp Pharm.
27. The NICE-SUGAR Study Investigators. Intensive versus 1977;34:353–357.
conventional glucose control in critically ill patients. N Engl J 45. American Diabetes Association. Nutrition principles and
Med. 2009;360(13):1283–1297. recommendations in diabetes. Diabetes Care. 2004;27(Suppl
28. Turchin A, Matheny ME, Shubina M, et al. Hypoglycemia and 1):S36–46.
clinical outcomes in patients with diabetes hospitalized in the 46. Jelalian E, Stark LJ, Reynolds L, Seifer R. Nutrition interven-
general ward. Diabetes Care. 2009;32(7):1153–1157. tion for weight gain in cystic fibrosis: a meta analysis. J Pediatr.
29. Arabi Y, Tamim HM, Rishu AH. Hypoglycemia with inten- 1998;132(3 Pt 1):486–492.
sive insulin therapy in critically ill patients: Predisposing 47. Erskine JM, Lingard C, Sontag M. Update on enteral
factors and association with mortality. Crit Care Med. nutrition support in cystic fibrosis. Nutr Clin Pract.
2009;37(9):2536–2544. 2007;22(7):223–232.
30. Vlasselaers D, Milants I, Desmet L, et al. Intensive 48. White H, Pollard K, Etherington C, et al. Nutritional decline in
insulin therapy for patients in paediatric intensive care: cystic fibrosis related diabetes: the effect of intensive nutritional
a prospective, randomized controlled study. Lancet. intervention. J Cyst Fibros. 2009;8(3):179–185.
2009;373(9663):547–556. 49. Ghirardello S, Garre ML, Rossi A, Maghnie M. The diagnosis
31. Agus MSD, Hirshberg EL. Pediatrics: Intensive insulin therapy of children with central diabetes insipidus. J Pediatr Endocrinol
in critically ill children. Nature Rev Endo. 2009;5(7):360–362. Metab. 2007;20(3):359–375.
32. Northam EA, Anderson PJ, Werther GA, Warne GL, Adler 50. Bryant WP, O’Marcaigh AS, Ledger GA, Zimmerman D.
RG, Andrewes D. Neuropsychological complications of Aqueous vasopressin infusion during chemotherapy in patients
IDDM in children 2 years after disease onset. Diabetes Care. with diabetes insipidus. Cancer. 1994;74(9):2589–2592.
1998;21(3):379–384. 51. Bolli GB, Fanelli CG. Physiology of glucose counterregu-
33. Rovet J, Alvarez M. Attentional functioning in children and lation to hypoglycemia. Endocrinol Metab Clin North Am.
adolescents with IDDM. Diabetes Care. 1997;20(5):803–810. 1999;28(3):467–493.

22
Inborn Errors of Metabolism
Bridget Reineking, MS, RD, CD and Sandy van Calcar, PhD, RD, CD

Background . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 232 1. Understand the basic principles of treating inborn
Phenylketonuria. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 234 errors of metabolism.
Natural History 2. Understand the biochemistry and medical nutrition
Maternal Phenylketonuria therapy for phenylketonuria.
Acute Management 3. Understand the biochemistry and medical nutrition
Chronic Management therapy for methylmalonic acidemia.
Methylmalonic Acidemia. . . . . . . . . . . . . . . . . . . . . . . . . . 237 4. Understand the biochemistry and medical nutrition
Natural History therapy for ornithine transcarbamylase deficiency.
Acute Management
Chronic Management
5. Understand the biochemistry and medical nutrition
therapy for very long-chain acyl Co-A dehydrogenase
Ornithine Transcarbamylase Deficiency. . . . . . . . . . . . . . 239
Natural History
deficiency.
Acute Management 6. Understand the biochemistry and medical nutrition
Chronic Management therapy for classic galactosemia.
Very Long Chain Acyl-CoA Dehydrogenase Deficiency. . . 240
Natural History Background
Acute Management Inborn errors of metabolism (IEM) are genetic disorders
Chronic Management caused by deficient production or function of specific
Galactosemia. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 241 enzymes, transport proteins, or enzyme cofactors in
Natural History protein, lipid, carbohydrate, or micronutrient metabolism.
Acute Management
The deficiency in enzyme activity results in accumulation
Chronic Management
of various abnormal metabolites that can cause detrimental
symptoms. Presentation of disease varies greatly depending
on the disorder, but severe forms of many disorders can
include overwhelming illness in the newborn period with
hypotonia, seizures, and coma associated with poor feeding
(Table 22-1). Many of these disorders can be fatal or cause
profound developmental delay if not treated promptly and
aggressively.
232
INBORN ERRORS OF METABOLISM 233
Table 22-1 Various Signs and Symptoms of Inborn Errors of Metabolism devoid of the amino acid(s) that cannot be fully metabo-
Overwhelming illness in the newborn period lized, but will provide all other amino acids, carbohydrates,
Recurrent vomiting fat sources, vitamins, and minerals. Medical foods often
provide a significant portion of a child’s nutrition needs. 3–5
Poor growth
Failure to thrive
Figure 22-1 Basic Principles of Nutrition Management of Inborn Errors
Developmental delay of Metabolism
Mental retardation
Loss of previously acquired skills
Hypotonia
Hypertonia
Seizures
Infantile spasms
Unusual odor
Episodes of rhabdomyolysis with intense exercise
Cardiomyopathy
Newborn screening is an important public health

program that can detect many IEM in the neonate, which
allows for early diagnosis and initiation of treatment.1
Newborn screening was initiated in the 1960s with detec-
tion of phenylketonuria (PKU). PKU is often referred to as
the model for newborn screening because the methodology
is reliable and cost-effective and there are clear benefits
from early intervention with medical nutrition therapy. In disorders where the blocked substrate is an essential
With the recent introduction of tandem mass spectrometry, amino acid, a limited but sufficient quantity of substrate
more than 30 IEM can now be detected from blood spots must be provided to allow for growth and protein mainte-
collected at 24 to 48 hours of age.1 The number of screened nance. This is accomplished by providing a source of intact
disorders varies by state, although a national uniform panel protein from regular infant formula or, for some disorders, a
has been recommended.2 Infants with abnormal screening limited quantity of breast milk is allowed. However, exces-
results are referred to specialized clinics with medical sive intake of the substrate(s) results in elevations in the
geneticists, metabolic dietitians, and genetic counselors to offending metabolites and can lead to detrimental symp-
assure prompt clinical evaluation and confirmatory testing. toms. Careful laboratory monitoring and proper nutrition
When the diagnosis is confirmed, appropriate medical and education is essential to treat IEM. 3–5
nutrition management is initiated. This chapter provides a basic overview of 5 disorders
The overall goal of treatment for IEM is to improve and to illustrate different types of IEM and their nutrition
maintain metabolic homeostasis. Medical nutrition therapy management. Various references are available that provide
plays a large role to achieve this goal. The basic principles detail about the biochemistry and treatment of the wide
of medical nutrition therapy for IEM include prevention range of IEM. 5–7 For any IEM, different phenotypes are
of catabolism with adequate caloric intake, restriction of possible and treatment can vary greatly depending on the
the offending substrate, supplementation of deficient prod- severity of the disorder. Presentation of a disorder can occur
ucts, and/or supplementation with the enzyme’s cofactor in infancy, childhood, or for some disorders, in adults. The
(Figure 22-1). In order to meet nutrient needs but prevent patient’s age, growth, and other clinical factors influence
excessive intake of substrates, specialized formulas, which the nutrition prescription. For many of these disorders, life-
are termed “medical foods,” have been developed for treat- long monitoring and treatment changes are required. The
ment of numerous IEM. Medical foods do not contain the involvement of a metabolic dietitian trained to manage IEM
substrate(s) that cannot be metabolized. For instance, a is imperative for successful treatment of these conditions.
medical food designed for an amino acidopathy will be

Phenylketonuria which 211 subjects with PKU were randomized at age 6 to

continue or discontinue the PKU diet.9 Results from this
Natural History study demonstrated that individuals with PKU who discon-
PKU is an inborn error of phenylalanine (phe) metabolism tinued the diet developed significant reductions in IQ and
caused by a deficiency of the hepatic enzyme phenylalanine academic performance by age 12 years.9 A follow-up study
hydroxylase (PAH), which catalyses the hydroxylation of 70 adults who participated in the PKU Collaborative
of phe to tyrosine (Figure 22-2). PKU is an autosomal Study found significantly fewer adverse medical, cognitive,
recessive disorder with a carrier frequency of 1 in 50 and and psychological outcomes in those who were random-
incidence of approximately 1 in 10,000 to 15,000 births in ized to remain on diet compared with those who stopped
those of European ancestry. More than 500 mutations have diet treatment at age 6.12 Conclusions from these and other
been identified in the PAH gene, but genotype/phenotype studies led to the recommendation of life-long treatment for
correlations have not proven to predict outcome. 8 PKU.13–15
Figure 22-2 Phenylketonuria (PKU) results from a deficiency of Maternal Phenylketonuria

phenylalanine hydroxylase (PAH) with elevated phenylalanine Phenylalanine is a known teratogen and in utero exposure
concentrations and tyrosine deficiency. PAH requires the cofactor
tetrahydrobiopterin (BH4). to elevated phe concentrations interferes with embryonic
development.16 Infants born to women with uncontrolled
phe levels during pregnancy are at risk for low birth weight,
microcephaly, congenital abnormalities, and mental retar-
dation. The National Maternal PKU Collaborative Study
(1984–2000) found that these detrimental effects to the
fetus could be prevented if maternal plasma phe concen-
trations remained below 6 mg/dL prior to conception and
throughout pregnancy.17,18 Education about the risks of
elevated phe concentrations during pregnancy should begin
early in adolescence for all females with PKU.
Adapted from Acosta PB, Yannicelli S. The Ross Metabolic Formula System Acute Management
Nutrition Support Protocols. 4th ed. Columbus, OH: Ross Products
Division/Abbott Laboratories; 2001. Copyright © 2001 with permission
from Abbott Nutrition. Initial Presentation
When an infant with PKU is identified by newborn
PKU is often classified based on the degree of phe screening, treatment should be initiated as soon as possible.
elevation in blood prior to initiation of treatment. Those Depending on the degree of elevation in plasma phe, dietary
with classic PKU show blood phe elevations > 20 mg/dL phe is eliminated or greatly reduced in the diet until blood
(normal phe is < 2 mg/dL). Untreated classic PKU results phe levels decrease to the treatment range of 2 to 6 mg/dL.
in profound mental retardation, seizures, and autistic-like This can be accomplished by feeding exclusively a phe-free,
behavior. Treatment with a phe-restricted diet ameliorates but otherwise nutritionally complete, medical food. Once
this outcome and those with classic PKU can have similar plasma phe concentrations are reduced to < 6 mg/dL, a
intelligence quotient (IQ ) and developmental potential as limited quantity of an intact protein is added to the medical
their unaffected siblings.9 On the other end of the spectrum, food to meet minimum phe needs for growth and protein
phe elevations in those with mild hyperphenylalaninemia maintenance (Table 22-2). 3–5 The intact protein source can
(HPA) remain < 10 mg/dL and may not require any diet be provided by a standard infant formula or breast milk.
modification. 3–5 Phe concentrations may increase during times of illness
Treatment recommendations for PKU have evolved since or severe injury. Prevention of catabolism can minimize
diet treatment was first described in the 1950s.10 Initially, these elevations. During illness, individuals with PKU are
metabolic specialists discontinued the phe-restricted diet at encouraged to reduce phe intake but continue to consume
6 years of age because it was felt that brain development was the phe-free medical food. If gastrointestinal symptoms
complete and continuation of the diet could cause nutri- develop, the medical food can be discontinued and carbo-
tion deficiencies.11 This practice was formally evaluated hydrate-based beverages can be provided to increase caloric
in the National PKU Collaborative Study (1968–1984) in intake to help slow catabolism. 3 Efforts should be made to

select medications that are phe-free. The source of phe in Figure 22-3. Calculating a Low-Phe Formula
pediatric medications is typically in the flavoring agents An infant weighing 3.6 kg is diagnosed with PKU with an initial blood phe
which may contain aspartame (Nutrasweet®) as the sweet- concentration of 15 mg/dL. Determine an appropriate formula for this
infant.
ener. Aspartame is a dipeptide derived from aspartic acid
Answer:
and phenylalanine.19
Provide a phe-free formula until phe concentrations are < 6 mg/dL. Then
add an intact protein source to meet nutrition needs.
TABLE 22-2 Recommended Daily Nutrient Intakes for Phenylketonuria
Nutrient Determine Needs
PHE TYR Protein Energy 1) Determine Phe Requirement Using Table 22-2.
Age
(mg/kg) (mg/kg) (g/kg) (kcal/kg) 3.6 kg × 45 mg of phe*/kg = 162 mg of phe per day
Infants *Phe requirements range from 25-70 mg/kg. Given the moderate
120 elevation in blood phe of 15 mg/dL, phe requirements are estimated
0 to < 3 mo 25 – 70 300 – 350 3.50 – 3.00 at 45 mg/kg.
(145 – 95)
120 2) Determine Tyrosine (Tyr) Requirement
3 to < 6 mo 20 – 45 300 – 350 3.50 – 3.00
(145 – 95) 3.6 kg × 325 mg of tyr/kg = 1170 mg
110
6 to < 9 mo 15 – 35 250 – 300 3.00 – 2.50 3) Determine Protein (Pro) Requirement
(135 – 80)
105 3.6 kg × 3.2 g of pro/kg = 11–12 g of pro
9 to < 12 mo 10 – 35 250 – 300 3.00 – 2.50
(135 – 80) 4) Determine Calorie (kcal) Requirement
Girls and Boys (mg/d) (g/d) (g/d) (kcal/d) 3.6 kg × ~ 120 kcal/kg = 430–450 kcal
1,300
1 to < 4 yr 200 – 400 1.72 – 3.00 ≥ 30 Calculate Formula
(900 – 1800)
1,700 1) Determine the Amount of Infant Formula Needed to Meet Phe Needs
4 to < 7 yr 210 – 450 2.25 – 3.50 ≥ 35
(1300 – 2300) Infant formula A contains 330 mg of phe in 100 g
2,400
7 to < 11 yr 220 – 500 2.55 – 4.00 ≥ 40 162 mg of phe needed per day ×
(1650 – 3300) = 49 g of Infant
100 g of infant formula
Women Formula A Needed
330 mg of phe
2,200
11 to < 15 yr 250 – 750 3.45 – 5.00 ≥ 50
(1500 – 3000) 2) Determine Amount of Kcals and Protein in Infant Formula
2,100 Infant formula A contains 10.8 g of protein and 518 kcal in 100 g
15 to < 19 yr 230 – 700 3.45 – 5.00 ≥ 55
(1200 – 3000)
2,100 49 g infant formula A × 10.8 g protein
≥ 19 yr 220 – 700 3.75 – 5.00 ≥ 60 = 5.3 g of protein
(1400 – 2500) 100 g of infant formula
Men 49 g of infant formula A × 518 kcal
= 254 kcals
2,700 100 g of infant formula
11 to < 15 yr 225 – 900 3.38 – 5.50 ≥ 55
(2000 – 3700) 3) Determine Amount of Phe-Free Medical Food B Needed to Meet
2,800 Protein Needs
15 to < 19 yr 295 – 1100 4.42 – 6.50 ≥ 65
(2100 – 3900)
Phe-free medical food B contains 15 g of protein in 100 g
2,900
≥ 19 yr 290 – 1200 4.35 – 6.50 ≥ 70 11.5 g total protein needs – 5.3 g of protein from Infant formula A =
(2000 – 3300)
6.2 or ~6 g of protein needed
Adapted from Acosta PB, Yannicelli S. The Ross Metabolic Formula System
Nutrition Support Protocols. 4th ed. Columbus, OH: Ross Products 6 g of protein needed × 100 g of
medical food B = 40 g of phe-free
Division/Abbott Laboratories; 2001. Copyright © 2001 with permission medical food
from Abbott Nutrition. 15 g of protein
4) Determine Kcal from Phe-Free Medical Food B
Chronic Management
The goal of chronic management for PKU is restriction of 40 g of medical food B × 480 kcal
= 192 kcal
dietary phe to maintain blood phe concentrations within 100 g of phe free medical food
the recommended treatment range of 2 to 6 mg/dL from Final Recipe
infancy to age 12 years and 2 to 10 mg/dL in adolescents.14 Product Amount Phe (mg) Pro (g) Calories
However, with the concern of maternal PKU, adoles- Infant Formula A 49 g 162 mg 5g 254 kcal
cent girls should be encouraged to maintain levels below Phe-free medical
40 g 0 mg 6g 192 kcal
6 mg/dL. Additional treatment goals include maintenance food B
of adequate growth velocity and weight gain, prevention Total — 162 mg 11 g 446 kcal
of protein deficiency, and achieving adequate macro- and Volume required at 20 kcal/oz = 22 fl oz (625 mL)
micronutrient status. 3–5

Dietary phe must be quantified to achieve blood phe Table 22-3 Example of Daily Meal Plan for Classic Phenylketonuria
control. Phe needs vary between individuals and change Age: 3 years, 9 months
with age, weight, and growth velocity (Table 22-2). In Weight: 15.2 kg
infancy, the phe requirement is supplied by a standard Height: 101 cm
infant formula or breast milk (Figure 22-3). Adjustments Sex: Female
in the phe prescription are based on frequent monitoring of Medical Food Prescription: 125 g of Phenex-2® unflavored + 18 fl oz of
blood phe concentrations. If blood phe concentrations are water = 20 fl oz total volume
elevated above the treatment range, the amount of intact Daily Phenylalanine Prescription from Foods: 200 mg
protein must be decreased incrementally until phe concen- Estimated Needs: Protein: > 30 g/d Kcal: 900 – 1800 kcal/d
trations are within the treatment range. 3–5 Food or Liquid Amount
Meal Phe Protein Calories
Breastfeeding is possible in the treatment of PKU; Offered Eaten
metabolic control in infants allowed to breastfeed is similar Medical Food 6 oz 0 mg 11 g 154 kcal
to those consuming a regular infant formula as their phe Froot Loops® 6g 17 mg 0.4 g 25 kcal
source.20,21 To maintain phe concentrations within the Crackles®
Breakfast Low-Protein 30 g 7 mg 0.2 g 120 kcal
treatment range, adjustments are made in the prescribed
Cereal
volume of phe-free medical food to effectively increase or Blueberries,
decrease the infant’s intake of breast milk. Medical food 32 g 8 mg 0.2 g 18 kcal
fresh
may be provided prior to each breastfeeding or feedings of Medical Food 7 oz 0 mg 13 g 179 kcal
medical food and breastfeeding may be alternated.20,21 The French Fries,
average phe content of breast milk is known and is higher in Ore-Ida® 56 g 50 mg 1.4 g 80 kcal
Golden Fries
colostrum than mature milk by approximately 60%.22,23
Broccoli,
Total protein needs for infants and children with PKU Lunch cooked
28 g 14 mg 0.6 g 6.0 kcal
may be greater than protein needs for the general popula- Thousand
tion (Table 22-2) because of rapid amino acid absorption Island 16 g 6 mg 0.1 g 59 kcal
and utilization when free amino acids rather than an intact Dressing
protein are given as the source of protein. 24 Caloric require- Peaches,
57 g 8 mg 0.3 g 42 kcal
canned
ments should be determined using dietary reference intake Cantaloupe,
(DRI) estimates and adjusted based on frequent growth Snack 27 g 8 mg 0.2 g 9 kcal
fresh
measurements.25 Medical Food 7 oz 0 mg 13 g 179 kcal
An individual’s phe requirement is the same regardless of Sweet Potato,
the source of intact protein consumed (formula, breast milk, with skin, 22 g 25 mg 0.4 g 23 kcal
Dinner baked
or solid food). When an infant transitions to solids, the infant
Green beans,
formula or breast milk is decreased and replaced by an equiv- canned
28 g 14 mg 0.4 g 6 kcal
alent amount of phe from foods. Caregivers are instructed Pears, canned 90 g 8 mg 0.2 g 66 kcal
to “count” milligrams of phe or use an exchange system (1 Zoo Animal
exchange = 15 mg phe). References are available that list the Crackers, 22 g 20 mg 1.6 g 94 kcal
phe content of various foods and beverages.3,26,27 Accuracy in Snack Farley’s®
Sorbet,
measuring medical food, infant formula, and foods is impera- strawberry
122 g 15 mg 0.4 g 119 kcal
tive for successful management of PKU. The use of a gram 200 1179
scale is recommended because small measurement errors can Total 43.4 g
mg kcal
lead to significant changes in blood phe concentrations. % from
Phe is found in any food containing protein. Meat, medical 0% 85.3% 43.4%
food
legumes, nuts, and dairy products are too high in phe and
are not allowed in the phe-restricted diet. Grains, fruits, and Low-protein food products, made primarily from wheat
vegetables must be precisely measured and the phe content starch (instead of wheat flour), are available to increase variety
carefully calculated to ensure proper blood phe control and meet the caloric needs of individuals with PKU. Products
(Table 22-3). For the PKU diet, “free” foods and beverages include low-protein baking mixes, bread, rice, pasta, peanut
are those that contain no protein (and no phe) such as sugars butter, cereals, and snack chips. Some food companies also
and fats. 3,27 market low-protein specialty items such as “chicken” nuggets,

“hamburgers,” “egg” replacers, and cheese. Several low- the low-phe diet or eliminates the need for medical food.42
protein cookbooks for PKU are also available.28,29 Continued involvement of a trained dietitian and geneticist is
In PKU, decreased PAH activity reduces the production imperative.
of tyrosine; thus, tyrosine becomes an essential amino acid
for this population (Figure 22-2). Medical foods for PKU Methylmalonic Acidemia
are supplemented with tyrosine and additional tyrosine
supplementation is indicated only if the combination of Natural History
intact protein and medical food does not meet tyrosine Methylmalonic acidemia (MMA) is an inborn error of
requirements. Plasma tyrosine concentrations should be isoleucine (ile), methionine (met), threonine (thr), valine
routinely monitored in individuals with PKU. 3,4 (val), and odd-chain fatty acid metabolism caused by a
Some micronutrients may be insufficient in the low-phe deficiency of the enzyme methylmalonyl-CoA mutase,
diet, particularly in those consuming a suboptimal amount which converts methymalonyl CoA to succinyl-CoA with
of medical food. Inadequate intake of iron, folate, vitamin eventual oxidation in the citric acid cycle (Figure 22-4). In
B12 , calcium, and vitamin D has been reported. 30–32 Dietary MMA, methylmalonyl CoA is not metabolized and leads
intake should be analyzed for micronutrient content and to accumulation of various methylmalonate metabolites.
additional supplementation prescribed as needed. 33 In addi- The degree of deficiency in the mutase enzyme affects
tion, intake of essential fatty acids (EFAs) may be low even the clinical outcome of this disorder.6,7,43 Those classi-
with sufficient intake of medical food and erythrocyte EFA fied with mut-deficiency have some residual activity and
profiles should be routinely assessed. 34–36 If low concentra- often a less severe clinical course than those with mut0
tions are found, vegetable oils such as canola or walnut oil or deficiency who have no remaining enzyme activity.43,44
a docosahexaenoic acid (DHA) supplement can be added to Methylmalonyl-CoA mutase requires the cofactor 5-dehy-
the diet. Some medical formulas designed for PKU are now droxyadenosylcobalamin, which is produced from vitamin
supplemented with arachidonic acid (ARA) and DHA. B12 . Defects in the production of the cobalamin cofactor can
Large neutral amino acids (LNAAs): Phenylalanine also cause MMA. The estimated prevalence of MMA is 1 in
and other LNAAs (leucine, valine, isoleucine, methionine, 80,000 births.45,46
tyrosine, tryptophan, and threonine) share common trans- Infants with classic MMA caused by a severe deficiency
porters at the blood-brain barrier and intestinal mucosa. In of the mutase enzyme often present in the first week of life
PKU, competitive inhibition from high concentrations of with overwhelming illness. Symptoms include poor feeding,
phe reduce the transport of other LNAAs into the cerebral failure to thrive, hypotonia, vomiting, and dehydration with
cells, which may reduce synthesis of various neurotrans- ketosis, acidosis, hyperammonemia, and hypoglycemia.43,44
mitters. 37 Supplementation with high doses of LNAAs Acute episodes are often fatal without aggressive manage-
can reduce both blood and brain concentrations of phe; ment. Screening for MMA is now included in the expanded
improved executive function skills have been measured newborn screening panel, which is expected to improve
in those with poor dietary control who were treated with early diagnosis and clinical outcomes of this disorder.47
LNAA supplements. 38,39 Several LNAA formulations are Individuals with a deficiency in the mutase enzyme
now commercially available. require medical nutrition therapy, described below. Despite
Cofactor supplementation: A newer therapy for the treat- treatment, those with severe mutase deficiency often have
ment of PKU is supplementation with a synthetic form impaired developmental and medical outcomes.48,49 For
of tetrahydrobiopterin, the cofactor for the PAH enzyme patients with MMA caused by a mild, late-onset mutase
(sapropterin dihydrochloride, Kuvan®) (Figure 22-2). deficiency or a defect in cofactor production, supplementa-
For some individuals, administration of sapropterin can tion with high doses of vitamin B12 may improve metabolic
improve PAH activity and, thus, lower blood phe levels.40,41 control and allow for more normal development. This is
In a phase III randomized, placebo-controlled, double-blind particularly true for those with a cbl A defect.43 Other
study, 44% of those taking sapropterin for 6 weeks showed cofactor deficiencies, such as cbl B and cbl C defect, can
a reduced phe concentration of 30% or greater.40 Response have a more complicated clinical course and require both
to sapropterin needs to be individually assessed as not all medical nutrition therapy and vitamin B12 supplementa-
individuals with PKU will respond to supplementation and tion.43,50 Liver transplantation is now an option for treatment
the degree of response to the drug varies. Supplementation of this disorder, particularly for those with severe enzyme
with sapropterin rarely allows for complete liberalization of deficiency. 51–53

Figure 22-4 Methylmalonic acidemia is caused by a defect in methylmalonyl CoA mutase. Two of 6 known cobalamin cofactor synthesis defects are
shown, which also cause methylmalonic acidemia.
Adapted from Nyhan WL, Barshop BA, Ozand PT. Atlas of Metabolic Diseases. 2nd ed. New York, NY: Oxford University Press Inc; 2005. Reproduced by
permission of Edward Arnold (Publishers) Ltd.
Acute Management For management of illness at home, a “sick-day diet”

is prescribed to reduce intact protein and increase caloric
Initial Presentation intake. If tolerated, medical food is continued to provide
Infants with MMA presenting in an acute episode require adequate amino acids and kilocalories to promote protein
immediate medical attention to control acidosis, hyperam- anabolism. For individuals with less severe febrile illness,
monemia, and hypoglycemia.43,54,55 Nutrition management the sick-day diet may prevent the need for further medical
during the acute phase of illness concentrates on delivery of intervention. For severe illness, aggressive medical interven-
nonprotein calories to help slow catabolism. Typically, intra- tion is required.6,55 Caretakers need to be educated about the
venous (IV) dextrose at the maximum glucose infusion rate signs of metabolic decompensation and provided with an
with additional lipid is provided to achieve maximal caloric emergency protocol that includes contact information for
intake. 55 IV carnitine may also be indicated.6 the metabolic team.
Medical foods for the treatment of MMA are available
which contain all amino acids except ile, met, thr, and val.56 Chronic Management
If enteral feedings are poorly tolerated, specialized parenteral The long-term medical nutrition therapy for individuals
solutions are available that lack the offending amino acids. with mutase deficiency includes restriction of the amino
As metabolic control improves, a standard infant formula acids ile, met, thr, and val with adequate caloric intake to
or standard total parenteral nutrition solution is added to prevent catabolism. 3,5,56 Often, a medical food restricted in
provide a complete source of protein and meet the individual’s these 4 amino acids provides the primary source of calo-
met, val, ile, and thr needs.3,5 Monitoring of ammonia, preal- ries, other amino acids, and micronutrients. Intact protein
bumin, bicarbonate, and plasma amino acids is necessary to from infant formula or expressed breast milk is added
adjust the dietary prescription to achieve optimal metabolic to provide adequate intake of ile, val, thr, and met. This
control. allows for adequate growth and protein maintenance, but
prevents excessive intake of these amino acids, which can
Illness lead to excessive production of methylmalonic acid and its
During illness and injury, an increase in the metabolic rate metabolites. 57 The amount of intact protein allowed in the
leads to catabolism of protein. In MMA, the offending diet depends on the individual’s tolerance for the offending
amino acids cannot be utilized and a metabolic episode, amino acids. Supplementation with individual amino acids,
with symptoms similar to those observed during the initial particularly ile and/or val, may be required to meet needs of
episode in infancy, can develop. Metabolic crisis associated these offending amino acids without increasing the concen-
with illness or injury can occur at any age and can be life tration of other offending amino acids. 3,56 Depending on the
threatening if not managed aggressively.48,55 child’s clinical status, foods such as fruits, vegetables, and

grains can replace the amino acids provided by the standard

Figure 22-5 Nitrogen metabolism in the urea cycle. Ornithine
infant formula or breast milk. transcarbamylase (OTC) deficiency results in hyperammonemia, elevated
For those responding to vitamin B12 supplementation, L-glutamine concentrations, and deficiency of L-arginine. Other enzymes in
typical oral doses include 1000 to 2000 mcg/d or similar the urea cycle include angininosuccinate synthetase (AS), argininosuccinate
lyase (AL), and arginase.
doses given 1 to 2 times per week via intramuscular (IM)
injection. 58 Hydroxycobalamin may be better metabolized
than cyanocobalamin in these disorders. 50
L-carnitine is often deficient in individuals with
MMA. 59 Carnitine binds to the metabolites produced
in this disorder; thus, individuals with MMA can have a
higher requirement for this nutrient. Supplementation
with prescription-strength L-carnitine (Carnitor®) is
common practice, especially if plasma carnitine deficiency
is observed. Doses for carnitine supplementation range
from 60 to 200 mg/kg.6 Side effects from excessive carni-
tine intake include diarrhea and a fishy odor.
Laboratory monitoring is required to assess metabolic
status and determine dietary prescription changes. Labs
typically include plasma or serum concentrations of amino
acids, carnitine, acyl carnitine profile, methylmalonic acid,
ammonia, and/or urine organic acid analysis.54,56 In addi-
tion to these indicators, labs to assess general nutrition status Adapted from Acosta PB, Yannicelli S. The Ross Metabolic Formula System
such as iron indices, calcium, vitamin D, EFAs, and albumin/ Nutrition Support Protocols. 4th ed. Columbus, OH: Ross Products
Division/Abbott Laboratories; 2001. Copyright © 2001 with permission
prealbumin concentrations should be routinely assessed. 3 from Abbott Nutrition.
Ornithine Transcarbamylase Deficiency Acute Management

Acute management may be necessary at the time of initial
Natural History presentation or with any intercurrent illness or injury. The
The most common inborn error of metabolism of the urea cycle goal of acute management of OTC deficiency is to slow
is deficiency of the enzyme ornithine transcarbamylase (OTC) protein catabolism and, thus, reduce ammonia production
(Figure 22-5). OTC deficiency impairs urea cycle function, by providing a nonprotein, high-calorie nutrition source
resulting in hyperammonemia as conversion of ammonia to via enteral or parenteral nutrition. 55,62,63 As clinical status
nontoxic urea is impaired. Production of arginine is decreased, improves, essential amino acids are provided to prevent
and arginine becomes an essential amino acid in this disorder.6,7 further protein breakdown. Essential amino acids can be
OTC deficiency is an X-linked disorder; therefore, males are provided with specialty total parenteral nutrition solutions
often more severely affected than females. However, there is or enteral medical foods designed for treatment of urea
a wide range of clinical presentations, including adult-onset cycle disorders. Providing essential amino acids promotes
OTC deficiency in affected women.60 protein anabolism, yet restricts intake of the nonessential
The severe form of the disease is characterized by amino acids that can contribute to the nitrogen load.62,63
overwhelming hyperammonemia (> 400 µmol/L) in the Since arginine is an essential amino acid in OTC defi-
newborn period causing recurrent vomiting, lethargy, ciency, supplementation with oral or IV L-arginine is often
irritability, and seizures, which can quickly cause coma indicated during illness. Arginine bypasses the enzymatic
and death if not treated aggressively. Mental retardation block to allow for conversion of urea rather than further
is common in those surviving the initial episode.60 Milder ammonia production. Acute medical management often
forms of the disorder may not present until later in life after includes use of nitrogen-scavenger drugs, which are avail-
a severe illness and can include neurological complications, able in both oral (Buphenyl®) and IV forms (Ammunol®).
such as psychosis.61 Long-term outcome with treatment These medications bind to accumulated precursors to
varies greatly and often depends on the ability to prevent reduce toxicity.64,65 Liver transplantation is now an option
further episodes of hyperammonemia. for treatment of this disorder.66,67

Chronic Management Figure 22-6. Fatty Acid Oxidation and VLCAD Deficiency.
There is a wide range of clinical phenotypes in OTC Fatty acid oxidation requires entry of long-chain fatty acids (LCFAs) into the
deficiency and, thus, dietary management needs to be mitochondria. This process requires L-carnitine. Carnitine cycle enzymes
individualized. Chronic management of OTC deficiency include acyl-CoA synthetase (AS), carnitine palmitoyltransferase I and II
(CPT I and CPT II), and acylcarnitine/carnitine translocase (CT). Once in the
includes dietary restriction of total protein; approximately mitochondria, the ß-oxidation spiral sequentially oxidizes the fatty acyl-CoA
50% of total protein from intact sources and 50% from a to the 2-carbon unit acetyl-CoA. Oxidation of LCFA requires very long-chain
medical food containing essential amino acids as the protein acyl-CoA dehydrogenase (VLCAD) and a trifunction protein which includes
3 enzyme activities. In treatment of LCFA, supplementation with medium
source is typically recommended. 5,62,63,68 Often, the protein chain triglycerides (MCTs) bypasses the long-chain fatty acid enzymes and
prescription for OTC deficiency is lower than the protein utilizes enzymes that oxidize medium and short-chain fatty acids including
requirements outlined in the DRIs. In infancy, the intact medium-chain acyl-CoA dehydrogenase (MCAD) and short-chain acyl-CoA
dehydrogenase (SCAD) enzymes.
protein source can include infant formula or expressed breast
milk with transition to lower protein foods in childhood.
The use of specialty low-protein food products is necessary
to meet caloric needs, increase satiety, and provide variety in
the diet. In addition, citrulline is routinely supplemented up
to 170 mg/kg as it is the precursor for arginine and utilizes
additional nitrogen via aspartate in the urea cycle.62
To assess metabolic control, frequent monitoring of
ammonia and plasma amino acids is necessary. Of partic-
ular interest are citrulline and arginine to evaluate citrulline
supplementation and glutamine which increases with exces-
sive protein intake (Figure 22-5).69 Additionally, assessment
of leucine, valine, and isoleucine is required as chronic use
of a nitrogen-scavenging medication may reduce concen-
trations of the branched-chain amino acids. 64 Additional
indices of nutrition status such as albumin/prealbumin and
iron status should be routinely monitored. 3
Very Long Chain Acyl-CoA Dehydrogenase

Deficiency
Natural History
Very long chain acyl-CoA dehydrogenase deficiency
(VLCADD) is an inborn error in the first step of mitochon-
drial β-oxidation of long-chain fatty acids (LCFAs) (14 to
20 carbons in length) resulting in disturbed energy produc-
tion with hypoglycemia, reduced ketone production, and Adapted from Nyhan WL, Barshop BA, Ozand PT. Atlas of Metabolic
production of abnormal long-chain fat metabolites (Figure Diseases. 2nd ed. New York, NY: Oxford University Press Inc; 2005.
22-6).6,7 Severe forms of this disorder can cause cardiomyo- Reproduced by permission of Edward Arnold (Publishers) Ltd.
pathy and myopathy and can be fatal in infancy without
medical intervention. Milder forms of this disorder may not Acute Management
present until later in life with episodes of muscle pain and The primary goal of acute management of VLCADD is to
rhabdomyolysis, especially after intense and/or prolonged provide sufficient kilocalories to prevent or reduce catabo-
exercise or during illness.70,71 Newborn screening can now lism of fat stores.6,7 A dextrose infusion at the upper threshold
detect infants with VLCADD. This disorder appears to of the glucose infusion rate is typically provided to reverse
be more common than earlier estimates since screening is catabolism.55,75 As enteral feeding becomes possible, sources
identifying those with milder forms of this disorder.72 Long- of glucose and medium-chain triglycerides (MCTs) can be
term development and outcome of those diagnosed and given to meet calorie demands. Intralipid® is contraindicated in
treated early can be favorable.73,74 VLCADD because it is a source of LCFAs.

Chronic Management typically includes measurement of fasting serum glucose,

Long-term management of VLCADD includes preven- creatine phosphokinase (CK), plasma carnitine and acyl-
tion of fasting, restriction of long-chain fat intake, and carnitine profiles, and erythrocyte essential fatty acids. 5,83
supplementation with MCTs. 5,74,76,77 Prevention of fasting,
especially in the newborn period when energy stores are Galactosemia
limited, is imperative to prevent breakdown of fat stores.
Fasting guidelines need to be individualized, but typically Natural History
fasting is limited to 4 hours for infants up to 4 months of Classic galactosemia is an autosomal recessive disorder
age.74,78 Longer periods of fasting can be allowed as the caused by the enzymatic deficiency of galactose-1-phos-
infant ages, but often a feeding during the night is recom- phate uridyl transferase (GALT) resulting in elevations of
mended during the first year.76 galactose-1-phosphate (Gal-1-P), galactitol, and galacto-
Nutrition therapy for VLCADD includes modifica- nate (Figure 22-7).6,7 The incidence of classic galactosemia
tion of fat sources to restrict intake of long-chain fat and is approximately 1 in 60,000 births. Various mutations
supplement with MCTs. Depending on the severity of the have been identified in the GALT gene. In the Caucasian
disorder, long-chain fat intake may need to be reduced population, a common mutation is Q188R; homozygosity
below 20% of total kilocalories during infancy. 5,74,76,77 The of this mutation results in a severe phenotype, often with
remaining fat kilocalories are supplied by MCTs, which 0% enzyme.84 Another common mutation is S135L, which
include fatty acids of 8 to 12 carbons in length and thus can results in a milder clinical course and is prevalent in the
bypass the enzymatic block in LCFA oxidation. There are African American population. Another form of galactosemia
several medical foods available for treatment of VLCADD is the Duarte variant, which results in a mild phenotype that
which contain limited amounts of long-chain fats and are may not require dietary intervention. 85
supplemented with MCTs. In mild forms of this disorder,
limited breastfeeding may be allowed.74,76,77
Figure 22-7 Classic galactosemia is a caused by a deficiency of
With the restriction in long-chain fat, it is important galactose-1-phosphate uridyl transferase (GALT). Elevations in galactose-
to assess the intake of the EFAs linoleic acid (LA) and 1-phosphate, galactose, galactitol and galactonate are present in this
alpha-linolenic acid (ALA). Supplementation with walnut, disorder.
flax, or safflower oil may be necessary to meet LA and ALA
needs.79 Some medical foods are supplemented with ARA
and DHA.
In older children with severe LCFA disorders, restric-
tion of long-chain fat to approximately 10% of total calories
may be necessary to maintain metabolic control.77,80 All
fat from food should be considered long-chain fat since
medium- and short-chain fats are limited in natural
food sources. Supplementation of low- or nonfat foods and
beverages with a commercial MCT source (available in
oil and powder) provides the remaining calories from fat.
With intense exercise, consuming MCT prior to activity
may be beneficial as an energy source during activity. 81
Addition of raw cornstarch to the nighttime feed may
be indicated in some children with VLCADD. Cornstarch
is a slowly digested source of glucose and is employed in
the treatment of glycogen storage disease to prevent hypo-
glycemia. 82 Cornstarch supplementation may be helpful
in fatty acid oxidation disorders to prevent low glucose
concentrations and reduce production of abnormal fat
metabolites during fasting.75 Because of poor digestion,
Adapted from Acosta PB, Yannicelli S. The Ross Metabolic Formula System
cornstarch is contraindicated before 9 months of age. 82 Nutrition Support Protocols. 4th ed. Columbus, OH: Ross Products
Routine monitoring to assess metabolic control Division/Abbott Laboratories; 2001. Copyright © 2001 with permission
from Abbott Nutrition.

Galactosemia is detected by newborn screening; however, amounts of both free and bound galactose.94–96 It remains
infants with severe galactosemia can present with symp- unclear if the minimal intake of galactose from some fruits
toms before newborn screening results are available. Acute and vegetables contributes excessive dietary galactose and
symptoms include cataracts, jaundice, failure to thrive, need to be eliminated from the diet.97 Calcium and vitamin
vomiting, sepsis, hepatomegaly, and liver failure. These D intake needs to be assessed in those on a galactose-
symptoms resolve quickly with medical intervention and a restricted diet. Supplementation is typically required for
diet restricted in galactose. 5,6,7 children who do not consume a soy-based formula or forti-
Treatment of classic forms of galactosemia requires a fied soy milk. 3,5
life-long galactose-restricted diet. Despite nutrition manage-
ment, long-term complications of classic galactosemia can Table 22-4 Foods and Ingredients That Contain Lactose or Galactose*
include mental retardation, neurological abnormalities, Milk Casein
speech delay, and ovarian failure in females.86,87,88 Abnormal Milk solids Calcium caseinate
bone metabolism has also been described in this popula- Nonfat dry milk Sodium caseinate
tion.89 The specific cause of these complications remains Nonfat dry milk solids Lactose
unknown, although endogenous production of galactose Dry milk Hydrolyzed whey protein
has been implicated.90 Butter Whey and whey solids
Buttermilk and buttermilk solids Lactalbumin
Cream Lactoglobulin
Acute Management
Garbanzo beans Dry peas/beans
Infants identified with classic galactosemia should be
Organ meats Milk chocolate
immediately placed on a soy-based infant formula. Soy Ice cream Sour cream
formulas, which contain soy protein isolate as the protein Sherbet Yogurt
source, have a very low galactose content compared to Cheese
cow’s milk-based formulas or breast milk. If an infant
* These foods and ingredients are eliminated in the dietary management
does not tolerate enteral feeds, standard total parenteral of classic galactosemia.
nutrition may be used. Efforts should be made to choose
medications that are free of lactose extenders. Unlike Erythrocyte Gal-1-P is the primary metabolite
some disorders of amino acid and fat metabolism, those monitored in galactosemia and maintenance of Gal-1-P
with galactosemia do not develop metabolic episodes concentrations below 4 mg/dL is considered optimal.91
associated with illness. When evaluating Gal-1-P concentrations, patient-specific
comparisons should be made; some individuals maintain
Chronic Management Gal-1-P concentrations above 4 mg/dL even with strict
Long-term management of classic galactosemia requires dietary management. Gal-1-P is not a sensitive measure
restriction of galactose in the diet. Galactose is primarily of treatment compliance; however, a significant increase
derived from lactose.91 During infancy, powdered soy above a patient’s typical Gal-1-P concentrations should be
formula is provided and breastfeeding is not allowed. investigated for possible dietary indiscretions.98
Powdered soy formula is recommended over ready-to-feed
or concentrated liquid soy formulas. Liquid soy formulas Test Your Knowledge Questions
contain a higher galactose content from the addition of 1. PKU is often referred to as the model for newborn
carageenan, although the digestive availability of galactose screening because:
from carageenan is unclear.92 Use of lactose-free elemental A. Screening is economically feasible and results are
formulas, which contain no galactose, have been used to reliable.
treat some infants with classic galactosemia with Gal-1-P B. Early medical nutrition therapy is available.
concentrations that have not decreased into the treatment C. Nutrition therapy prevents mental retardation asso-
range by 4 to 6 months of age.93 ciated with untreated PKU.
When starting solids, all dairy products are contrain- D. All of the above.
dicated. Caregivers are instructed to check food labels 2. When is total parenteral nutrition indicated for an indi-
for lactose- and galactose-containing foods and ingredi- vidual with methylmalonic acidemia (MMA)?
ents (Table 22-4). Galactose is also found in organ meats A. Standard total parenteral nutrition solutions should
and some legumes. Fruits and vegetables contain varying never be given to patients with this disorder.

B. Only specialty total parenteral nutrition solutions 10. Bickel H, Gerrard J, Hickmans EM. The influence of phenylala-
containing no isoleucine, methionine, threonine, nine intake on phenylketonuria. Lancet. 1953; 265:812–813.
11. Berry HK, Wright S. Conference on treatment of phenylketo-
and valine should be provided.
nuria. J Pediatr. 1967;70:142–147.
C. Depending on a patient’s clinical status, a combi- 12. Koch R, Burton B, Hoganson G, et al. Phenylketonuria
nation of specialty total parenteral nutrition and in adulthood: a collaborative study. J Inherit Metab Dis.
standard total parenteral nutrition can be provided. 2002;25:333–346.
D. Total parenteral nutrition is always contraindicated 13. Azen CG, Koch R, Friedman EG, et al. Intellectual develop-
in this disorder. ment in 12-year-old children treated for phenylketonuria. Am
J Dis Child. 1991;145:35–39.
3. In very long chain acyl CoA dehydrogenase deficiency 14. National Institutes of Health. Phenylketonuria (PKU):
(VLCADD), is/are contraindicated Screening and Management. NIH Consensus Statement.
because : Washington DC; 2000.
A. Medium chain triglycerides; they cannot be 15. Waisbren SE, Noel K, Fahrbach K, et al. Phenylalanine blood
metabolized levels and clinical outcomes in phenylketonuria: a system-
atic literature review and meta-analysis. Mol Genet Metab.
B. Intralipid®; of its long chain fat content
2007;92:63–70.
C. Carbohydrates; they interfere with oxidation of 16. Levy H, Ghavami M. Maternal phenylketonuria: A metabolic
fatty acids teratogen. Teratology. 1996;53:176–184.
D. Cornstarch; it helps prevent hypoglycemia and 17. Waisbern SF, Hanley W, Levy HL, et al. Outcomes at age
rhabdomyolysis 4 years in offspring of women with maternal phenylke-
tonuria: the Maternal PKU Collaborative Study. JAMA.
2000;283:756–762.
See p. 487 for answers. 18. Waisbren SE, Azen C. Cognitive and behavioral develop-
ment in maternal phenylketonuria offspring. Pediatrics.
References 2003;112:1544–1547.
1. Garg U, Dasouki M. Expanded newborn screening of 19. Yagasaki M, Hashimoto S. Synthesis and application of
inherited metabolic disorders by tandem mass spec- dipeptides; current status and perspectives. Appl Microbiol
trometry: clinical and laboratory aspects. Clin Biochem. Biotechnol. Epub. 2008;81:13–22.
2006;39:315–332. 20. van Rijn M, Bekhof J, Dijkstra T, Smit PG, Moddermam P, van
2. Watson AS, Mann MY, Lloyd-Puryear MA, Rinaldo P, Howell Spronsen FJ. A different approach to breast-feeding of the infant
RR. Newborn screening: toward a uniform panel and system. with phenylketonuria. Eur J Pediatr. 2003;162:323–326.
Executive summary. Genet Med. 2006;8:1–11S. 21. Greve LC, Wheeler MD, Green-Burgeson DK, Zorn EM.
3. Acosta PB, Yannicelli S. The Ross Metabolic Formula System Breast-feeding in the management of the newborn with
Nutrition Support Protocols. 4th ed. Columbus, OH: Ross phenylketonuria: a practical approach to dietary therapy. J Am
Products Division/Abbott Laboratories; 2001. Diet Assoc. 1994;94:305–309.
4. Elsas LJ, Acosta PB. Inherited metabolic disease: amino acids, 22. Lawrence RL. Breastfeeding: A Guide for the Medical Profession.
organic acids, and galactose. In: Shils ME, Shike M, Ross AC, 5th ed. St. Louis, MO: C.V. Mosby Co; 2005.
Caballero B, Cousins RJ, eds. Modern Nutrition in Health and 23. Leamons JA, Reyman D, Moye L. Amino acid composition
Disease, 10th ed. Philadelphia, PA: Lippincott, Williams & of preterm and term breast milk during early lactation. Early
Wilkins; 2006:909–959. Hum Dev. 1983;8:323–329.
5. Acosta PB, ed. Nutrition Management of Patients with Inherited 24. Gropper SS, Acosta PB. Effect of simultaneous ingestion of
Metabolic Disorders. Sudbury, MA: Jones & Bartlett; 2009. L-amino acids and whole protein on plasma amino acid and
6. Nyhan WL, Barshop BA, Ozand PT. Atlas of Metabolic Diseases. urea nitrogen concentrations in humans. J Parenteral Enteral
2nd ed. New York, NY: Oxford University Press Inc; 2005. Nutr. 1991;15:48–53.
7. Scriver CR, Beaudet AL, Sly WS, Valle D, eds. The Online Meta- 25. Otten JJ, Helwig JP, Meyers LD. Dietary Reference Intakes: The
bolic & Molecular Bases of Inherited Disease. New York, NY: Essential Guide to Nutrient Requirements. Washington, DC: The
McGraw-Hill, 2007. Available from http://www.ommbid.com. National Academies Press; 2006.
8. Guldberg P, Romano V, Ceratto N, et al. Mutational spectrum 26. Singh R, Lesperance E, Crawford K. PKU Food List. 2nd ed.
of phenylalanine hydroxlyase deficiency in Sicily: implications Atlanta, GA: Emory University, Department of Human
for diagnosis of hyperphenylalaninemia in southern Europe. Genetics, Division of Medical Genetics; 2006.
Hum Mol Genet. 1993;2:1703–1707. 27. Schuett V. Low Protein Food List for PKU. 2nd ed. Seattle, WA:
9. Koch R, Azen C, Friedman EG, Williamson ML and Writing National PKU News; 2002.
Committee for the PKU Collaborative Study. Paired compari- 28. Schuett V. Low Protein Cookery for PKU. 4th ed. Madison, WI:
sons between early treated PKU children and their matched The University of Wisconsin Press; 1996.
sibling controls on intelligence and school achievement test 29. Schuett V, Corry D. Apples to Zucchini: A Collection of Favorite
results at eight years of age. J Inherit Metab Dis. 1984;7:86–90. Low Protein Recipes. Seattle, WA: National PKU News; 2005.

30. Acosta PB, Yannicelli S, Singh RH, Elsas LJ, Mofidi S, Steiner 45. Sniderman LC, Lambert M, Giguere R, et al. Outcome of
RD. Iron status of children with phenylketonuria undergoing individuals with low-moderate methylmalonic aciduria
nutrition therapy assessed by transferrin receptors. Genet Med. detected through a neonatal screening program. J Pediatr.
2004;6:96–101. 1999;134:675–680.
31. Robinson M, White FJ, Cleary MA, et al. Increased risk of 46. Chace D, DiPerna J, Kalas T, Johnson R, Naylor E. Rapid diag-
vitamin B12 deficiency in patients with phenylketonuria on an nosis of methylmalonic and propionic acidemias: quantitative
unrestricted or relaxed diet. J Pediatr. 2000;136:545–547. tandem mass spectrometric analysis of propionylcarnitine in
32. Acosta PB, Yannicelli S. Plasma micronutrient concentrations filter-paper blood specimens obtained from newborns. Clin
in infants undergoing therapy for phenylketonuria. Biol Trace Chem. 2001;47:2040–2044.
Elem Res. 1999;67:75–84. 47. Dionisi-Vici C, Deodato F, Röschinger W, Rhead W, Wilcken
33. Hvas AM, Nexo E, Nielsen JB. Vitamin B12 and vitamin B6 B. ‘Classical’ organic acidurias, propionic aciduria, methylma-
supplementation is needed among adults with phenylketo- lonic aciduria and isovaleric aciduria: Long-term outcome and
nuria (PKU). J Inherit Metab Dis. 2006;29:47–53. effects of expanded newborn screening using tandem mass
34. Moseley K, Koch R, Moser AB. Lipid status and long-chain spectrometry. J Inherit Metab Dis. 2006;29:383–389.
polyunsaturated fatty acid concentrations in adults and adoles- 48. Van der Meer SB, Poggi F, Spada M, et al. Clinical outcome of
cents with phenylketonuria on phenylalanine-restricted diet. J long-term management of patients with vitamin B12-unrespon-
Inherit Metab Dis. 2002;25:56–64. sive methylmalonic acidemia. J Pediatr. 1994;125:903–908.
35. Koletzko B, Beblo S, Demmelmair H, Hanebutt FL. Omega-3 49. de Baulny HO, Benoist JF, Rigal O, Touati G, Rabier D,
LC-PUFA supply and neurological outcomes in children Saudubray JM. Methylmalonic and propionic acidae-
with phenylketonuria (PKU). J Pediatr Gastroenterol Nutr. mias: management and outcome. J Inherit Metab Dis.
2009;48(suppl):S2–7. 2005;28:415–423.
36. Beblo S, Reinhardt H, Demmelmair H, Muntau AC, Koletzko 50. Andersson HC, Shapira E. Biochemical and clinical response
B. Effect of fish oil supplementation on fatty acid status, coordi- to hydroxocobalamin versus cyanocobalamin treatment in
nation, and fine motor skills in children with phenylketonuria. patients with methylmalonic acidemia and homocystinuria
J Pediatr. 2007;150:479–484. (cblC). J Pediatr. 1998;132:121–124.
37. Puglisi-Allegra S, Cabib S, Pascucci T, et al. Dramatic brain 51. Nyhan WL, Gargus JJ, Boyle K, Selby R, Koch R. Progres-
aminergic deficit in a genetic mouse model of phenylketo- sive neurologic disability in methylmalonic acidemia despite
nuria. Neuroreport. 2000;11:1361–1364. transplantation of the liver. Eur J Pediatr. 2002;161:377–379.
38. Matalon R, Michals-Matalon K, Bhatia G, et al. Double blind 52. Morioka D, Kasahara M, Horikawa R, Yokoyama S, Fukuda
placebo controlled trial of large neutral amino acids in treat- A, Nakagawa A. Efficacy of living donor transplantation
ment of PKU: effect on blood phenylalanine. J Inherit Metab for patients with methylmalonic acidemia. Am J Transplant.
Dis. 2007;30:153–158. 2007;7:2782–2787.
39. Schindeler S, Ghosh-Jerath S, Thompson S, et al. The effects 53. McGuire PJ, Lim-Melia E, Diaz GA, et al. Combined liver-
of large neutral amino acid supplements in PKU: an MRS and kidney transplant for the management of methylmalonic
neuropsychological study. Mol Genet Metab. 2007;91:48–54. aciduria: A case report and review of the literature. Mol Genet
40. Levy HL, Milanowski A, Chakrapani A, et al. Efficacy of Metab. 2008;93:22–29.
sapropterin dihydrochloride (tetrahydrobiopterin, 6R-BH4) 54. Lee NC, Chien YH, Peng SF, et al. Brain damage by mild
for reduction of phenylalanine concentrations in patients with metabolic derangements in methylmalonic acidemia. Pediatr
phenylketonuria: a phase III randomized placebo-controlled Neurol. 2008;39:325–329.
study. Lancet. 2007;370:504–510. 55. Prietsch V, Lindner M, Zschocke J, Nyhan WL, Hoffmann
41. Burton BK, Grange DK, Milanowski A, et al. The response GF. Emergency management of inherited metabolic diseases.
of patients with phenylketonuria and elevated serum pheny- J Inherit Metab Dis. 2002;25:531–546.
lalanine to treatment with oral sapropterin dihydrochloride 56. Yannicelli S. Nutrition therapy of organic acidaemias with
(6R-tetrahydrobiopterin): a phase II, multicentre, open-label, amino acid-based formulas: emphasis on methylmalonic and
screening study. J Inherit Metab Dis. 2007;30:700–707. propionic acidaemia. J Inherit Metab Dis. 2006;29:281–287.
42. Singh R, Jurecki E, Rohr F. Recommendations for person- 57. Ney DM, Bay C, Saudubray JM, et al. An evaluation of protein
alized dietary adjustments based on patient response to requirements in methylmalonic acidaemia. J Inherit Metab
tetrahydrobiopterin (BH4) in phenylketonuria. Top Clin Nutr. Dis. 1985;8:132–142.
2008;23:149–157. 58. Wedel U, deBaulny HO. Branched-chain organic acidurias/
43. Merinero B, Perez C, Perez-Cerda A, et al. Methylmalonic acidemias. In: Fernandes J, Saudubray JM, van den Berghe G,
acidemia: examination of genotype and biochemical data in Walter JH, eds. Inborn Metabolic Diseases: Diagnosis and Treat-
32 patients belonging to mut, cbIA or cbIB complementation ment, 4th ed., rev. Heidelberg Germany: Springer Medizen
group. J Inherit Metab Dis. 2008;31:55–66. Verlag, 2006:245–260.
44. Shevell M, Matiaszuk N, Ledley F, Rosenblatt D. Varying 59. Chalmers RA, Roe CR, Stacey TE, Hoppel CL. Urinary
neurological phenotypes among mut0 and mut– patients excretion of L-carnitine and acylcarnitines by patients with
with methylmalonyl CoA mutase. Am J Med Genet. disorders of organic acid metabolism: evidence for secondary
1993;45:619–624. insufficiency of L-carnitine. Pediatr Res. 1984;18:1325–1328.

60. Maestri N, Clissold D, Brusilow S. Neonatal onset ornithine 77. Arnold GL, Van Hove J, Freedenberg D, et al. A Delphi
transcarbamylase deficiency: a retrospective analysis. J Peds. clinical practice protocol for the management of very long
1999;134:268-272. chain acyl-CoA dehydrogenase deficiency. Mol Genet Metab.
61. Bachmann C. Outcome and survival of 88 patients with urea 2009;96:85–90.
cycle disorders: a retrospective evaluation. Eur J Pediatr. 78. Walter J. Tolerance to fast: rational and practical evalua-
2003;162:410–416. tion in children with hypoketonaemia. J Inherit Metab Dis.
62. Leonard JV. The nutritional management of urea cycle disor- 2009;32:214–217.
ders. J Pediatr. 2001;138:S40–45. 79. Roe CR, Roe DS, Wallace M, Garritson B. Choice of oils for
63. Singh RH. Nutritional management of patients with urea essential fat supplements can enhance production of abnormal
cycle disorders. J Inherit Metab Dis. 2007;30:880–887. metabolites in fat oxidation disorders. Mol Genet Metab.
64. Scaglia F, Carter S, O’Brien W, Lee B. Effect of alterna- 2007;92:346–350.
tive pathway therapy on branched chain amino acid 80. Gillingham M, Connor W, Matern D, et al. Optimal dietary
metabolism in urea cycle disorder patients. Mol Genet Metab. therapy of long-chain 3-hydroxyacyl-CoA dehydrogenase
2004;81:79–85. deficiency. Mol Gen Metab. 2003;79:114–123.
65. Batshaw ML, MacArthur RB, Tuchman M. Alternative 81. Gillingham MB, Scott B, Elliott D, Harding CO. Metabolic
pathway therapy for urea cycle disorders: twenty years later. J control during exercise with and without medium chain
Pediatr. 2001;138:S46–54. triglycerides (MCT) in children with long-chain 3-hydroxy
66. Puppi J, Tan N, Mitry RR, et al. Hepatocyte transplantation acyl-CoA dehydrogenase (LCHAD) or trifunctional protein
followed by auxiliary liver transplantation—a novel treatment (TFP) deficiency. Mol Genet Metab. 2006;89:58–63.
for ornithine transcarbamylase deficiency. Am J Transplant. 82. Goldberg T, Slonim AE. Nutrition therapy for hepatic glycogen
2008;8:452–457. storage diseases. J Am Diet Assoc. 1993;93:1423–1430.
67. McBride K, Miller G, Carter S, et al. Developmental outcomes 83. Spiekerkotter U, Schwahn B, Korall H, Trefz FK, Andresen
with early orthotopic liver transplantation for infants with BS, Wendel U. Very-long-chain acyl-coenzyme A dehydro-
neonatal-onset urea cycle defects and a female patient with genase (VLCAD) deficiency: monitoring of treatment by
late-onset ornithine transcarbamoylase deficiency. Pediatrics. carnitine/acylcarnitine analysis in blood spots. Acta Paediatr.
2004;114:523–526. 2000;89:492–495.
68. Acosta PB, Yannicelli S, Ryan AS, et al. Nutritional therapy 84. Elsas LJ, Langley S, Paulk EM, Hjelm LN, Dembure PP.
improves growth and protein status of children with a urea A molecular approach to galactosemia. Eur J Pediatr.
cycle enzyme defect. Mol Genet Metab. 2005;86:448–455. 1995;154:S21–7.
69. Wilson CJ, Lee PJ, Leonard JV. Plasma glutamine and 85. Ficicioglu C, Thomas N, Yager C, et al. Duarte (DG)
ammonia concentrations in ornithine carbamoyltrans- galactosemia: A pilot study of biochemical and neurode-
ferase deficiency and citrullinaemia. J Inherit Metab Dis. velopmental assessment in children detected by newborn
2001;24:691–695. screening. Mol Genet Metab. 2008;95:206–212.
70. Pons R, Cavadini P, Baratt S, et al. Clinical and molecular 86. Waggoner DD, Buist NMR, Donnell GN. Long-term prog-
heterogeneity in very-long chain acyl-coenzyme A dehydro- nosis in galactosemia: results of a survey of 350 cases. J Inherit
genase deficiency. Pediatr Neurol. 2000;22:98–105. Metab Dis. 1990;13:802–818.
71. Smelt A, Poorthuis B, Onkenhout W, et al. Very long chain 87. Ridel KR, Leslie ND, Gilbert DL. An updated review of the
acyl-coenzyme A dehydrogenase deficiency with adult onset. long-term neurological effects of galactosemia. Pediatr Neurol.
Ann Neurol. 1998;43:540–544. 2005;33:153–161.
72. Liebig M, Schymik I, Mueller M, et al. Neonatal screening for 88. Bosch A. Classical galactosaemia revisited. J Inherit Metab
very long-chain acyl-CoA dehydrogenase deficiency: enzy- Dis. 2006;29:516–525.
matic and molecular evaluation of neonates with elevated 89. Panis B, Forget P, van Kroonenburgh MJPG, et al. Bone
C14:1-carnitine levels. Pediatrics. 2006;118:1065–1069. metabolism in galactosemia. Bone. 2004;35:982–987.
73. Vianey-Saban C, Divry P, Brivet M, et al. Mitochondrial 90. Berry GT, Moate PJ, Reynolds RA, et al. The rate of de
very-long-chain acyl-coenzyme A dehydrogenase deficiency: novo galactose synthesis in patients with galactose-1-
clinical characteristics and diagnostic considerations in 30 phosphate uridyltransferase deficiency. Mol Genet Metab.
patients. Clin Chim Acta. 1998;269:43–62. 2004;81:22–30.
74. Spiekerkoetter U, Lindner M, Santer R, et al. Treatment 91. van Calcar S, Wolff J. Galactosemia. In: Ekval S, Ekval VK,
recommendations in long-chain fatty acid oxidation eds. Pediatric Nutrition in Chronic Disease and Developmental
defects: consensus from a workshop. J Inherit Metab Dis. Disorders. 2nd ed. New York, NY: Oxford University Press.
2009;32:498–505. 2005:335–339.
75. Vockley J, Singh RH, Whiteman DA. Diagnosis and manage- 92. Acosta PB, Gross K. Hidden sources of galactose in the envi-
ment of defects of mitochondrial beta-oxidation. Curr Opin ronment. Eur J Pediatr. 1995;154:1–6.
Clin Nutr Metab Care. 2002;5:601–609. 93. Ficicioglu C, Hussa C, Yager C, Segal S. Effect of galactose
76. Rohr F, van Calcar S. Very long chain acyl CoA dehydroge- free formula on galactose-1-phosphate in two infants with
nase deficiency (VLCADD). Genetic Metabolic Dietitians classical galactosemia. Eur J Pediatr. 2008;167:595–596.
International, 2008. Available at: http://www.gmdi.org/
guidelines. Accessed September 4, 2008.

94. Gross K, Acosta PB. Fruits and vegetables are a source of 97. Kim H, Hartnett C, Scaman CH. Free galactose content in
galactose: implications in planning the diets of patients with selected fresh fruits and vegetables and soy beverages. J Agric
galactosaemia. J Inherit Metab Dis.1991;14:253–258. Food Chem. 2007;55:8133–8137.
95. Scaman C, Jin Wai Jim V, Hartnett C. Free galactose 98. Hutchesson AC, Murduck-Davis C, Green A, et al. Biochem-
concentrations in fresh and stored apples (malus domes- ical monitoring of treatment for galactosemia: biological
tica) and processed apple products. J Agric Food Chem. variation in metabolic concentrations. J Inherit Metab Dis.
2004;52:511–517. 1999;22:139–148.
96. Gropper S, Weese S, West P, Gross K. Free galactose content
of fresh fruits and strained fruit and vegetable baby foods:
more foods to consider for the galactose-restricted diet. J Am
Diet Assoc. 2000;100:573–575.

23
Cardiac Disease
Anupama Chawla, MD, CNSP, DCH (UK) Janice Antino, RD, MS, CNSD, CSP, and Mindy Freudenberg, RD, MS, CNSD

Congenital Heart Disease . . . . . . . . . . . . . . . . . . . . . . . . . 247 1. Identify factors contributing to growth failure in chil-
Malnutrition and Growth dren with congenital heart disease.
Nutrition Assessment 2. Summarize the components of nutrition assessment
Nutrition Management and optimal methods of nutrient delivery in children
Complications After Congenital Heart Disease Surgery
with congenital heart disease.
Cardiovascular Disease in the Pediatric Patient. . . . . . . 252 3. Recognize and manage postoperative complications
Summary. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 254 and prescribe appropriate nutrition therapy.
Congenital Heart Disease

Congenital heart diseases are abnormalities in the heart
structure that are present at birth. Approximately 8 out of
every 1,000 infants are born with congenital heart disease.
Congenital heart disease can be classified into 2 major cate-
gories, cyanotic and acyanotic1 (Table 23-1).
Pediatric heart disease can be a congenital or an acquired
condition. This population is presented with unique chal-
lenges in meeting their energy requirements for optimal
Table 23-1 Two Major Categories of Congenital Heart Disease
Acyanotic Cyanotic
Atrial septal defect (ASD) Interrupted aortic arch
Ventricular septal defect (VSD) Pulmonary atresia
Patent ductus arteriosus (PDA) Ebstein’s anomaly
Common A-V canal (CAVC)
Pulmonary stenosis*
Coarctation of aorta*
Aortic stenosis
Tetralogy of Fallot*
Transposition of the great vessels*
Total anomalous pulmonary venous return*
Truncus arteriosus*
Tricuspid atresia*
Hypoplastic left heart syndrome*
* These conditions may transition to cyanotic state.
247
growth and development. Depending on the congenital heart survivors. Children who died had impaired weight gain
disease lesion and its severity, a child with cogenital heart postoperatively compared to the long-term survivors who
disease may face feeding difficulties and malnutrition during showed a mean increase in weight age z scores.
a critical developmental period. Depending on the type of cardiac lesion, an infant with
congenital heart disease may undergo complete corrective
Malnutrition and Growth surgery or a staged palliative intervention leading to complete
Failure to thrive and malnutrition is well documented repair. The type of surgical treatment and the remaining
in infants and children with congenital heart disease. 2–4 cardiac defect can have a profound impact on the nutri-
Malnutrition has been identified in both acyanotic and tion rehabilitation process. The age and timing of corrective
cyanotic congenital heart disease however the degree of surgery may affect the potential for growth and nutrition
growth delay is often related to the severity of the anatom- recovery in infants with congenital heart disease.8 Infants
ical lesion and tends to be most severe in lesions associated with congenital heart disease will experience fewer deficits
with congestive heart failure (CHF). Cyanotic heart disease in weight and height if corrective surgery is performed in the
patients usually tend to be more undernourished due to first 10 days of life compared to infants undergoing surgery
their chronic hypoxic state and relatively prolonged course after the newborn period.9 Vaidyanathan et al evaluated the
until final correction, as these infants require surgery in nutrition status of infants with congenital heart disease who
several stages. underwent corrective surgery. Significant catch-up growth
At birth, the weight of infants with congenital heart was evident after 3 months, suggesting that correction of the
disease is usually appropriate for gestational age. Despite cardiac anomaly favorably influences the nutrition status of
normal or near-normal birth weights, infants with congen- infants with congenital heart disease.4 Corrective and timely
ital heart disease commonly experience a rapid decline in surgical intervention has been proposed as critical to avoid
weight for age percentiles reflecting acute malnutrition. If the long- and short-term consequences of malnutrition.4,9
malnutrition persists, height velocity will be affected within Although somatic growth is often impaired before surgical
a few months, resulting in stunting. Weight gain can be intervention, growth usually dramatically improves to normal
considerably less than expected to maintain normal growth or near-normal values after corrective surgery. In most infants
patterns. 5 Cameron et al reported the prevalence of acute catch-up growth is largely complete within 6 to 12 months of
and chronic malnutrition to be as high as 33% and 64%, surgery.4
respectively.6
Surgical correction has emerged as the most efficient Etiology of Growth Impairment
method to improve the nutrition status of these infants. The exact etiology for growth impairment in children with
Surgical correction eliminates the cardiac factors contributing congenital heart disease remains unclear. Many factors have
to malnutrition. Mitchell et al evaluated the nutrition status been identified as contributing to growth failure in this popu-
of 48 children with congenital heart disease before corrective lation (Table 23-2).
surgery.7 Significant undernutrition was evident in all children
Table 23-2 Factors Contributing to Growth Failure in Congenital Heart
irrespective of the cardiac lesion or the presence or absence of Disease
cyanosis. Fifty-two percent of the children had a weight under Etiology
the third percentile for age, 83% had abnormal biochemical Increased energy requirements Tachypnea and tachycardia can
and hematological measurements reflecting compromised increase metabolic demands
nutrition status, and 33% had abnormally high 3-methyhisti- Decreased energy intake Anorexia, dysphagia, reflux,
dine suggesting a degree of active muscle wasting. fatigue during feeding
Corrective surgery is usually not performed until a Increased nutrient losses Protein-losing enteropathy, renal
electrolyte losses
patient achieves an ideal weight and appropriate age or when
Insufficient utilization of nutrients Acidosis, hypoxia
growth failure or defect requires early correction. Eskedal Malabsorption Gut edema
et al also emphasized the role of nutrition in this popula-
tion during the postoperative period. 8 They evaluated the Decreased Nutrient Intake and Utilization
growth of 2 groups of infants with congenital heart disease Inadequate caloric intake, increased metabolic demands,
who underwent cardiac corrective surgery. Children who or a combination of both may be responsible for signifi-
survived past the thirtieth postoperative day but subse- cant growth impairment.9 Energy imbalance is a major
quently died were compared to children who were long-term factor contributing to malnutrition in these patients, and it

CARDIAC DISEASE 249
influences outcomes after corrective cardiac surgery. heart disease and normalized within 1 week after corrective
Feeding difficulties and intolerances are common surgery. It was also observed that standard equations fail to
during the first year of life in infants with congenital heart accurately predict REE in this population. When utilizing
disease. Vomiting occurs frequently in this population and the gold standard of measuring energy expenditure, using
has been identified as the most common feeding intoler- the doubly labeled water technique, TEE was considerably
ance.10,11 The energy intake of infants with congenital heart and consistently elevated compared to healthy controls.5,11
disease is often insufficient and loss of nutrients as a result of Although this method is considered the gold standard to
vomiting can further decrease the amount of energy avail- measure energy expenditure it is costly, requires specialized
able for growth. It has been estimated that vomiting after equipment, and is rarely used.
feeding can result in a loss of 12% of the infant’s energy Therefore, indirect calorimetry and predictive equa-
intake.11 Utilization of nutrients is compromised in the tions should be used cautiously as both may underestimate
setting of chronic hypoxia and acidosis is often seen in the energy needs of children with congenital heart disease.
infants with congenital heart disease.
Schwarz et al assessed the growth and energy intake of 19 Nutrition Assessment
infants with congenital heart disease who were not candidates A thorough and accurate nutrition assessment is the primary
for early corrective surgery.12 Anthropometric measurements step for early recognition of feeding difficulties and growth
began to improve only when energy intakes reached 150 kcal/ delay in children with congenital heart disease. This will result
kg. Considering the diversity of the population and varying in early intervention to help prevent nutrition deficiencies and
degrees of anomalies, an infant with congenital heart disease optimize growth. A complete nutrition assessment includes a
may require energy intakes of 140 to 200 kcal/kg body weight combination of methods that should include an accurate feed-
to induce growth.4 ing history, visual clinical assessment, anthropometric evalu-
ation, and biochemical indices (Table 23-3). Anthropometric
Energy Expenditure data such as weight, length/height, weight-for-length, and head
Infants with congenital heart disease have increased require- circumference can be evaluated using published growth charts
ments of energy and protein needed to promote growth and from the Centers for Disease Control and Prevention (CDC)
development. Studies examining an energy deficit whether or the World Health Organization (WHO) (see Chapter 33).
due to a decreased intake or increased energy expenditure Measurements should be plotted and monitored over time
can be difficult to interpret due to the heterogenicity of the to determine growth velocity and degree of growth failure.
congenital anomaly, severity of illness, and age.2 Congenital heart disease may be present in conjunction with
Several studies have been performed to evaluate the an underlying chromosomal abnormality. In these condi
methods traditionally used to determine the energy require- tions anthropometric data can be evaluated using specialized
ments in this patient population. Leitch et al used respiratory growth charts as available for children with trisomy 21, tri-
calorimetry to measure resting energy expenditure (REE) somy 18, Turners syndrome, and for infants born preterm.
and total energy expenditure (TEE) in 12 infants with uncor- Table 23-3 Components of Nutrition Assessment
rected cyanotic congenital heart disease and compared them in Congenital Heart Disease
to a group of age-matched controls at 2 weeks and again at 3 Medical history Type of lesion (cyanotic vs. acyanotic),
months of age. No significant differences in REE were iden- current medications, other medical
conditions
tified at either time, however a significant increase in TEE
Feeding history Type of formula, concentration of formula,
was identified at 3 months of age.2,3 Therefore an increased preparation methods, and amount
TEE but not an increased REE may be a primary factor in consumed; duration of feeds
the reduced growth of infants with cyanotic congenital heart Physical exam Fluid status/edema, cyanosis, respiratory
rate (tachypnea)
disease. This suggests that the use of REE should not be
Biochemical indices Serum electrolytes, albumin, prealbumin.
extrapolated to determine TEE, and that caloric recommen- Total lymphocyte count and stool for alpha-
dations determined by indirect calorimetry may significantly 1-antitrypsin if suspicious of protein-losing
underestimate the actual energy needs of these patients. enteropathy
Anthropometric data Weight, length/height, weight-for-length,
Nydegger et al used indirect calorimetry to assess the triceps skinfolds, mid-arm circumference
energy expenditure of 108 infants with various forms of Evaluation of growth Monitor weight gain and linear growth
congenital heart disease.9 When compared to healthy controls over time
an increased REE was observed in infants with congenital Gastrointestinal function Evaluation of bowel pattern (eg, frequency
and consistency), GI reflux

Biochemical evaluation should include prealbumin, longer than 8 weeks) then placing a gastrostomy tube should
serum albumin, and serum electrolytes including calcium, be considered. A gastrostomy tube is better accepted socially
magnesium, and phosphorus. Serum albumin results must and also decreases the risks associated with prolonged naso-
be interpreted with caution as it is highly sensitive to the gastric tube feeds. Dislodgement of the tube, stenting of the
patient’s hydration status. Prealbumin is influenced by infec- lower esophageal sphincter with increased reflux, sinusitis,
tion, sepsis, inflammation, and operative course and should be and nasal skin and cartilage breakdown are associated with
evaluated with consideration of non-nutrition factors. Fluid long-term use of nasogastric tubes.13
overload secondary to congestive heart failure, or dehydration
secondary to diuretics, can alter fluid and electrolyte balance Table 23-4 Concentrating Term Infant Formula
and may affect renal function. If the serum albumin is low then When using most infant powder: Preparing smaller volumes
protein-losing enteropathy (PLE) is a consideration and stool Desired Concentration Level Scoop from
Water (fl oz)
(cal/oz) Can
for alpha-1-antitrypsin and total lymphocyte count should be
24 5 3
obtained to assess for PLE (see Protein-Losing Enteropathy in
27* 4.25 3
this chapter).
For specialized infant formulas check manufacturer’s guidelines.
Nutrition Management
Concentrating liquid formula with term infant powder
Adequate nutrition intake is not always easily achieved in
Term Infant
infants and children with congenital heart disease. These Starting
Volume
Desired
Formula
infants require increased energy intakes to achieve significant Concentration Concentration
Powder
growth but are often unable to achieve their nutrition goal due 20 cal/oz
to anorexia and increased fatigue during feeding. (breast milk,
3 oz 24 cal/oz 1 teaspoon
ready-to-feed
formula)
Nutrient Delivery 24 cal/oz 4 oz 27* cal/oz 1 teaspoon
The primary goal is to maximize energy intake orally. When
oral intake alone fails to support growth and development, Using modulars to concentrate formulas
alternative methods of nutrition delivery are indicated and
To prepare 24 to 28 cal/oz from 20 cal/oz formula
should be initiated relatively early. Tube feedings should be
To Prepare To Prepare
considered to supplement inadequate oral intake. Volume of 24–25 cal/oz 27–28* cal/oz
In an effort to maintain the infant’s hunger and satiety Modular Formula Formula Formula
cycle, intermittent bolus tube feeds may be used to supple- 20 cal/oz (amount of (amount of
modular) modular)
ment oral nutrition intake. In order to preserve the infant’s oral
Duocal (14 kcal/
motor function and desire to eat, supplemental feeds should tsp) (Nutricia)
3 oz 1 teaspoon 1½ teaspoons
be delivered after allowing the infant to feed orally for 10 to 15
Vegetable Oil
minutes duration at each feed time. (9 kcal/5 mL)
Infants and children with CHF often need to be fluid Triglyceride
3 oz 1.5 mL 2.5 mL
restricted. Concentrating formula helps provide adequate Oil (MCT Oil)
(7.7 kcal/mL)
calories while limiting fluid intake. Increasing the formula (Nestle)
concentration from 20 cal/oz to 24 or 27 cal/oz can be Polycose (8 kcal/
achieved by the addition of modular components or by 3 oz 2 teaspoons 3 teaspoons
tsp) (Abbott)
reducing the water-to-powder ratio (Table 23-4). If intermit- *27–28 cal/oz may not supply enough water for some infants. Hydration
tent bolus feeds are not tolerated because of compromised status and renal solute load should be carefully monitored.
motility, reflux, or concomitant respiratory distress, then
continuous feeds should be considered. Continuous feeds Infants and children who are unable to meet their nutri-
allow delivery of daily requirements with smaller hourly tion needs via the enteral route should be considered for
volumes with decreased energy expenditure.12 Continuous, parental nutrition (PN). PN can be initiated pre- or postop-
24-hour nasogastric feedings are a safe and effective method eratively with a therapeutic goal of restoring or maintaining
of achieving increased nutrient intake resulting in improved nutrition status and inducing somatic growth. The optimal
overall nutrition status. If it is anticipated that the infant will timing for initiating PN is dependent on the child’s baseline
require supplemental feeds for a prolonged duration (eg, for nutrition status and disease acuity. In view of the relatively

CARDIAC DISEASE 251
high prevalence of malnutrition in infants and children with infants weighing less than 3 kg transesophageal echocar-
congenital heart disease, aggressive nutrition support via diography should be used cautiously.17
PN is an appropriate approach to prevent a further decline in
their nutrition status. PN formulation in children with con- Protein-Losing Enteropathy
genital heart disease requires close electrolyte monitoring, Protein-losing enteropathy (PLE) is an abnormal loss of pro-
especially in patients on diuretics and digoxin therapy. tein from the digestive tract or the inability of the digestive
Growth impairment is frequently documented in children tract to absorb proteins. The prevalence of PLE in infants
with congenital heart disease. It has been well documented and children with congenital heart disease seems most
that growth in children with congenital heart disease can be prominent after the Fontan procedure (anastomosis of the
significantly improved with adequate caloric intake.14 Signifi- inferior vena cava to the pulmonary artery, preferred sur-
cant caloric intake not only considerably impacts the surgical gical correction for tricuspid atresia, hypoplastic left heart,
outcomes but also the ultimate growth and development in and single ventricle physiology). PLE can be a life-threaten-
children with congenital heart disease. ing complication with onset of the disease occurring from
2 months to 10 years postoperatively.18 Within 10 years of
Complications After Congenital Heart Disease Surgery Fontan procedure surgery, approximately 13% of patients
will develop PLE. Forty-six percent of PLE patients develop
Feeding Difficulties significant morbidity and mortality within 5 years.18 Chil-
Infants and children often experience feeding difficulties dren with PLE lose protein molecules from the blood into
following cardiac surgery. Increased risk adjusted congen- the intestinal tract resulting in changes in bowel habits,
ital heart surgery (RACHS) score, prolonged intubation, abdominal discomfort, and diarrhea. Over time the con-
and intraoperative transesophageal echocardiography have centrations of serum protein can become severely depleted,
been identified as risk factors associated with feeding diffi- resulting in hypoproteinemia and especially hypoalbu-
culties among infants and children with congenital heart minemia. Hypocalcemia and lymphocytopenia are often
disease after surgery.15 Problems encountered may include seen in this condition as well. The loss of serum proteins
a prolonged time to reach feeding goals, prolonged transi- decreases the vascular oncotic pressure and promotes the
tion to oral feeds requiring tube feeding at discharge, and development of edema, ascites, and pleural as well as peri-
aspiration or reflux.15 Postoperative vocal cord dysfunc- cardial effusion. Edema of the intestinal wall secondary to
tion is also a clinically important complication following chronic hypoalbuminemia may result in poor absorption of
cardiac surgery and may increase the risk of aspiration due nutrients and promote worsening of the diarrhea.19
to an impaired airway protection. In a study by Sachdeva
et al patients whose surgery involved manipulation of the Nutrition Management
laryngeal nerves were at greater risk for vocal cord injury Nutrition management of infants and children with PLE
with the presumed cause being injury to the vagus nerve. should be tailored to the severity of bowel dysfunction,
An infant or child with vocal cord dysfunction may benefit diarrhea, and malabsorption. Dietary changes should
from a swallowing evaluation to identify the presence of include increasing protein intake and transition from long-
aspiration.16 Although in this particular study only 1.7% chain triglycerides (LCTs) to a medium-chain triglyceride
were identified as having vocal cord dysfunction, of these (MCT) based diet. The use of a MCT-enriched diet is based
patients 100% had abnormal swallowing study results. on the understanding that enterocytes directly absorb
Most of these patients need modified oral feeds and or MCTs into circulation, allowing delivery of adequate calo-
nutrition support. ries while reducing lymphatic flow to allow for healing.
Patients who undergo cardiac surgery with the use MCTs are rapidly absorbed and reduce the amount of high-
of transesophageal echocardiography have been associ- protein lymph fluid moving through the vessels within the
ated with a high risk of dysphagia as well. Transesophageal intestines, thereby reducing the quantity of protein loss. 20
echocardiography has been identified to cause airway ob- Specialized nutrition support with the use of very high
struction, common pulmonary vein compression, vascular MCT (80% to 90% of the total fat content) containing
compression, tracheal extubation, esophageal perforation, formulas (Table 23-5) should be provided to infants and
gastric perforation, and dental injury. Transesophageal children with intractable diarrhea who are unable to main-
echocardiography probe size in relation to the patient’s tain their nutrition status with standard formula.20 When
weight was identified as a risk factor for dysphagia. In using these formulas for long-term use, essential fatty acid

(EFA) deficiency should be monitored. In severe cases the 8 days if a chylous leak develops. 23 Conservative manage-
use of total parenteral nutrition may be implemented to ment is usually attempted prior to surgery for the resolution
allow complete enteric rest to minimize lymphatic flow and of the leak.
promote healing. Conservative management includes pleural space
evacuation, the use of low-fat diets with MCTs, or total
Table 23-5 Medium Chain Triglyceride Formulas for Infants parenteral nutrition for complete enteric rest. The use
and Children > 1 Year of Age of a MCT-enriched diet is based on the understanding
MCT FORMULAS FOR INFANTS that MCTs are readily absorbed by the enterocytes into
Formula MCT:LCT ratio circulation, providing adequate calories and minimizing
Pregestemil® (Mead Johnson) 55:45 lymphatic flow to allow for healing. 23 For formula feed-
Alimentum® (Abbott) 33:67 ings, a high-MCT low-LCT formula may be used (Table
Portagen® (Mead Johnson) 87:13
23-5). To prevent EFA deficiency, 2% to 4% of total calories
Monogen® (Nutricia) 90:10
should be in the form of linoleic acid with 0.25% to 0.5%
EleCare® (Abbott) 33:67
from linolenic acid. 24 If patients are on oral feedings and
Enfaport® (Enfamil) 84:16
adequate calories can be consumed, a low-fat diet may be
MCT FORMULA FOR CHILDREN > 1 YEAR OF AGE sufficient. In the study by EH Chan 34 of 48 patients (71%)
Formula MCT:LCT ratio had resolution with changes to their enteral diet. 23
Vivonex® Pediatric (Nestle Nutrition) 69:31 Octreotide, a long-acting synthetic analogue of soma-
Peptamin Junior® (Nestle Nutrition) 60:40 tostatin, has been used as a treatment for chylothorax
Vital jr™ (Abbott) 50:50 drainage that did not respond to dietary manipulations
Neocate® One + (Nutricia) 35:65 alone. In a study conducted between 1981–2004, 83% of
Neocate® Junior (Nutricia) 35:65 patients receiving octreotide responded with complete
Pepdite® Junior (Nutricia) 35:65 resolution of their chylothorax after approximately 15
days of treatment and no side effects from the octreotide
Chylothorax therapy were noted after 2 weeks of treatment. 20 In a study
Chylothorax, a known complication of pediatric cardiac by EH Chan et al the patients had variable results. There
surgery, requires special nutrition support considerations. was no decrease in drainage over the treatment period
Chylothorax is the accumulation of chyle within the pleural in 4 of 5 patients and it was thought that octreotide has a
space. The chyle leak can be the result of injury to the better outcome with a low-flow leak versus higher drainage
thoracic duct, disruption of accessory lymphatics, or from patterns noted in patients in this study.
an increased systemic venous pressure exceeding that in the The early diagnosis and treatment of chylothorax can
thoracic duct.21–24 Studies have suggested that the increase reduce the length of the chylous leak. At present, dietary
in postoperative chylothorax complications from 1% or less management is the mainstay of treatment when managing
in the 1970s and 1980s to 2.5% to 4.7% currently may be these patients conservatively.
due to the increased complexity of the surgeries performed
and possibly to the earlier initiation of enteral feeds. 21 Chan Cardiovascular Disease in the
reported an incidence of 3.8% from 2000 to 2002 with a Pediatric Patient
higher percentage occurring after heart transplant and the Obesity is a rising epidemic in children. As obesity rises
Fontan procedure. there is a potential for the increase of early onset coronary
The challenge in managing chylothorax is in main- artery disease. Childhood obesity significantly increases
taining fluids and electrolytes while minimizing the morbidity and mortality from cardiovascular disease
lymphatic leak. Chylothorax can be corrected surgically (CVD). 24 Freedman et al studied obese children using
but the results are not always favorable and not always the Bogalusa Heart Study database, and found a relation-
feasible for children who are possibly already compromised ship between obesity and blood pressure, low-density
after having had congenital heart surgery. Adverse affects lipoprotein (LDL) cholesterol, triglycerides, insulin
of chylothorax include immunosuppression, need for long- concentration, and low levels of high-density lipoprotein
term chest tubes and intravenous access, and prolonged (HDL) cholesterol, all of which are risk factors for CVD.
hospitalization. 22 Postoperative length of stay is reported There is evidence that atherosclerosis, the progressive nar-
to be significantly longer with a median of 22 days versus rowing and hardening of the arteries, begins in childhood. 25

CARDIAC DISEASE 253
Preventive measures must be taken in children who have The individualized approach aims to identify and treat
been identified at risk for CVD. Table 23-6 helps identify children and adolescents who are at the greatest risk of CVD.
these children. This approach aims at screening children who are from fami-
lies with a history of premature CVD or at least one parent
Table 23-6 Classification of Total and LDL Cholesterol Levels in Children with high cholesterol. Universal screening is not cost effec-
and Adolescents From Families With Hypercholesterolemia or Premature
Cardiovascular Disease tive and may impose an unnecessary stigma on a child.27
Category Total Cholesterol (mg/dL) LDL Cholesterol (mg/dL)
Children identified with an elevated cholesterol level at
Acceptable < 170 < 110
an early age should be treated. Initial therapy should always
Borderline 170–199 110–129 be diet modification accompanied by life-style changes,
High > 200 > 200 minimizing sedentary life style and promoting physical
Adapted from American Academy of Pediatrics Policy Statement.
activity. Once identified through the screening protocol as
Cholesterol in Childhood (RE9805). Pediatrics. 1998;101(1):141–147. having elevated LDL levels, diet therapy should be initiated.
The Step I Diet mimics the recommendations of the popula-
The National Cholesterol Education Program (NCEP) tion approach (Table 23-7). If LDL levels remain elevated
discusses the effects of early elevated lipid levels on adult after 3 months of adhering to the Step I Diet, the Step II
atherosclerosis and coronary heart disease risk. The program Diet should be initiated. The Step II Diet reduces saturated
focuses on prevention and lowering of lipids in children and fat to less than 7% of calories and cholesterol to less than
adolescents. Eating behavior and genetics affect cholesterol 200 mg/d. Drug therapy is suggested in children 10 years
levels. Behavioral changes require intervention at several or older if diet fails after 6 to 12 months for those with LDL
levels. Individual approach by itself is less effective. The key levels greater than 190 mg/dL or > 160 mg/dL if other risk
to success requires both a population and also an individu- factors are also present.
alized approach. In 2006 the American Academy of Pediatrics came
One of the goals of lowering cholesterol levels in out with a policy statement on cardiovascular risk reduc-
children and adolescents is through changing the eating tion in high-risk pediatric populations. This policy outlines
behaviors on a population-wide basis. The panel concurs CVD risk stratification based on existing comorbidities
with the recommendations issued by the National Choles- and assesses cardiovascular risk factors to stratify patients
terol Education Program Expert Panel on Population into At Risk, Moderate Risk, and High Risk categories.
Strategies for Blood Cholesterol Reduction, as well as the Life-style changes to include diet, exercise, and cessation
guidelines of the American Heart Association.27 It is recom- of smoking as well as disease-specific management are the
mended to include a variety of food and consume calories basis of its recommendations in all 3 groups. Pharmacologic
adequate to support growth and maintain an ideal body intervention is recommended only if goals are not met. 28
weight while keeping fat intakes at the recommended levels Reis et al looked at risk factors in children and investi-
(Table 23-7). gated whether families at risk for CVD can be identified.29
The authors looked at children to see if identification of
Table 23-7* Recommendations for Fat and Cholesterol Intake in Children risk factors in them would help predict risk factors in their
> 2 Years of Age parents. This population was targeted as children are more
Saturated fat < 10% of total calories likely to receive regular primary care than adults. The
Total fat intake < or equal to 30% participants underwent assessment of cardiovascular risk
of total calories
factors: obesity, hypertension, dyslipidemia, and metabolic
Cholesterol < 300 mg/d
syndrome. Parent-child association was strong for BMI,
*Step I Diet
waist circumference, systolic blood pressure, triglyceride,
Infants require additional calories and fat to support and total cholesterol. Risk factors in children were found to
growth and development and therefore restricting fat intake be significant predictors for the same risk factors for their
is not recommended for children less than 2 years of age. parents. This study suggests that CVD risk factors in chil-
To support their efforts for population-wide changes, the dren can predict elevated CVD risk factors in parents.
NCEP also provides recommendations for organizations Obesity, hypertension, insulin resistance, and dyslipi-
that influence the eating behaviors of children such as demia, also known as the metabolic syndrome or syndrome
schools, health professionals, government agencies, and the X (Chapter 14), are risk factors for childhood CVD. Studies
food industry. suggest that obese children with risk factors for CVD

become obese adults with increased risk of morbidity 3. Failure to thrive in infants with congenital heart disease
from CVD. Prevention and early intervention should is secondary to:
be a primary goal of health professionals and govern- A. Poor caloric intake
ment agencies. The NCEP has reported on these issues B. Increased energy expenditure
and implemented recommendations for dietary changes, C. Hypoxia
screening, and treatment of children and adolescents who D. All of the above
are identified as at risk for CVD and for developing into an 4. When selecting a formula for treatment of infants with
adult with CVD. 30 a chylous leak the following characteristics should be
considered:
Summary A. Only long-chain triglycerides (LCTs)
Children with congenital heart disease often have difficulty B. Only medium-chain triglycerides (MCTs)
achieving adequate caloric intake to support their growth C. Fat blend (high MCT and low LCT)
and development. A child should be provided with nutri- D. Fat blend (high LCT and low MCT)
tion support to maximize growth and development prior to
corrective surgery. Enteral or parenteral nutrition support See p. 487 for answers.
may be needed postoperatively until the child’s condition
allows for adequate oral intake. Surgical outcomes and References
catch-up growth rates have significantly improved with 1. Prsa M, Saroli T et al. Birth prevalence of congenital heart
adequate calories being delivered to this population.4,9 disease. Epidemiology. 2009;20:466–468.
2. Leitch C, Karn C, Peppard R, et al. Increased energy expen-
Postsurgical complications may occur depending on diture in infants with cyanotic congenital heart disease. J
the complexity of the defect and surgical intervention. Pediatr. 1998;133(6):755–760.
Complications that may arise postoperatively include 3. Leitch C. Growth, nutrition and energy expenditure in pedi-
protein-losing enteropathy and chylothorax, which require atric heart failure. Prog Pediatr Cardiol. 2000;11:195–202.
specialized nutrition modifications. 4. Vaidyanathan B, Nair S, Sundarum KR, et al. Malnutrition in
children with congenital heart disease (CHD): determinants
Pediatric cardiac disease over the past two decades has
and short-term impact of corrective intervention. Indian
extended to include CVD. Preventing, recognizing, and Pediatr. 2008;45:541–546.
treating these children holds promise of impacting CVD 5. Barton JS, Hindmarsh PC, Scrimgeour CM, Rennie MJ,
and its complications in the adult population. CVD risk Preece MA. Energy expenditure in congenital heart disease.
factors have been well identified in children. The NCEP has Arch Dis Child. 1994;70:5–9.
put forth recommendations and guidelines for early identi- 6. Cameron JW, Rosenthal A, Olsen AD. Malnutrition in hospi-
talized children with congenital heart disease. Arch Pediatr
fication and intervention in children at risk for CVD. Adolesc Med. 1995;149(10):1098–1102.
7. Mitchell IM, Logen RW, Pollock JCS, Jamieson MPG. Nutri-
Test Your Knowledge Questions tional status of children with congenital heart disease. Br
1. The potential for growth and nutrition recovery in chil- Heart J. 1995;73:277–283.
dren with congenital heart disease seems to be most 8. Eskedal LT, Hagemo PS, Seem E, et al. Impaired weight gain
predicts risk of late death after surgery for congenital heart
affected by:
disease. Arch Dis Child. 2008;93:495–501.
A. Degree of growth impairment 9. Nydegger A, Bines JE. Energy metabolism in infants with
B. Feeding difficulties congenital heart disease. Nutrition. 2006;(22):697–704.
C. Energy intake/expenditure 10. da Silva VM, de Oliveira Lopes MV, de Araujo TL. Growth
D. Age and timing of corrective surgery and nutritional status of children with congenital heart
2. Infants with congenital heart disease may require disease. J Cardiovasc Nurs. 2007;22(5):390–396.
11. van der Kuip M, Hoos MB, Forget PP, Westerterp KR, Gemke
caloric intake of to thrive. RJ, de Meer K. Energy expenditure in infants with congen-
A. 100 kcal/kg/d ital heart disease, including a meta-analysis. Acta Paediatr.
B. 120 kcal/kg/d 2003;92:921–927.
C. 90 kcal/kg/d 12. Schwartz MS, Gewitz HM, See CC, et al. Enteral nutrition in
D. 140–200 kcal/kg/d infants with congenital heart disease and growth failure. Pedi-
atrics. 1990;86(3):368–373.

CARDIAC DISEASE 255
13. Durai R, Venkatraman R, Ng P. Nasogastric tubes 2: risks and 22. Pelletier GJ. Invited commentary. Ann Thorac Surg.
guidance on avoiding and dealing with complications. Nurs 2005;80:1870–1871.
Times. 2009;105(17):14–16. 23. Chan EH, Russell JL, Williams WG, et al. Postoperative
14. Sy K, Dipchand A, Atenafu E, et al. Safety and effectiveness chylothorax after cardiothoracic surgery in children. Ann
of radiologic percutaneous gastrostomy and gastrojejunos- Thorac Surg. 2005;80(5):1864–1879.
tomy in children with cardiac disease. Am J Roentgenol. 24. Hise M, Brown C. Lipids. In: Gottschlich MM, DeLegge
2008;191(4):1169–1174. MH, Mattox T, Mueller C, Worthington P, eds. The A.S.P.E.N.
15. Kogon BE, Ramaswamy V, Todd K, et al. Feeding difficulty in Nutrition Support Core Curriculum: A Case-based Approach –
newborns following congenital heart surgery. Congenit Heart The Adult Patient. Silver Spring, MD: American Society for
Dis. 2007 Sep; 2(5):332–337. Parenteral and Enteral Nutrition; 2007:48–70.
16. Sachdeva R, Hussain E, Moss M, et al. Vocal cord dysfunction 25. Zalesin KC, Franklin BA, Miller WM, et al. Impact of obesity
and feeding difficulties after pediatric cardiovascular surgery. on cardiovascular disease. Endocrinol Metab Clin N Am.
J Pediatr. 2007;151:312–315. 2008;37:663–684.
17. Kohr LM, Dargan M, Hague A, et al. The incidence of 26. Freedman DS, Khan LK, Dietz WH, et al. Relation-
dysphagia in pediatric patients after open heart procedures ship of childhood obesity to coronary heart disease risk
with transesophageal echocardiography. Ann Thorac Surg. factors in adulthood: The Bogalusa Heart Study. Pediatrics.
2003;76:1450–1456. 2001;108(3):712–718.
18. Feldt RH, Driscoll DJ, Offord KP, et al. Protein-losing 27. American Academy of Pediatrics Policy Statement.
enteropathy after the Fontan procedure. J Thorac Cardiovasc Cholesterol in Childhood. (R E9805). Pediatrics.
Surg. 1996;112:672–680. 1998;101(1):141–147.
19. Ostrow MA, Hudsen F, Rychik J. Protein-losing enteropathy 28. American Academy of Pediatrics Policy Statement. Cardio-
after Fontan operation: investigations into possible pathophys- vascular risk reduction in high-risk pediatric populations.
iologic mechanisms. Ann Thorac Surg. 2006;83(2):695–700. Pediatrics. 2007;119(3):618–621.
20. Parrish RC, Krenitky J, Willcutts K, Radigan A. Gastroin- 29. Reis EC, Kip KE, Marroquin OC, et al. Screening children to
testinal disease. In: Gottschlich MM, DeLegge MH, Mattox identify families at increased risk for cardiovascular disease.
T, Mueller C, Worthington P, eds. The A.S.P.E.N. Nutrition Pediatrics. 2006;118:1789–1797.
Support Core Curriculum: A Case-based Approach – The Adult 30. National Cholesterol Education Program (NCEP): highlights
Patient. Silver Spring, MD: American Society for Parenteral of the report of the Expert Panel on Blood Cholesterol Levels
and Enteral Nutrition; 2007:524–525. in Children and Adolescents. NCEP Expert Panel on Blood
21. Chan S, Lau W, Wong W, et al. Chylothorax in chil- Cholesterol Levels in Children and Adolescents. Pediatrics.
dren after congenital heart surgery. Ann Thorac Surg. 1992;89:496–501.
2006;82:1650–1656.

24
Renal Disease
Christina L. Nelms, MS, RD, CSP, CNSC, LD, Marisa Juarez, MPH, RD, LD, and Bradley A. Warady, MD

Background . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 256 1. Describe normal kidney physiology and causes of pedi-
Kidney Development and Function . . . . . . . . . . . . . . . . . . 257 atric renal failure.
2. Discuss nutrition care for chronic kidney disease and
Chronic Kidney Disease. . . . . . . . . . . . . . . . . . . . . . . . . . . 258
Hemodialysis acute kidney injury in pediatric patients.
Peritoneal Dialysis 3. Review nutrition needs and specifications for infants,
Growth and Development children, and adolescents receiving supplemental
Nutrition Assessment enteral and parenteral nutrition.
Nutrition Requirements 4. Discuss specific nutrition needs for other kidney disor-
Fluid and Electrolyte Balance
Cardiovascular Disease and Lipid Management
ders in pediatrics, including nephrotic syndrome,
nephrolithiasis, and renal tubular disorders.
Renal Transplant . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 268
Acute Kidney Injury (AKI) . . . . . . . . . . . . . . . . . . . . . . . . . 269 Background
Continuous Renal Replacement Therapy
Neonatal Issues
Kidney disease in children is rare, with an incidence of about
75 per million of the age-related population for all stages of
Enteral Nutrition. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 272
Infant and Toddler Feeding
chronic kidney disease (CKD).1 Children may have acute
Tube Feeding for Older Children kidney injury (AKI) from infections such as Escherichia coli
Parenteral Nutrition. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 274 or from other comorbid conditions, such as sepsis or multi-
Intradialytic Parenteral Nutrition system organ failure. CKD is often progressive in nature
Nephrotic Syndrome. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 274 and may develop as a result of congenital or autoimmune-
type conditions. Pediatric patients with CKD are more
Nephrolithiasis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 274
Hypercalciuria and Calcium-Based Stones
commonly male because congenital posterior urethral
Other Kidney Stones valves, which only occurs in males, is a leading cause of
Renal Tubular Disorders. . . . . . . . . . . . . . . . . . . . . . . . . . . 276 CKD.2 However, CKD may present acutely at an advanced
Renal Tubular Acidosis stage. Many children only exhibit mild symptoms such as
Bartter’s Syndrome fatigue or flu-type illness until there has been a substantial
Nephrogenic Diabetes Insipidus progression of the kidney damage. Irrespective of the cause
Other Renal Dysfunction . . . . . . . . . . . . . . . . . . . . . . . . . . 278 of kidney injury, these patients typically have a variety of
Oxalosis nutrition issues that should be addressed for optimal patient
Other management. This chapter is intended to review those issues
for the clinician.
256
RENAL DISEASE 257
Kidney Development and Function systemic lupus erythematosus, membranoproliferative

Human kidney development, or nephrogenesis, begins diseases, and Henoch-Schönlein purpura); nephrotoxins
during week 5 of gestation. The first functioning nephrons (eg, aminoglycosides, amphotericin B, and heavy metals);
are formed by week 9 and the entire process is completed interstitial nephritis; hemolytic-uremic syndrome; or acute
by 32 to 34 weeks gestation. Once nephrogenesis has been tubular necrosis (ATN). Finally, postrenal or obstructive
completed, the kidney is unable to respond to injury by de AKI can be the sequela of disorders such as nephrolithiasis,
novo generation of nephrons. Key components of nephro- neurogenic bladder, hemorrhage, renal tumors, or posterior
genesis include formation of the pelvicalyceal system, renal urethral severe valves in newborns. Strict attention to the
tubular development, and glomerulogenesis. Urine produc- etiology of AKI and prompt therapeutic intervention often
tion begins at about 10 weeks gestation and by 20 weeks result in a return to baseline kidney function.
gestation, it accounts for approximately 90% of amniotic In contrast to the reversible nature of AKI, CKD is a
fluid. 3 The fraction of cardiac output received by the kidneys manifestation of irreversible renal injury. It often progresses
is only 2.5% during late gestation. It increases to nearly to end-stage renal disease (ESRD), also known as CKD5,
20% during the initial 6 weeks of life.4 Kidney function, as and the need for dialysis (CKD5D) and/or transplanta-
measured by creatinine clearance, doubles during the first tion. The National Kidney Foundation Kidney Disease
2 weeks of life in term infants and reaches adult values by 2 Outcomes Quality Initiative (NKF KDOQI) guidelines
years of age. 5 Normal serum creatinine values also increase classify CKD in children greater than 2 years of age, adoles-
with age.6 Most important from the clinical perspective is cents, and adults by the presence of kidney damage and the
the fact that the kidney is key to a variety of functions that, level of estimated glomerular filtration rate (GFR) (Table
if impaired, may significantly alter body homeostasis. These 24-1).8
functions influence solute removal, fluid/electrolyte/water A variety of disorders are associated with the develop-
status, calcium, phosphorus and vitamin D metabolism, ment of CKD in pediatrics, as reflected by data from more
erythropoietin production, acid-base balance, and blood than 7,000 patients enrolled in the North American Pedi-
pressure, all of which must be addressed medically if kidney atric Renal Trials and Collaborative Studies (NAPRTCS)
function is decreased on an acute or chronic basis. registry (Table 24-2).2 The 2 most common diagnoses are
Acute renal failure, more accurately called AKI, is obstructive uropathy and a/hypo/dysplastic kidneys and
commonly characterized as an abrupt (hours to weeks) and only 4 diagnoses individually represent greater than 4% of
prolonged loss of kidney function that is reversible in most the patients enrolled in the registry. There is clear evidence
cases.7 It is typically accompanied by a change in creatinine from clinical studies that both hypertension and protein
clearance and possibly in urine output. The causes of AKI are uria play a key role in the progression of CKD to ESRD.9,10
divided into 3 categories: prerenal, renal, and postrenal. The The developmental abnormalities of the urinary tract that
categories localize the predominant site of injury and help account for the largest percentage of patients with CKD
describe the mechanism of injury. For example, prerenal AKI stages I-IV logically account for the largest (eg, 30%–50%)
primarily includes the state of reduced renal blood flow that number of children with ESRD (stage V CKD), resulting
might result from diarrhea and vomiting, burns, bleeding, in the affected children having a life-long experience with
or congestive heart failure. Insults to the renal glomeruli their respective kidney disorders and the requirement for
or tubules can give rise to renal or intrinsic AKI. Sources long-term medical and nutrition intervention. 2
of injury include glomerulonephritis (eg, postinfection,
Table 24-1 NKF KDOQI Classification of the Stages of Chronic Kidney Disease8
Stage GFR (mL/min/1.73 m2) Description
1 > 90 Kidney damage with normal or increased GFR
2 60–89 Kidney damage with mild reduction of GFR
3 30–59 Moderate reduction of GFR
4 15–29 Severe reduction of GFR
5 < 15 (or dialysis) Kidney failure
GFR = Glomerular Filtration Rate

Table 24-2 CKD Primary Diagnosis2 According to the 2009 NKF KDOQI Clinical Practice
All Patients Guideline for Nutrition in Children with CKD, the energy
N % requirements for CKD stages 3 to 5 should be the estimated
Total 7037 100.0 energy requirements (EER), with an adjustment for phys-
Primary Diagnosis ical activity and body size.12 There is no evidence suggesting
Obstructive uropathy 1454 20.7 patients with CKD stages 3 to 5 have higher energy needs
A/hypo/dysplastic kidney 1220 17.3 compared to healthy controls. However, these patients need
Focal segmental glomerulosclerosis 613 8.7 regular assessments to adjust for inappropriate weight gain
Reflux nephropathy 594 8.4 or loss. If energy needs cannot be met with regular solid
Polycystic disease 278 4.0 food intake, consider oral supplementation with a product
Prune Belly 193 2.7 that meets any electrolyte, mineral, and/or fluid restric-
Renal infarct 158 2.2 tions. Supplementation can include modulars of glucose
Hemolytic uremic syndrome 141 2.0 polymers, protein, or fat if necessary to meet nutritional
SLE nephritis 114 1.6 needs. Many of the metabolic complications of CKD are
Familial nephritis 111 1.6 similar to those of AKI and ESRD, which will be discussed
Cystinosis 104 1.5 later.
Pyelo/interstitial nephritis 99 1.4
Medullary cystic disease 90 1.3 Hemodialysis
Chronic glomerulonephritis 82 1.2 Hemodialysis (HD) is the use of a machine to dialyze soluble
Congenital nephrotic syndrome 75 1.1 substances and water from the blood by diffusion through a
Membranoproliferative glomerulonephritis – Type I 75 1.1 semipermeable membrane, using a catheter placed centrally
Berger’s (IgA) nephritis 66 0.9 or a fistula. It is often done for 3 to 5 hours, 3 or more times
Idiopathic crescentic glomerulonephritis 47 0.7 per week for patients in CKD5 who cannot live without
Henoch-Schönlein nephritis 43 0.6 regular dialysis.
Membranous nephropathy 37 0.5 Malnutrition is a significant complication of CKD and
Wilms tumor 32 0.5 a strong predictor for morbidity and mortality for adults
Membranoproliferative glomerulonephritis – Type II 30 0.4 receiving maintenance HD.13–15 Protein-energy malnu-
Other systemic immunologic disease 26 0.4 trition (PEM) produces profound effects on growth and
Wegener’s granulomatosis 25 0.4 development and may be associated with increased risk of
Sickle cell nephropathy 14 0.2 hospitalization and mortality in children on HD.13,16,17
Diabetic glomerulonephritis 11 0.2 In addition to dry weight, length/height, weight-for-
Oxalosis 7 0.1 length, body mass index (BMI)-for-age, head circumference,
Drash syndrome 6 0.1 dietary intake, and serum albumin, the 2009 NKF KDOQI
Other 1110 15.8 nutrition guidelines now include recommendations on
Unknown 182 2.6 monitoring normalized protein catabolic rate (nPCR) for
children on HD. The primary biochemical marker of nutri-
tion status has been albumin. However, recent studies
indicate nPCR is superior to albumin as a marker of nutri-
Chronic Kidney Disease tion status in children on maintenance HD.16,18,19 These
CKD is a permanent condition that involves a progressive studies show serum albumin to be a poor indicator of nutri-
loss of kidney function. The National Kidney Foundation tion status. Research also demonstrates that intradialytic
describes 5 stages of CKD partially defined according to parenteral nutrition (IDPN) significantly improves weight
GFR that apply to children > 2 years of age11 (Table 24-1). A gain and nPCR in malnourished patients on HD.16,18 A
GFR of 90 or greater is considered normal. Stage 1 is a GFR nPCR of < 1 g/kg/d is a strong predictor of weight loss in
of > 90 mL/min/1.73 m 2 with evidence of kidney damage, adolescent patients.19
such as protein in the urine. There are added clinical signs of The protein catabolic rate (PCR) is a measure of protein
impaired kidney function as GFR decreases. At stage 5, the intake. The nPCR is the PCR normalized to a function of
final stage defined by a GFR of < 15 mL/min/1.73 m 2 , the body weight, measured in grams of protein per kilogram
child requires dialysis or transplantation. per day. nPCR is determined by first calculating the urea
generation rate (G):

RENAL DISEASE 259
G (mg/min) = {(C2 × V2) – (C1 × V1)}/t Children receiving PD typically have a poor energy
intake, often taking in less than 75% of needs.20 Even after
where accounting for glucose calories derived from the dialysis
C2 = predialysis blood urea nitrogen (BUN) (mg/dL) fluid, energy intake is still often insufficient. On the other
C1 = postdialysis BUN hand, protein intake is generally sufficient. Reduced height,
V2 = predialysis total body water (dL; V2 = 5.8 dL/kg × weight, and muscle mass are common findings, although
predialysis weight in kg) the reduced weight and muscle mass for age may be consis-
V1 = postdialysis total body water (dL; V1 = 5.8 dL × post- tent with overall short stature and size as these patients
dialysis weight in kg) are often proportional. Many plasma proteins, including
t = time (minutes) from end of the dialysis treatment to the albumin, total protein, transferrin, and individual amino
beginning of next treatment. acids, are found to be decreased in patients undergoing PD.
Although these patients do lose about 7% to 10% of protein
Then, using a modified Borah equation, nPCR is calculated: intake (depending on body surface area) into the dialysis
effluent, inadequate caloric intake or uremia can affect
nPCR (g/kg/d) = 5.43 × est G/V1 + 0.17 amino acid and protein profiles.20,21 Infants on PD have
twice the protein losses per square meter of body surface
where area than “adult-sized” adolescents22 and thus may need
V1 = postdialysis total body water (L; V1 = 0.58 × postdi- greater protein supplementation per kilogram. However, it
alysis weight in kg) is important not to provide excessive protein intake. Excess
protein has been shown to increase body acidity, creating
poor bone mineralization. Sometimes patients may have
Peritoneal Dialysis extreme protein losses in urine or through the peritoneum.
Peritoneal dialysis (PD) is typically recommended for Increasing protein far above the dietary reference intake
infants, toddlers, and approximately 50% of adolescents (DRI) may just exacerbate further protein loss in these
needing dialysis treatment. It is usually a nightly process. PD patients and create a high acid load. Use clinical judg-
involves infusion of a glucose-based solution through a cath- ment when assessing protein-related laboratory values to
eter surgically inserted into the peritoneal cavity. Diffusion determine if added protein will benefit hypoalbuminemic
allows for waste products to cross the peritoneal membrane. patients. Adequate, but not excessive, amounts of protein
Fluid is then drained from the peritoneal cavity and fresh are important in this population.23
fluid is infused. In most children, this process occurs over Serum triglycerides and cholesterol are often elevated,
10 to 12 hours while they sleep. A “daytime dwell” is often likely due to dextrose infusion of PD. Younger children
left in the cavity during the day and drained before nightly (< 10 years of age) often have more lipid abnormalities than
dialysis is resumed. The peritoneal membrane transport older children.20
capacity can be determined by conducting the Peritoneal Similar to nPCR in HD, protein equivalent of nitrogen
Equilibration Test (PET). Patients may be classified as appearance (PNA) has been recommended to assess dietary
“high,” “high-average,” “low-average,” or “low” transporters protein intake in adults receiving PD. In adults PNA is
depending on how rapid solute (eg, creatinine, glucose) calculated by measuring urea nitrogen content of both urine
moves across the peritoneal membrane during a 4-hour test and dialysate, and then multiplying the result by 6.25 with
exchange. High transporters tend to have more porous peri- a modification for pediatrics. However, it is only valid when
toneal membranes and thus rapidly remove waste products the patient is not anabolic or catabolic and can have great
such as creatinine, but also tend to lose significant amounts variability.12 Protein metabolism is age dependent, with
of potassium and protein across the peritoneum. The rapid younger children having greater differences. Due to these
absorption of glucose from the dialysate decreases the factors and limited pediatric data, PNA is not routinely
osmotic gradient and results in less fluid removal from these performed in pediatric patients.24
same patients. In contrast, low transporters tend to remove
less kidney waste, but also lose less protein and potassium Growth and Development
and remove fluid well. The nutrition prescription for the Poor growth is a common manifestation of CKD in chil-
peritoneal dialysis patient is, in turn, often influenced by dren. Growth velocity suffers as GFR declines. Many
what kind of transporter the PD patient is. factors contribute to growth failure, including decreased

appetite with poor energy intake, acidosis, excessive urinary nutrition and treatment of growth hormone resistance are
sodium losses, renal osteodystrophy, and abnormalities of treatable components and will be discussed in this context.
the growth hormone-insulin-like growth factor (GH-IGF) Linear growth in children with CKD is often impacted
axis.25 Steroid therapy may also contribute to poor growth. by the nutrition status of the patient. Adequacy of nutri-
One of the goals of nutrition intervention in the pediatric tion should be assessed prior to consideration of growth
CKD patient is to promote growth. hormone (GH) therapy (Figure 24-1).12,26 Evidence suggests
that improved dialysis, as indicated by better solute clear-
Linear Growth and Growth Hormone ance, along with caloric and protein intake at or above the
There are many factors that may affect growth, such as age at recommended intake for age, helps prevent growth failure.27
onset of kidney disease, the primary renal disease, and the Supplementation by gavage feedings may be needed to meet
quantity of residual kidney function. However, adequacy of nutrition needs.
Figure 24-1 Short Stature Assessment and Treatment Algorithm26
Reprinted with permission from: Mahan JD, Warady BA. Assessment and treatment of short stature in pediatric patients with chronic kidney disease: a
consensus statement. Pediatr Nephrol. 2006;21:917–930.

RENAL DISEASE 261
In young children, growth failure is primarily mediated explanation. According to the authors, many of the factors
by inadequate nutrition. Adequate caloric intake, adjusting leading to nonuse may have been resolved with intervention.
calories based on height and weight gains, is essential for Although kidney transplantation may improve the growth
adequate growth in infants and toddlers. Common causes of of younger children, many older children do not achieve
CKD in infants and toddlers are congenital disorders, such adequate catch-up growth with transplantation alone. This
as obstructive uropathy and renal dysplasia, with associated situation may change with the introduction of steroid-free
sodium wasting and polyuria. In children with these disor- immunosuppressive regimens. Most important is that
ders, supplementation of water and 2 to 4 mEq of sodium poor final adult height affects quality of life, and there may
(as chloride, bicarbonate, or both) per 100 mL of formula be other psychosocial implications for short children and
is recommended.28 KDOQI pediatric nutrition guidelines adolescents. Although likely not a direct relationship, poor
recommend correcting the serum bicarbonate level to at height has been associated with increased mortality and
least 22 mmol/L.12,26 Adequate sodium supplementation hospitalizations. Figure 24-1 reviews the process of growth
and correction of acidosis is essential for growth. evaluation and rhGH initiation and monitoring, including
GH insensitivity/resistance and alterations in the the essential assessment of nutrition parameters prior to its
somatotropic hormone axis are other significant factors initiation.26 A dose of 0.35 mg/kg/wk is suggested for chil-
influencing the growth of children with CKD. Typically, dren with renal disease.
growth occurs as a result of the action of insulin-like growth
factor 1 (IGF-1), a product released from the liver following Adequacy of Weight Gain
stimulation by endogenous GH. In children with CKD, Weight gain should be monitored often, with the most
serum levels of IGF-1 binding proteins may be increased frequent assessments occurring with infants and toddlers
seven- to tenfold, due to a reduction in renal filtration. with CKD. Dry weight should be used when assessing
The increase in IGF-1 binding proteins decreases the free weight parameters (see Dry Weight, below). If poor weight
or bioactive levels of IGF-1 and, as a result, limits growth gain occurs, contributing factors should be identified and
despite normal or elevated levels of circulating GH. Addi- corrected. Many patients with CKD have a compromised
tionally, inadequate protein or caloric intake may impair and/or restricted dietary intake, and nutritional supple-
GH’s ability to stimulate IGF-1. In this situation, therapeutic ments are required to meet age-appropriate nutrition goals.
doses of recombinant human growth hormone (rhGH) Oral supplements should be provided first, followed by tube
may be given to patients with CKD, resulting in improved feeding (nasogastric or gastrostomy) if deemed necessary.
height velocity.29 The KDOQI Clinical Practice Guideline Infants with significant CKD typically demonstrate delays
for Nutrition in Children with CKD indicates that children in feeding and often require enteral tube-feeding support
with CKD (including transplant patients) and a height or for an extended period of time.16 In fact, tube feeding may
height velocity standard deviation score (SDS) < –1.88 or provide relief to parents and caretakers concerned about
height-for-age < 3rd percentile qualify for treatment with their child’s poor intake. Some children may require more
rhGH.12 aggressive nutrition therapy (eg, IDPN) to help reverse
A Cochrane review of studies assessing GH in children a catabolic state (see Intradialytic Parenteral Nutrition,
with CKD, including predialysis, dialysis, and transplant below). It is important to recognize that all infants receiving
patients, indicates that treated children had a significant a substantial portion of their daily nutrition needs by a
increase in height SDS and height velocity at 1 year after non-oral route need continued oral stimulation to promote
starting therapy. The reported side effects are similar normal oral motor development. Finally, there is some
to control patients. 30 Despite the safety and efficacy of preliminary evidence suggesting intensified and daily HD
the therapy, rhGH is currently used in only a minority of may be associated with improved growth and nutrition
growth-retarded children with CKD, which is especially status. 32,33 More research on this subject is needed.
concerning for those who could benefit the most—young
children and those in the early stages of CKD. Some of the Nutrition Assessment
reasons for the underutilization of rhGH include family Malnutrition is a serious complication of CKD, especially
refusal, secondary hyperparathyroidism, and noncompli- in CKD5D. There is no single measurement to adequately
ance, as recently reported by Greenbaum et al. 31 However, in define nutrition status in CKD.25,16 It is challenging to assess
this study 51% of patients with short stature did not receive this population due to the metabolic and growth complexi-
GH and 25% of those patients did not have an apparent ties that are present. Early nutritional intervention may be

critical in optimizing growth and development. KDOQI gaining a better understanding of actual intake patterns
recommends routine monitoring of the following param- and eating behaviors.12
eters in children with CKD.12 The recommended frequency • Serum Albumin: The 2000 KDOQI pediatric nutri-
of assessment can be found in the KDOQI guidelines. tion guidelines include serum albumin as a marker of
• Dry Weight: Dry weight is the patient’s weight at a nutrition status. However, recent studies highlight the
euvolemic state. Dry weight should be assessed regu- limitations of using albumin in this manner, including
larly and used when assessing growth, including its long half-life and the dilutional effect of excess fluid.
weight-for-age and BMI-for-age. In oliguric or anuric Also, lower levels are often a manifestation of inflam-
patients requiring dialysis, fluid overload will influence mation, increasing the association of increased risk of
weight as well as will other anthropometric measures mortality with hypoalbuminemia. 37 Therefore, serum
such as head circumference and mid-arm circumfer- albumin may be used as a nutrition status marker, but
ence. Fluid overload is the most common source of error with caution if hypoalbuminemic factors such as acute
in measuring anthropometric data in this population. 34 physiological stress or fluid overload are present. 35
In other renal diseases in which urine-concentrating Specifics on nutrition assessment (Table 24-3) are included
capacity is impaired and volume depletion is common, in the chapter on nutrition assessment (Chapter 33). Unless
dry weight is equally important in assessing growth. specifically described, the calculation and assessment of
• Length/Height: Length or height should be measured these measurements apply to patients with renal disease as
as in other pediatric populations. Length- and height- well as other populations.
for-age trends are an indication of the chronic nutrition
status. Height velocity can be assessed using reference Table 24-3 Nutrition Assessment12,34-37
data from the Fels Longitudinal Study. 34 This can be Anthropometrics
assessed in 6-month intervals. • Dry
(Target) Weight & Weight-for-age percentile
• Weight-for-Length: This calculation is used for children • Length-
or Height-for-age percentile
< 2 years to assess weight-to-length proportion. • Length-
or height velocity-for-age percentile
• Weight/Length
percentile (for < 2 years)
• BMI-for-age: BMI should be used in patients with • BMI-for-age
percentile (for > 2 years)*
kidney disease as with assessment of other pediatric • Ideal
Body Weight*
populations. Dry weight should be used when calcu- • Head
circumference-for-age percentile (for < 3 years)
lating BMI-for-age. Because there is a predisposition * BMI-for-height age percentile and ideal wt based on BMI-for-height
age may be more appropriate
for stunted growth and developmental delays in CKD,
BMI-for-height age (the age at which height is at the Medical History
50th percentile) may be more appropriate in assessing • Assess
for conditions relevant to nutrition status and care
BMI and ideal body weight. Using chronological age to Intake Assessment Tools
assess BMI and ideal body weight may actually over- • Food diary
estimate ideal body weight. 35 Studies have shown a • Diet
recall: 24-hour recall x 3
U-shaped curve in BMI-for-age versus mortality risk, Labs
meaning that both a very high and a very low BMI is • Electrolytes:
Na, K, Cl, bicarbonate
associated with an increased risk of mortality in kidney • Minerals:
Ca, Phos, Mg
• Glucose

disease. 36 • Lipids:
Triglycerides, cholesterol
• Head Circumference: As described in the nutrition • Renal
Function: BUN, Cr
assessment chapter (Chapter 33), regular measure- • Malnutrition signs
ments should be taken through 3 years of age and nPCR (HD)
plotted on the 2006 World Health Organization head Fluid Status
circumference-for-age curve.12 Note any variance not • Blood
pressure
associated with a comorbidity. • Urine
output
• I/O

• Dietary Intake: Dietary intake should be assessed regu- • HD:
non-invasive monitoring, intradialytic weight gain
larly. A 3-day food diary or 3 24-hour diet recalls with at
Medications
least 1 weekend day are acceptable methods to measure
• Assess
for medications that may influence nutrition parameters
intake. Both have limitations, but they can be useful in

RENAL DISEASE 263
Nutrition Requirements Micronutrients

Children with CKD are at risk for micronutrient deficien-
Macronutrients cies due to poor intake, poor absorption, abnormal renal
Energy metabolism, medication interactions, and potential dialysis
The estimated energy requirement (EER) for energy is the losses. Adequate intake of fat-soluble and water-soluble
recommended starting point for pediatric patients with vitamins, zinc, and copper should be encouraged. There is
CKD stages 3 to 5.12 A balance of calories from all 3 macro- risk to growth and overall health if these micronutrients are
nutrients—carbohydrate, protein, and fat—is desirable. deficient. Supplementation of these vitamins and minerals
The recommended range of 45% to 65% of energy is necessary if dietary intake is low or if there is clinical
from carbohydrate and 30% to 40% from fat as set by the evidence of a deficiency and/or low blood levels. Because
Institute of Medicine (IOM) is acceptable for children excess losses of water-soluble vitamins are possible in all
with CKD. Because cardiovascular disease (CVD) is a dialysis patients, all children with stage 5D CKD should
significant and frequent complication of CKD in children, take a water-soluble vitamin supplement.12
carbohydrate and fat sources should be closely monitored
and altered in the setting of dyslipidemia. Diet manage- Fat-Soluble Vitamins
ment of dyslipidemia should include heart-healthy fats such Both dialysis and predialysis patients with significant
as monounsaturated and polyunsaturated fat rather than renal impairment have high retinol levels, despite having
saturated or trans fats. 38,39 Complex carbohydrates should a normal intake of vitamin A. This may be because of
replace simple sugars. If carbohydrate and fat modules increased retinol-binding protein found in renal failure.
are needed to increase calories to promote growth while Although elevated retinol levels are not found to be toxic
conforming to fluid restrictions, add them proportionally to these patients, supplemental vitamin A to patients with
to keep the macronutrient content consistent with the base/ renal impairment is not recommended.40–42 There has been
standard formula. (See Cardiovascular Disease and Lipid some concern that excess vitamin A levels may be associated
Management section, below, for further discussion.) with altered calcium homeostasis and hyperparathyroid
bone disease in adults with CKD. More evidence indicates
Protein the association is not a concern and oral intake from food
Children with CKD may demonstrate lower dietary protein should not be limited.43
intakes compared to healthy children. If children are unable Vitamin D has a significant and unique role when
to consume adequate amounts of protein to meet their discussed in the context of CKD. It is well known that
needs, protein modulars or concentrated formula may be vitamin D synthesis from the inactive to active form takes
used. However, if there is evidence of a high protein intake, place in the kidney, and patients with CKD typically
it may be beneficial to restrict protein intake to 100% to need supplementation with the active form of vitamin
140% of the DRI in children with CKD stage 3 and up D, calcitriol. As GFR declines, plasma concentrations of
to 100% to 120% of the DRI in CKD stages 4 and 5.12 By 1,25-dihydroxyvitamin D (1,25-(OH)2D) decline concur-
restricting protein, phosphorus is also restricted which may rently. There usually is a concurrent increased parathyroid
prove beneficial in terms of preventing CVD and helping to hormone (PTH) level, inducing secondary hyperparathy-
control renal osteodystrophy, the so-called chronic kidney roidism.44 Limitation of dietary phosphorus can improve
disease–metabolic bone disorder (CKD-MBD). Because 1,25-(OH)2D levels, which will be discussed later.45
CVD increases mortality and an abnormal calcium and Recent research indicates that dietary or “inac-
phosphorus balance is a nontraditional risk factor for CVD tive” vitamin D (25-hydroxyvitamin D) may also have
(see section on Cardiovascular Disease), regularly evaluate an important role in bone metabolism. Low plasma
protein intake as a source of excessive phosphorus intake. 25-hydroxyvitamin D is an independent and major risk
Patients on HD may only require 0.1 g/kg/d more factor for hyperparathyroidism, infection, and autoimmune
than the DRI to account for dialytic losses. PD patients diseases, even in healthy children.46,47 Recent evidence also
may only require 0.2 g/kg/d to 0.3 g/kg/d more than the indicates that 25-hydroxyvitamin D may be necessary for
DRI.12 However, other factors, such as inflammation or bone metabolism and is often deficient in children with
recent infection, which may contribute to protein catabo- CKD. The KDOQI Clinical Practice Guideline for Nutri-
lism should be considered when making recommendations tion in Children with CKD suggests measuring serum
on protein needs. 25-hydroxyvitamin D levels at least once per year and

supplementing with vitamin D2 (ergocalciferol) or vitamin A large study of adult patients treated with high-dose folic
D3 (cholecalciferol) if levels are < 30 ng/mL. Once levels acid, vitamin B6, and vitamin B12 did have lower serum
are replete, a maintenance supplement of up to 800 Interna- homocysteine levels, but no evidence was found of improved
tional Units and yearly serum levels are appropriate.12 cardiovascular morbidity or mortality. This study was
Serum vitamin E levels are often elevated in CKD and consistent with studies in the general population regarding
vitamin E is not cleared well by dialysis.42 However, recent cardiovascular risk with homocysteine. High doses of folic
evidence suggests that vitamin E may be beneficial in the acid can potentially mask a vitamin B12 deficiency. 52
treatment of anemia. In one center’s study of 10 children on Another consideration for folic acid supplementation
HD, patients given 15 mg/kg/d of vitamin E had improved is to improve erythropoietin-resistant anemia. Five milli-
hemoglobin and hematocrit when compared to control grams of folic acid has been found to improve hemoglobin
patients on epogen alone. Vitamin E therapy was also found and reduce epogen requirements in pediatric and adolescent
to reduce oxidative stress and insult. Some vitamin E supple- HD patients. 53 In light of this evidence, folic acid supplemen-
mentation may be beneficial for patients who are anemic.48 tation is likely beneficial to pediatric patients in moderate
However, excessive vitamin E intake is not recommended doses as part of a standard renal multivitamin supplement.
due to poor renal clearance. It may not be as critical as earlier research indicated.
Vitamin K is synthesized by the intestine and there is Although vitamin B6 losses are minimal in children
no evidence of dialysis losses. Unless a patient is receiving on PD, intake is typically limited due to poor appetite and
long-term antibiotic therapy, there is no need for supple- dietary restrictions, resulting in low serum levels. Supple-
mentation in CKD.12 mentation of 2 mg/d is considered appropriate. 54
Intake of vitamin C, like the B vitamins noted above,
Water-Soluble Vitamins is often poor in CKD. Vitamin C is also lost through dial-
A water-soluble vitamin supplement may be appropriate ysis treatment. Supplementation of vitamin C, as part of
for children with CKD stages 3 to 5 if dietary intake and/ a water-soluble vitamin supplement, is recommended for
or laboratory values are low. Supplementation is recom- CKD patients stages 3 to 5 who are at risk for deficiency and
mended for CKD stage 5D due to potential dialysis losses. for all CKD stage 5D patients. However, excess amounts
Low intakes of many water-soluble vitamins are common of vitamin C may be detrimental. Ascorbic acid and amino
in patients with CKD, often because of dietary phosphorus acids are precursors to oxalate. High doses of vitamin C may
restrictions and poor intake due to uremia. Additionally, contribute to higher blood oxalate levels which, along with
many water-soluble vitamins are lost during dialysis treat- the reduced oxalate clearance common in renal damage,
ments. Adult patients who receive continuous ambulatory can contribute to secondary oxalosis. Therefore, it is key to
peritoneal dialysis (CAPD) have been documented to have assess predialysis patients for adequate vitamin C intake to
low levels of vitamin B1 (thiamin), vitamin B6 (pyridoxine), determine need for supplementation, remembering vitamin
folic acid, and vitamin C.42 Vitamin B12 (cyanocobalamin) C excretion is not impaired with declining renal function.
and B2 (riboflavin) were normal. Low intakes of vitamins For dialysis patients supplement only to approximately the
B1, B6, and B12 were also noted. Supplementation of water- DRI or slightly higher, enough to replace dialysis losses.12,55
soluble vitamins produced increased levels of B6, folic acid, There are currently no pediatric renal vitamins avail-
and vitamin C. Similar vitamin losses have been noted in able on the market in the United States. However, many
HD patients. Biotin, riboflavin, and vitamin B12 have been adult-formulated vitamins are appropriate for older chil-
found to be normal in these same HD patients. Vitamin C dren and adolescent patients. The goal is to find a vitamin
and folic acid levels, while low, have been easily corrected with a content that is close to or slightly above the DRI for
with low-dose supplementation. Vitamin B6 and vitamin B1 age for the patient in question. Adult preparations of liquid
are typically low, requiring supplementation.49 renal vitamins are also available and smaller doses can be
Hyperhomocysteinemia is common in children with titrated to more closely meet the DRI requirements for
CKD. However, only a small percentage of these have low younger children and infants.12 Many “adult” renal vitamins
folate levels, and a smaller percentage have low vitamin B12 provide much more than the DRI for younger children and,
levels. 50 Treatment with 1 mg of folic acid has been shown to consequently, supplemented children may have normal or
improve homocysteine levels significantly and to increase above-normal serum concentrations of vitamins, including
serum folic acid levels in pediatric patients. 51 Whether there thiamin, riboflavin, vitamin B6, and folic acid. Because these
is improved morbidity and morbidity outcomes is unknown. vitamins are water soluble, it is not likely to cause harm.41

RENAL DISEASE 265
Infants may receive more vitamins and minerals than older disease, and serum levels. Fluid control is important to
children due to the use of infant formula. 56 However, a small minimize interdialytic weight change in dialysis patients.
dose of a renal-appropriate vitamin may still be necessary to An intradialytic change of < 5% is optimal.12 Fluid control is
replenish dialysis losses. also necessary to control blood pressure.
Minerals Sodium
An inadequate intake of zinc and copper is frequently found Sodium is often restricted to help control volume over-
in patients with CKD due to diet restrictions, dialysis load and blood pressure. According to the 2005 Dietary
losses, and poor oral intake. Zinc metabolism has been Guidelines for Americans older than 2 years, all indi-
noted in chronic renal disease and nephrotic syndrome viduals with hypertension should limit sodium intake to
with low serum levels, especially in the face of proteinuria <1500 mg/d.62 This is complicated by the environmental
and uremia. 57 Zinc levels typically improve within one year cues and peer pressures that promote high sodium intake,
of renal transplant. Zinc deficiency can cause impaired especially where fast food is concerned. Stringent sodium
wound healing, skin changes, anemia, taste changes, and restrictions are challenging. A more reasonable sodium
growth retardation, among other problems. Children on restriction of 2000 to 3000 mg/d may be better accepted
PD have been found to have losses of zinc across the perito- and hence adhered to in older children or adolescents. The
neum with resultant low serum levels. These levels improve amount of sodium restriction needed should be based on
with supplementation of zinc. 58 A small, single-center study individual patient parameters such as blood pressure, fluid
indicates that copper levels may be low in CKD stage 5D gains, and nutrition intake. Most sodium in the diet comes
patients due to medication interaction. 59 Thus, assess both from processed foods. Therefore, an increased intake of
zinc and copper levels on a regular basis in dialysis patients; fresh foods versus processed or canned foods will decrease
semi-annually is suggested. Supplementation to the DRI if dietary sodium intake. Using natural herbs and spices
low, or to therapeutic levels if critically low, may improve to season foods versus table salt is extremely helpful in
serum values. Nondialysis patients may need to have zinc reducing sodium content in foods. It is not only important
levels checked if they present with poor intake or show clin- to educate patients on low-sodium foods, but also on how
ical symptoms of zinc deficiency. to read nutrition facts labels. According to the U.S. Depart-
Abnormalities of selenium metabolism have also been ment of Agriculture (USDA), foods with < 5 mg sodium per
noted in patients with CKD. In a study of adult HD patients, serving are considered sodium- or salt-free. Foods with < 35
plasma selenium levels were found to be significantly lower mg sodium per serving are considered very low sodium; and
than controls, but corrected with supplementation. 60 Sele- foods with < 140 mg sodium per serving are low sodium.62
nium is noted to be involved with the regulation of thyroid The use of salt substitutes is often contraindicated in CKD
function, and low thyroid-stimulating hormone (TSH) patients because potassium chloride is typically substituted
levels and increased T3 levels were found in these patients. for sodium chloride. Potassium chloride can cause hyper-
However, there have been no studies of selenium in children kalemia in those at risk for the condition. Some PD patients
with CKD and supplementation is not recommended at this may lose large amounts of potassium across their perito-
time.12 neal membrane and may actually benefit from additional
Iron deficiency, manifesting as anemia, is typical in potassium.
CKD. The primary cause is insufficient production of eryth- Infants and children with CKD often have primary
ropoietin (EPO) by the impaired kidneys. Iron deficiency, disorders such as posterior urethral valves that cause
blood loss from medical procedures, hyperparathyroidism, polyuria and salt wasting. These children must have supple-
and acute or chronic inflammation may all contribute. mental sodium and free water to maintain proper balances.
Anemia is typically managed with therapeutic doses of EPO
and iron supplementation, as needed. 61 However, the intri- Potassium
cacies of anemia require medical management and thus are Dietary potassium is often restricted to prevent hyperkalemia
outside the scope of this chapter. because as kidney failure progresses, the ability to excrete
potassium is decreased. Hyperkalemia can, in turn, lead to
Fluid and Electrolyte Balance impaired muscle function, including the heart, resulting in
Fluid and electrolyte restrictions will vary among indi- cardiac death. When dietary management is not sufficient to
viduals according to urine output, stage of CKD, primary keep serum potassium levels acceptable, medication may be

necessary to prevent or treat hyperkalemia. It is important levels should be maintained within age-appropriate refer-
to remember that certain medications, such as steroids and ence ranges for CKD stages 1 to 4; and between 4 to 6 mg/
ace-inhibitors, have a drug-nutrient interaction that causes dL for ages 1 to 2 years and 3.5 to 5.5 mg/dL for adolescents
hyperkalemia. for CKD stage 5 and 5D. Hypophosphatemia that arises
Hypokalemia can occur in certain diseases such due to phosphate wasting disorders, overcorrection, or
as Fanconi’s syndrome in which a renal tubular defect other causes should be corrected by liberalization of diet or
is present. CKD5D patients on PD may filter out large medication changes. Hypophosphatemia is associated with
amounts of potassium, often requiring a high-potassium increased morbidity or mortality and poor growth.
diet to maintain normal serum levels.12,63 Adult patients are The KDOQI pediatric bone guidelines also suggest
typically advised to limit potassium to 2000 to 3000 mg/d. that when PTH levels are elevated for the given stage of
There is no direct evidence for appropriate amounts for chil- CKD, dietary phosphorus should be limited to the DRI for
dren. However, an extrapolation of the 2000- to 3000-mg age. When phosphorus values and PTH values exceed refer-
recommendation is < 30 to 40 mg/kg/d or 0.8 to 1 mmol/ ence ranges for age and stage of CKD, phosphorus should
kg/d. However, for infants and young children, 1 to 3 mmol/ be limited to 80% of the DRI.12,66 However, this guideline
kg/d may be an appropriate place to start.12 Restriction can can equate to low intake in children younger than age 8. It
be adjusted based on individual tolerance and serum lab should be noted that less than 500 mg of phosphorus, even
values. in young children, may not allow for adequate caloric intake.
An exception are children who get a controlled amount of
Phosphorus phosphorus via a set amount of enteral formula by mouth or
It is well known that elevated phosphorus levels increase feeding tube.
PTH levels in patients with CKD, even as early as stage 3 Limiting phosphorus in the pediatric diet may be a chal-
CKD. Elevated PTH levels lead to high bone turnover, lenge, especially as fast food and convenience food increases
increasing risk for bone calcium loss and consequent in the usual diet of children and adolescents. About 60% of
calcium deposition in organs and small vessels (CKD- dietary phosphorus is absorbed from the typical natural-
MBD). A low oral intake of phosphorous in the diet can help food mixed diet. Assuming natural foods are consumed, the
prevent elevated serum phosphorus and PTH levels. Even average adult man consumes an average of 1550 mg of phos-
when phosphorus levels are normal in the earlier stages of phorus per day, with over half consuming more than 1600
CKD, limiting oral phosphorus intake can improve PTH mg daily. The average woman consumes about 1000 mg
values and increase 25-hydroxyvitamin D levels.45 Low daily. Foods high in protein typically contribute the most
levels of active Vitamin D (calcitriol) exacerbate phosphate phosphorus in a natural diet with dairy and meats, including
retention, which increases calcium bone loss. Supplementa- fish, providing 20% to 30% each of the usual daily intake.
tion of vitamin D is necessary to increase calcium uptake These numbers are increasing as more instant and restruc-
by the gut and suppress the parathyroid to prevent calcium tured foods as well as colas, which have phosphate additives,
bone loss. The downside of vitamin D therapy is that it are on the market. Foods made with phosphate additives,
also increases phosphorus absorption, possibly increasing including many instant and restructured foods, have almost
serum phosphorus levels.64 Consequences of excess phos- 100% absorption of phosphate content. Estimates are that
phorus intake in patients with advanced stages of CKD these foods could contribute to dietary phosphorus intake by
are increased cardiovascular morbidity and mortality. An about 1 gm daily, even with unchanged protein and calcium
elevated calcium X phosphorus product can result in calci- intakes.67 Additionally, Sullivan et al looked at chicken
fication of soft tissues and small vessels. In adult patients, products with phosphate-containing additives and found
a phosphorus level above 6.5 mg/dL is correlated with an that the phosphorus content of these products was higher
increased risk of death, and those with the highest calcium in every instance than the phosphorus content expected
X phosphorus product have the greatest risk.65 The KDOQI from a nutrient database, averaging 84 mg/100 g of product
“Clinical Practice Guidelines for Bone Metabolism and or greater. This study concludes that standard nutrition
Disease in Children With Chronic Kidney Disease” indicate databases do not currently account for the recent influx of
that the calcium X phosphorus product in pediatric patients phosphate additives in foods. This, coupled with the great
should be < 65 mg2/dL2 in children 12 years of age and variation of phosphorus content between products, makes
younger and < 55 mg2/dL2 in adolescents > 12 years of age.65 it difficult to estimate phosphorus content of foods and to
These guidelines also recommend that serum phosphorus advise patients who need to limit dietary phosphorus. The

RENAL DISEASE 267
increase in processed foods with phosphate additives on calcium, or 2500 mg for adolescents in which twice the DRI
the market makes controlling phosphorus and having a would exceed 2500 mg.66
healthful diet difficult for CKD patients as well as practitio- If intake is inadequate, a calcium supplement is useful.
ners who advise them.68 It should be offered away from mealtime and iron supple-
A common treatment for elevated serum phosphate ments to allow maximum calcium absorption. Calcium
levels is phosphorus binders. These medications induce gluconate, lactate, acetate, or carbonate are all alternatives
excretion of phosphorus through fecal elimination when and should be given in doses < 500 mg at a time for best
taken with meals. Phosphorus binders that are available absorption. Calcium citrate should not be given as it can
include calcium-based binders, notably calcium carbonate increase aluminum absorption. Calcium chloride should
and calcium acetate (Phoslo®), sevelamer carbonate also be avoided as it can contribute to metabolic acidosis.12
(Renvela®), and lanthanum carbonate (Fosrenol®). If patients are hypocalcemic (< 8.8 mg/dL), calcium and
Lanthanum carbonate is not recommended for pediatric vitamin D therapy should be considered.66 The KDOQI
patients at this time as long-term bone effect is not known. pediatric bone guidelines indicate that serum calcium levels
Sevelamer has been shown to be as effective in lowering should not exceed norms for age in CKD, and should be on
serum phosphorus levels as calcium-based binders and, the lower end of normal in ESRD.
because it does not contribute to calcium intake, it is much As noted above, calcium carbonate (TUMS® or others)
less likely to increase serum calcium levels.69 The KDOQI and calcium acetate (Phoslo®) are often used as phosphorus
guidelines indicate that phosphorus binders should be used binders in children with CKD. Research indicates that use
when the serum phosphorus level is elevated and does not of calcium-based binders may contribute to hypercalcemia,
normalize with dietary restriction alone. The guidelines also and as mentioned previously, may contribute to the develop-
indicate calcium-based binders should be the initial therapy ment of soft tissue calcification with organ and small vessel
in infants and young children, but noncalcium-based binders damage. Calcium acetate has a higher binding capacity than
may be used if further correction of hyperphosphatemia is calcium carbonate. Forty-five milligrams of phosphorus is
needed.66 Either type may be used in adolescents. Calcium- bound by 667 mg of calcium acetate as opposed to 39 mg of
based binders are discussed below. phosphorus per 1250 mg of calcium carbonate. Twenty-five
Factors such as residual kidney function and dialysis percent of calcium is absorbed from calcium acetate versus
also play a large role in determining serum phosphorus 40% from calcium carbonate, resulting in a lower calcium
levels. Creatinine clearance provides a good estimate load from calcium acetate.72
of phosphorus clearance. If creatinine levels are higher, Intestinal calcium absorption is suboptimal in patients
patients typically have less phosphorus losses through urine with CKD, especially as renal failure advances, due to low
and dialysis. High transporters receiving PD also enjoy levels of 1,25-(OH)2D. Low dietary intake due to poor
greater phosphorus clearance than patients who are low or appetite and dietary restrictions is also common.73 Conse-
average transporters.70 Increased dialysis time also improves quently, higher doses of active vitamin D can decrease the
phosphorus clearance. Patients receiving nocturnal HD, patient’s need for calcium supplements.12
which is typically 6 to 10 hours nightly while the patient is Elevated serum calcium levels are also a concern. If
sleeping, typically have twice the phosphorus clearance of PTH is low, bone is not turning over at a rate necessary for
patients who receive standard 3 times per week HD.71 proper growth and bone maintenance, a state known as
adynamic bone disease. In this case, or if serum calcium
Calcium levels exceed 10.2 mg/dL on 2 consecutive measurements,
Insufficient dietary calcium intake may result in poor bone excess calcium is not appropriate as the bone cannot incor-
mineralization. However, excess intake may contribute to porate calcium appropriately. In these cases excess vitamin
an increased risk for CVD. Consequently, a balance of an D therapy or calcium supplementation should be lowered or
adequate, but not excessive, intake of calcium is important ceased. If discontinuation of binders and vitamin D therapy
for children with CKD. Although at least 100% of the DRI is not enough to lower serum calcium levels, low-calcium
for age is recommended for children with CKD, there are dialysate should be considered but is not the preferred
many sources that may contribute to calcium intake. The option.66,74
total elemental calcium intake derived from dietary intake,
enteral supplementation, and calcium-based phosphorus
binders should not provide more than 200% of the DRI for

Other Electrolytes of Concern to the AHA, treatment starts with lifestyle changes of diet
Magnesium metabolism is often altered in patients with and exercise. Drug therapy is added when diet and exercise
CKD resulting in low ionized levels and high total circu- are not sufficient to keep lipids at acceptable levels. 38 The
lating levels.75 Typically, serum magnesium levels will be KDOQI guidelines do not recommend dietary interven-
elevated or high-normal in dialysis patients; however, at this tion for dyslipidemia in malnourished children with CKD.
time, dietary alterations are not generally recommended. However, in non-malnourished children, a change to a
Other minerals of concern are those that may be impacted heart-healthy fat, increased fiber, and a limitation in sugar
by ongoing dialysis treatments. Minerals such as lead, intake are recommended.12,39
mercury, and cadmium have been noted to be elevated in Obesity, especially in the posttransplant population,
long-term dialysis patients. Contamination of dialysis fluids contributes to CVD risk and the development of other risk
may contribute to these mineral abnormalities.76 factors for CVD including dyslipidemia, HTN, and diabetes
Aluminum has been found very harmful to patients mellitus. Therefore, weight management should be included
with renal impairment, and toxicity historically has caused in the nutrition intervention (see Renal Transplant section).
severe bone disease and encephalopathy in patients with A non-traditional risk factor for CVD is abnormal
kidney disease. Prevention of excess aluminum intake by calcium and phosphorus levels. Calcifications form in the
choosing non-aluminum-based medications and avoiding vessels and soft tissues, including the heart. As many as 60%
aluminum contamination in dialysate or parenteral solu- of pediatric patients on dialysis have soft-tissue calcifications
tions is critical. at time of death (see Phosphorus and Calcium sections).79
Inflammation is another non-traditional risk factor that
Cardiovascular Disease and Lipid Management appears to contribute to CVD risk. Systemic inflammation
CVD is the major cause of mortality in patients with CKD, is often characterized by elevated serum c-reactive protein
accounting for about 25% of deaths.77 Children with ESRD (CRP) levels. Evidence suggests an elevated CRP level is
have a 1000-fold higher risk of cardiac death compared to associated with cardiac morbidity and mortality in CKD
non-ESRD children.77 Additionally, children with CKD patients.80 Causes of inflammation include the presence
are among the American Heart Association’s (AHA’s) list of uremic toxins increasing oxidative stress, chronic infec-
of high-risk pediatric populations. 39 Traditional risk factors tions, increased presence of proinflammatory cytokines,
including hypertension (HTN), left ventricular hyper- and abnormal calcium and phosphorus metabolism.81
trophy (LVH), and dyslipidemia are highly prevalent in There is also evidence of reverse epidemiology for low
adult CKD patients. However, recent data show that nontra- serum cholesterol levels, low serum homocysteine levels,
ditional markers or uremic factors are also contributing to and low BMI.78,82 Just as hypercholesterolemia, possibly
CVD in adult patients. These factors include dyslipidemia, high serum homocysteine levels, and a high BMI can be risk
abnormal calcium and phosphorus levels, vascular injury factors for CVD, low cholesterol, low homocysteine, and a
due to vascular calcifications and arteriosclerosis, inflam- low BMI can be risk factors, suggesting that malnutrition is
mation, anemia, fluid overload, and proteinuria.78 a risk factor for CVD.
Uncontrolled HTN is the most significant risk factor A syndrome known as MIA (malnutrition, inflamma-
for CVD and develops early in CKD. As CKD progresses, tion, and atherosclerosis syndrome) is thought to be the
HTN becomes more profound. Therefore, HTN control main cause of mortality in adults. This syndrome is based
should be a major goal in decreasing not only CVD risk, but on evidence of a strong link between these 3 factors and
the risk of CKD progression as HTN exacerbates the rate of an increased risk of mortality in CKD patients. 80 There are
kidney failure. Volume and pressure overload contribute to not significant data in the pediatric literature to suggest the
the HTN and LVH present in many children with CKD. 38 If same parameters increase the risk of mortality in pediatric
uncontrolled, LVH may lead to cardiomyopathy and cardiac patients. More studies in this area are needed.
failure. Therefore, blood pressure and volume control are
needed to help reduce manifestations of CVD. Renal Transplant
Dyslipidemia also typically occurs as CKD progresses. The ultimate medical goal for children with ESRD is renal
It is characterized by hypertriglyceridemia, and elevated transplantation, either from a living donor or a deceased
levels of very low-density lipoproteins (VLDL), low-density organ donor. However, transplantation is considered a treat-
lipoproteins (LDL), and total cholesterol. Low levels of high- ment modality and not a cure for CKD. Children who have
density lipoprotein (HDL) are present as well. According received a renal transplant should be considered to have

RENAL DISEASE 269
CKD. Unfortunately, until advances in medicine provide Adequate intake of calcium is important for bone health,
improved medication treatment or alternatives to human not only given the potential for transplant medication-
organs, slow deterioration of a renal transplant is probable. related side effects such as osteoporosis, but also because
Close attention to the nutrition and overall health care of of bone damage that may have already occurred related to
the transplant recipient is often paramount to the longevity CKD. Calcium and vitamin D intakes of at least 100% of
of the transplanted kidney. the DRI are usually suggested. However, if transplant func-
CVD is not only a significant risk for mortality in pedi- tion has deteriorated such that serum phosphorus and PTH
atric and young adult ESRD patients, but is also much more levels are elevated, total elemental calcium intake should
common in kidney transplant patients of this age group than not exceed 200% of the DRI, as indicated for other CKD
in the general population. The reduction of risks for CVD, patients at a similar stage.12,84 Dietary inclusion of high-
infection, and psychosocial issues compared to patients magnesium foods and limitation of high-potassium foods
on dialysis typically makes transplant the more desir- may be warranted if laboratory values dictate. However,
able alternative for renal replacement therapy. However, pharmacological management may be necessary with
hyperlipidemia, hyperhomocysteinemia, inflammation, treatment of hypomagnesemia with magnesium oxide, or
malnutrition, anemia, and hyperglycemia or insulin resis- less frequently gluconate-based magnesium preparations.
tance can all occur in the transplant patient and are factors Persistent or severe hyperkalemia can be treated with medi-
that may contribute to the development of CVD. cations such as fludrocortisone or with Kayexalate®-treated
Several medications used for immunosuppression formula. Hyperlipidemia can be treated with diet modifica-
and prevention of graft loss may have side effects that are tion (eg, increase in polyunsaturated fats and decrease in
damaging to the kidney and to the overall health of the saturated fat) and medication. The use of 3 to 4 grams of
recipient. Although many centers have developed proto- omega-3 fatty acids daily may also lower serum lipids.84
cols that minimize corticosteroid usage, these medications Fluid intake is key for the transplant recipient to assure
are still frequently used in transplant recipients. Adverse adequate perfusion and renal artery flow to the transplanted
effects of transplant medications include HTN, hyperlipi- kidney. In pediatric patients, this is typically 1.5 to 4 L/d
demia, hyperglycemia, increased appetite leading to weight depending on the size and activity of the child. 84 Intake
gain, peptic ulcer disease, osteoporosis, muscle wasting, of 2 to 3 L is typical for adult-sized adolescents. In young
and an increased risk of infection. Calcineurin inhibitors children, including infants and toddlers, adequate fluid
(CNIs) such as cyclosporine and tacrolimus can cause intake may be especially important to prevent ATN, graft
hyperglycemia, hypomagnesemia, hyperkalemia, HTN, thrombosis, and graft nonfunction. Transplant success in
and nephrotoxicity. T-cell receptor (mTOR) inhibitors this age population is best when adult-sized kidneys are
such as sirolimus have potential side effects of hypertrigly used. However, due to a child’s small heart, blood volume,
ceridemia, hypercholesterolemia, diarrhea, delayed wound and blood vessels, the need for a large blood flow may be
healing, and mouth ulcers. The use of antiproliferative difficult to meet, resulting in loss of kidney function. One
agents such as mycophenolate mofetil and azathioprine center’s experience indicates that total fluid intake (enteral
may result in gastrointestinal side effects such as nausea and formula and water orally and via tube feeding) of 2500
diarrhea, sore throat, or altered taste acuity.83 A clinician mL per body surface area (2500 mL/cm2/d) and sodium
must be aware of these potential side effects and work with intake of 8 to 10 mEq/kg/d prevented these complications.
the patient to optimize nutrition intake while minimizing Salvatierra et al describe an increased sodium and fluid
side effects. protocol that reversed a high creatinine in one infant who
Transplant patients should be advised to limit concen- had a low sodium and fluid intake. Lower GFRs were noted
trated sweets, especially when medication doses are highest, in the non-protocol patients.85,86 This type of protocol may
such as soon after transplant or when treating rejection. be necessary for 6 months to a year after transplant.85
Unless patients are underweight, water and other fluids low
in simple sugars are recommended to control weight gain, Acute Kidney Injury (AKI)
limit hyperglycemia, and promote good dental health. After AKI, formerly referred to as acute renal failure (ARF), is a
transplant, patients often need to continue to limit their temporary condition of kidney dysfunction typically char-
sodium intake to prevent or control HTN. Correction of acterized by electrolyte imbalances, an increase in blood
abnormal mineral or electrolyte concentrations is recom- urea nitrogen (BUN) and serum creatinine, and a decrease
mended if needed.12,84 in urine output.87 (For further discussion of physiology,

refer to the section on Kidney Development and Func- hemodialysis (CAVHD), and continuous venovenous
tion.) Although kidney function is usually restored once hemodialysis (CVVHD). CRRT replaces kidney function
the etiology of AKI is eliminated or corrected, supportive on a continuous or nearly continuous basis in terms of solute
therapy is required in the interim. Therapy may or may not and fluid removal and has been found to increase survival in
include temporary dialysis. If dialysis is required, there is no critically ill children, even infants less than 10 kg.89 Because
standard treatment modality. PD, HD, and continuous renal CRRT is a relatively new technology, there is little literature
replacement therapy (CRRT) are all used. CRRT is chosen regarding nutrition needs associated with it, especially in
by an increasing number of pediatric centers because of the children.
safety and efficacy of the technique, even in those patients Consistent with adult studies, enteral nutrition is the
who are experiencing hemodynamic instability.87,88 first choice for the route of nutrition support in children
Nutrition assessment and planning for the patient with receiving CRRT. Because CRRT efficiently improves
AKI typically follow the same guidelines for CKD5D and clearance of solutes, phosphorus, potassium, sodium, and
critical illness. There are no set standards for estimating other electrolytes or minerals typically do not need to be
caloric and protein needs in the setting of AKI, either limited. They may actually need to be supplemented. A
with or without the use of dialysis. Needs are based on renal formula may increase gastrointestinal complications,
the age-related needs of the patients, in addition to modi- such as diarrhea or emesis, due to high osmolality, and use
fications based on comorbid medical conditions such as of a standard formula is appropriate. Gastric emptying can
sepsis. Hypercatabolism and alterations in metabolism are be problematic in this population with slow gut motility.
common in AKI. Some of the alterations of metabolism It may be alleviated by using transpyloric feeding. A stan-
include decreased protein synthesis and inefficient use dard tube-feeding formula started at a slow, continuous rate
of proteins by the cells, altered amino acid pools, hyper and monitored for tolerance is optimal, even in children on
glycemia secondary to insulin resistance, lipid alterations vasoactive and sedative drugs.90
caused by impaired lipolysis, acidosis, and electrolyte imbal- Caloric needs of the primary condition should deter-
ances. The primary goal of nutrition therapy in patients with mine caloric needs during CRRT. Acute renal failure,
AKI is to prevent catabolism as much as possible. itself, is typically not thought to increase calorie needs.
The patient with AKI and not on dialysis may need Oftentimes CRRT is used to support patients with AKI
more rigid electrolyte and fluid restrictions. If a nutri- secondary to conditions such as burns or sepsis in which
tional supplement is required, use a renal supplement, caloric requirements may be markedly increased. Although
such as Suplena® or Nepro®, that is nutrient dense and has dialysis may cause some inaccuracies in measurement of
a low renal solute load. For infants, Similac PM 60/40® is caloric needs due to carbon dioxide removal by the dialysis
usually the most appropriate choice. Once renal function is membrane, indirect calorimetry (IC) is still considered the
restored, a regular diet and/or supplement is appropriate. “gold standard” and has been used in studies to determine
However, when dialysis is performed, depending on the caloric needs of pediatric patients receiving CRRT.91
modality, restrictions may vary (see sections on Continuous Protein losses may be very high in patients receiving
Renal Replacement Therapy, Hemodialysis, and Peritoneal CRRT. Maxvold et al91 attempted to assess nitrogen
Dialysis). Nutrition guidelines in AKI when patients are balance and amino acid loss in pediatric patients. In this
provided HD or PD are similar to those for CKD and HD study, children receiving 120% to 130% of IC-predicted
and PD. However, fluid and electrolyte concerns as well as resting energy expenditure (REE) and 1.5 g/kg protein
prevention of catabolism take priority to more long-term were in negative nitrogen balance. That amount of protein
concerns associated with CKD, such as CVD, growth, and seemed inadequate for this population. A recent study with
renal osteodystrophy. adult patients indicated that at least 2.5 g/kg protein may
be necessary to achieve a positive nitrogen balance.92 Thus,
Continuous Renal Replacement Therapy protein needs for children receiving CRRT are likely to be
CRRT is an umbrella term that can include continuous at least as high, if not higher because the baseline protein per
arteriovenous hemofiltration (CAVH), continuous kilogram needs are greater in children than adults. Studies
venovenous hemofiltration (CVVH), slow continuous in both adults and pediatrics demonstrate a 10% to 25% loss
ultrafiltration (SCUF), continuous arteriovenous hemo- of amino acids in CRRT via the dialysis filter.93
diafiltration (CAVHDF), continuous venovenous There are no published studies assessing the micronu-
hemodiafiltration (CVVHDF), continuous arteriovenous trient needs for children receiving CRRT. However, adult

RENAL DISEASE 271
studies indicate micronutrient loss is high in this patient serum potassium levels. Diuretics may cause potassium and
population. High losses of trace elements and vitamins, chloride losses that need to be replaced. Antibiotic therapy
such as selenium, copper, and thiamin, are common. It is may result in the need for vitamin K supplementation, espe-
speculated that other water-soluble vitamins are lost in a cially as gut flora and vitamin K production may not be
similar fashion.94,95 Experts recommend doubling the stan- established in the neonate.99
dard trace element preparations for adult patients receiving The energy and protein needs for a neonate with AKI
CRRT plus an additional 100 mg of thiamin and 100 mcg are estimated to be 120 kcal/kg/d and 2.5 g/kg/d, respec-
of selenium supplementation.96 It is likely that additional tively.99 Another proposed guideline has been 8 to 12 kcal/
micronutrient supplementation, proportional to the DRI cm/d.99 Patients on PD may receive some carbohydrate
for age, would also be appropriate for children. calories from dialysate solution.100 A patient on dialysis
may need greater amounts of protein because of urine and
Neonatal Issues dialysate protein losses. Whereas the above recommen-
AKI is common in the neonatal intensive care unit and dations are a good starting place, the quantity of protein
may be of primary origin, such as congenital renal disease, administered may need to be adjusted based on laboratory
or secondary to conditions such as sepsis, drug toxicity, values and individual needs. For example, a child with poor
obstruction, hypoxia, or respiratory distress. Twenty urine output not receiving renal replacement therapy will
percent of new dialysis cases are reported to be newborns.97 need reduced amounts of protein in contrast to the child
Mortality is high (46%) in neonates and low-birth-weight receiving continuous dialysis.99
infants with AKI.98 Dialysis, including PD, CRRT, or less Often, nutrition needs are not able to be met by oral
commonly HD, may be used to maintain fluid, acid-base, intake alone and tube feeding is a commonly used alterna-
and electrolyte balance as well as remove toxins in the short tive. It should be emphasized that neonates who are tube
or long term. It is important to remember that serum labora- fed should still be encouraged to take at least a portion of
tory values, such as phosphorus and potassium, may have their feedings by mouth. Breast milk is the optimal choice
higher normal limits for neonates than for older infants and and partial breastfeeding or bottle-fed breast milk should
children. Fluid balance is important because patients may be considered. If oral intake is not well tolerated, regular
have high urine output due to sodium and fluid-wasting oral stimulation is necessary. If breast milk is not an option,
renal disorders, stomas, emesis, or suction. This may neces- a whey-based formula, especially a low-electrolyte, low-
sitate a high fluid intake, replacing losses and providing aluminum, and vitamin A formula, discussed later, is the
maintenance needs. Poor urine output or additional next best option. Caloric density of breast milk or formula
sources of fluids, such as medication drips, may lead to fluid can be gradually increased from 20 kcal/oz to more than
restrictions, and the need to concentrate formula with addi- 30 kcal/oz as needed if there is volume intolerance or
tives or to use parenteral nutrition (PN).99 Oliguric and restriction. Typically it is done with glucose polymer or fat
anuric infants typically should receive 25 to 30 mL/kg/d, modulars as opposed to volume concentration to reduce
with infants < 26 weeks gestational age possibly needing renal solute load.99 Some concentration of formula may be
more.100 acceptable in premature infants with increased needs for
Controlling HTN and edema are often critical in this calcium and phosphorus for bone accretion, especially if
population. Maintenance fluid needs are a good starting serum phosphate levels are appropriate. However, phos-
point, with adjustment based on clinical conditions.101 Often phate retention related to renal failure should be kept in
children with high fluid and sodium losses require sodium mind. Calcium needs should especially be assessed and
supplementation of 1 to 3 mEq/kg/d.100 Correct acidosis supplementation may be needed.100 However, calcium-
with supplementation of sodium bicarbonate.97 Sodium based medications and vitamin D that patients with kidney
bicarbonate supplementation of 1 to 2 mEq/kg/d may be disease may be receiving may increase calcium uptake and
needed to prevent hyperkalemia. If serum potassium levels lessen the need for calcium supplementation to the level
are high, limit potassium to 1 to 2 mEq/kg/d.100 that other premature infants need. Increasing formula
It is important to be aware of medications that may concentration may not be appropriate even if higher phos-
affect nutrition. Pressors or narcotics may decrease gastric phate and calcium load is needed as aluminum and other
motility and may affect tolerance to enteral feeding. Contin- solute concentration also increases.
uous jejunal or transpyloric feedings may be better tolerated Feeding tolerance should be closely monitored.
than nasogastric feedings. Anti-hypertensives can increase Reflux and delayed gastric emptying are common in renal

impairment and should be treated if needed. Treatment occur include high blood pressure and proteinuria associ-
options include decreasing concentration of the formula ated with a low GFR. Height and weight gains tend to be
with a slow increase back to desired concentration, slowing impaired in these patients and mandate close monitoring/
the rate of delivery, using continuous feeds, and possibly supervision of their nutrition status. Growth goals are the
adding medications to enhance gastric motility.99 Bolus same as other neonates. Further discussion of the neonate is
feeds, if tolerated, are most physiologic. Some infants may found in the chapter on nutrition, growth, and development
do best with a combination of bolus feeds during the day (Chapter 13).
and continuous feeds overnight.
In some cases, oral and/or tube feeding cannot meet Enteral Nutrition
the nutrition needs of the neonate, mandating the use of Inadequate intake is common in children with CKD.
parenteral nutritional (PN) support. Glucose monitoring Gastroesophageal reflux, medication taste, uremia, as well
with PN is mandatory, with consideration for the use of an as thirst for water instead of formula may contribute to
insulin drip if needed to provide adequate carbohydrate this problem. The KDOQI Clinical Practice Guidelines for
calories while keeping serum glucose levels normal. Use Nutrition for Children indicate that supplemental nutrition
of a neonatal amino acid solution, such as Trophamine®, support should be considered in CKD stages 3 to 5 or 5D
is appropriate as is the use of 20% intralipids to provide to meet energy needs if the child is not growing or gaining
energy and essential fatty acids. Lipids are started at 1 g/kg weight well. Additionally, oral intake of an energy-dense
and then increased to increase calorie intake, but typically diet and/or supplements is the preferred source of nutrition
not greater than 3 g/kg. Triglycerides should be monitored support, followed by tube feeding, if energy needs are not
and lipids should be advanced only if triglyceride values met orally.12
are < 250 mg/dL. If triglyceride values are > 300 mg/dL, The majority of infants and young children who receive
lipids should be reduced or stopped.99 Parenteral solu- PD as treatment for ESRD require supplemental enteral
tion additives, particularly micronutrients cleared renally, feedings for adequate growth. There is some concern that
should be based on an individual patient’s response. Small the use of a gastrostomy may be a risk for peritonitis. Perito-
amounts of potassium in the parenteral solution, especially nitis is the most significant risk of PD and can permanently
if the patient is on dialysis, are often still appropriate. Start damage or alter a patient’s peritoneal cavity and limit the
with half or less of standard amounts for neonates without use of this dialysis modality in the future. Consequently,
renal impairment. Likewise, the reduction of magnesium most experts recommend placement of a percutaneous
and phosphorus in PN to one-third or one-half the normal gastrostomy (PEG) or an open gastrostomy if an anti-reflux
amount may be beneficial and prevent low serum levels. procedure is needed, prior to the initiation of PD. If a gastros-
Selenium, chromium, and molybdenum may need to be tomy is needed after initiating dialysis, an open gastrostomy
intermittently given or avoided due to impaired renal clear- has a lower risk of peritonitis than a PEG placement.101
ance and liver impact. Zinc and copper intakes should When supplemental feedings are given via tube feeding,
remain standard, unless liver impairment is present, in intake needs can typically be met in young children. In one
which case copper may need to be limited. In high-output study, both caloric and protein needs were met or exceeded
renal failure, additional zinc may be needed and assessing in infants and young children receiving gastrostomy feeding
serum values may be beneficial.97,100 A multivitamin is with 61% of needs coming from supplemental feeding.100
needed to provide water-soluble vitamins while limiting the However, whether intake from supplemental feedings,
quantity of fat-soluble vitamins99 (see discussion on micro- even if meeting estimated nutrition needs, improves
nutrients in Chronic Kidney Disease section). height and weight standard deviation scores remains
Close follow-up of a neonate with previous or ongoing controversial.102,103
renal impairment is important, and growth and feeding
tolerance should be monitored postdischarge. Easy-to-read Infant and Toddler Feeding
formula mixing instructions in household measurements as Frequent nutrition assessment and revision of plan of care
well as demonstration of mixing is important.99 Preterm or is essential for optimal management of the infant and
low-birth-weight infants who suffered AKI may be at partic- young child with CKD or on dialysis. One dialysis center’s
ular risk for medical complications later in life, likely due to experience reports that dietetic contacts, including
the loss of renal mass from the early insult or as a result of direct, phone, and patient-related activities such as school
failure to complete glomerulogenesis.98 Problems that may contacts, averaged about 6 per month for children < 5

RENAL DISEASE 273
years of age, as opposed to about 3 per month for children oral feeding acceptance and ignore feeding refusal. Gradual
> 5 years of age.104 introduction of oral feeding in children with food aversion
Breast milk, which is low in phosphorus, calcium, and is preferred to rapidly stopping tube feeding to promote
other minerals, is an optimal food source for infants with growth and adequate intake as well as appropriate advance-
CKD. As a second choice, a whey-based formula is most ment to a regular diet. Many children advance to an oral
appropriate for this population. Of note, the potential for diet after transplantation, when factors such as uremia,
aluminum toxicity is an important concern for patients with excess thirst, or gastrointestinal reflux may be reduced.12,106
kidney impairment. Breast milk has the lowest content of The latter problem may occur in as many as 70% or more
aluminum and infants fed breast milk have the lowest serum of infants with chronic renal disease and may result in
aluminum levels.105 Whey-based formulas have the next- impaired intake, increased feeding refusal, and excess
lowest aluminum concentration, followed by whey-based emesis. The potential need for standard reflux precautions,
formula fortified with carbohydrate and lipid modulars. medication, or even surgical intervention (fundoplication)
Preterm formulas are higher yet in aluminum followed by should be assessed in this situation.108
casein hydrolysate formulas. Consequently, soy and casein Infants and toddlers often suffer from high potassium
hydrolysate formulas are not recommended for children levels. One method to reduce potassium content of the
with renal impairment. formula is to treat it with sodium polystyrene sulfonate
As noted in the discussion of neonates, concentrating (Kayexalate®). Work by Bunchman et al indicates that
formula with a reduction of the water-to-formula ratio is not adding Kayexalate® to formula and allowing it to precipi-
an ideal approach for patients with CKD due to the elec- tate for 30 minutes in a refrigerator, and then pouring off
trolyte and renal solute load. Adding fat and carbohydrate the formula from the residue that has settled to the bottom
modulars, as well as protein modulars as needed based upon of the container, is an effective way to reduce potassium
the protein needs of the infant, is the most appropriate way content of liquid beverages including breast milk and
to increase caloric intake or to concentrate the formula formula.109 Although potassium content reduces signifi-
density in this population. cantly (and calcium and magnesium to lesser degrees),
Infants often require supplemental tube feeding to meet sodium content greatly increases. In these experiments,
nutrition needs, as discussed above. Infants may benefit from sodium content of the treated liquids increased an average
continuous overnight feeding and bolus feedings during of 234%. The greatest removal of potassium coupled with
the day.12,106 Renal wasting disorders such as renal dysplasia the lowest addition of sodium was found to be at the
are a common cause of renal impairment in this age group, 30-minute time point. This sodium exchange may be of
and sodium supplementation using sodium bicarbonate or benefit in the infant with wasting disorders, and should be
sodium chloride is often needed.107 Sometimes phosphate taken into account. The Bunchman group used Kayexalate®
additives are also needed to correct serum phosphate levels in the amount of 1 g/mEq of potassium in the formula;
in patients who use a low-phosphorus formula. however, this approach may overcorrect potassium levels if
Introducing solids at age-appropriate times is impor- potassium is only moderately elevated, and the dose should
tant, limiting but not avoiding foods high in electrolytes or be adjusted on an individualized basis per patient tolerance
protein based on the child’s underlying renal condition.12 and requirement.
Children with CKD may have oral hypersensitivity and
food-aversive behavior. It is important to offer a wide array Tube Feeding for Older Children
of foods, increasing texture gradually and allowing infants Older children and adolescents may benefit from tube
to experience food exploration and other good feeding feeding to meet their nutrition needs, but social and
habits such as family mealtimes. Many of these children cosmetic reasons often prevent initiation of tube feed-
exhibit aversive tendencies. Speech, occupational, or child ings in this age group. However, some children who were
psychology therapists as part of a multidisciplinary team infants or toddlers with CKD or on dialysis remain on
may aid normal feeding skill advancement. Need for inter- tube feeding past toddler years because of both parent and
vention should be identified in a timely manner to prevent patient desires or where inadequate intake is an issue. In
more lengthy feeding delays. Even for children who are tube this situation, it may be best to only provide tube feeding
fed, oral stimulation, including non-threatening contact overnight to allow for hunger during daytime hours to help
with food or pacifier use, is beneficial to encourage oral advance feeding skills and transition to a completely oral
development. It is recommended to positively reinforce feeding regimen.12

Parenteral Nutrition IDPN is shown to be an effective and safe treatment

Malnutrition is caused by multiple factors including for adults on chronic hemodialysis with PEM.93,111–113 The
anorexia, poor food intake, the catabolic effects of dialysis, updated KDOQI nutrition guidelines now provide recom-
and the demands of growth.15,16 Because of these issues, mendations for its use in children.12
meeting the needs of catch-up growth can be challenging
with oral and enteral supplementation alone. Network 14 Nephrotic Syndrome
data suggest that 4.5% to 7.5% of the dialysis population has Nephrotic syndrome (NS) is a combination of symptoms
malnutrition to a degree that requires a greater nutrition occurring in association with various renal and systemic
intervention than nutrition counseling, diet liberation, and diseases; it is not a single disease. NS is characterized by
oral or enteral supplementation can provide. 33 proteinuria, hypoalbuminemia, hyperlipidemia, anasarca,
In the case of mild to severe intolerance of oral or enteral and oliguria. Weakness, anorexia, and headaches are
supplements due to gastrointestinal dysfunction, PN may common. Most children with NS have what is known as
be necessary to ensure adequate nutrition. Patients with minimal change disease. The cause of minimal change
CKD5 often have a fluid restriction. Hence, this approach disease is unknown. Most patients will have more than one
to therapy requires central venous access to accommodate episode of severe proteinuria, but most will outgrow the
the concentrated high osmolar parenteral solution. disease and not develop permanent kidney damage.114
These guidelines provide general recommendations The main treatment goals are to increase urine output
for CKD and AKI patients. For specific recommendations and decrease/correct proteinuria. The major rationale for
for PN for neonates or in CRRT, see sections on Neonatal making diet changes in the patient with NS is to diminish
Issues and Continuous Renal Replacement Therapy. manifestations of the syndrome, replace nutrients lost in
urine, and reduce the risk of causing further renal damage.
Intradialytic Parenteral Nutrition The dietary reference intake (DRI) for age based on ideal
Intradialytic parenteral nutrition (IDPN) is a non-invasive body weight (IBW) is the appropriate standard to be used
method of providing carbohydrate, protein, and lipids to for energy and protein needs. Although proteinuria and
undernourished patients during HD via venous access. It is hypoalbuminemia may be present, a high-protein diet is not
supplemental to other forms of nutrition, including PN. The recommended because it can contribute to further kidney
main goals of this therapy are to replace nutrients lost during damage. Edema and diuretic therapy make the patient’s
HD, increase dry body weight, prevent further muscle weight parameters unreliable. Patients are usually sodium
wasting, improve the patient’s appetite and strength, increase and fluid restricted to control edema. As a guide to sodium
albumin and nPCR, and decrease hospital admissions. restriction, a sodium content of 1 to 2 mEq/kg is used in
IDPN is typically composed of a concentrated dextrose most circumstances (Table 24-4). Fluids are restricted if a
and amino acid solution and a separate lipid solution.110 The patient is fluid overloaded.114
solution must be formulated based on the patient’s needs
and tolerance. Concentrate dextrose is used to minimize Nephrolithiasis
the amount of free water given but keep glucose infusion Nephrolithiasis refers to kidney stones or calculi within the
rate to 5 to 9 mg/kg/min. While the energy provided may urinary tract. Calcium and oxalate, sometimes with phos-
seem minimal, its purpose is to maximize protein utiliza- phate, are the primary components of the most common
tion. Serum glucose levels must be monitored because of the kind of stone in all age groups (50% to 75%), followed by
potential for hyperglycemia. Serum glucose levels should uric acid stones (10% to 20%), struvite (ammonium-magne-
be maintained at < 200 mg/mL, using insulin if needed. sium phosphate) stones (5% to 10%), and cystine stones
Because of increased insulin levels, there is a potential for (1% to 2%). Nephrolithiasis is most common in Caucasians
hypokalemia and hypophosphatemia; therefore, serum and males. Being overweight, having HTN, and living in a
potassium and phosphorus levels should be monitored as warm climate are additional risk factors for stone formation.
well. Amino acids typically provide about 1.3 g protein per Although the majority of stones are primary and idiopathic
kilogram per treatment. Lipids are given as a 20% intralipid in nature, a variety of kidney or urinary tract disorders can
solution. Triglycerides must be monitored before and after be associated with the development of stones; they include
the initial lipid infusion to assure tolerance. If there is a 50% medullary sponge kidney, distal tubular acidosis, secondary
rise above baseline levels, there may be inadequate clear- hyperuricemia, and obstructive uropathy. Other disorders
ance of fat and lipids should be discontinued. such as sarcoidosis, Crohn’s disease, thyroid or parathyroid

RENAL DISEASE 275
disease, disorders of calcium or vitamin D metabolism, and citrate increases the solubility of urine calcium.118,119 Fruit
drug ingestion may contribute as well. Nephrolithiasis may and vegetable intake has an integral role in decreasing some
lead to CKD with some conditions, such as infection stones of these risk factors. Research indicates that increasing fruit
and primary hyperoxaluria, being particularly troublesome, and vegetable intake not only increases potassium intake,
potentially causing scarring.1,115 an important protective factor, but also increases citrate
Renal stone disease appears to be increasing in pedi- intake. Additionally, fruits and vegetables confer an alkali
atric patients. In one center, the overall incidence of kidney load, reducing the risk of calcium loss and stone formation.
stones increased more than fourfold from the 1990s to the A high sodium intake is another important risk factor
2000s, with the most significant increase present in children for stone formation. Sodium increases urinary calcium
younger than 10. There was distinct familial tendency for losses and may lower urinary citrate. It may also interfere
stone formation, and obese children comprised 31% of the with the actions of some medications used to treat hyper-
patients with stones.113 Hypercalciuria and hypocitraturia calciuria.119 Of interest, although excessive calcium intake
are found in pediatric stone formers116,117 and are common is not advised, restriction of calcium is detrimental to stone-
metabolic abnormalities in these patients. Changing soci- formers. Patients with hypercalciuria have bone calcium
etal and environmental dietary habits in children, such as loss, and limiting calcium intake can put patients at further
increased sodium and animal protein intake, as well as a risk for poor bone status. Additionally, many calcium-rich
decreased fruit and vegetable intake, may play a role. Such foods are high in potassium. Finally, limiting calcium may
habits reduce potassium and citrate and increase sodium increase the stone-forming factor oxalate in the urine, due to
and acid load in the typical childhood diet. Children who decreased availability of calcium to bind with oxalate.119,120
form kidney stones are likely to have repeat kidney stones. Potassium citrate may be recommended as a medication if
However, proper nutrition care is paramount in treatment compliance with diet is poor. A high magnesium intake may
and may significantly reduce or eliminate recurrence of also be a protective factor as well as limiting cola-containing
stone formation.1,116 beverages, however both interventions’ mechanisms of
action are unknown.1
Hypercalciuria and Calcium-Based Stones Fluid intake is an important preventive measure for
Hypercalciuria, or an excessive loss of calcium in the urine, all types of kidney stones. Adequate fluid intake has been
predisposes a patient to calcium-based kidney stones. shown to almost eliminate super-saturation of stone-
Hypercalciuria is thought to be both familial and related forming agents.119 Urine output, and thus fluid intake,
to environmental factors.115 In this type of stones, calcium appears to be inadequate in more than half of pediatric
typically combines with oxalate or phosphate. Preventing patients, in one center’s experience. It has been suggested
the loss of calcium is key to reducing the incidence of that a urine output of 1 mL/kg/h is adequate to avoid satu-
kidney stone formation. Acid may contribute to this kind ration of stone components in the urine, thus limiting stone
of stone formation. Diets high in animal protein can reduce formation.117 Other recommendations are that the urine
urine citrate and increase acid load, predisposing bones to output should be as high as 35 mL/kg/d. The 1 mL/kg/h
calcium loss. Some patients who form calcium-based stones rule can be equated, for practical purposes and to account
and have hypocitraturia have a higher risk of stones because for insensible losses, to a recommendation of 1 oz/kg of
Table 24-4 Nutrition for Kidney Stone Management1,115–121

Increase Fluid Increase Fruit and Limit Acid-Based Limit Meats Limit Limit DRI Calcium
(at least 1 oz/kg) Vegetable Intake Foods and Protein Oxalate Sodium Intake*
Calcium-based stones X X X X X X
Oxalosis or hyperoxaluria X X X X X X X
with calcium-based stones
Uric acid stones X X X DRI, especially
limit purines
Cystine stones X X X X X
Struvite stones X
Other kidney stones X ? ? X ?
*Although DRI calcium intake is appropriate general medical management for general pediatric health, including patients with a variety of kidney stone
disorders, avoidance of excessive or inadequate intakes of calcium are especially important in the types of kidney stones notated.

body weight or more per day.117 Another guideline for fluid children to reduce cystine concentration. A patient ideally
intake is 2 L or more for adults or adult-sized adolescents.119 should drink prior to bedtime, upon waking, and also at
A more general qualitative guideline is that a child or teen night. Neutral or alkali beverages are recommended. Addi-
should be encouraged to consume enough fluid so that their tionally, limiting methionine intake, which is metabolized
urine is near colorless.1,117 to cystine, is helpful. Limiting protein-rich foods including
Reducing protein intake may also be helpful to prevent meat, fish, eggs, soy, and wheat can reduce methionine intake
kidney stones but does not seem to be as critical as high and thus urinary cystine excretion. However, strict protein
fluid and potassium intake and limited sodium. Although restriction is not advised in children. Protein to the DRI
limiting meat intake may be difficult for some, certainly in children is appropriate for growth and may limit excess
discouraging particularly high-protein intake is a goal at cystine production. Unfortunately, adherence to a low-
minimum.1 sodium and lower-protein diet may be poor. High vitamin
In turn, practical dietary recommendations would C intake is often recommended for treatment of cystinuria,
indicate the need to limit sodium to 2000 to 2400 mg daily; but it is controversial. Cystinuric patients often produce
provide 100% of the DRI for potassium with at least 5 fruits other types of kidney stones and excess ascorbic acid may
and vegetables, particularly those high in potassium; 100% increase oxalate production. In the absence of other types of
of the DRI for calcium; and adequate fluid intake for size stones, 3 g of vitamin C has been recommended for adoles-
and age. cents with cystinuria.121
Oxalate Other Kidney Stones

Primary hyperoxaluria is rare, and will be discussed further Uric acid stones, found in 2% to 4% of pediatric stone
below. However, secondary hyperoxaluria may result from formers, are often a consequence of a high purine load. Limi-
fat malabsorption or idiopathic increased absorption of tation of animal protein and other high-purine foods should
oxalate. Oxalate intake may need to be restricted in hyper- be considered. Meat, including fish, should be reduced to
oxaluric stone formers.119 Because hyperoxaluria is rare, the DRI for protein. Other foods that should be limited
reported at only 6% of stone formers in one pediatric study, include meat extracts such as bullion, meat gravies, cocoa,
it may be unnecessary to restrict oxalate to prevent stones in mushrooms, high-yeast products, peas, and beans. Organ
hypercalciuria alone or in other types of kidney stones.117 In meat should be avoided.1, 119
fact, limiting oxalate in hypercalcuric patients is not shown Struvite calculi consist of magnesium ammonium
to reduce stone formation in a study of adult patients.120 phosphate or a calcium phosphorus mix and are often called
“infection stones” as they frequently result from urinary
Cystinuria tract infections. Unlike other stone disease, these stones
Cystinuria is an autosomal-recessive disorder and is the form in an alkali environment and increasing urine acidity
cause of about 10% of kidney stones in children. The disorder may help. Ascorbic acid is suggested as a treatment.1
is related to impaired transport of the amino acids cystine, Other stones include 2,8-dihydroxyadenine calculi,
ornithine, lysine, and arginine. Of these, cystine is insoluble which should be treated with purine restriction, and
in the urine and thus it can cause stone formation. Recurrent xanthine stones, which should be treated with increased
stone formation is common without medical management, fluid intake.1
but even with medical management adherence may be poor
due to side effects and lack of treatment efficacy. Cystinuria Renal Tubular Disorders
often leads to renal insufficiency, including ESRD, due to
recurrent stone formation and frequent intervention. Male Renal Tubular Acidosis
patients tend to be more severely affected. Medications Renal tubular acidosis in characterized by an inability to
are often used in treatment; however, dietary interven- acidify urine and, left untreated, growth impairment is
tions may be beneficial as well. As in other types of stones, common as are nephrolithiasis and nephrocalcinosis, or
high fluid intake, low-sodium diet, and foods high in alkali, calcium deposits in the kidney. Typical treatment of this
such as fruits and vegetables, are recommended. Limiting condition is alkali therapy.122 In clinical practice, monitoring
acid load by limiting excess protein intake is appropriate. A for failure to thrive and for renal stone disease is imperative.
2 g sodium diet has been shown to reduce urinary cystine Metabolic bone disease and bone calcium loss may require
concentration. A fluid intake of 3 L/d is recommended in nutrition monitoring as well.1

RENAL DISEASE 277
Bartter’s Syndrome Nephrogenic Diabetes Insipidus

Bartter’s syndrome is an autosomal-recessive disorder Nephrogenic diabetes insipidus (NDI) is typically an
with symptoms of poor growth, hypokalemia, and meta- X-linked autosomal recessive disorder and impairs water
bolic alkalosis. Some mixed forms of Gitelman syndrome reabsorption in the kidney. It manifests as vomiting,
and Bartter’s syndrome may include hypomagnesemia. anorexia, failure to thrive, and constipation in young infants.
Gitelman syndrome resembles Bartter’s but is a milder Hypernatremia is common. Aggressive water supplementa-
disorder. Lack of sodium, chloride, and water reabsorption tion is needed, and infants will often need overnight tube
cause urine losses in the 4 to 8 L/m 2/d range. Chloride loss feedings to meet fluid needs. The amount of fluid needed
causes alkalosis, increasing potassium wasting. Sometimes may inhibit adequacy of caloric intake, and growth and
calcium absorption is impaired, creating hypercalciuria. intake should be carefully monitored in this population.1
Treatment includes replacement of sodium, chloride, potas- The NDI Foundation recommends a sodium intake of 500
sium, and often magnesium. Monitoring for growth failure mg daily and potential benefit from a low-protein diet. The
is important.1 low-sodium diet, however, is the cornerstone of treatment.
The goal of this diet is to reduce solute load on the kidneys
and thus the amount of urine the kidneys must excrete.123
Table 24-5 General Nutrition Management of Renal Dysfunction

Nephrotic ARF ARF ARF CKD CKD5 CKD5
Syndrome No dialysis PD or HD CRRT (Stage 3-5) HD PD
Energy* DRI EER for age EER for age EER for age or EER for age EER for age EER for age
or original or original original disease
disease state disease state state
Protein DRI—do not DRI or less DRI with At least 2.5 g/ Stage 3: DRI + 0.1** DRI + 0.15-
supplement per BUN 0.2 g/kg kg or greater 100%–140% x g/kg IBW 0.3** g/
to replace monitoring increases for DRI/kg IBW kg IBW
urinary losses hemo, 0.4 g/ Stage 4-5: (dependent on
kg increases 100%–120% x age)
for PD DRI/kg IBW
Sodium 1–3 mEq/kg Will vary. Will vary. Typically no 1–3 mEq/ 1–3 mEq/ 1–3 mEq/
will vary Consult with Consult with restriction; may kg will vary kg will vary kg will vary
according to renal/primary renal/primary need electrolyte according to according to according to
edema or HTN team to team to supplementation edema or HTN edema or HTN edema or HTN
determine. determine. unless sodium unless sodium unless sodium
wasting wasting wasting
Potassium Restriction not Tightly limit Limit Most will 1–3 mEq/kg Generally
needed tolerate > 3 but will vary unrestricted
mEq/kg/d according to unless low
serum levels transporter.
and age Will need to be
monitored.
Phosphorus Restriction not Tightly limit Limit Limit to 80%–100% x DRI to keep serum levels WNL.
needed
Fluids Will vary Will vary Will vary May need Generally Replace UOP, Replace UOP,
according to according to according to additional unrestricted insensible insensible
UOP. Consult UOP. Consult UOP. Consult replacement losses, + UF losses, + ~1
with renal with renal with renal fluids. L/d
team to team to team to
determine. determine. determine.
Micronutrients DRI Tightly limit Limit fat- May need 100% DRI. 100% DRI. Water-soluble vitamin
*DRI typically fat-soluble soluble supplementation Supplement supplement is recommended.
appropriate unless vitamins vitamins especially water soluble if
specific notation. selenium and needed.
thiamin.
*Energy requirements may need to be adjusted for physical activity level and/or based on rate of weight gain or loss.
**Protein requirements may need to be adjusted according to dialytic protein and amino acid losses.

In clinical practice, growth may be impaired with limited children. Close attention to electrolytes and growth are
caloric intake from such a strict diet. Sodium allowance often the primary role of nutrition care in these diseases.
should be adjusted according to the patient’s tolerance,
growth, and clinical picture, but should be limited as much Test Your Knowledge Questions
as possible. 1. What is the optimal feeding route for children in acute
renal failure receiving CRRT that need supplemental
Other Renal Dysfunction nutrition?
A. Parenteral nutrition
Oxalosis B. Nasogastric feeding of a “renal” formula
Primary hyperoxaluria (type 1) is an autosomal-reces- C. Transpyloric feeding of a standard tube feeding
sive disorder characterized by a deficiency in glyoxalate formula
aminotransferase. Oxalosis is the final stage of primary D. Nasogastric feeding of a standard tube feeding
hyperoxaluria in which calcium oxalate accumulates in the formula
blood and tissues due to an abundance of oxalate production 2. Which of the following vitamins or minerals may be
and deposition of crystals in the kidneys. This accumula- beneficial to supplement to pediatric patients receiving
tion in the kidneys is known as nephrocalcinosis and causes dialysis treatments?
progressive renal failure. As renal failure progresses, oxalate A. Vitamin B6
accumulates because of the continued excessive production B. 25-hydroxyvitamin D
and the impaired renal excretion. While frequent HD can C. Folic acid
help clear oxalate and attempt to control oxalate deposition, D. All of these
success is often limited and further buildup in the tissues 3. Which of the following comorbid diseases is respon-
can occur. Oxalate can deposit in the bones, eyes, heart, sible for 25% of deaths in CKD patients?
vessels, and nerves. The optimal treatment is a combined A. ESRD
liver-kidney transplantation. A kidney transplant alone is B. Respiratory arrest
not recommended because the liver continues to produce C. Cardiovascular disease
oxalate and can cause renal failure in the transplanted D. Diabetes mellitus
kidney. Typically, the treatment protocol during the imme- 4. Which of the following statements regarding nPCR is
diate posttransplantation period will include hyperdilution false?
or hyperdiuresis through superhydration methods to keep A. Recent studies show that serum albumin is a better
the concentration of urine crystals at low levels. A low- nutrition marker than nPCR.
oxalate diet is recommended. Excessive vitamin C intake B. KDOQI does not recommend monitoring nPCR in
may increase risk of oxalate stone formation and should be chronic hemodialysis patients.
avoided. Secondary hyperoxaluria can occur in the context C. It is a measure of protein intake in g/kg/d.
of fat malabsorption because unabsorbed fat binds with D. nPCR is an algebraic equation.
calcium making it unavailable to bind oxalate. A low-fat diet
with increased calcium intake is recommended. A high fluid See p. 487 for answers.
intake is important for urine oxalate removal. Potassium
citrate, pyridoxine, magnesium citrate, and other medica- References
tions may be helpful.1 1. Kher KK, Schnaper HW, Makker SP, eds. Clinical Pediatric
Nephrology. 2nd ed. London, UK: Informa Healthcare; 2007.
2. North American Pediatric Renal Trials and Collaborative
Other Studies. NAPRTCS 2008 Annual Report. www.naprtcs.org.
There are many other renal disorders, including phosphate Accessed December 9, 2008, and February 2009.
metabolism disorders, cystinosis, Fanconi’s syndrome, 3. Vanderheyden T, Kumar S, Fisk NM. Fetal renal impairment.
Liddle syndrome, Gordon syndrome, and others that are too Semin Neonatol. 2003;8(4):279–289.
numerous to discuss in this context. Other disorders may 4. Paton JB, Fisher DE, DeLannoy CW, Behrman RE.
Umbilical blood flow, cardiac output, and organ blood
be primary renal disorders or renal disease secondary to a
flow in the immature baboon fetus. Am J Obstet Gynecol.
systemic disease. In either case, the nutrition needs of these 1973;117(4):560–566.
patients should routinely be assessed because of the impact 5. Bueva A, Guignard JP. Renal function in preterm neonates.
that they have on the growth and development of these Pediatr Res. 1994;36(5):572–577.

RENAL DISEASE 279
6. Ceriotti F, Boyd JC, Klein G, et al. Reference intervals for 24. Mendley SR, Majkowski NL. Urea and nitrogen excre-
serum creatinine concentrations: assessment of available data tion in pediatric peritoneal dialysis patients. Kidney Int.
for global application. Clin Chem. 2008;54(3):559–566 and 2000;58:2564–2570.
Erratum in Clin Chem. 2008;54(7):1261. 25. Rees L, Shaw V. Nutrition in children with CRF and on dial-
7. Lameire N, Van Biesen W, Vanholder R. Acute renal failure. ysis. Pediatr Nephrol. 2007;22:1689–1702.
Lancet. 2005;365(9457):417–430. 26. Mahan JD, Warady BA. Assessment and treatment of short
8. National Kidney Foundation. K/DOQI Clinical Practice stature in pediatric patients with chronic kidney disease: a
Guidelines for Chronic Kidney Disease: Evaluation, Clas- consensus statement. Pediatr Nephrol. 2006;21:917–930.
sification and Stratification. Am J Kidney Dis. 2002 (suppl 1) 27. Tom A, McCauley L, Bell L, et al. Growth during maintenance
10;39:S1–S266. hemodialysis: impact of enhanced nutrition and clearance. J
9. Wong CS, Pierce CB, Cole SR, et al. Association of proteinuria Pediatr. 1999;134:464–471.
with race, cause of chronic kidney disease, and glomerular 28. Parekh RS, Flynn JT, Smoyer WE et al. Improved growth
filtration rate in the Chronic Kidney Disease in Children in young children with severe chronic renal insufficiency
Study. Clin J Am Soc Nephrol. 2009;4(4):812–819. who use specified nutritional therapy. J Am Soc Nephrol.
10. Flynn JT, Mitsnefes M, Pierce C, et al. Blood pressure 2001;12:2418–2426.
in children with chronic kidney disease: report from the 29. Tonshoff B, Kiepe D, Ciarmatori S. Growth hormone/
Chronic Kidney Disease in Children Study. Hypertension. insulin-like growth factor system in children with chronic
2009;52(4):631–637. renal failure. Pediatr Nephrol. 2005;20:279–289.
11. National Kidney Foundation. Glomerular Filtration Rate (GFR). 30. Vimalachandra D, Hodson EM, Willis NS, Craig JC, Cowell C,
http://www.kidney.org/kidneydisease/ckd/knowGFR. Knight JF. Growth hormone for children with chronic kidney
cfm#what. Accessed February 22, 2009. disease. Cochrane Database Syst Rev. 2006;3:CD003264.
12. National Kidney Foundation. KDOQI Clinical Practice pub003262.
Guideline for Nutrition in Children with CKD: 2008 update. 31. Greenbaum, LA, Hidalgo G, Chand D, et al. Obstacles to
Am J Kidney Dis. 2009;53(suppl 2):S1–S124. the prescribing of growth hormone in children with chronic
13. Goldstein SL, Baronette S, Gambrell TV, et al. nPCR assess- kidney disease. Pediatr Nephrol. 2008;23:1531–1535.
ment and IDPN treatment of malnutrition in pediatric 32. Tom A, McCauley L, Bell L, et al. Growth during maintenance
hemodialysis patients. Pediatr Nephrol. 2002;17:531–534. hemodialysis: impact of enhanced nutrition and clearance. J
14. Kopple JD. Effect of nutrition on morbidity and mortality Pediatr. 1999;134:464–471.
in maintenance dialysis patients. Am J Kidney Dis. 33. Fischbach M, Terzic J, Menouer S, et al. Intensified and daily
1994;24:1002–1009. hemodialysis in children might improve statural growth.
15. Wolfson M. Management of protein and energy intake in Pediatr Nephrol. 2006;21:1746–1752.
dialysis patients. J Am Soc Nephrol. 1999;10:2244–2247. 34. Baumgartner RN, Roche AF, Himes JH. Incremental growth
16. Brewer ED. Pediatric experience with intradialytic parenteral tables: supplementary to previously published charts. Am J
nutrition and supplemental tube feeding. Am J Kidney Dis. Clin Nutr. 1986;43:711–722.
1999;33:205–207. 35. Foster BJ, Leonard MB. Measuring nutritional status in
17. Krause I, Shamir R, Davidovitis M, et al. Intradialytic children with chronic kidney disease. Am J Clin Nutr.
parenteral nutrition in malnourished children treated with 2004;80:801–814.
hemodialysis. J Ren Nutr. 2002;12:55–59. 36. Wong CS, Gipson DS, Gillen DL, et al. Anthropometric
18. Orellana P, Juarez-Congelosi M, Goldstein SL. Intradia- measures and risk of death in children with end-stage renal
lytic parenteral nutrition treatment and biochemical marker disease. Am J Kidney Dis. 2000;36:811–819.
assessment for malnutrition in adolescent maintenance hemo- 37. Wong CS, Hingorani S, Gillen DL, et al. Hypoalbuminemia
dialysis patients. J Ren Nutr. 2005;15:312–317. and risk of death in pediatric patients with end-stage renal
19. Juarez-Congelosi M, Orellana P, Goldstein SL. Normalized disease. Kidney Int. 2001;61:630–637.
protein catabolic rate versus serum albumin as a nutrition 38. Kavey RW, Allada V, Daniels SR, et al. Cardiovascular Risk
status marker in pediatric patients receiving hemodialysis. J Reduction in High-Risk Pediatric Patients: A Scientific State-
Ren Nutr. 2007;17:269–274. ment from the American Heart Association Expert Panel on
20. Salusky IB, Fine RN, Nelson P, Blumenkrantz MJ, Kopple JD. Population and Prevention Science; the Councils on Cardio-
Nutritional status of children undergoing continuous ambula- vascular Disease in the Young, Epidemiology and Prevention,
tory peritoneal dialysis. Am J Clin Nutr. 1983;38:599–611. Nutrition, Physical Activity and Metabolism, High Blood
21. Kaiser BA, Polinsky MS, Stover J, Morgenstern BZ, Baluarte Pressure Research, Cardiovascular Nursing, and the Kidney
HJ. Growth of children following the initiation of dialysis: in Heart Outcomes Research: Endorsed by the American
a comparison of three dialysis modalities. Pediatr Nephrol. Academy of Pediatrics. Circulation. 2006;114:2710–2738.
1994;8:733–738. 39. American Academy of Pediatrics Endorsed Policy Statement.
22. Quan A, Baum M. Protein losses in children on continuous Cardiovascular risk reduction in high-risk pediatric popula-
cycler peritoneal dialysis. Pediatr Nephrol. 1996;10:728–731. tions. J Pediatr. 2007;119:618–621.
23. Azocar MA, Cano FJ, Marin V, Delucchi MA, Rodrigues EE.
Body composition in children on peritoneal dialysis. Adv Perit
Dial. 2004;20:231–236.

40. Vannucchi MTI, Vannucchi H, Humphreys M. Serum levels 57. Mahajan, SK. Zinc in kidney disease. J Am Coll Nutr.
of vitamin A and retinol binding protein in chronic renal 1989;8(4):296–304.
patients treated by continuous ambulatorial peritoneal dial- 58. Tamura T, Vaughn WH, Waldo FB, Kohaut EC. Zinc and
ysis. Int J Vitam Nutr Res. 1992;62:107–112. copper balance in children on continuous ambulatory perito-
41. Kriley M, Warady BA. Vitamin status of pediatric patients neal dialysis. Pediatr Nephrol. 1989;3:309–313.
receiving long-term peritoneal dialysis. Am J Clin Nutr. 59. Warady BA, Nelms C, Jennings J, Johnson S. Copper defi-
1991;53:1476–1479. ciency: a common cause of erythropoietin (rHuEPO)
42. Blumberg A, Hanck A, Sander G. Vitamin nutrition in patients resistant anemia in children on hemodialysis? Hemodial Int.
on continuous ambulatory peritoneal dialysis (CAPD). Clin 2005;9(1):99.
Nephrol. 1983;20(5):244–250. 60. Napolitano G, Bonomini M, Bomba G, et al. Thyroid function
43. Cundy T, Earnshaw M, Heyen G, Kanis JA. Vitamin A and and plasma selenium in chronic uremic patients on hemodi-
hyperparathyroid bone disease in uremia. Am J Clin Nutr. alysis treatment. Biol Trace Elem Res. 1996;55:221–230.
1983;38:914–920. 61. National Kidney Foundation. K/DOQI clinical practice
44. Portale AA, Booth BE, Tsai HC, Morris RC Jr. Reduced guidelines and clinical practice recommendations for anemia
plasma concentration of 1,25-dihydroxyvitamin D in in chronic kidney disease. Am J Kidney Dis. 2006;47(Suppl
children with moderate renal insufficiency. Kidney Int. 3):S1–S146.
1982;21:627–632. 62. US Department of Health and Human Services and US
45. Portale AA, Booth BE, Halloran BP, Morris RC Jr. Effect Department of Agriculture. Dietary Guidelines for Americans
of dietary phosphorus on circulating concentrations of 2005. 6th ed. Washington, D.C. U.S. Government Printing
1,25-dihydroxyvitamin D and immunoreactive parathyroid Office. 2005. http://www.health.gov/DietaryGuidelines/.
hormone in children with moderate renal insufficiency. J Clin Accessed December 9, 2008.
Invest. 1984;73:1580–1589. 63. Council of Renal Nutrition of the National Kidney Founda-
46. Ghazali A, Fardellone P, Pruna A. Is low plasma 25-(OH) tion. L McCann, ed. Pocket Guide to Nutrition Assessment of the
vitamin D a major risk factor for hyperparathyroidism Patient with Chronic Kidney Disease, 3rd ed.. New York, NY:
and Looser’s zones independent of calcitriol? Kidney Int. National Kidney Foundation; 2002.
1999;55:2169–2177. 64. Combe C, Aparicio M. Phosphorus and protein restriction
47. Wagner CL, Greer FR. Prevention of rickets and vitamin D and parathyroid function in chronic renal failure. Kidney Int.
deficiency in infants, children, and adolescents. Pediatrics. 1994;46:1381–1386.
2008;122:1142–1152. 65. Block GA, Hulbert-Shearon TE, Levin NW, Port FK. Associ-
48. Nemeth I, Turi S, Haszon I, Bereczki C. Vitamin E alleviates ation of serum phosphorus and calcium X phosphate product
the oxidative stress of erythropoietin in uremic children on with mortality risk in chronic hemodialysis patients: a national
hemodialysis. Pediatr Nephrol. 2000;14:13–17. study. Am J Kidney Dis. 1998;31(4):607–617.
49. Descombes E, Hanck AB, Fellay G. Water soluble vitamins in 66. National Kidney Foundation Kidney Disease Outcomes
chronic hemodialysis patients and need for supplementation. Quality Initiative. Clinical practice guidelines for bone metab-
Kidney Int. 1993;1319–1328. olism and disease in children with chronic kidney disease: Am
50. Canepa A, Carrea A, Caridi G, et al. Homocysteine, folate, J Kidney Dis. 2003;42(4 suppl 3):S1–S201.
vitamin B12 levels, and C677T MTHFR mutation in children 67. Uribarri J, Calvo MS. Hidden sources of phosphorus in the
with renal failure. Pediatr Nephrol. 2003;18:225–229. typical American diet: does it matter in nephrology? Semin
51. Kang HG, Lee BS, Hahn H, et al. Reduction of plasma homo- Dial. 2003;16(3):186–188.
cysteine by folic acid in children with chronic renal failure. 68. Sullivan CM, Leon JB, Sehgal AR. Phosphorus-containing
Pediatr Nephrol. 2002;17:511–514. food additives and the accuracy of nutrient databases: impli-
52. Sunder-Plassmann G, Winkelmayer, WC, Fodinger M. cations for renal patients. J Ren Nutr. 2007;17(5):350–354.
Approaching the end of the homocysteine hype? Am J Kidney 69. Chertow GM, Burke SK, Raggi P. Sevelamer attenuates the
Dis. 2008;51(4):549–553. progression of coronary and aortic calcification in hemodi-
53. Bamgbola OF, Kaskel F. Role of folate deficiency on eryth- alysis patients. Kidney Int. 2002;62:245–252.
ropoietin resistance in pediatric and adolescent patients on 70. Sedlacek M, Dimaano F, Uribarri J. Relationship between phos-
chronic dialysis. Pediatr Nephrol. 2005;20:1622–1629. phorus and creatinine clearance in peritoneal dialysis: clinical
54. Stockberger RA, Parrott KA, Alexander SR, Miller LT, implications. Am J Kidney Dis. 2000;36(5):1020–1024.
Leklem JE, Jenkins RD. Vitamin B-6 status of children under- 71. Koolenga L. Phosphorus balance with daily dialysis. Semin
going continuous ambulatory peritoneal dialysis. Nutr Res. Dial. 2007;20(4):342–345.
1987;7:1021–1030. 72. Wallot M, Klaus-Eugen B, Winter A, Georger B, Lettgen B,
55. Rolton HA, McConnell KM, Modi KS, Macdougall Bald M. Calcium acetate versus calcium carbonate as oral
AI. The effect of vitamin C intake on plasma oxalate in phosphate binder in pediatric and adolescent hemodialysis
patients on regular haemodialysis. Nephrol Dial Transplant. patients. Pediatr Nephrol. 1996;10:625–630.
1991;6:440–443. 73. Coburn JW, Koppel MH, Brickman AS, Massry SG. Study of
56. Warady BA, Kriley M, Alon U, Hellerstein S. Vitamin status intestinal absorption of calcium in patients with renal failure.
of infants receiving long-term peritoneal dialysis. Pediatr Kidney Int. 1973;3:264–272.
Nephrol. 1994;8:354–356.

RENAL DISEASE 281
74. Kurz, P, Monier-Faugere MC, Bognar B, et al. Evidence for 93. Zappitelli M, Goldstein SL, Symons JM, Somers MJ, et al.
abnormal calcium homeostasis in patients with adynamic Protein and calorie prescription for children and young
bone disease. Kidney Int. 1994;46:855–561. adults receiving continuous renal replacement therapy: A
75. Pedrozzi NE, Truttman, AC, Faraone R, et al. Circulating report from the Prospective Pediatric Continuous Renal
ionized and total magnesium in end-stage kidney disease. Replacement Therapy Registry Group. Pediatr Crit Care Med.
Nephron. 2002;92(3):616–621. 2008;36:3239–3245.
76. Skarupskiene, I, Kuzminskis V, Bumblyte IA, et al. Changes of 94. Nakamura AT, Btaiche IF, Pasko DA, Jain JC, Mueller BA. In
trace elements in blood of patients with chronic renal failure. vitro clearance of trace elements via continuous renal replace-
Dial Transplantation. 2005;34(12):870–880. ment therapy. J Ren Nutr. 2004;14(4):214–219.
77. Parekh RS, Carroll CE, Wolfe RA, Port FK. Cardiovascular 95. Berger, MM, Shenkin, A, et al. Copper, selenium, zinc, and
mortality in children and young adults with end-stage renal thiamine balances during continuous venovenous hemodiafil-
disease. J Pediatr. 2002;141:191–197. tration in critically ill patients. Am J Clin Nutr. 2004;80:410.
78. Mitnefes MM. Cardiovascular complications of pediatric 96. Chiolero, R. Berger M. Nutritional support during renal
chronic kidney disease. Pediatr Nephrol. 2008;23:27–39. replacement therapy. Acute Kidney Inj. 2007;156:267–274.
79. Milliner DS, Morgenstern BZ, Murphy M, Gonyea J, Sterioff 97. Moghal NE, Embleton ND. Management of acute renal failure
S. Lipid levels following renal transplantation in pediatric in the newborn. Semin Fetal Neonatal Med. 2006;11:207–213.
recipients. Transplant Proc. 1994;26:112–114. 98. Abitbol CL, Bauer CR, Montane B, Chandar J, Duara S,
80. Stenvinkel P, Heimburger O, Paultre F, et al. Strong associa- Zilleruelo G. Long-term follow-up of extremely low birth
tion between malnutrition, inflammation, and atherosclerosis weight infants with neonatal renal failure. Pediatr Nephrol.
in chronic renal failure. Kidney Int. 1999;55:1899–1911. 2003;18:887–893.
81. Sylvestre LC, Fonseca KP, Stinghen AE, Pereira AM, Meneses 99. Spinozzi NS, Nelson P. Nutrition support in the newborn
RP, Pecoits-Filho R. The malnutrition and inflammation axis intensive care unit. J Ren Nutr. 1996;6(4):188–197.
in pediatric patients with chronic kidney disease. Pediatr 100. Groh-Wargo S, Thompson M, Hovasi Cox J, eds. ADA Pocket
Nephrol. 2007;22:864–873. Guide to Neonatal Nutrition. Chicago, IL: American Dietetic
82. Wong CS, Gipson DS, Gillen DL, et al. Anthropometric Association; 2009.
measures and risk of death in children with end-stage renal 101. Ledermann SE, Spitz L, Moloney J, Rees L, Trompeter RS.
disease. Am J Kidney Dis. 2000;36:811–819. Gastrostomy feeding in infants and children on peritoneal
83. McPartland KJ, Pomposelli JJ. Update on immunosuppressive dialysis. Pediatr Nephrol. 2002;17:246–250.
drugs useds in solid-organ transplantation and their nutrition 102. Coleman JE, Watson AR, Rance CH, Moore E. Gastrostomy
implications. Nutr Clin Pract. 2007;22:467–473. buttons for nutritional support on chronic dialysis. Nephrol
84. Fine RN, Webber SA, Olthoff KM, Kelly DA, Harmon WE, Dial Transplant. 1998;13:2041–2046.
eds. Pediatric Solid Organ Transplantation. 2nd ed. Oxford 103. Ellis EN, Yiu V, Harley F, et al. The impact of supplemental
UK: Blackwell Publishing; 2007. feeding in young children on dialysis: A report of the North
85. Salvatierra O Jr, Singh T, Shifrin R, et al. Successful transplan- American Pediatric Renal Transplant Cooperative Study.
tation of adult-sized kidneys into infants requires maintenance Pediatr Nephrol. 2001;16:404–408.
of high aortic blood flow. Transplantation. 1998;66:819–823. 104. Coleman JE, Norman LJ, Watson AR. Provision of dietetic
86. Salvatierra O Jr, Millan M, Concepcion, W. Pediatric renal care in children on chronic peritoneal dialysis. J Ren Nutr.
transplantation with considerations for successful outcomes. 1999;9(3):145–148.
Semin Pediatr Surg. 2006;15:208–217. 105. Hawkins NM, Coffey S, Lawson MS, Delves HT. Potential
87. Andreoli SP. Acute renal failute. Pediatrics. 2002;14:183–188. aluminum toxicity in infants fed special infant formula. J
88. Star RA. Treatment of acute renal failure. Kidney Int. Pediatr Gastroenterol Nutr. 1994;19:377–381.
1998;54:1817–1831. 106. Warady BA, Kriley M, Belden B, Hellerstein S, Alon U. Nutri-
89. Symons JM, Brophy PD, et al. Continuous renal replace- tional and behavioural aspects of nasogastric tube feeding in
ment therapy in children up to 10kg. Am J Kidney Dis. infants receiving chronic peritoneal dialysis. Adv Perit Dial.
2003;41(5):984–989. 1990;6:265–268.
90. Lopez-Herce J, Sanchez C. Transpyloric enteral nutrition in 107. Rodriguez-Soriano J, Arant BS, Brodehl J, Norman ME. Fluid
the critically ill child with renal failure. Intensive Care Med. and electrolyte imbalances in children with chronic renal
2006;32:1599–1605. failure. Am J Kidney Dis. 1986;7(4):268–274.
91. Maxvold NJ, Smoyer WE, Custer JR, Bunchman TE. Amino 108. Ruley EJ, Bock GH, Kerzner B, Abbott AW, Majd M, Chatoor
acid loss and nitrogen balance in critically ill children with I. Feeding disorders and gastroesophageal reflux in infants
acute renal failure: A prospective comparison between classic with chronic renal failure. Pediatr Nephrol. 1989;3:424–429.
hemofiltration and hemofiltration with dialysis. Crit Care 109. Bunchman TE, Wood EG, Schenck MH, Weaver KA, Klein
Med. 2000;28(4):1161–1165. BL, Lynch RE. Pretreatment of formula with sodium poly-
92. Scheinkestel F, Adams F, et al. Impact of increasing parenteral styrene sulfonate to reduce dietary potassium intake. Pediatr
protein loads on amino acid levels and balance in critically Nephrol. 1991;5:29–32.
ill anuric patients on continuous renal replacement therapy. 110. Council on Renal Nutrition of New England. Intradialytic
Nutrition. 2003;19:733–740. parenteral nutrition. In: Renal Nutrition Handbook for Renal
Dietitians. Massachusetts National Kidney Foundation;
1993:86–98.

111. Cherry N, Shalansky K. Efficacy of intradialytic parenteral 118. Meschi T, Maggiore U, Fiaccadori E, et al. The effect of fruits
nutrition in malnourished hemodialysis patients. Am J Health and vegetables on urinary stone risk factors. Kidney Int.
Syst Pharm. 2002;15:1736–1741. 2004;66:2402–2410.
112. Chertow GM, Ling J, Lew NL, Lazaras JM, Lowrie EG. The 119. Pak CYC. Medical management of urinary stone disease.
association of intradialytic parenteral nutrition administra- Nephron Clin Pract. 2004;98:49–53.
tion with survival in hemodialysis patients. Am J Kidney Dis. 120. Bataille P, Pruna A, Gregoire I, et al. Critical role of oxalate
1994;24:912–920. restriction in association with calcium restriction to decrease
113. Kopple JD, Foulks CJ, Piraino B, Beto JA, Goldstein J. the probability of being a stone former: insufficient effect in
Proposed Health Care Financing Administration Guidelines idiopathic hypercalciuria. Nephron. 1985;39:321–324.
for Reimbursement of Enteral and Parenteral Nutrition. Am J 121. Knoll T, Zollner A, Wendt-Nordahl G, Michel MS, Alken
Kidney Dis. 1995;26:995–997. P. Cystinuria in childhood and adolescence: recommenda-
114. National Kidney Foundation. Childhood Nephrotic Syn tions for diagnosis, treatment and follow-up. Pediatr Nephrol.
drome. http://www.kidney.org/atoz/atozItem.cfm. Accessed 2005;20:19–24.
November 6, 2008. 122. Caldas A, Broyer M, Dechaux M, Kleinknecht C. Primary
115. Ramello A, Vitale C, Marangella M. Epidemiology of nephro- distal tubular acidosis in childhood: clinical study and long-
lithiasis. J Nephrol. 2000;13(3):S45–S50. term follow-up of 28 patients. J Pediatr. 1992;121:233–241.
116. VanDervoort K, Wiesen J, Frank R, et al. Urolithiasis in 123. NDI Foundation. Diagnosis and Treatment of NDI.
pediatric patients: a single center study of incidence, clinical http://w w w.ndif.org/pages/6-Diagnosis_Treatment.
presentation and outcome. J Urol. 2007;177:2300–2305. Accessed December 9, 2008.
117. Lande MB, Varade W, Erkan E, Niederbracht Y, Schwartz GJ.
Role of urinary supersaturation in the evaluation of children
with urolithiasis. Pediatr Nephrol. 2005;20:491–494.

25
Gastrointestinal Disease
Donald George, MD and Elizabeth Bobo, MS, RD, LDN, CNSD

Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 283 1. Enumerate the mechanisms leading to nutrition defi-
Mechanisms of Nutrition Deficiency ciency in gastrointestinal diseases.
Nutrition Assessment 2. List several common gastrointestinal diseases in chil-
Gastroesophageal Reflux. . . . . . . . . . . . . . . . . . . . . . . . . . 286 dren and review the pathophysiology as it applies to
Celiac Disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 287 nutrition.
Inflammatory Bowel Disease. . . . . . . . . . . . . . . . . . . . . . . 289 3. Describe the role of nutrition support as primary treat-
ment of inflammatory bowel disease, celiac disease,
Diarrhea . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 291
and functional gastrointestinal disorders.
Pancreatic Insufficiency . . . . . . . . . . . . . . . . . . . . . . . . . . 292
Pancreatitis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 293 Introduction
Disorders of Chyle Loss. . . . . . . . . . . . . . . . . . . . . . . . . . . 294 The tasks of ingesting, processing, digesting, and absorbing
Functional Disorders . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 295 nutrients are coordinated through a complex network of
Gastroparesis neural and hormonal factors that help direct the function
Constipation of specialized gastrointestinal (GI) cells. GI diseases may
Cyclic Vomiting Syndrome
cause malnutrition by affecting nutrient intake, nutrient
Irritable Bowel Syndrome
absorption, or nutrient requirements. When dealing with a
Eosinophilic Conditions of the Gut. . . . . . . . . . . . . . . . . . 296
patient who has a GI disease, the clinician must determine if
Summary. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 297 the patient is malnourished, whether nutrition deficiencies
are likely to occur, and whether the patient would benefit
from nutrition therapy.
Mechanisms of Nutrition Deficiency

Mechanisms responsible for nutrition deficiency are
summarized in Table 25-1. They include the following:
Disordered Ingestion
Disordered ingestion may result from refusal to feed, an
inadequate diet, or from difficulty swallowing. Difficulty
swallowing can be related to oral, neurological, or esoph-
ageal diseases. Inability to chew or produce saliva also
interferes with the ability to swallow. In addition, a number
of behavioral problems (eg, food aversion, depression, and
283
eating disorders) influence the ability to ingest nutrients. Table 25-1 Mechanisms of Nutrition Deficiency
Gastric inflammation or vomiting of any cause will limit Mechanism Examples
the ability to eat. Disordered Ingestion Anorexia
Dental disease
Failure of Digestion Dysphagia of any cause
Failure of digestion occurs in diseases that affect the produc- Esophagitis
tion of digestive enzymes from the stomach (pepsin), Foreign body
pancreas (pancreatic insufficiency), or the surface of the GI Inadequate access to food
tract (lactase deficiency or sucrase-isomaltase deficiency). Failure of Digestion Pancreatic enzyme deficiency
Bile acids are important in the solubilization of fat, and Sucrase-isomaltase deficiency
patients with cholestasis of any cause will have impaired Cholestasis with failure of bile salt secretion
digestion. Failure of Absorption Short bowel syndrome due to surgery
Celiac disease
Failure of Absorption Liver disease
Failure of absorption occurs if there is an inadequate Movement disorders
surface area available either due to mucosal injury or to Increased Needs Fever
surgical foreshortening of the GI tract. There may be failure
of systems involved in particular nutrient absorption (eg, Nutrition Assessment
pernicious anemia, glucose-galactose malabsorption). Lack Nutrition assessment is an essential component of the
of luminal factors such as biliary secretions will impair evaluation of all children. Monitoring of growth should be
absorption, especially of lipids. Deficiency of luminal bile part of the routine well-child examination. Assessment of
salts occurs in liver disease, gallbladder disease, or disease both linear and ponderal growth of the child or adolescent
of the biliary ducts. is central to evaluation of nutrition status. Alterations in
In rare instances, absorption may not occur despite patterns of linear growth and weight gain (both inadequate
an adequate surface area. Congenital anomalies such as as well as excessive weight gain) may be the earliest mani-
microvillus inclusion disease preclude normal absorption festation of disease. Malnutrition is commonly diagnosed
while motility problems such as pseudoobstruction may in hospitalized patients and is also a common comorbidity
interfere with absorption by inhibiting movement of the in patients with GI disease.1–3 Malnutrition during illness
food bolus. may complicate the response to therapies or impair recovery
(Table 25-2). Thus, nutrition assessment is an integral part
Increased Needs of both the initial and ongoing evaluation of all children
A hypermetabolic state resulting in increased energy needs with acute and/or chronic disease and is of crucial impor-
can occur in diseases with fever, increased work of breathing, tance in the evaluation of the child with GI disease.
or because of medications needed. The initial nutrition evaluation includes both subjec-
Nutrition deficiency usually involves multiple mecha- tive and objective assessment of the patient’s current
nisms. For example, a patient with Crohn’s disease may have nutrition status and projected nutrition requirements. The
a poor appetite or be unable to eat because of pain or oral subjective assessment includes the presence and duration
ulcers. In addition, there may be small bowel involvement or of GI symptoms, fever, frequent infections, fatigue, food
intestinal resection that affects absorption (eg, vitamin B12 aversion, allergies to particular foods, or feeding intoler-
in the terminal ileum). Some patients with Crohn’s disease ance. Specific attention is paid to previous growth, detailed
will have lactase deficiency. Further, the presence of fever diet history, changes in body weight and dietary intake, GI
or underlying inflammation may increase needs for energy symptoms (eg, abdominal pain, diarrhea, and vomiting),
and protein. and anorexia. The objective assessment should include
data from clinical, anthropometric, and laboratory evalu-
ations (Table 25-3). Clinical data include the diagnosis,
current medical or surgical problems, allergies, and medica-
tions that may affect nutrition support options. Objective
measures of nutrition status include growth indices (both
previous and current), current weight, and Tanner stage.

GASTROINTESTINAL DISEASE 285
The determination of body mass index (BMI) for children Table 25-3 Nutrition Assessment
> 3 years of age provides important information regarding History Gastrointestinal Symptoms
the nutrition status. In children < 2 years of age, weight-for- (diarrhea, vomiting)
length is used. In children between the ages of 2 and 3, BMI Feeding tolerance
is used when a standing height is obtained while weight-for- Allergies/Aversion
length is used when a recumbent length is obtained. Specific Developmental feeding skills
normative data are available. Recent changes in growth or intake
Clinical Data Diagnosis
Table 25-2 GI Nutrient Deficiencies4,44,57 Medications
Nutrient Signs/Symptoms of Laboratory Markers Anthropometry (height, weight, Tanner stage)
Deficiency Laboratory
Iron Fatigue ↓ hgb Blood: Electrolytes, CRP, albumin, prealbumin, CBC,
Microcytic anemia ↓ hct vitamin levels, minerals (eg, iron and zinc)
↓ MCV Stool: pH and reducing substances (carbohydrate
↑ RDW malabsorption)
↓ % TIBC Quantitative fat
↓ ferritin
↓ serum iron Body composition: DEXA, bioelectric impedance
Folate Megaloblastic anemia ↓ serum folate
Glossitis ↓ red blood cell folate Careful examination of the child is the initial step
Diarrhea ↑ MCV
Forgetfulness in evaluation.4 Obesity and wasting are obvious. Edema,
Vitamin B12 Megaloblastic anemia ↑ MCV dehydration, excess fat, or decreased muscle mass can be
Ataxia ↓ hgb appreciable. Anthropometric measurements, including
Diarrhea ↓ serum vitamin B12
Mental status changes midarm circumference and skinfold thickness determina-
Paresthesias tions, are useful. It is standard practice to measure these
Glossitis parameters in patients at risk for chronic malnutrition such
Calcium Osteopenia ↓ serum total calcium as those with pancreatic insufficiency, inflammatory bowel
Osteoporosis ↓ serum ionized calcium
Tetany disease, celiac disease, or short bowel syndrome in which
Vitamin D Bone pain ↓ serum alk phos maldigestion or malabsorption may be prominent. It is rare
Muscle weakness ↓ 25-hydroxyvitamin D to find many stigmata of severe malnutrition in children.
Tetany
Osteomalacia Most often wasting, sometimes accompanied by edema, is
Rickets seen. The clinician, however, should have special concern
Vitamin A Night blindness ↓ plasma vitamin A for micronutrient deficiencies, especially in children with
Decreased appetite
Decreased immune function inflammatory disorders or disorders of absorption.
Hyperkeratosis Specific attention is paid to examination of the
Vitamin K Bleeding ↑ PTT abdomen. Abdominal tenderness, abdominal distention,
Bruising and the presence of bowel sounds not only provide helpful
Vitamin E Hemolytic anemia ↓ serum creatinine
Truncal ataxia creatinuria clues to the nature of the disease process but also influ-
Hypo — or areflexia ↓ serum vitamin E:total ence treatment decisions. There may be other findings
serum lipid ratio that suggest nutrient deficiency. Angular stomatitis and
Zinc Diarrhea ↓ serum alk phos dermatitis may suggest riboflavin deficiency. Dry cracked
Dry skin ↓ serum zinc*
Skin sloughing on palms ↓ urinary zinc** skin in areas exposed to sunlight suggests niacin deficiency.
Mental status changes Dystrophic nails, spooning of the nails, or pallor of the
Hair loss conjunctiva or skin may suggest iron deficiency. Peripheral
Growth stunting
Anorexia neuropathy can be seen with a number of vitamin deficien-
Magnesium Muscle cramps ↓ serum magnesium cies including thiamin, B6, B12 , and niacin. Zinc deficiency
Bone pain is often manifested by alopecia and perioral or perianal
Nausea
Seizures rash. Bowing of the legs, tetany, or rickets suggest vitamin
* Zinc binds to serum proteins, which can make levels appear low if
D deficiency. Petechiae, bruising of the skin, or bleeding
protein levels are depleted. gums may indicate vitamin K deficiency as may be seen in
** Associated with disease status. liver disease.

Gastroesophageal Reflux intake.15 In these cases specialized nutrition support may

Gastroesophageal reflux (GER) is the passage of gastric be needed. This may be accomplished orally with the use of
contents into the esophagus with or without regurgitation. specialized formulas or supplements. In some patients with
It can occur several times a day in healthy infants, children, complicated GER or GERD, alternate enteral access may be
and adults. 5–7 Regurgitation occurs daily in 40% of healthy needed. Factors that influence this decision include aspira-
infants and usually resolves spontaneously by 12 to 24 tion risk, degree of malnutrition, the age of the child, and
months of age.8–10 However, regurgitation occurs at least associated anatomical or neurological problems.
weekly in 12% to 15% of children ages 3 to 17 years 6 (Table
25-4). Gastroesophageal reflux disease (GERD) refers to Table 25-5 Common Presentation of GERD
reflux-associated tissue damage (eg, esophagitis) or symp- Age Examples
toms severe enough to impair quality of life.11 Infant Regurgitation
Vomiting
Table 25-4 Incidence of Regurgitation Feeding difficulties (acute)
Infancy (Daily GERD) 3 mo 40% Unexplained crying
6 mo 30% Failure to thrive
12 mo 15% Posturing
Children (Weekly) 3–9 y 12% Child Vomiting
10–17 y 15% Cough
Abdominal pain
The genesis of reflux-related injury and reflux symptoms Sore throat
is not the same. Each relates to a combination of factors that Respiratory difficulties
lead to an excessive number of reflux events, impaired clear- Adolescent Hoarseness
ance of material from the esophagus, increased acidity, or Regurgitation
decreased buffering of the refluxed material or impaired Chest pain
protection of the esophageal or supraesophageal mucosa.12 Heartburn
The most important mechanism causing GER is transient Epigastric pain
lower esophageal sphincter (LES) relaxations.13 Delayed Dysphagia
gastric emptying, increased intra-abdominal pressure, and
chronically reduced LES resting pressure have also been Disordered ingestion or nutrient losses due to vomiting
implicated.14 Studies of gastric emptying have shown it is or regurgitation dominate the clinical picture. In children
related to both the composition and caloric density of the who have poor weight gain, or weight loss, attention is paid
feedings. Higher fat diets or diets of higher caloric density to modalities to increase calories. Insufficient oral intake
will slow the emptying and thereby promote reflux. can be related to pain associated with eating, food aversion
GER and GERD have a variety of presentations that due to vomiting, or dysphagia associated with esophagitis.
vary with age. Regurgitation associated with poor growth, Treatments to reduce emesis in infants with regurgita-
irritability, or airway compromise are common reasons for tion include smaller feedings, thickening the formula with
evaluation in infancy. Heartburn and epigastric abdominal cereal or a pre-thickened formula, and positioning. Smaller,
pain are more common complaints in older children and more frequent feeds are often suggested but are sometimes
adolescents. Abnormal posturing (Sandifer’s syndrome) impractical and poorly tolerated by babies and parents.
and acute life-threatening events (ALTEs) are typical Thickening of feedings has been shown to reduce symp-
manifestations in the infant with GERD but are rarely seen tomatic GER. Agents commonly used to thicken formula
in older children or adults (Table 25-5). include rice cereal, guar gum, carob bean gum, locust bean
Regurgitation in infancy most often is nothing serious. gum, pectin, pre-gelatinized waxy rice starch, and soy poly-
Most instances of infantile GER resolve spontaneously. saccharides.15,16 Thickened formulas lessen the frequency
However, a minority of infants may have severe or prolonged of emesis, but may contribute to some undesirable side
problems that lead to caloric insufficiency and malnutrition. effects. Despite a significantly reduced number of episodes
Some severe cases result in failure to thrive (FTT). FTT may of obvious reflux and emesis, pH probe studies do not indi-
be due to persistent vomiting, difficulty feeding (coughing cate a reduction in exposure to acid in the esophagus.17,18
or gagging), and feeding aversion with subsequent lack of Further, studies found increased postprandial coughing

in infants fed thickened formula, suggesting continued Prokinetic medications are often suggested to improve
reflux despite improvement in emesis.19 Thickening infant gastric emptying. Metoclopramide is often prescribed
formulas is relatively free of major side effects; however, although evidence supporting its effectiveness is scant. It
complications such as increased cough and increased acid reduces symptoms, however it is associated with many side
exposure are documented.20,21 effects that limit its use. 33 Erythromycin has prokinetic
Also of concern is the effect of thickened formulas on activity and improves gastric emptying although it has not
the macronutrient content of formula as well as micronu- been shown to improve GER symptoms. These medications
trient absorption. Thickening of formulas with rice cereal are most commonly used in patients with weight loss or
alters the macronutrient composition of the formula by failure to gain related to GER.
providing additional calories and protein. Importantly, Clinical outcome in GER can be measured in a variety
indigestible carbohydrate thickening agents, such as locust of ways. Symptom reduction can be monitored by recall
bean gum, have been linked with decreased bioavailability or the use of diaries with symptom severity and frequency
of calcium, zinc, and iron. Conversely, digestible carbo- estimates. For GER causing poor weight gain, improvement
hydrate thickening agents, such as pre-gelatinized waxy in weight gain over time is the accepted measure. Lower
rice starch, have not been linked with decreased nutrient esophageal pH recording is accepted as a valid measure of
absorption. 22 Due to lack of definite data regarding the GER, however serial recordings are rarely used in clinical
efficacy of thickened formulas it is recommended that they practice.
only be used under medical supervision.16,20,23
In older children with GER, the nutrition therapy is Celiac Disease
dependent on individual tolerance to various foods. There Celiac disease is a T-cell mediated autoimmune, chronic
is sparse evidence to support avoidance of caffeine, coffee inflammatory disorder. It is characterized by damage to the
in particular, peppermint, chocolate, and spicy foods.23–26 small intestinal mucosa in genetically susceptible individ-
Obesity and exposure to alcohol and tobacco smoke may uals and is due to abnormal reactions to the gliadin fraction
worsen GER.23 Spearmint does not have an effect on esoph- of wheat gluten and similar peptides present in barley and
ageal reflux nor does the fat content of a meal except in rye. There is a specific peptide fragment of gliadin, made up
the absence of delayed gastric emptying.26–28 Data suggest of 33 amino acids, that is resistant to degradation by pancre-
that GER may be reduced in malnourished, neurologi- atic, gastric, or small intestinal conditions or enzymes, that
cally hindered children when they have been nutritionally passes through the epithelial barrier and interacts with
repleted.29 immune cells of the intestine. Immune responses affecting
Medications commonly used in the treatment of GER both the adaptive and innate immunity promote an inflam-
include proton pump inhibitors (PPIs) and H2 histamine matory reaction in the lamina propria of the intestinal wall
receptor antagonists. These medications are associated with leading to villus atrophy. The genetic factors are linked to
various nutrition-related side effects (Table 25-6). Also the human leukocyte antigen (HLA) system, which regu-
worthy of mention is the decreased absorption of supple- lates the immune response.
mental iron associated with PPI usage. 30 There are concerns The availability of serologic testing for celiac disease
as well about possible infection risk from long-term use of has changed our understanding of both the prevalence and
PPIs. 31,32 presentation of the disease. Previously celiac disease was
diagnosed mainly in patients who had typical symptoms
Table 25-6 Potential Effects of Medications Used for GERD30 (Table 25-7). Screening studies now suggest that celiac
Side effect Proton pump H2 Histamine disease occurs in roughly 1% of the population. There is
inhibitor receptor antagonist little difference in the rates in Europe compared to North
Diarrhea X X America, North Africa, or the Middle East. 34
Constipation X X The typical presentation of celiac disease usually occurs
Abdominal pain X X in the first few years of life and manifests as diarrhea with
Nausea/vomiting X X
growth failure and anemia. It is now recognized that celiac
Anorexia X
disease can present at any age following inclusion of gluten
Anemia X
in the diet and has a variety of manifestations, many of
Weight gain/loss X
Hepatotoxicity X
which are extraintestinal in nature. Indeed, with the devel-
opment and implementation of screening of patients “at

risk” (Table 25-8) it is clear that some patients with celiac patients with unexplained GI symptoms, anemia, or poor
disease are asymptomatic despite significant intestinal growth. Further, they are used to screen high-risk groups,
mucosal injury. Further, patients may have symptoms that and to aid in monitoring compliance with diet. Serologic
do not immediately call to mind intestinal disease. Older tests available include the tissue transglutaminase (tTG)
children and adolescents may present with constitutional IgG and IgA and anti-endomysial (AEM) antibodies. Anti-
symptoms such as fatigue or lassitude. GI symptoms may reticulin antibodies are rarely used as the more sensitive and
be mild or even absent. Patients with celiac disease often specific tests are commonly available. Recently serology
have derangements of bone and mineral metabolism and using antibodies to deamidated gliadin have become avail-
idiopathic osteopenia may be the sole clinical feature. 35,36 able. These appear to have sensitivity and specificity similar
to those of the tTG antibodies.
Table 25-7 Presentation of Celiac Disease The effects of celiac disease on nutrition status are
Typical (Usually Young) Weight loss profound. A patient may have linear and/or ponderal growth
Failure to grow failure. Diarrhea and weight loss may also be present. In
Vomiting addition vitamin and mineral deficiencies may be present
Diarrhea at the time of diagnosis. A thorough physical assessment
Bloating of the patient and assessment of laboratory values when
Anorexia indicated are necessary to identify such deficiencies. Atten-
Abdominal pain tion is paid to growth, bony abnormalities, and pigmentary
Atypical (Adolescent Constipation changes. Laboratory investigation, including serology, is
Young Adult) Short stature often revealing. In particular microcytic or macrocytic
Dermatitis Herpetiformis anemia may be present due to impaired absorption of iron
Osteopenia or folic acid in the proximal intestine37,38or B12 in the distal
Elevated liver enzymes small bowel. Other nutrients of concern include, but are not
Arthritis limited to, fat-soluble vitamins (A, D, E, and K), zinc, and
Iron deficiency calcium. Special attention is paid to vitamin D. Calcium
Anemia supplementation may also be needed. Inadequate calcium
Dental enamel defects may be due to malabsorption or poor dietary intake. Lactose
Silent (Any age) No obvious signs or symptoms; patient intolerance is common in untreated patients due to damage
identified when tested because of to the villi. Most often this improves with treatment;
risk factors and on biopsy has typical
enteropathy however, “adult-type” lactase deficiency, not associated with
Latent (Any age) Mild or non-specific symptoms identified intestinal injury, may complicate the clinical picture.
by screening; positive serology but normal The primary nutrition management of celiac disease
biopsy. May develop typical disease at a includes complete avoidance of all gluten and correction
later time.
of any vitamin/mineral deficiencies. The fundamental
basis of the gluten-free (GF) diet includes avoidance of
Table 25-8 Groups at Risk for Celiac Disease wheat, barley, and rye. Oats that are specifically labeled
Relative of Patient with Celiac Disease gluten free may be consumed in the diet; however, general
Diabetes Mellitus (Type 1) commercial oats may not be consumed secondary to cross-
Down Syndrome contamination with wheat in processing. 39 Refer to Table
Thyroiditis 25-9 for a list of gluten-containing and gluten-free grains.
Turner Syndrome The diet is more cumbersome than simply avoiding the
William Syndrome grains listed as containing gluten as there may be secondary
Other Autoimmune Diseases hidden sources of gluten in processed foods in the form of
additives. Detailed patient instruction on label reading and
avoiding cross-contamination is crucial for proper adher-
The mainstay of diagnosis of celiac disease remains the ence to the GF diet. When replenishing vitamin/mineral
small intestinal biopsy with demonstration of the typical stores with dietary supplements it is important to read the
features of enteropathy. Serologic tests are a valuable adjunct label for the presence of gluten as many dietary supplements
in the diagnosis and are often the initial diagnostic tool in are not GF.

Table 25-9 Grains and Gluten The most important risk factor for developing IBD is a posi-
Gluten Containing Gluten Free tive family history.
Barley Amaranth The incidence of Crohn’s disease seems to be increasing
Bulgur Arrowroot in childhood while the rates of ulcerative colitis are steady.
Couscous Buckwheat IBD may present at any age. Ulcerative colitis is more
Dinkle (spelt) Corn common in younger children. Peak age of incidence of
Durum Flaxseed Crohn’s disease is in the second decade of life.
Einkorn Rice Inflammation of the bowel leads to a number of
Emmer Millet derangements that culminate in diarrhea, GI bleeding, and
Farina® Milo
abdominal pain. Other symptoms depend on the location
Fu Potato flour
of inflammation within the GI tract. For example, vomiting
Graham flour Quinoa
is more prominent in patients with gastric or small bowel
Kamut Sorghum
Seitan Soy
disease. The most common presentation is a patient with
Semolina Tapioca abdominal pain and diarrhea. Stools may be bloody. Weight
Rye Tef loss is common, especially in patients with Crohn’s disease.
Wheat Taro flour However, non-specific manifestations of the disease may
Triticale Urd be the initial manifestations and failure to recognize their
importance may lead to delay in the diagnosis. Joint pain and
Note: This is not an all-inclusive list.
swelling, skin rashes, muscle pain, elevated liver enzymes,
Removal of gluten from the diet usually results in clin- or eye changes (uveitis, iritis, or episcleritis) may be present
ical and histological recovery. Specialized oral feedings or prior to any specific GI manifestation. Oral ulcerations can
enteral feedings are rarely necessary in a patient with celiac range from painless to severe pain with bleeding. It is well
disease. Parenteral feedings are not used unless there is recognized that deterioration of linear and ponderal growth
some other indication for that therapy. may precede the development of more specific symptoms
When the diagnosis of celiac disease is confirmed, by months or in some cases even years.
routine nutrition follow-up of the child is necessary to The effect of IBD on nutrition status is multifaceted.
monitor growth parameters, promote adherence to the Growth, bone health, and macronutrient and micronutrient
diet, and to assure proper nutrition, particularly because stores are commonly affected and malnutrition is common.42
many of the gluten-free products are not fortified. Ongoing Weight loss is a common presenting symptom in all forms
monitoring of vitamins (especially A, D, B12 , and folate), as of IBD. Linear growth failure can occur as well but is more
well as assessment of anemia and markers of bone health, is frequently associated with Crohn’s disease.
suggested.40 Fortunately, with proper nutrition and adher- Nutrition assessment of children with IBD includes
ence to the GF diet, bone density in children returns to measurements of weight, height, and calculation of body
normal 1 year post-initiation of the diet.41 mass index (BMI). These values should be plotted and
Clinical outcome is measured by resumption of normal followed serially on appropriate Centers for Disease Control
growth and weight gain and by monitoring of serologic and Prevention (CDC) growth charts.43 The importance
markers, especially tTG and IgA. Failure of tTG IgG and of tracking these measurements is emphasized by the fact
IgA levels to return to normal values after adherence to a that upon diagnosis the majority of children with ulcer-
gluten-free diet for 6 to 12 months warrants further inspec- ative colitis and especially Crohn’s disease will have growth
tion of the child’s diet for inadvertent gluten consumption. failure.44 In fact, reduced linear growth velocity may precede
GI manifestations of IBD by months or even years.45–47
Inflammatory Bowel Disease Criteria for defining growth failure include a height velocity
Inflammatory bowel disease (IBD) refers to chronic inflam- < 3rd percentile, a height < 3rd percentile, or a bone age less
mation anywhere along the GI tract. The term includes than chronological age by 2 or more standard deviations.48
Crohn’s disease, ulcerative colitis, and indeterminate colitis Males may be more susceptible to growth failure, but all
(ie, IBD with features that do not allow clear distinction children with IBD are at risk.43,49 Factors affecting risk
between Crohn’s disease and ulcerative colitis). These are include malnutrition, treatment modality, and intestinal
chronic conditions that affect children of any age although inflammation.
they most commonly manifest in the second decade of life. Malnutrition in IBD patients is multifactorial and

includes energy losses, increased requirements, malab- to obtain values within normal limits. Research suggests
sorption, and decreased energy intake due to diarrhea, that supplementation of vitamin D above the standard
abdominal pain, and other disease-related side effects. 50 recommendation may be necessary to achieve an appro-
Further contributing to malnutrition is poor appetite priate 25-hydroxyvitamin D level. 58 Children with Crohn’s
related cytokine activity in the inflammatory process. 51,52 disease of the upper intestine and children with darker
Inflammatory cytokines have also been shown to reduce complexions may have an increased need for vitamin D
insulin-like growth factor 1 (IGF-1). 53–55 Children with supplementation. 58,59 The winter season may also dictate
active Crohn’s disease often have lower levels of serum increased need. 58
IGF-1 levels than controls. In addition, chronic usage of Zinc and magnesium deficiencies are associated with
corticosteroids as treatment can suppress IGF-1 and also increased stool output and may require supplementation.
decrease osteoblast activity.43,56 Limited data suggest that Treatment is usually given empirically as interpretation
nutrition therapy in comparison to corticosteroid usage of serum zinc levels is sometimes difficult. Oral magne-
may be beneficial in the treatment of Crohn’s disease and sium supplementation is important, but can worsen
spare linear growth.48 More research is needed to substan- diarrhea if administered at increased doses over a short
tiate these findings.48 time frame.43,57
Assessment of nutrition status includes sufficiency of Energy and protein needs of the child with IBD are
vitamin and mineral stores. Analyses of dietary records based on collected anthropometric data as well as disease
and/or 24-hour food recall as well as laboratory values are status. In the adequately nourished child with IBD, resting
helpful in assessing micronutrient status. Commonly defi- energy expenditure (REE) is no different than in healthy
cient nutrients include iron, folate, vitamin B12 , vitamin children.43 However, in children with insufficient energy
D, calcium, zinc, and magnesium.43,57 Refer to Table 25-2 stores and increased inflammation, energy needs may be
for information regarding deficiency signs/symptoms and elevated 5% to 35% above estimated needs.43 There are
laboratory markers. Reduced iron stores are associated with no guidelines for protein supplementation at this time.43
decreased intake, reduced absorption, and increased losses However, it may be prudent to increase protein delivery in
(ie, blood loss). Often, iron supplementation is required a child with inflammation, infection, or postoperatively. 57
along with a diet rich in iron and vitamin C to correct Enteral nutrition (EN) is the recommended route of nutri-
the deficiency. 57 Laboratory values to monitor iron status tion support in IBD when needs cannot be met through oral
include hemoglobin, reticulocyte count, mean corpuscular intake alone. Parenteral nutrition (PN) may be indicated if
volume red blood cell (RBC) distribution width, ferritin, the enteral route is not feasible or insufficient to solely meet
transferrin saturation, and iron. 50 nutrient needs.43 Furthermore, PN may be indicated pre-
Folate stores may be affected by insufficient intake, and/or postoperatively. Refer to the chapter on pediatric
because many good sources of folate (eg, leafy green surgery (Chapter 32) for more information regarding PN
vegetables) are often not tolerated by the child with active and surgery.
inflammation. In addition, medications used in disease There is evidence that nutrition therapy may be as effec-
treatment such as methotrexate and sulphasalazine have tive in inducing disease remission as corticosteroid usage in
direct and deleterious effects on folate metabolism. Chil- children with active Crohn’s disease. 60–63 This method of
dren on these medications need folate supplementation.43,57 treatment may be particularly beneficial in children with
Vitamin B12 deficiency may occur in children with ileal or ileocolonic IBD. With EN as primary therapy the
involvement of the stomach and terminal ileum and in child follows a supplement-only diet, either orally or with
cases of bacterial overgrowth.44,57 Notably, deficiency may tube feedings, for approximately 8 weeks. 53,62 There is no
be masked by supplementation of folate. Deficiency is significant difference in outcomes of patients receiving
corrected by intramuscular injection, oral supplementation, a polymeric or elemental diet.64,65 After 8 weeks solids
or nasal gel. 57 are gradually reintroduced as the nutrition supplement
Maintenance of adequate calcium and vitamin D stores is concurrently reduced. 53,62 There may also be a role for
is imperative in children with IBD, particularly in those nutrition therapy in maintaining disease remission. 66–68
receiving steroid therapy due to the relationship of steroid However, in North America the primary mode of treat-
usage and decreased bone mineral density. Lactose intoler- ment for pediatric IBD patients is corticosteroids, in part
ance often limits consumption of milk and dairy products, secondary to compliance issues with nutrition-based treat-
rich in these nutrients. 57 Supplementation may be required ment regimens.43,69 Conversely, nutrition therapy is more

commonly employed in Western European countries.69 bowel and produces increased fluid losses. This can be due to
Decreased bone mineral density, as determined by either congenital or acquired disease. A common example is
dual energy x-ray absorptiometry (DEXA) scan, is an diarrhea associated with lactose intolerance. Excessive sugar
unfortunate side effect of IBD. Osteopenia may result from intake by children, either juices or sodas, may contribute to
malnutrition, inadequate calcium intake or malabsorption, osmotic diarrhea. Ingestion of non-absorbable materials
vitamin D deficiency, physical inactivity, or corticosteroid such as sorbitol or xylitol, used in some candies, will cause
use or may be related to cytokines released as part of the diarrhea as well. This type of diarrhea will stop with fasting
inflammatory disease. Children receiving 7.5 mg/d of or the removal of the offending solute.
steroids, a lifetime dose of 5 g, or 12 months of exposure Secretory diarrhea occurs when the intestinal surface
are particularly at increased risk and should be monitored cells secrete fluid into the lumen of the bowel. This may be
closely. 50 due to congenital disorders, such as congenital chloridor-
rhea, or acquired. Toxins may induce fluid and electrolyte
Diarrhea secretion. This is seen with cholera and some other infec-
Worldwide, diarrheal disease is a major cause of morbidity tions. Also some tumors may produce hormones that induce
and mortality in children. Despite improvements in sanita- secretion. Secretory diarrhea does not stop with fasting.
tion, aggressive use of oral rehydration therapy and early Children with motility-type diarrhea often have normal
refeeding, diarrhea remains a significant cause of undernu- absorption and digestion; however, they have rapid transit
trition and malnutrition in both developed and developing with resultant looseness and fluidity of stools. This mecha-
countries. nism predominates in toddler’s diarrhea or irritable bowel
Diarrhea is defined as the excessive loss of fluid and syndrome.
electrolyte in the stool. This may also be associated with Intestinal inflammation is associated with diarrhea.
nutrient loss. Acute diarrhea (ie, diarrhea of sudden onset) is It often involves elements of the other 3 mechanisms. In
most often related to infection or specific food intolerance. addition there may be increased loss of blood and protein.
Chronic diarrhea (diarrhea that lasts more than 2 weeks Infectious enteritis, celiac disease, IBD, eosinophilic disease
without obvious cause) has a number of possible etiologies. of the GI tract, and certain medications can cause intestinal
It is beyond the scope of this chapter to discuss in detail the inflammation.
many different causes of diarrhea. Emphasis here is on the Diarrhea can affect nutrition status in numerous
general principles guiding nutrition therapy in patents with ways. Reduced and/or altered dietary intake, fecal loses
the symptoms. of macronutrients and micronutrients, fluid losses, and
The basis for diarrhea is impaired transport of intestinal malabsorption of ingested nutrients are all factors that can
content including nutrients, electrolytes, and other solutes. compromise the child with diarrhea. Prolonged diarrhea
Water movement across the intestinal mucosa depends on coupled with insufficient dietary intake may result in growth
the active and passive fluxes of solute. Diarrhea encom- failure.70,71 Interestingly, malnutrition is an independent
passes 4 mechanisms that often overlap. Each mechanism risk factor for development of diarrhea.70 Thus, correction
may present a unique nutrition challenge (Table 25-10). In of diarrhea-associated malnutrition is not only crucial for
addition, patients with diarrhea often do not ingest adequate assuring proper growth of the child but also for prevention
amounts of nutrients. of future diarrheal episodes.
Impaired absorption and/or increased losses of carbo-
Table 25-10 Pathophysiology of Diarrhea hydrates, particularly lactose, protein, fat, and fluids, are
Osmotic Increased osmotic load due to failure to absorb associated with acute and chronic diarrhea episodes.70,72–74
Secretory Net intestinal secretion of fluid and electrolytes In cases of acute diarrhea the degree of malabsorption and/
Motility Rapid transit with failure to dry or loss is dependent upon the type and severity of infec-
Inflammatory Combination of the above with added exudative tion.73 A common occurrence during infectious diarrhea
loss of protein
is the development of dehydration. Subsequently, acidosis
Medication Opioids
Calcium Channel Blockers secondary to high output of bicarbonate may occur. To
Anti-cholinergic correct severe dehydration (> 10% loss in body weight)
100 mL/kg of sodium-containing fluid should be admin-
Osmotic diarrhea happens when a non-absorbed mate- istered intravenously. The amount of sodium depends on
rial, often carbohydrate, creates an osmotic load in the distal the type of dehydration. Within the first hour, half of the

dosage may be administered while the remaining fluids screening as appropriate. Supplementation of probiotics,
may be given over a 3- to 6-hour period. Plasma expanders particularly of Lactobacillus GG and Saccharomyces boulardii,
may also be indicated. Following correction of dehydration, may be beneficial in the management of diarrhea.80,81
maintenance fluids may be given. If dehydration is mild, oral However, there are currently no standard guidelines for
fluids may be given using an oral rehydrate solution (ORS) using probiotics in the management of pediatric diarrhea.
containing sodium, chloride, bicarbonate, and potassium at
a dosage of 50 to 120 mL/kg over 4 to 6 hours, then followed Pancreatic Insufficiency
by maintenance fluids. Fluids with a high osmotic load, such The pancreas is a small but metabolically active organ that
as sodas, should not be given as they may worsen the diar- has both manufacturing (exocrine) and control (endocrine)
rhea.70 In the absence of vomiting, feeding of a regular diet functions. Islet cells within the pancreas make insulin and
(ie, breast milk, infant formula, and/or solids) should begin glucagon, central to glucose homeostasis. The exocrine
after rehydration commences to reduce or prevent malnu- pancreas consists of cells organized into acini and the
trition and subsequent growth stunting.70,71,74 Caloric intake duct system providing a pathway to the small intestine.
enhances recovery.74 The pancreatic juice secreted by these cells contains bicar-
The approach to management of chronic diarrhea is bonate as well as digestive enzymes. Some of these enzymes
dependent on the etiology of the condition. For example, (amylase, lipase, and phosphor lipase) are secreted in an
in cases of sucrase-isomaltase deficiency the management active form. Others (eg, trypsin, chymotrypsin) are secreted
strategy is avoidance of dietary sucrose due to the absence in inactive forms (zymogens). Activation of the zymogens
of the sucrase-isomaltase enzyme on the intestinal surface. occurs when pancreatic juice mixes with enterokinase in
This condition usually presents when juices, formula, or the duodenum. Secretion of pancreatic juice in response to
solids containing sucrose are introduced to the infant’s a meal is controlled by many factors including the nervous
diet.75 Absence of the sucrase-isomaltase enzyme prevents system and hormones such as pancreozymin and secretin
breakdown and absorption of the sucrose disaccharide, among others. This secretion of the digestive enzymes is a
which in turn results in osmotic diarrhea.76 Other symp- tightly regulated “feedback” loop. If the amount of diges-
toms include, but are not limited to, failure to thrive, colic, tive enzyme delivered to the intestine is inadequate for the
abdominal distention, and gassiness.75,77 Similarly, indi- digestion of the fat, carbohydrate, and protein in the meal,
viduals with chronic lactose intolerance also may present pancreatic insufficiency exists.
with abdominal distention, gassiness, and diarrhea. Lactose Cystic fibrosis (Chapter 28) is the most common cause
intolerance is a result of absence of the lactase enzyme to of pancreatic insufficiency in childhood. Other causes
break down the dairy carbohydrate lactose. Management of pancreatic insufficiency in childhood are rarer (Table
of this condition involves avoidance of lactose-containing 25-11).
foods/beverages or supplementing with lactase pills prior to
Table 25-11 Pancreatic Insufficiency Not CF
ingestion of lactose-containing foods. Fructose is found in
Congenital Shwachman-Diamond syndrome
the diet as the free sugar, as a component of the disaccharide
Pearson syndrome
sucrose, and in a polymeric form (fructans). Free fructose
Johanson-Blizzard syndrome
has limited absorption in the small intestine. Fructans are
Specific enzyme defects
neither digested nor absorbed. Fructose malabsorption
Acquired Chronic pancreatitis
contributes to osmotic load. In addition, it provides substrate
Common duct obstructions
for bacterial fermentation and may affect GI motility, all
leading to diarrhea. This malabsorption may contribute to Shwachman-Diamond syndrome is the second most
abdominal pain. Treatment is dietary restriction of fructose common cause of pancreatic insufficiency in children. It is
and fructan intake. estimated to occur in 1 in 20,000 live births. It results from
In both acute and chronic diarrhea various micronutri- the failure of normal development of pancreatic exocrine
ents may be compromised either due to failure of absorption tissue in utero. The normal tissue is replaced with fat. 82,83
or increased losses in the stool. Losses commonly associ- The ductal tissue remains intact and over time there is
ated with diarrhea include zinc, copper, folate, magnesium, improvement in pancreatic function. 84 A specific gene
vitamin A, vitamin B12 , and trace elements, particularly defect has been described.85 The presenting features include
selenium.70,72,78,79 The clinician should be mindful of signs pancreatic insufficiency, hematologic abnormalities (espe-
of deficiency of these nutrients and conduct laboratory cially variable neutropenia), bone abnormalities (especially

metaphyseal dysostosis), and short stature. Steatorrhea is Pancreatitis

most prominent early in life. Because of the neutropenia, Pancreatitis is an inflammatory process of the pancreas
there is concern for infectious complications. with variable involvement of other organs and tissues.
Johanson-Blizzard syndrome is a rare disorder and the Exposure to a causal factor initiates a cascade of events in
incidence and natural history are unknown. Patients have which trypsinogen is converted to trypsin in quantities
pancreatic insufficiency with midline ectodermal defects that overwhelm the innate protective mechanisms. Causes
and hypoplasia of the alae nasae.86 Even more rare is Pearson of pancreatitis include trauma, infection, drugs or toxins,
syndrome, which is exocrine pancreatic insufficiency asso- multisystem disease, and congenital abnormalities of the
ciated with sideroblastic anemia.87 It results from defects in pancreatic or biliary ductal system. Many cases do not have
mitochondrial DNA.88 Because it is a mitochondrial disease, a clear trigger identified. In children most cases are either
there can be multiorgan involvement. acute and isolated or recurrent acute attacks. Chronic
In addition, isolated congenital deficiencies in lipase and pancreatitis is seen more commonly in adults. In children it
trypsinogen are described but are exceedingly rare. These is most often related to structural malformation or a specific
are treated with enzyme replacement therapy. Amylase gene defect as seen in hereditary pancreatitis.
deficiency with associated starch intolerance is described in The incidence of acute pancreatitis in childhood is
infants but is typically developmental in nature and no cases uncertain. Though not rare, it accounts for a small propor-
are described in adults. It can cause diarrhea but is rarely a tion of pediatric admissions.93,94 Likewise, the incidence of
cause of poor growth and rarely requires treatment. chronic pancreatitis is not clear.
Failure to thrive, as indicated by growth failure and Most of the pancreas is composed of acinar cells.
malnutrition, is commonly associated with pancreatic Ductules and ducts connect the acini to the duodenum.
insufficiency. It is a result of maldigestion, malabsorption, The islet cells (which secrete insulin and glucagon) func-
insufficient caloric intake, and increased caloric require- tion independently of the acinar cells. The acinar cells
ments. As a product of malabsorption, fat-soluble vitamin synthesize and store digestive enzymes. All enzymes except
deficiency may develop.89 Malabsorption, calorie loss, amylase and lipase are stored as inactive proenzymes that
and failure to thrive are treated with dietary intervention, require activation by the action of trypsin. Trypsinogen
pancreatic enzyme replacement therapy, and supplementa- (the inactive form of trypsin) is activated in the lumen of
tion of fat-soluble vitamins. the bowel by the mucosal enzyme enterokinase. In some
Nutrition management of diseases of pancreatic instances, trypsinogen may “auto-activate.” This premature
insufficiency dictates a diet liberal in fats and calories activation of trypsin with subsequent activation of other
and supplemented with pancreatic enzyme replacement proteases leads to digestion of the pancreas itself. There are
therapy.89 Research indicates that pancreatic insufficient a number of mechanisms for protection of acinar cells from
individuals have a higher resting energy requirement this auto-activation including presence of trypsin inhibitors
than pancreatic sufficient individuals.90 Thus, calories will that block the action of trypsin; also, trypsin can inacti-
likely need to be provided in greater than 100% of esti- vate itself through autolysis. This inactivation reaction is
mated needs.89 Pancreatic enzyme replacement should be a calcium-dependent process and aberrations of calcium
conducted using proprietary preparations due to the lack concentration may trigger an episode of acute pancreatitis.
of data with the usage of generic enzyme preparations.91 If any of these mechanisms are disturbed, pancreatic injury
Enzymes should be ingested prior to meals, snacks, and will result.
consumption of milk products to aid in digestion of fat. Pancreatitis is diagnosed by the combination of abdom-
Enzyme dosage should not exceed 2500 lipase units/kg per inal pain with elevation of the levels of amylase and lipase
meal or 4000 lipase units/g fat per day to avoid fibrosing in the serum. The levels of the enzymes do not predict the
colonopathy.92 For more detailed information pertaining severity of pancreatitis. There are no scoring systems appli-
to pancreatic enzyme replacement therapy refer to the cable to children as there are for adults. Clinical features
chapter on pulmonary diseases (Chapter 28). Also in need suggestive of more severe disease include hypotension,
of supplementation may be the fat-soluble vitamins A, D, renal failure, altered sensorium, and hemorrhage.
E, and K. These vitamins should be supplemented with a Initial management of children with acute pancreatitis
water miscible form. Refer to the chapter on pulmonary is analgesia and intravenous fluids. If vomiting is present,
diseases (Chapter 28) for a more detailed discussion of a nasogastric tube is used to decompress the stomach. In
these vitamins. patients with mild disease, enteral feedings are withheld for

a short period. Re-initiation of feedings is based on resolu- fibrosis (Chapter 28). Both polymeric as well as elemental
tion of abdominal pain and ileus and vomiting. Most patients dietary supplements have been used for nutrition support,
with mild disease recover quickly without complications. and there are scant data evaluating the effectiveness in chil-
Patients with severe pancreatitis often show signs of dren. It deserves to be restated that a major goal of nutrition
hemodynamic instability and are at risk for multiple compli- support in these patients is maintenance of normal growth.
cations including severe nutrition depletion. Nutrition
support is important in these patients and is considered an Disorders of Chyle Loss
active therapeutic intervention.95 Patients can be fed enter- Chyle is a creamy fluid consisting of fat, protein, electro-
ally by nasogastric (NG) or nasojejunal (NJ) tube or by the lytes, and lymphocytes and is an important aspect of the
intravenous route. Although there are a number of studies metabolism of fat. Triglycerides are broken down in the
in adults, data concerning nutrition support in pediatric intestinal lumen to fatty acids and mono-acyl glycerols.
patients with pancreatitis are scarce. Adult studies suggest They are absorbed into the intestinal epithelial cells. This
a trend to fewer adverse outcomes in patients who receive process is aided by the action of bile salts mixing with the
enteral as opposed to parenteral feedings, however the fatty acids forming micelles that enhance the transport of
effect on outcome is not clear.96 There does not seem to be a the molecules. Within the enterocytes, the absorbed fatty
difference in feedings of polymeric versus semi-elemental or acids are re-esterified to glycerol and the resultant lipid
“immune-enhancing” formulas.97 A study in children with is complexed with proteins (forming chylomicrons) and
severe acute pancreatitis found little difference between EN transported through the lymphatic system of the GI tract
and PN in length of stay, infection, mortality, or need for and abdomen ultimately into the thoracic duct and then
surgery.98 into the blood stream. Disorders of chyle loss are rare with
Chronic pancreatitis is a condition where continued the most common disorders being chylothorax or chylous
inflammation of the pancreas produces irreversible changes ascites. Chylothorax is defined by pooling of lymphatic
in the gland. In some cases it is related to continued recur- fluid, chyle, in mediastinal or pleural cavities. Chylous
rent injury from acute attacks. Often the etiology is not ascites occurs when there is lymphatic disruption in the
clear even when risk factors are present. In adults, repeated abdominal cavity with resultant pooling of chyle in the
exposure to toxins (eg, alcohol) is often implicated. In chil- abdomen. This condition is usually seen as a complication
dren, hereditary factors such as mutation of the trypsinogen of surgery100 although congenital defects of lymph flow are
molecule, or mutations of the cystic fibrosis transmembrane also described. For more detailed information refer to the
regulator (CFTR) gene or trypsin inhibitor genes are often chapter on cardiac disease (Chapter 23). A less common
sought. Autoimmune disorders, both isolated autoimmune disorder of chyle is that of intestinal lymphangiectasia. This
pancreatitis as well as systemic autoimmune diseases, are condition results from failure of lymph flow often related
seen. Patients with recurrent acute pancreatitis are at risk to inflammation, causing enlargement of intestinal lymph
for developing chronic pancreatitis.99 vessels, which causes breakage of the lacteals and spillage
Treatment of chronic pancreatitis revolves around of chyle into the intestinal lumen.101 As a result protein
several concerns: chronic pain, development of diabetes losing enteropathy, hypoalbuminemia, and edema may
due to islet cell destruction, and pancreatic insufficiency result. Hypogammaglobulinemia is often present. Edema
due to acinar cell destruction. Pain impacts ability to ingest of the intestinal mucosa causes malabsorption. Steator-
nutrients, and the treatment of chronic pain is beyond the rhea is typically seen.102 Even more rare are the disorders
scope of this chapter. In addition the treatment of diabetes of chylomicron formation such as abetalipoproteinemia in
mellitus is discussed elsewhere (Chapter 21). Digestive which there is a defect in the ability to complex the lipids
enzyme insufficiency is a late complication of chronic with carrier proteins and therefore the lipid is not carried
pancreatitis. The treatment for pancreatic digestive enzyme into the lymphatic system.
insufficiency is enzyme replacement. The goal is to provide Regardless of the specific disorder of chyle processing,
enzyme supplements enough to restore digestive function. the nutrition approach is similar. The initial treatment is
The dose of pancreatic enzyme is calculated according to restriction of dietary fat. A low-fat, high-protein diet is
the lipase content. A usual dose of enzyme is 1000 to 2500 recommended because there is usually associated protein
units of lipase per kilogram of body weight per meal. This is loss in the GI tract. Because medium-chain length fatty
often altered based on the estimated fat content of the meal. acids and triglycerides can be metabolized without entry
This is discussed in more detail in the chapter on cystic into the lymphatic system, dietary fats should be primarily

from medium-chain triglycerides (MCTs), often by using a considered. Poor absorption of ingested carbohydrate may
specialized high MCT, low long-chain triglyceride (LCT) trigger symptoms in susceptible individuals. Therefore,
formula.101 The rationale of this diet is twofold. One, restrictions of lactose (milk), fructose (carbonated bever-
the decreased amount of fat lowers the amount of circu- ages and certain fruits), or dietary starches (corn, wheat, oat,
lating chyle. This reduction lowers the risk of lacteal cells and potato) are sometimes tried. Restriction of non-absorb-
becoming dilated and releasing chyle. Two, MCTs are able sugar alcohols, often used as artificial sweeteners (eg,
directly transported via the portal system, which reduces sorbitol, xylitol), is advised. It is important to avoid multiply
lymphatic circulation.101,102 Most often, this diet is needed restrictive diets as they may lead to nutrition insufficiency.
for 4 to 8 weeks.100 One should be cautious to supply suffi-
cient amounts of essential fatty acids, linoleic and linolenic Gastroparesis
acids, to prevent deficiency. The American Academy of Gastroparesis is the delay of emptying of the stomach in
Pediatrics recommends that a minimum of 3% of calories the absence of a mechanical obstruction. There are multiple
should come from these essential fatty acids.100 PN may causes (Table 25-12). Disorders of the intestinal muscu-
be initiated in instances when EN is not adequate to meet lature (myopathic) and the intestinal nervous system
nutrient needs or not indicated for other reasons. Lipids in (neuropathic), both congenital and acquired, are described.
PN are not absorbed via the lymphatic system and have no Common causes are immaturity (especially in premature
affect on the condition. infants), viral infections, systemic diseases, and drugs.
Gastroparesis often complicates the management of type 1
Functional Disorders diabetes mellitus. Evaluation should include assessment of
The functional disorders are a diverse group of conditions gastric anatomy and function (eg, upper GI series x-ray or
in which symptoms persist for a prolonged period and there gastric emptying study) but also the search for and treat-
is no specific tissue change associated with the symptom. ment of any underlying condition and bacterial overgrowth.
These include recurrent and/or chronic abdominal pain, Importantly, malnutrition may be both a cause as well as a
chronic non-specific diarrhea, gastroparesis, cyclic vomiting result of gastroparesis.
syndrome, and constipation. Because the underlying
pathophysiology is unclear, both the evaluation and treat- Table 25-12 Conditions Associated with Gastroparesis
ment is related to the predominant symptom. Malnutrition Infection Postviral illness (eg, rotovirus)
is rare in this group of patients and, if present, suggests an Neurological Disease Mitochondrial disorders
alternative diagnosis. Frequently, dietary interventions are Familial dysautonomia
suggested for symptom control. These include increasing Systemic Disease Diabetes
fiber, reducing fermentable carbohydrate, and altering the Malnutrition
fat content of the diet. These interventions are often recom- Connective tissue disorders
mended and frequently reported to be helpful though data
documenting effectiveness are lacking. There are many symptoms of gastroparesis including
Chronic abdominal pain is a common symptom in chil- nausea, vomiting, bloating, upper abdominal discomfort,
dren and adolescents and it is estimated to affect 10% to 15% early satiety, heartburn, esophageal reflux, and decreased
of the population at some time.103 The etiology and patho- appetite.104–106 These symptoms may lead to malnutrition
genesis are unknown and there are no specific diagnostic and the need for nutrition support. Initial treatment of
markers to help in diagnosis. The clinical presentation and gastroparesis should include maximizing the therapy of
careful history and physical examination will often suggest treatable systemic illness (eg, optimizing glycemic control
that the diagnosis is functional abdominal pain. A few labo- in the diabetic patient) and eliminating causes such as
ratory or x-ray studies may assist in the evaluation and are medications.
remarkable for their normality. The nutrition assessment of a child with gastroparesis
The role of dietary modifications in the management of should include a dietary recall and/or dietary record, evalu-
the functional abdominal pain disorders is not established. ation of changes in weight over time, laboratory studies,
If symptoms are mainly post-prandial or include the sensa- description of symptoms, and listing of medications as
tion of bloating, a low-fat diet is sometimes recommended. well as nutrition supplements.107 The dietary recall and
If diarrhea or constipation is prominently associated with or/record provides important information regarding both
the pain, an increase in the amount of fiber in the diet is symptoms and feeding. Factors to consider are meal volume

tolerance, preference of liquids over solids, and fiber and in some children it may be beneficial to undergo a trial of a
fat tolerance.107 Because early satiety is commonly seen in high-fiber (0.75 g soluble fiber per year of age), lactose-free,
gastroparesis, small frequent meals may be better tolerated and low-fructose diet for symptom management.115
than 3 large meals.104,107 Liquids are often better tolerated
than solids. Thus, a diet of liquids and/or purees may be Cyclic Vomiting Syndrome
more effective in delivering ample nutrition than a conven- Although increasingly recognized in children, the patho-
tional solid-based diet.104,106,107 Avoidance of a high-fiber and genesis of cyclic vomiting syndrome remains unknown. The
high-fat diet, with the exception of fat in liquid nutrition, is clinical features overlap with those of abdominal migraine.
also often beneficial in delivering nutrition as both of these The distinguishing characteristic is a repeated pattern of
nutrients delay gastric emptying.107 Dietary osmolality is stereotypical episodes of severe vomiting often associated
less an issue in managing gastroparesis.107 with pallor, lethargy, and abdominal pain. The episodes
Laboratory markers include ferritin, glucose, and are similar in onset and usually duration. There is often a
hemoglobin A1C. Iron deficiency anemia is common in this prodrome of variable duration. An important feature is that
cohort of patients, in part due to symptom management. the children return to baseline health in between episodes.
Usage of acid-reducing medications to manage reflux and In cyclic vomiting syndrome the primary nutri-
heartburn decreases gastric acid, needed to convert dietary tion concern is management of any fluid and electrolyte
iron to its more absorbable form. Further, usage of jejunal disturbances that may arise as there is no known dietary
tube feeds to control vomiting and promote weight gain can intervention to prevent onset or reduce duration of the
increase the risk of iron deficiency anemia as the duodenum condition.103
is the main area of iron absorption.107 Ferritin is a more
appropriate marker to screen for iron deficiency anemia Irritable Bowel Syndrome
than hemoglobin and hematocrit. However, it is important In irritable bowel syndrome (IBS) there is no significant
to remember that ferritin is an acute phase respondent and evidence to support that diet causes or can treat the condi-
will not be accurate during acute inflammation.107,108 tion. It may be prudent to undergo an elimination trial
of lactose-, fructose-, and/or sorbitol-containing foods
Constipation as intolerance to these foods manifests as abdominal
Constipation is a common symptom among humans of all pain.116–118 The role of dietary fiber, particularly that of
ages and is often especially troubling in infants and young soluble fiber, in symptom management, especially of
children. It is most often both self-limited and short lived. constipation, is debatable. Soluble fiber is found in fruits,
However, a substantial number of patients have symptoms vegetables, and whole grains. When ingested, fiber helps
that persist for 6 months or more. Constipation may be to give the stool a gel-like consistency and serves as a fuel
related to inadequate intake of fluid or fiber, side effects of source for colonic bacteria. The end result is a reduction in
medication, inactivity, or disordered bowel motility. Most gut transit time and, subsequently, a reduction in consti-
cases are idiopathic and fulfill the definitions of functional pation and intracolonic pressure.119,120 To date, there are
constipation. Although most recognize a role for diet in no definitive conclusions as to the benefit of fiber in IBS
both the etiology and the treatment of constipation, there symptom management.121 Nutrition counseling should
are little data to allow identification of specific foods as be individualized based on the patient’s reported food-
either causal or beneficial. symptom correlations secondary to limited pediatric data
The role of cow’s milk in constipation has been recog- on the topic.122 The suspected offending food should be
nized for some time, although the mechanism is unclear.109 removed from the diet for 2 to 3 weeks. If no relief in symp-
There is increasing evidence to suggest a role of cow’s milk toms is observed, the food may be added back to the diet.
protein sensitivity in constipation.110,111 In addition, it is
known that the fat content of milk may also be associated Eosinophilic Conditions of the Gut
with harder or more difficult-to-pass stools. Eosinophilic gastroenteritis is a condition characterized by
Historically, a high-fiber diet has been recommended either patchy or diffuse infiltration of eosinophils anywhere
for children with constipation. However, few studies docu- in the GI tract. Damage to the GI tract is due to both the
ment benefit.112,113 There is also no conclusive evidence that infiltration and degranulation of eosinophils. The trig-
fiber supplements or a lactose-free diet is beneficial in alle- gering process is not clear. Both IgE and non-IgE mediated
viating recurrent abdominal pain in children.114 However, sensitivities are described. Many patients (especially older

patients) have conditions such as a high eosinophil count, abdominal pain, diarrhea, hematochezia, poor growth/
asthma, allergic rhinitis, or eczema suggesting underlying weight gain, and iron deficiency anemia.124 The recom-
atopy. Allergies to food or inhalants are sometimes impli- mended dietary treatment is avoidance of the offending
cated. In addition there is often a family history of atopy. It allergens. Particular attention should be paid to the quality
may affect children of any age. of the diet as malnutrition may develop if numerous foods
The signs and symptoms are non-specific and the are eliminated.123 For some children usage of an amino acid
presentation varies by location, depth and extent of the based formula may be appropriate.124
eosinophilic infiltration (Table 25-13). There may be
involvement of the mucosal, muscular, or serosal layers. Summary
Mucosal disease presents as nausea and vomiting, diarrhea Because of the central role of the digestive system in main-
(often bloody), malabsorption, and weight loss. When the taining normal nutrition, disease of the GI tract, liver, or
muscular layers are involved, there are signs and symptoms pancreas has a profound influence on growth and develop-
of obstruction. If there is serosal involvement there may be ment of children. Provision of adequate nutrition support
ascites. The most common symptom is colicky abdominal can not only improve nutrition parameters and growth but
pain. also in many cases can treat the underlying disease. Careful
evaluation of the child with assessment of nutrition needs is
Table 25-13 Presentation Characteristics of Eosinophilic Gastroenteritis the initial step in effective management. The clinical exami-
by Tissue nation and judiciously applied laboratory investigation will
TISSUE PRESENTATION CHARACTERISTICS identify nutrition deficiencies. With understanding of the
Mucosal Diarrhea underlying disease process, appropriate nutrition manage-
GI bleeding ment can improve growth, quality of life, and outcomes of
Vomiting these patients.
Abdominal pain
Muscular Vomiting Test Your Knowledge Questions
Colicky A 15 year old boy is admitted to the hospital because of diar-
Abdominal pain rhea and abdominal pain. He has had unintentional weight
Serosal Ascites loss of 15 pounds in the last 3 months. Laboratory evalua-
Abdominal pain tion reveals:
• Albumin 3.1
The most frequently seen form of eosinophilic gastro- • Total Protein 6.2
enteritis is proctitis in infants. The disorder is characterized • Hemoglobin/hematocrit 9.3/27
by the bloody diarrhea in an infant less than 2 months of • MCV 71 (nl >79)
age. • WBC 11,500
Cases of food-induced eosinophilic proctocolitis are Radiology studies demonstrated inflammation of the ileum
reported regardless of being breastfed or formula fed. and cecum.
Infants presenting with this condition usually have normal 1. Diet therapy should include:
linear and ponderal growth. The infants will have diarrhea, A. A polymeric defined formula diet
usually accompanied by mucous and/or blood, and often B. A semi-elemental defined formula diet
with pain or straining at the time of bowel motion. Biopsy of C. An elemental defined formula diet
the rectal mucosa will show eosinophilic infiltration of the D. Any of A, B, or C
mucosa. Frequently the diagnosis is made on clinical presen- E. A clear liquid diet
tation alone. The dietary management of this condition 2. His medical therapy includes methotrexate and
involves elimination of the offending protein until approxi- sulphasalazine. Supplementation should include:
mately 9 to 12 months of age. If an infant is breastfed then A. Folate, B12, and iron
the offending protein should be removed from the mother’s B. Pyridoxine, thiamin, and magnesium
diet. Earlier introduction of the protein will usually result in C. B12, vitamin C, and manganese
bleeding.123 D. Folate, vitamin C, and copper
In older children with eosinophilic conditions of the
gut symptoms include, but are not limited to, vomiting,

10. Nelson SP, Chen EH, Syniar GM, Christoffel KK. One year
3. In a patient with celiac disease, a gluten-free diet should
follow up of symptoms of gastroesophageal reflux during
be maintained: infancy. Pediatric Practice Research Group. Pediatrics.
A. Until diarrhea subsides 1998;102:e67.
B. Until normal linear growth is established 11. Vandenplas Y. Gastroesophageal reflux. In: Wyllie R, Hyams
C. Until new and as yet undiscovered treatments are JS, Kay M, eds. Pediatric Gastrointestinal and Liver Disease.
available Pathophysiology, Diagnosis, Management. 3rd ed. London:
Saunders Elsevier; 2006:305–325.
D. Until bone mineral density has returned to normal 12. Pandolfino JE, Kwiatek MA, Kahrilas PJ. ��
The pathophysio-
E. A gluten-free diet is not necessary logic basis for epidemiologic trends in gastroesophageal reflux
4. Enterokinase is synthesized by: disease. Gastroenterol Clin North Am. 2008;37:827–843.
A. Pancreatic acinar cells 13. Vandenplas Y, Hassall E. Mechanics of gastroesophageal
B. Intestinal mucosal cells reflux and gastroesophageal reflux disease. J Pediatr Gastroen-
terol Nutr. 2002;35:119–136.
C. Liver cells
14. Kawahara H, Dent J, Davidson G. Mechanics responsible
D. Neutrophils for gastroesophageal reflux in children. Gastroenterology.
5. Enterokinase is an enzyme that: 1997;113:399–408.
A. Digests fat 15. Vanderhoof JA, Moran JR, Harris CL, Merkel KL, Orenstein
B. Activates eosinophil degranulation SR. Efficacy of a pre-thickened infant formula: a multicenter,
C. Transports glucose into the cell double-blind, randomized, placebo-controlled parallel group
trial in 104 infants with symptomatic gastroesophageal reflux.
D. Activates trypsinogen to trypsin Clin Pediatr. 2003;42:483–495.
16. Aggett PJ, Agostoni C, Axelsson I, et al. Anti-reflux or anti-
See p. 487 for answers. regurgitation milk products for infants and young children: a
commentary by the ESPGHAN Committee on Nutrition. J
References Pediatr Gastroenterol Nutr. 2002;394:496–498.
1. Gibbons T, Fuchs GJ. Malnutrition: a hidden problem in 17. Vandenplas Y, De Wolf D, Sacre L. Influence of xanthines on
hospitalized children. Clin Pediatr. 2009;48:356–361. gastroesophageal reflux in infants at risk for sudden infant
2. Naber TH, Schermer T, de Bree A, Nusteling K, et al. Preva- death syndrome. Pediatrics. 1986;77:807–810.
lence of malnutrition in nonsurgical hospitalized patients and 18. Wenzl TG, Schneider S, Scheele F, Silny J, Heimann G,
its association with disease complications. Am J Clin Nutr. Skopnik H. Effects of thickened feeding on gastroesophageal
1997;66:1232–1239. reflux in infants: a placebo-controlled crossover study using
3. Motil KJ, Phillips SM, Conkin CA. Nutritional assessment. intraluminal impedance. Pediatrics. 2003;111(4 Pt 1):e355-
In: Wyllie R, Hyams JS, Kay M, eds. Pediatric Gastrointestinal e359.
and Liver Disease. Pathophysiology, Diagnosis, Management. 3rd 19. Orenstein SR, Shalaby TM, Putnam PE. Thickened feedings
ed. London: Saunders Elsevier; 2006:1095–1111. as a cause of increased coughing when used as therapy for
4. Baker SS, Baker RD, Davis AM. Pediatric Nutrition Support. gastroesophageal reflux in infants. J Pediatr. 1992;121:913-
Sudbury, MA: Jones and Bartlett Publishers; 2007:459–475. 915.
5. Shay S, Tutian R, Sifrim D, et al. Twenty-four hour ambulatory 20. Huang R-C, Forbes DA, Davies MW. Feed thickener
simultaneous impedance and pH monitoring: a multicenter for newborn infants with gastro-oesophageal reflux.
report of normal values from 60 healthy volunteers. Am J Cochrane Database of Syst Rev. 2002;(3):CD003211.
Gastroenterol. 2004;99:1037–1043. doi:10.1002/14651858.CD003211.
6. Nelson SP, Chen EH, Syniar GM, et al. Prevalence of 21. Craig WR, Hanlon-Dearman A, Sinclair C, Taback SP,
symptoms of gastroesophageal reflux during childhood: a Moffatt M. Metoclopramide, thickened feedings and posi-
pediatric practice-based survey. Arch Pediatric Adol Med. tioning for gastro oesophageal reflux in children under two
2000;154:150–154. years. Cochran Database Syst Rev. 2009;(3):CD003502.
7. Vandenplas Y, Goyvaerts H, Helven R, Sacre L. Gastroe- doi:10.1002/14651858.CD003502 pub 2.
sophageal reflux, as measured by 24-hour pH monitoring, in 22. Bosscher D, Van Caillie-Bertrand M, Van Dyck K, Robberecht
509 healthy infants screened for risk of sudden infant death H, Van Cauwenbergh R, Deelstra H. Thickening infant
syndrome. Pediatrics. 1991;88:834–890. formula with digestible and indigestible carbohydrate: avail-
8. Martin AJ, Pratt N, Kennedy JD, et al. Natural history and ability of calcium, iron, and zinc in vitro. J Pediatr Gastroenterol
familial relationships of infant spilling to 9 years of age. Pedi- Nutr. 2000;30:373–378.
atrics. 2002;109:1061–1067. 23. Rudolph CD, Mazur LJ, Liptak GS, et al.; North American
9. Nelson SP, Chen EH, Syniar GM, et al. Prevalence of Society for Pediatric Gastroenterology and Nutrition. Guide-
symptoms of gastroesophageal reflux during infancy: A lines for evaluation and treatment of gastroesophageal reflux
pediatric practice-based survey. Arch Pediatr Adolesc Med. in infants and children: recommendations of the North Amer-
1997;151;569–572. ican Society for Pediatric Gastroenterology and Nutrition. J
Pediatr Gastroenterol Nutr. 2001;32:Supp 2:S1–31.

24. Hills JM, Aaronson PI. The mechanism of action of pepper- 43. Kleinman RE, Baldassano RN, Caplan A, et al. Nutrition
mint oil on gastrointestinal smooth muscle. Gastroenterology. support for pediatric patients with inflammatory bowel
1991;101:55–65. disease: a clinical report of the North American Society for
25. Wendl B, Pfeiffer A, Pehl C, Schmidt T, Kaess H. Effect of Pediatric Gastroenterology, Hepatology and Nutrition. J
decaffeination of coffee or tea on gastro-oesophageal reflux. Pediatr Gastroenterol Nutr. 2004;39:15–27.
Aliment Pharmacol Ther. 1994;8:283–287. 44. Seidman E, LeLeiko N, Ament M, et al. Nutritional issues in
26. Pehl C, Pfeiffer A, Wendl B, Kaess H. The effect of decaffeina- pediatric inflammatory bowel disease. J Pediatr Gastroenterol
tion of coffee on gastroesophageal reflux in patients with reflux Nutr. 1991;12:424–438.
disease. Aliment Pharmacol Ther. 1997;11:483–486. 45. Kanof ME, Lake AM, Bayless TM. Decreased height velocity
27. Bulat R, Fachnie E, Chauhan U, Chen Y, Tougas G. Lack of in children and adolescents before the diagnosis of Crohn’s
effect of spearmint on lower esophageal sphincter function disease. Gastroenterology. 1988;95:1523–1527.
and acid reflux in healthy volunteers. Aliment Pharmacol Ther. 46. Saha MT, Ruuska T, Laippala P, Lenko HL. Growth of prepu-
1999;13:805–812. bertal children with inflammatory bowel disease. J Pediatr
28. Penagini R, Mangano M, Bianchi PA. Effect of increasing the Gastroenterol Nutr. 1998;26:310–314.
fat content but not the energy load of a meal on gastro-oesoph- 47. Markowitz J, Grancher K, Rosa J, Aiges H, Daum F. Growth
ageal reflux and lower oesophageal sphincter motor function. failure in pediatric inflammatory bowel disease. J Pediatr
Gut. 1998;42:330–333. Gastroenterol Nutr. 1993;16:373–380.
29. Lewis D, Khoshoo V, Pencharz PB, Golladay ES. Impact of 48. Newby EA, Sawczenko A, Thomas AG, et al. Interventions for
nutritional rehabilitation on gastroesophageal reflux in neuro- growth failure in childhood Crohn’s disease. Cochrane Data-
logically impaired children. J Pediatr Surg. 1994;29:167–169. base of Syst Rev. 2005;(3):CD003873. doi:10.1002/14651858.
30. Skidmore-Roth L. Mosby’s Drug Guide for Nurses. 4th ed. St. CD003873.pub2.
Louis, MO: Mosby; 2001. 49. Sentongo TA, Semeao EJ, Piccoli DA, Stallings VA, Zemel BS.
31. Herzig SJ, Howell MD, Ngo LH, Marcantonio GR. Acid- Growth, body composition and nutritional status in children
suppressive medication use and the risk for hospital-acquired and adolescents with Crohn’s disease. J Pediatr Gastroenterol
pneumonia. JAMA. 2009;301(20):2120–2188. Nutr. 2000;31:33–40.
32. Canani RB, Cirillo P, Roggero P, Romano C, Malamisura B, 50. Mamula P, Markowitz JE, Baldassano RN. Inflammatory
et al. Therapy with gastric acid inhibitors increases the risk of bowel disease in early childhood and adolescence: special
acute gastroenteritis and community-acquired pneumonia in considerations. Gastroenterol Clin N Am. 2003;32:967–995.
children. Pediatrics. 2006;117(5):e817–e820. 51. Bodnar RJ, Pasternak GW, Mann PE, Paul D, Warren R,
33. Craig WR, Hanlon-Dearman A, Sinclair C, Taback SP, Donner DB. Mediation of anorexia by human recombinant
Moffatt M. Metoclopramide, thickened feedings and posi- tumor necrosis factor through a peripheral action in the rat.
tioning for gastro oesophageal reflux in children under two Cancer Research. 1989;49:6280–6282.
years. Cochrane Database of Syst Rev. 2004;(3):CD003502. 52. Hellerstein MK, Meydani SN, Meydani M, et al. Interleukin-1
doi:10.1002/14651858.CD003211. induced anorexia in the rat. J Clin Invest. 1989;84:228–235.
34. Green PHR, Collier C. Celiac disease. N Engl J Med. 2007; 53. Wiskin AE, Wootton SA, Beattie RM. Nutrition issues in
357:1731–1743. pediatric Crohn’s disease. Nutr Clin Pract. 2007;22:214–222.
35. D’Amico MA, Holmes J, Stavropoulos SN, et al. Presenta-�� 54. Motil KJ, Grand RJ, Davis-Kraft L, Ferlic LL, O’Brian Smith E.
tion of celiac disease in the United States: prominent effect of Growth failure in children with inflammatory bowel disease:
breast feeding. Clin Pediatr (Phila). 2005;44:249–258. a prospective study. Gastroenterology. 1993;105:681–691.
36. Rampertab SD, Poorfan N, Baur P, Singh P, et al. Trends in 55. Ballinger AB, Azooz O, El-Haj T, Poole S, Farthing MJG.
the presentation of celiac disease. Am J Med. 2006;119(4): Growth failure occurs through a decrease in insulin-like
355.e9–355.e14. growth factor 1 which is independent of undernutrition in a
37. Haapalahti M, Kulmala P, Karttunen TJ, et al. Nutritional rat model of colitis. Gut. 2000;46:694–700.
status in adolescents and young adults with screen-detected 56. Navarro FA, Hanauer SB, Kirschner BS. Effect of long-term
celiac disease. J Pediatr Gastroenterol Nutr. 2005;40:566–570. low-dose prednisone on height velocity and disease activity in
38. Fasano A, Catassi C. Current approaches to diagnosis and pediatric and adolescent patients with Crohn disease. J Pediatr
treatment of celiac disease: an evolving spectrum. Gastroen- Gastroenterol Nutr. 2007;45:312–318.
terology. 2001;120:636–651. 57. Eiden KA. Nutritional considerations in inflammatory bowel
39. See J, Murray JA. Gluten-free diet: The medical and nutrition disease. Practical Gastroenterol. 2003;27:33–54.
management of celiac disease. Nutr Clin Pract. 2006;21:1–15. 58. Sentongo TA, Semaeo EJ, Stettler N, Piccoli DA, Stallings
40. Hallert C, Grant C, Grehn S, et al. Evidence of poor vitamin VA, Zemel BS. Vitamin D status in children, adolescents
status in celiac patients on a gluten-free diet for 10 Years. and young adults with Crohn disease. Am J Clin Nutr.
Aliment Pharmacol Ther. 2002;16:1333–1339. 2002;76:1077–1081.
41. Mora S, Barera G, Beccio S, et al. A prospective, longitudinal 59. Pappa HM, Gordon CM, Saslowsky TM, et al. Vitamin D
study of the long-term effect of treatment on bone density in status in children and young adults with inflammatory bowel
children with celiac disease. J Pediatr. 2001;139(4):473–475. disease. Pediatrics. 2006;118:1950–1961.
42. Shamir R. Nutritional aspects in inflammatory bowel disease.
J Pediatr Gastroenterol Nutr. 2009;48:586–588.

60. Sanderson IR, Udeen S, Davies PS, Savage MO, Walker-Smith 77. Treem WR, McAdams L, Stanford L, Kastoff G, Justinich
JA. Remission induced by an elemental diet in small bowel C, Hyams J. Sacrosidase therapy for congenital sucrase-
Crohn’s disease. Arch Dis Child. 1987;61:123–127. isomaltase deficiency. J Pediatr Gastroenterol Nutr.
61. Borrelli O, Cordischi L, Cirulli M, et al. Polymeric diet alone 1999;28:137–142.
versus corticosteroids in the treatment of active pediatric 78. Castillo-Duran C, Vial P, Uauy R. Trace mineral balance
Crohn’s disease: a randomized controlled open-label trial. during acute diarrhea in infants. J Pediatr. 1988;113:452–457.
Clin Gastroenterol Hepatol. 2006;4:744–753. 79. Matoth Y, Zamir R, Bar-Shani S, Grossowicz N. Studies in
62. Canani RB, Terrin G, Borrelli O, et al. Short- and long-term folic acid in infancy. II. folic and folinic acid blood levels in
therapeutic efficacy of nutritional therapy and corticosteroids infants with diarrhea, malnutrition, and infection. Pediatrics.
in pediatric Crohn’s disease. Dig Liver Dis. 2006;38:381–387. 1964;33:694–699.
63. Lochs H, Dejong C, Hammarqvist F, et al. ESPEN Guide- 80. Guandalini S. Probiotics for children with diarrhea. J Clin
lines on Enteral Nutrition: Gastroenterology. Clin Nutr. Gasteroenterol. 2008;42:S53–57.
2006;25:260–274. 81. Wallace B. Clinical use of probiotics in the pediatric popula-
64. Zachos M, Tondeur M, Griffiths AM. Enteral nutritional tion. Nutr Clin Pract. 2009;24:50–59.
therapy for induction of remission in Crohn’s disease. 82. Bodian M, Sheldon W. Lightwood R. Congenital hypoplasia
Cochrane Database of Syst Rev. 2007;(1):CD000542. of the exocrine pancreas. Acta Pediatric. 1964;53:282–293.
doi:10.1002/14651858.CD000542.pub2. 83. Shwachman H, Diamond LK, Oski FA, Khan KT. The
65. Griffiths AM, Ohlsson A, Sherman PM, Sutherland LR. Meta- syndrome of pancreatic insufficiency and bone marrow
analysis of enteral nutrition as a primary treatment of active dysfunction. J Pediatr. 1964; 65:645–663.
Crohn’s disease. Gastroenterology. 1995;108:1056–1067. 84. Mack DR, Forstner GG, Wilschanski M, Freedman MH,
66. Akobeng AK, Thomas, AG. Enteral nutrition for maintenance Durie PR. Shwachman syndrome: exocrine pancreatic
of remission in Crohn’s disease. Cochrane Database of Syst Rev. dysfunction and variable phenotypic expression. Gastroenter-
2007;(3):CD005984. doi:10.1002/14651858.CD005984.pub2. ology. 1996;111:1593–1602.
67. Takagi S, Utsunomiya K, Kuriyama S, et al. Effectiveness of 85. Boocock GR, Morrison JA, Popovic M, et al. Mutations in
an ‘half elemental diet’ as maintenance therapy for Crohn’s SBDS are associated with Shwachman-Diamond syndrome.
disease: a randomized-controlled trial. Aliment Pharmacol Nat Genetics. 2003;33:97–101.
Ther. 2006;24:1333–1340. 86. Johanson AJ, Blizzard RM. A syndrome of congenital
68. Wilschanski M, Sherman P, Pencharz P, Davis L, Corey M, hypoplasia of the alae nasi, deafness, hypothyroidism,
Griffiths A. Supplementary enteral nutrition maintains remis- dwarfism, absent permanent teeth and malabsorption. J
sion in pediatric Crohn’s disease. Gut. 1996;38:543–548. Pediatr. 1971;79:982–987.
69. Levine A, Milo T, Buller H, Markowitz J. Consensus 87. Pearson HA, Lobel JS, Kochshis SA, et al. A new syndrome of
and controversy in the management of pediatric Crohn’s refractory sideroblastic anemia with vacuolization of marrow
disease: an international survey. J Pediatr Gastroenterol Nutr. precursors and exocrine pancreatic dysfunction. J Pediatr.
2003;36:464–469. 1979;95:976–984.
70. Gracey M. Nutritional effects and management of diarrhea in 88. Rotig A, Cormier V, Knoll F, et al. Site-specific deletions of
infancy. Acta Paediatr Suppl. 1999;430:110–126. the mitochondrial genome in the Pearson marrow-pancreas
71. Lutter CK, Habicht JP, Rivera JA, Martorell R. The relationship syndrome. Genomics. 1991;10:502–504.
between energy intake and diarrhoeal disease in their effects 89. Lerner A, Branski D, Lebenthal E. Pancreatic diseases in chil-
on child growth: biological model, evidence, and implications dren. Pediatr Clin North Am. 1996;43:125–156.
for public health policy. Food Nutr Bull. 1992;14:36–42. 90. Moudiou T, Galli-Tsinopoulou A, Nousia-Arvanitakis S. Effect
72. Rosenberg IH, Solomons NW, Schneider RE. Malabsorption of exocrine pancreatic function on resting energy expenditure
associated with diarrhea and intestinal infections. Am J Clin in cystic fibrosis. Acta Paediatrica .2007;96:1521–1525.
Nutr. 1977;30:1248–1253. 91. Stallings VA, Stark LJ, Robinson KA, Feranchak AP, Quinton,
73. Molla A, Molla AM, Rahim A. Intake and absorption of nutri- H. Evidence-based practice recommendations for nutrition-
ents in children with cholera and rotavirus infection during related management of children and adults with cystic fibrosis
acute diarrhea and after recovery. Nutr Res. 1982;2:233–242. and pancreatic insufficiency: results of a systematic review. J
74. Islam M, Roy SK, Begum M, Chisti MJ. Dietary intake and Am Diet Assoc. 2008;108:832–839.
clinical response of hospitalized patients with acute diarrhea. 92. Borowitz D, Baker RD, Stallings V. Consensus report on
Food Nutr Bull. 2008;29:25–31. nutrition for pediatric patients with cystic fibrosis. J Pediatr
75. Treem WR. Congenital sucrase-isomaltase deficiency. J Gastroenterol Nutr. 2002;35:246–259.
Pediatr Gastroenterol Nutr. 1995; 21:1–14. 93. Lopez MJ. The changing incidence of acute pancreatitis
76. Belmont JW, Reid B, Taylor W, et al. Congenital sucrase- in children: a single institution perspective. J Pediatr.
isomaltase deficiency presenting with failure to thrive, 2002;140:622–624.
hypercalcemia and nephrocalcinosis. BMC Pediatrics. 94. Park A, Latif SU, Shah AU, et. al. Changing referral trends of
2002;2:4. acute pancreatitis in children: a 12–year single center analysis.
J Pediatr Gastroenterol Nutr. 2009;49:316–322.

95. March PC. What is the best way to feed patients with pancrea- 112. Guimãres EV, Goulart EM, Penna FJ. Dietary fiber intake,
titis. Curr Opin Crit Care. 2009;15:131–138. stool frequency and colonic transit time in chronic func-
96. Al-Omran M, Groof A, Wilke D. Enteral versus parenteral tional constipation in children. Braz J Med Biol Res.
nutrition for acute pancreatitis. Cochrane Database of Syst Rev. 2001;34:1147–1153.
2003;(1):CD002837. doi:10.1002/14651858.CD002837 113. Pijpers, MA, Tabbers MM, Benninga MA, et al. Currently
97. Petrov MS, Loveday BP, Pylypchuk RD, McIlroy K, Phil- recommended treatments of childhood constipation are not
lips AR, Winsdor JA. Systematic review and meta-analysis of evidence based: a systematic literature review on the effect
enteral nutrition formulations in acute pancreatitis. 2009; Br of laxative treatment and dietary measures. Arch Dis Child.
J Surg. 96:1243–1252. 2009;94:117–131.
98. Doley RP, Yadav TD, Wig JD, et al. Enteral nutrition in severe 114. Huertas-Ceballos AA, Logan S, Bennett C, Macarthur C.
acute pancreatitis. J Pancreas (Online). 2009;9:157–162. Dietary interventions for recurrent abdominal pain (RAP) and
99. Werlin SL, Kugathasan S, Frautschy BC. Pancreatitis in chil- irritable bowel syndrome (IBS) in childhood. Cochrane Data-
dren. J Pediatr Gastroenterol Nutr. 2003;12:47–52. base of Syst Rev. 2009;(1)CD003019. doi:10.1002/14651858.
100. Suddaby EC, Schiller S. Management of chylothorax in chil- CD003019.pub3.
dren. Pediatr Nurs. 2004;30:290–295. 115. Whitfield KL, Shulman RJ. Treatment options for functional
101. McDonald KQ , Bears CM. A preterm infant with intestinal gastrointestinal disorders: from empiric to complementary
lymphangiectasia: a diagnostic dilemma. Neonatal Network. approaches. Pediatr Ann. 2009;38:288–294.
2009;28:29–36. 116. Sood MR. Treatment approaches to irritable bowel syndrome.
102. Bliss CM, Schroy PC. Primary intestinal lymphangiectasia. Pediatr Ann. 2009;38:272–276.
Curr Treat Options Gastroenterol. 2004;7:3–6. 117. Goldstein R, Braverman D, Stankiewicz H. Carbohydrate
103. Hyams J, Colletti R, Faure C, et al. Functional gastrointestinal malabsorption and the effect of dietary restriction on symp-
disorders: Working Group Report of the First World Congress toms of irritable bowel syndrome and functional bowel
of Pediatric Gastroenterology, Hepatology and Nutrition. J complaints. Israel Med Assoc J. 2000;2:583–587.
Pediatr Gastroenterol Nutr. 2002;35:S110–117. 118. Fernández-Bañares F, Esteve-Pardo M, de Leon R, et al. Sugar
104. Feigenbaum K. Treating gastroparesis. Diabetes Self Manag. malabsorption in functional bowel disease: clinical implica-
2006;23(5):24.26, 28–30, 32. tions. Am J Gastroenterol. 1993;88:2044–2050.
105. Kim CH, Nelson DK. Venting percutaneous gastrostomy in 119. Shen YA, Nahas R. Complementary and alternative medicine
the treatment of refractory idiopathic gastroparesis. Gastroin- for treatment of irritable bowel syndrome. Can Fam Physician.
test Endosc. 1998;47(1):67–70. 2009;55:143–148.
106. Parkman HP, Hasler WL, Fisher RD. American Gastro- 120. Bijkerk CJ, Muris JWM, Knottnerus JA, Hoes AW, de Wit
enterological Association technical review on the NJ. Systematic review: the role of different types of fibre in
diagnosis and treatment of gastroparesis. Gastroenterology. the treatment of irritable bowel syndrome. Aliment Pharmacol
2004;127:1592–1622. Ther. 2004;19:245–251.
107. Parrish CR, Yoshida CM. Nutrition intervention for the 121. Quartero AO, Meiniche-Schmidt V, Muris J, Rubin G, de
patient with gastroparesis: an update. Pract Gastroenterol. Wit N. Bulking agents, antispasmodic and antidepressant
2005;30:29–66. medication for the treatment of irritable bowel syndrome.
108. Gabay C, Kushner I. Acute-phase proteins and other Cochrane Database of Syst Rev. 2005;(2):CD003460.
systemic responses to inflammation. New Engl J Med. doi:10.1002/14651858.CD003460.pub2.
1999;320:448–454. 122. Torii A, Toda G. Management of irritable bowel syndrome.
109. Clein NW. Cow’s milk allergy in infants. Pediatr Clin North Intern Med. 2004;43:353–358.
Am. 1954;25:949–962. 123. Talley NJ. Gut eosinophilia in food allergy and systemic
110. Iacono G, Cavataio F, Montalto G, et al. Intolerance of cow’s and autoimmune diseases. Gastroenterol Clin N Am.
milk and chronic constipation in children. N Engl J Med. 2008;37:307–332.
1998;339:1100–1104. 124. Salvatore S, Hauser B, Devreker T, Arrigo S, Vandenplas Y.
111. Dahr S, Tahan S, Sole D, et al. Cow’s milk protein intolerance Chronic enteropathy and feeding in children: an update.
and chronic constipation in children. Pediatr Allergy Immunol. Nutrition. 2008;24:1205–1216.
2001;12:339–342.

26
Hepatic Disease
Samuel A. Kocoshis, MD and Renee A. Wieman, RD, CSP, LD, CNSD

Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 302 1. Recognize the energy and protein requirements of chil-
Malnutrition in Liver Diseases . . . . . . . . . . . . . . . . . . . . . 303 dren with chronic liver disease.
Inadequate Intake 2. Describe nutrition support modalities for children with
Iatrogenic Factors chronic liver disease.
Malabsorption 3. Understand the diagnosis and management of meta-
Hypermetabolism bolic liver diseases such as glycogenoses and Wilson’s
Specific Pediatric Liver Disorders. . . . . . . . . . . . . . . . . . . 305 disease.
Neonatal Cholestasis 4. Comprehend the factors causing malabsorption in
Non-Cholestatic Liver Disease
pediatric liver disease.
Nutrition as Primary Therapy for Select Liver Disorders. 306
Glycogen Storage Disease
Wilson’s Disease
Introduction
Nonalcoholic Fatty Liver Disease (NAFLD) Children with liver disease face an important nutrition
Assessment of Nutrition State . . . . . . . . . . . . . . . . . . . . . 307 impediment because the liver is so crucial for maintaining
homeostasis. The liver is responsible for synthesis, storage,
Specific Nutrient Requirements . . . . . . . . . . . . . . . . . . . . 307
Energy
and metabolism of carbohydrate, protein, and fat. Addi-
Protein tionally, major growth factors such as insulin-like growth
Lipids and Fat-Soluble Vitamins factor-1 (IGF-1) and its binding proteins are directly
Fluids synthesized by the liver. Under conditions of severe liver
Other Vitamins and Minerals dysfunction, pediatric patients become growth-hormone
Enteral Nutrition Support . . . . . . . . . . . . . . . . . . . . . . . . . 308 resistant.1 In addition to growth hormone resistance,
Parenteral Nutrition. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 308 the pediatric patient suffering from chronic liver disease
Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 308 is prone to hypoglycemia because the liver is the major
storage organ for glycogen, and a malfunctioning liver has
reduced glycogen stores. Protein synthesis may be directly
impaired and amino acid utilization for energy may also be
accelerated in the face of reduced glycogen stores. 2 Further-
more, detoxification of ammonia and synthesis of clotting
proteins may also be impaired. Finally, the synthesis of
cholesterol and high-density lipoproteins may be impaired
as can uptake, hydrolysis, and transport of triglycerides. 3
These changes can result in hypertriglyceridemia and
concomitant hypocholesterolemia under conditions of
severe hepatic dysfunction.
302
HEPATIC DISEASE 303
Nutrition management of infants and children with liver anorexia is hepatic encephalopathy. Anorexia has long been
disease is a critical component of the overall care required recognized as a major symptom of encephalopathy, and it
for optimal interventions and metabolic control of these is remarkably difficult to treat without successfully treating
patients. It is best accomplished via a team approach with the underlying cause of liver disease. Among children with
the team being composed of multiple medical disciplines inflammatory hepatitides, pro-inflammatory cytokines
including hepatologists, nurses, dietitians, pharmacists, are released. The relationship between these cytokines
social workers, speech therapists, occupational therapists, and anorexia is very well established. While the phenom-
and physical therapists. enon of hyperinsulinemia and insulin resistance has not
Nutrition requirements are dependent on the disease been established in children with chronic liver disease,
being treated, the anticipated disease course, and the like- it has been established in adults, and may also contribute
lihood that liver transplantation will be necessary. Acute to their anorexia. 5 Yet another factor potentially contrib-
diseases such as viral or toxin-induced hepatitis typically uting to anorexia is zinc deficiency, which is known to be
require no supportive therapy alone, whereas nutrition quite common among patients with chronic liver disease. 6
therapy is the definitive therapy for some metabolic Finally, the gastric capacity of children with either massive
disorders. hepatosplenomegaly or ascites may be so restricted due to
gastric compression by viscera or ascitic fluid that adequate
Malnutrition in Liver Diseases oral intake becomes impossible.
Malnutrition is common in pediatric liver disease and ad-
versely affects survival prior to and following liver trans- Iatrogenic Factors
plantation. Beyond the impaired intermediate metabol ism The effect of iatrogenic factors upon the nutrition state of
of carbohydrate, protein, and fat, a variety of factors ac pediatric liver patients should not be minimized. Excessive
counts for malnutrition in the context of primary hepatic restriction of sodium in the absence of fluid overload will
disease. Most studies exploring mechanisms of malnutri- result in a salt depletion syndrome, and may actually induce
tion in liver disease have been performed in adults, but it a secondary hyperaldosteronism that would not have been
is known that malnutrition can occur both prior to and present otherwise. This factor can lead to both malnutri-
after liver transplantation in children. Even though those tion and growth failure. Unwarranted protein restriction
mechanisms may not have been fully investigated in pedi- can also result in deficiencies of both somatic and visceral
atric patients, it is quite likely that they contribute to pe- proteins with subsequent malnutrition. Therefore, clini-
diatric as well as adult malnutrition among patients with cians caring for children with liver dysfunction should
liver disease. refrain from restricting either salt or protein in the absence
of ascites or encephalopathy refractory to pharmacotherapy.
Inadequate Intake Known to be relatively safe, large-volume paracentesis has
A foremost concern among adult and pediatric liver patients been a popular therapy for adults with ascites, but it has
is inadequate dietary intake. A simple reason that intake been relatively unpopular in the pediatric setting because
might be inadequate is that these patients are frequently of concerns about the large, rapid fluid shifts that might be
offered low-protein, low-sodium diets that are unappe- induced.6 This potential complication notwithstanding,
tizing and unappealing. This practice may not only result the practice now has advocates within the pediatric hepa-
in suboptimal oral intake but also provide a diet of poor tology community. If large-volume paracentesis is used
caloric quality. Secondly, many forms of liver disease result in pediatric patients, the loss of plasma proteins can be
in anorexia. One potential mechanism is elevation of serum prodigious, rendering the patient deficient in both visceral
and tissue leptin levels.4 Leptin, an appetite-suppressing and somatic proteins. Hence, for patients undergoing para-
hormone, is probably cleared via the liver, and serum levels centesis, adequate protein intake should be maintained in
are elevated in patients with hepatic fibrosis as well as the absence of overt encephalopathy. Many of the medica-
other forms of liver disease. The role of leptin in producing tions administered to children with hepatic disease may
anorexia among patients with liver disease remains contro- negatively impact upon their nutrition state. Diuretics, if
versial, specifically because leptin levels are consistently administered overzealously, may salt-deplete them. Broad-
normal in some forms of liver disease such as primary spectrum systemic or enteral antibiotics may eliminate
biliary cirrhosis and consistently elevated in other forms vitamin K-synthesizing enteric flora, resulting in vitamin
such as Laennec’s cirrhosis.4 A third factor accounting for K deficiency among cholestatic patients. Additionally,

neomycin, commonly administered for hepatic enceph- result in reduced activity of the FXR nuclear receptor, which
alopathy, is believed to produce villous atrophy, to reduce maintains intra-hepatocyte bile acid homeostasis along
intestinal surface area, and to result in malabsorption of with moduating the activity of the cystic fibrosis trans-
multiple nutrients. Administration of lactulose for enceph- porter (CFTR). As a result, patients with PFIC1 frequently
alopathy may speed intestinal transit enough to result in experience diarrhea, malabsorption, recurrent pancreatitis,
malabsorption as well. Finally, cholestyramine, an anion and pancreatic fibrosis which results in exocrine pancreatic
exchange resin used to treat the pruritis of cholestasis by insufficiency.9 Patients with Alagille syndrome also experi-
binding bile acids, may be so efficient that the intraluminal ence exocrine pancreatic insufficiency. Alagille syndrome
bile acid concentration may fall below the critical micellar arises due to mutations in the Jagged 1 gene that participates
concentration, resulting in fat and fat-soluble vitamin in the notch signaling pathway.10 These mutations result in
malabsorption.7 Because cholestyramine exchanges organic bile duct malformations leading to intrahepatic bile duct
anions for chloride, hyperchloremic metabolic acidosis paucity. Children with Alagille syndrome frequently have
with resultant growth failure and malnutrition may occur steatorrhea disproportionate in magnitude to their degree
in children on this medication. of cholestasis. Studies have documented pancreatic insuf-
ficiency in Alagille syndrome patients which is due to
Malabsorption pancreatic ductal and acinar malformations. Similar pancre-
Pediatric patients with liver disease are more likely to have atic histology is seen in Jagged 1 knock-out animals whose
cholestatic disease than their adult counterparts. In chole- pancreatic ductules and acini are malformed in a fashion
static patients, bile acids are retained within the liver, and similar to bile ductules.11 It is notable that any form of
excreted very poorly into bile. Therefore, intraduodenal chronic liver disease, whether cholestatic or noncholestatic,
primary bile acid concentrations customarily fall below may be associated with exocrine pancreatic insufficiency.
the critical micellar concentration necessary for efficient Longstanding cirrhosis and portal hypertension occasion-
solubilization and transport of fat and fat-soluble vita- ally result in exocrine pancreatic insufficiency due to either
mins across the unstirred water layer into the enterocyte. pancreatic fibrosis on the basis of venous congestion or due
Thus malabsorption is very common and requires enteral to the absence of hepatic regulatory mechanisms for satis-
administration of large quantities of fat-soluble vitamins factory pancreatic enzyme secretion in response to a dietary
as well as an enteral “cocktail” of medium-chain triglycer- stimulus.12
ides (MCTs) and long-chain triglycerides (LCTs) in food Intestinal function itself may become impaired among
or formula. Patients must receive enough long-chain fat children with chronic liver disease. Portal hypertension
to prevent essential fatty acid deficiency (EFAD) and they with or without cholestasis may be so severe as to result in
must receive enough medium-chain fat to optimize their protein-losing enteropathy. In addition, the elevated serum
enteric fat balance. Linoleic and linolenic acids, which are bile acid concentrations observed in cholestasis may have a
essential fatty acids (EFAs), are long-chain fats that can deleterious effect upon small intestinal function. In studies
only be derived via dietary LCTs. MCT formulas that were performed among dogs with surgically created Thirry-Vella
designed during the late 1960s for cholestatic patients were loops, exposure of the mesenteric artery to bile acids at
deficient in LCTs, commonly resulting in EFAD among this concentrations of 8 to 22 μmol results in impaired transport
population.8 of water and electrolytes.13
Malabsorption may occur in select cases of pediatric
cholestasis from not only intraluminal bile acid deficiency Hypermetabolism
but also from exocrine pancreatic insufficiency. Both cystic The prevalence of hypermetabolism is unknown in chil-
fibrosis and Shwachman-Diamond syndrome, systemic dren with liver disease, but at least 30% of cirrhotic adults
disorders characterized by exocrine pancreatic insufficiency, are hypermetabolic.2 Even though some cirrhotic adults
may present during the neonatal period with cholestasis. are normometabolic and a few are hypometabolic, those
Exocrine pancreatic insufficiency is a less-recognized who are hypermetabolic display measured resting energy
feature of two childhood disorders characterized by severe expenditure (REE) 20% or more above predicted energy
cholestasis: progressive familial intrahepatic cholestasis, expenditure. Hypermetabolism in cirrhotic adults is closely
type 1 (PFIC1) and Alagille syndrome. PFIC1, previously associated with suboptimal total body mass and total body
known as Byler disease, is due to a mutation in the ATP8B1 protein. One documented mechanism for this phenomenon
gene, previously known as the FIC1 gene. ATP8B1 mutations is increased adrenal tone presumably because of reduced

HEPATIC DISEASE 305
hepatic catecholamine metabolism. Those patients with be secondary rather than primary. Unlike the therapy of
documented hypermetabolism express a starvation pattern adult-onset hemochromatosis associated with mutations
when their respiratory quotient is measured. They have in the HFE gene, therapy of neonatal iron storage prob-
respiratory quotients approaching 0.6, documenting that ably should not include chelation, which can theoretically
they begin utilizing fat for energy quite early after a fast render infants susceptible to bloodstream infections with
suggesting reduction in glycogen stores. Under these condi- siderophagic bacteria.
tions, gluconeogenesis is increased and protein catabolism Whatever the cause of neonatal cholestasis, the basic
is accelerated. Thus hypermetabolic patients with cirrhosis nutrition strategy should be to provide ample quantities
are best served by taking 4 or 5 meals per day and receiving of fat-soluble vitamins (A, D, K, and E) and to monitor
adequate dietary protein even in the face of encephalopathy. vitamin levels and/or coagulation studies frequently to
For this reason, pharmacologic management of encephal- prevent fat-soluble vitamin deficiency. Because some
opathy should be attempted prior to reduction of protein in element of fat malabsorption nearly always occurs during
cirrhotic patients. cholestatic periods a substantial percentage of fat calories
should be given in the form of MCTs, which do not require
Specific Pediatric Liver Disorders micellar solubilization prior to absorption into the portal
circulation. However, infants should not be overloaded
Neonatal Cholestasis with MCTs insofar as they cannot be stored and must be
Infantile liver disease is quite commonly cholestatic in immediately oxidized, rendering infants at risk for meta-
nature.14 Extrahepatic biliary atresia is responsible for bolic acidosis from the short-chain fatty acid oxidation
approximately 50% of cases among infants with cholestasis. products.17 Furthermore, MCTs are less calorically dense
Others suffer from a wide variety of infectious and meta- than LCTs because of the reduced number of carbon atoms
bolic disorders. As molecular medicine has advanced, in their skeleton. Finally, in the 1980s, overenthusiastic
disorders previously lumped within the “wastebasket” efforts to provide MCTs to cholestatic infants resulted in
diagnosis of “neonatal hepatitis” are now being recognized providing diets inadequate in EFAs thereby producing
as discrete entities. Infantile cholestatic disorders such as EFAD. At worst, with complete biliary diversion, about
Alagille syndrome, neonatal iron storage disease, PFIC1, 50% of long-chain fats can be absorbed without full solubi-
PFIC2, PFIC3, citrin deficiency, Niemann-Pick type C, lization. Therefore, infants with cholestasis should receive
type I tyrosinemia, galactosemia, hereditary fructose intol- a mixture of MCTs and LCTs. 8 Formulas with a 1:1 mix of
erance, and type IV glycogenosis are but a few of the myriad the two types of fat tend to result in optimal fat balance for
infantile disorders characterized by cholestasis at the time cholestatic infants.
of presentation. Cholestasis, while not universally present,
may also be the dominant symptom for selected patients Non-Cholestatic Liver Disease
with α-1-antitrypsin deficiency or cystic fibrosis. Some pediatric liver disorders result in cholestasis only
Nutrition strategies may be the definitive therapy for intermittently. Among these disorders are the viral hepa-
some of these disorders. For example, elimination of dietary titides, autoimmune hepatitis, α-1-antitrypsin deficiency,
galactose for galactosemia and fructose for hereditary fruc- the glycogenoses, mitochondrial hepatopathies, Wilson’s
tose intolerance are curative. For other disorders, such as disease, and nonalcoholic steatohepatitis. When the patient
tyrosinemia, reduction of dietary tyrosine is helpful, but not is not cholestatic, absorption is customarily normal and
curative. Because the block in tyrosine metabolism results specialized formulas may be unnecessary, but it is impera-
in the overabundance of toxic intermediates such as succi- tive to provide adequate caloric and protein intake. It is also
nylacetone, succinylacetoacetate, fumarylacetoacetate, important to recognize the underlying metabolic abnor-
and maleylacetoacetate, upstream inhibition of tyrosine malities that impede adequate assimilation of calories and
metabolism with 2-(2-nitro-4-trifluoromethylbenzoyl)- to design nutrition regimens that maximize energy avail-
1,3-cyclohexanedione (NTBC) has been life saving insofar ability. The provision of 150% of the estimated caloric and
as metabolism is shunted to nontoxic intermediates such as protein requirement to cirrhotic patients is quite reasonable
parahydroxy-phenylpyruvate.15 The etiology for neonatal based upon adult data suggesting hypermetabolism. 2 Addi-
iron storage disease is uncertain, but evidence is accu- tionally, patients with primary mitochondrial disorders or
mulating that it is an alloimmune disorder with maternal glycogenoses should be advised to avoid prolonged fasting.
antibodies affecting the fetal liver.16 Iron storage may thus The incomplete beta oxidation in mitochondrial disease

and absent glycogenolysis will result in hypoglycemia and/ for central nervous system and renal manifestations.
or the production of other toxins. Wilson’s disease, if diagnosed early, can be treated with
copper chelators. The hepatic manifestations vary from
Nutrition as Primary Therapy for mild transaminase elevation to fulminant hepatic failure.
Select Liver Disorders Customarily when the total body copper level is elevated,
there is a reciprocal deficiency in zinc which is a cofactor
Glycogen Storage Disease for alkaline phosphatase synthesis. Therefore, in Wilson’s
The glycogen storage diseases (GSDs), also known as disease, the alkaline phosphatase level is disproportionally
glycogenoses, are a group of disorders whereby enzyme low in the presence of severe liver dysfunction. Chelation
defects adversely affect glycogen degradation or glycogen is employed to increase copper excretion or to decrease
synthesis. There are at least 10 of these disorders of which copper absorption. D-penicillamine has been used for
some affect liver, some affect muscle, and some affect both. years, but trientene is just as effective with a lower risk of
Dietary therapy is variably effective for these disorders18 complications. Zinc can be used to prevent copper absorp-
(eg, the only effective therapy for type IV GSD is liver tion by competitive inhibition of intestinal transporters. A
transplantation). Among those for which dietary therapy newer agent, tetrahydromolybdenate, shows great promise
is beneficial, types II and VI have shown only modest insofar as it complexes with copper in the intestinal lumen
responses to high-protein diets with the only definitive rendering copper unabsorbable, and it is absorbed itself,
therapy for type II being enzyme replacement. The greatest complexing with serum copper and albumin, thereby
dietary advances have been made for type I. This disorder, preventing cellular uptake of copper. Beyond chelation,
caused by impaired movement of glucose-6-phosphatase dietary therapy is important, especially in the early phases of
into or out of the endoplasmic reticulum, is characterized treatment. High-copper foods such as shellfish, nuts, gelatin,
by fasting hypoglycemia, hyperuricemia, lactic acidosis, mushrooms, liver, and soy products should be avoided. In
and hyperlipidemia. Type IB is also characterized by addition, the copper content of the patient’s major water
neutrophil dysfunction and frequently inflammatory bowel supply should be analyzed if well water is consumed.
disease. Late complications include hepatic adenomas,
pulmonary hypertension, and renal hyperfiltration. Initial Nonalcoholic Fatty Liver Disease (NAFLD)
trials of continuous enteral glucose or polycose infusions It is ironic that overnutrition should be the etiology of a liver
instituted during the 1980s in order to prevent hypogly- disease that is seen in pandemic proportions throughout
cemia had the unexpected benefit of totally or partially the world. Approximately 20% of the population of the
reversing lactic acidosis, hyperuricemia, and hyperlipi- United States is obese, and 75% of obese individuals have
demia. Glucose infusion rates of 8 mg/kg/min for infants, some degree of fatty liver. NAFLD may range in severity
6 mg/kg/min for children, and 4 mg/kg/min for adults from simple fatty infiltrate on one end of the spectrum to
were empirically noted to be beneficial. More recently, raw nonalcoholic steatohepatitis (NASH) on the other end. 20 By
cornstarch has been utilized in preference to glucose poly- definition, NASH is characterized by both fat and inflam-
mers because of its longer duration of action obviating the mation, and its prognosis is far worse than that of fatty
need for a nasogastric tube or gastrostomy tube feedings. liver alone. Natural progression or a second hepatic insult
It is important that the cornstarch be uncooked, because of any sort may result in fibrosis and eventually cirrhosis.
cooking partially hydrolyzes it and produces a glucose The factors governing the progression of NAFLD to NASH
tolerance curve similar to that of glucose. A dose of 1.75 to are not fully understood, but oxidative stress seems to
2.75 g/kg will deliver about 5 to 7 mg/kg/min of glucose play a role in the process. Therapy should target comorbid
for approximately 6 hours.18 conditions such as type 2 diabetes mellitus and hypertri
glyceridemia as well as emphasizing weight reduction. In
Wilson’s Disease addition, treatment with betaine, n-acetylcysteine, vitamin
Wilson’s disease is due to a mutation in a p-type ATPase E, or ursodeoxycholic acid may lower liver enzyme levels.
responsible for transporting copper across membranes to Oral hypoglycemics such as gemfibril or metformin may
permit formation of metallothionein and to permit biliary decrease hepatic steatosis and improve liver enzyme levels
excretion of copper.19 Defective copper excretion results in whereas clofibrate seems to be ineffective. Ultimately, the
excessive hepatic copper stores leading to hepatic dysfunc- most reliable therapy is a sensible weight loss regimen. The
tion. Excessive brain and renal copper stores are responsible optimal rate of loss should be < 0.9 kg/wk because too rapid

HEPATIC DISEASE 307
a rate may result in excessive lipid peroxidation and more Specific Nutrient Requirements
rapid progression to fibrosis.20
Energy
Assessment of Nutrition State Increased energy needs have been shown in some pediatric
A subjective global assessment is one of the most reliable clients with liver disease with elevated REEs up to 127% to
and acceptable standards of assessment when compared 140% of the predicted REE values. 25 Energy requirements
with other objective measures. Based on this assessment, vary as well, based on age, activity level, degree of malnu-
patients can be evaluated and grouped into those who trition, and malabsorption. These infants and children can
require immediate and aggressive nutrition interventions, require up to 130% to 150% of the recommended daily allow-
those at risk of developing malnutrition, and those who will ance (RDA) for energy based on ideal weight for length.
do well without nutrition interventions. 21,22 Infants with cholestatic liver disease generally require 120
A comprehensive nutrition assessment is imperative to 150 kcal/kg/d based on estimated dry weight rather than
in infants and children with liver disease. Reassessments measured weight in the presence of ascites. 25
should be done periodically (~monthly) to evaluate lean
body mass changes and the complicating side effects that Protein
lead to changes in intake (ie, anorexia, early satiety, nausea), Goals for age are generally provided unless encephalopathy
in addition to diarrhea and the use of diuretics which leads to with fulminant hepatic failure and an elevated ammonia
increased losses. Continual nutrition evaluations are imper- level are observed. Enough protein must be provided to
ative to determine the degree of malnutrition and execute preserve lean body mass and prevent catabolism with the
individualized nutrition care plans adapted to preserve breakdown of endogenous protein stores, but not contribute
somatic and adipose body reserves while curtailing the to hyperammonemia and encephalopathy. Infants generally
metabolic instability universal with progressive disease. require 3 to 4 g/kg/d.24 The use of branched-chain amino
The assessment should begin with a complete and acid (BCAA) formulas or supplements in infants and chil-
meticulous review of medical, laboratory, and physical infor- dren, though improving nitrogen balance, 26 has fallen out of
mation focusing on nutrition-related problems. A detailed favor because the cost/benefit ratio remains low.
diet history of usual dietary intake of calories, protein, and
fat sources; weight changes; and medication intake should Lipids and Fat-Soluble Vitamins
also be evaluated. This information will assist in tailoring an There is no rationale for restricting lipids and fats in chil-
attainable and realistic plan for maximal nutrition preserva- dren with liver disease insofar as they are the main source
tion. The usual anthropometric markers of nutrition status of calories during infancy and early childhood. Increased
are not reliable in patients with advanced liver disease. Body dietary fat intake may augment the amount of steatorrhea
weight can be dramatically elevated from ascites, edema, observed, but potentially increases the overall amount
and hepatosplenomegaly, masking weight loss. 23 of calories absorbed. Formulas that contain ~50% of the
Malnutrition is best appraised through serial upper fat as MCT oil are recommended for infants and children
extremity measurement of mid-arm muscle circumferences with cholestatic liver disease, but the clinician should make
(MAMCs) and triceps skinfolds (TSFs). The upper extrem- certain that proper intake of long-chain fatty acids (~10%
ities are less subject to fluid accumulation and provide of calories) is maintained to prevent EFAD. MCT oil can
insight into body mass stores.23 These anthropometric affect the palatability and acceptance of oral formula so
measures are easily performed, inexpensive, non-invasive, choosing a formula with a lower concentration of MCT oil
and can provide key information for detecting nutrition may be required to achieve sufficient intake.24
decline, mandating urgent restoration of these stores with Fat-soluble vitamin (A, D, E, and K) supplementa-
aggressive nutrition interventions. tion is standard in infants and children with cholestatic
Plasma protein levels of albumin, prealbumin, and liver disease and customary doses are listed in Table 26-1.
retinol-binding protein, which are synthesized in the liver, Vitamin K deficiency has dire consequences because of the
are more a marker of the severity of the liver disease than risk of fatal hemorrhagic disease, and prophylactic supple-
the visceral protein status.24 mentation is indicated. Vitamin D deficiency may take
longer to develop, but becomes evident in children during
periods of rapid bone growth. Children with liver disease
can easily develop rickets and osteoporosis, and pathologic

fractures may result. Vitamin E deficiency can lead to polymers and medium-chain fats. By not concentrating the
neuromuscular abnormalities, which are reversible when formula base alone, protein concentrations can be main-
adequate vitamin E supplementation is initiated. Vitamin tained within appropriate ranges for age and weight. Free
A deficiency is rarely seen in these children because it is water should be sufficiently provided to keep osmolality of
the least sensitive to malabsorption. These vitamin levels the formula low. A 30 cal/oz MCT-containing formula is
should be evaluated at least every 3 months and aggressive ideal for infants. Formula selections should contain at least
supplementation initiated to normalize plasma level. 27 50% of the fat as MCT oil for maximized enteral absorption
of fat calories. Several palatable infant and pediatric enteral
TABLE 26-1 Fat-Soluble Vitamin Recommendations formulas containing at least 50% of the fat as MCT oil are
Vitamin Amount Given currently marketed.
Vitamin A (aqueous) 1000 IU/kg/d up to 25000 IU Patients with arm muscle circumferences below the
25-OH vitamin D 3–5 mcg/kg/d 5th percentile should receive supplemental nutrition
Vitamin E 20–25 IU/kg/d as TPGS prior to transplantation. 30 When infants and children are
Vitamin K 2.5–5 mg/d 3 times per week unable to consume adequate calories to maintain their lean
body mass, supplemental enteral tube feeding should be
Fluids initiated. Nasogastric tubes are preferred if patients can
Management of fluid homeostasis, ascites, and sodium tolerate adequate formula volume to achieve goals because
balance mandate maintaining a delicate balance for pedi- they are easily placed and replaced if removed. However, in
atric patients with liver disease. The decision to diurese a many instances nasojejunal feeding tubes must be utilized
patient with hyponatremia generally depends upon a global because of emesis and volume intolerance secondary to
assessment of fluid status. A patient with signs of dehydra- poor gastric emptying. Gastrostomy tubes are generally
tion should be given salt when hyponatremic whereas a not placed in the face of ascites, and organomegaly may
patient appearing overhydrated may actually be suffering preclude their placement percutaneously. Nocturnal drip
from dilutional hyponatremia and require diuresis with feedings are frequently used so that normal oral feeding
fluid and salt restriction. Only non-nutritive fluids should during the day can be maintained. This feeding schedule
be limited when fluid restriction is initiated. 28 Salt restric- may also be beneficial for patients with progressive liver
tion should not be excessive, because salt elimination is disease or infants with small body mass who are unable
much more benignly accomplished via loop diuretics. to maintain normal glucose levels overnight. Progres-
sion to 24-hour continuous tube feeding infusions may
Other Vitamins and Minerals be required to provide the increased calories required for
The incidence of water-soluble vitamin deficiency in chil- proper nutrition.
dren with liver disease has not been comprehensively
studied, and clinical manifestations are rare given that Parenteral Nutrition
infant and pediatric formulas that are supplemented with Parenteral nutrition (PN) should be considered only when
these vitamins are required in large volumes in order to enteral supplementation fails or cannot be utilized (ie,
increase caloric intake. during periods of gastrointestinal hemorrhage). In some
Iron supplementation may be required if recurrent cases it may be required in addition to enteral support when
mucosal hemorrhage from varices or gastropathy takes lean body mass cannot be maintained. If possible, some
place. enteral alimentation should be given if only to maintain gut
Urinary excretion of zinc is increased in chronic integrity.
cholestatic liver disease, but the cause and associated conse- When long-term PN is required, careful monitoring
quences are unknown based on the current literature.29 of copper levels is mandatory to prevent either toxicity or
deficiency. Most centers employ standard amino acids,
Enteral Nutrition Support dextrose, lipids, electrolytes, and minerals in quantities
Caloric intake can be improved via the use of supplemental meeting nutrition needs while minimizing metabolic
nasoenteric tube feedings with high-calorie formulas when complications. Even though enrichment in BCAAs may
oral intake is inadequate to achieve goals. Increased caloric improve nitrogen balance marginally, adequate protein
intake can first be achieved through increasing formula nutriture may be attained by providing standard amino
concentration and adding modular additives such as glucose acids. 30

HEPATIC DISEASE 309
4. Ben-Ari Z, Schafer Z, Sulkes J, et al. Alterations in serum

Conclusion leptin in chronic liver disease. Dig Dis Sci. 2002;47:183–189.
The goals of nutrition for pediatric patients with liver disease 5. Selberg O, Burchert W, Van Der Hoff J. Insulin resistance
are to optimize their potential for normal growth and devel- in liver cirrhosis. Positron-emission tomography scan
opment, prevent further liver injury, prevent worsening of analysis of skeletal muscle glucose metabolism. J Clin Invest.
the patient’s nutrition status, minimize the risk of infec- 1993;91:1897–1903.
tion, avoid vitamin and mineral deficiency, and improve the 6. Gines P, Arroyo V. Is there still a need for albumin infusions to
treat patients with liver disease? Gut. 2000;46:588–590.
patient’s quality of life. This requires detailed attention to 7. West RJ, Lloyd JK. The effect of cholestyramine on intestinal
all of the components of nutrition support by caregivers, by absorption. Gut. 1975;16:93–98.
the patient, and by the patients’ family working as a team to 8. Pettei MJ, Daftary S, Levine JJ. Essential fatty acid deficiency
provide optimal care. associated with the use of a medium-chain-triglyceride infant
formula in pediatric hepatobiliary disease. Am J Clin Nutr.
1991;53(5):1217–1221.
Test Your Knowledge Questions 9. Knisely AS. Progressive familial intrahepatic cholestasis: a
1. What is the best serial marker of nutrition status in personal perspective. Pediatr Dev Pathol. 2000;3:113–125.
pediatric patients with liver disease? 10. Piccoli DA, Spinner NB. Alagille syndrome and the Jagged1
A. Fat-soluble vitamin levels gene. Semin Liver Dis. 2001;21:525–534.
B. Upper extremity anthropometric measurements 11. Golson ML, Loomes KM, Oakey R, et al. Ductal malfor-
C. Prealbumin mation and pancreatitis in mice caused by conditional Jag1
deletion. Gastroenterology. 2009;136:1761–1771.e1.
D. Weight/length or BMI 12. Lee SP, Lai KS. Exocrine pancreatic function in hepatic
E. A & D cirrhosis. Am J Gastroenterol. 1976;65(3):244–248.
2. Which of the following liver disorders is most likely to 13. Berant M, Diamond E, Alon U, et al. Effect of infusion of bile
be associated with exocrine pancreatic insufficiency? salts into the mesenteric artery in situ on jejunal mucosal
A. Hepatitis C transport function in dogs. J Pediatr Gastroenterol Nutr.
1988;7:588–593.
B. Alagille syndrome
14. Bezerra JA, Balistreri WF. Cholestatic syndromes of infancy
C. Autoimmune hepatitis and childhood. Semin Gastrointest Dis. 2001;12:54–65.
D. Extrahepatic biliary atresia 15. Masurel-Paulet A, Poggi-Bach J, Rolland MO, et al. NTBC
3. In the nutrition therapy of Wilson’s disease which treatment in long-term tyrosinaemia type I outcome in French
should be avoided? patients. J Inherit Metab Dis. 2008;31:81–87.
A. Grapefruit 16. Rand EB, Karpen SJ, Kelly S, et al. Treatment of neonatal
hemochromatosis with exchange transfusion and intravenous
B. Red meat immunoglobulin. J Pediatr. 2009;155:566–571.
C. Endive 17. Wanten GJ, Naber AH. Cellular and physiological effects
D. Lobster of medium-chain triglycerides. Mini Rev Med Chem.
4. Which of the following have been utilized for the nutri- 2004;4:847–857.
tion therapy of glycogen storage disease, type I? 18. Heller S, Worona L, Consuelo A. Nutritional therapy for
glycogen storage diseases. J Pediatr Gastroenterol Nutr.
A. Subcutaneous octreotide
2008;47(Suppl 1):S15–S21.
B. Glucagon infusions 19. Pfeil S, Lynn DJ. Wilson’s disease: copper unfettered. J Clin
C. Cooked cornstarch Gastroenterol. 1999;29:22–31.
D. Metformin 20. McCullough AJ. Update on nonalcoholic fatty liver disease. J
E. Raw cornstarch Clin Gastroenterol. 2002;34:255–262.
21. Merli M, Romiti A, Riggio O, et al. Optimal nutritional indexes
in chronic liver disease. J Parenter Enteral Nutr. 1987;11(Suppl
See p. 487 for answers. 5):S130–S134.
22. Hasse J, Strong S, Gorman MA, Liepa G. Subjective global
References assessment: alternative nutrition assessment technique for
1. Bucuvalas JC, Horn JA, Chernausek SD. Resistance to growth liver transplant candidates. Nutrition. 1993;339–343.
hormone in children with chronic liver disease. Pediatric 23. Sokol RJ, Stall C. Anthropometric evaluation of children with
Transplantation. 1997;1:73–79. chronic liver disease. Am J Clin Nutr. 1990;52:203–208.
2. Merli O, Riggio M, Leonetti F, et al. Impaired nonoxidative 24. Protheroe SM. Feeding the child with chronic liver disease.
glucose metabolism in patients with liver cirrhosis: effects of Nutrition. 1998;14:796–800.
two insulin doses. Metabolism. 1997;46:840–843. 25. Pierro A, Koletzko B, Carnelli V, et al. Resting energy expen-
3. Muller P, Felin R, Lambrecht J, et al. Hypertriglyceridaemia diture is increased in infants with extra hepatic biliary atresia
secondary to liver disease. Eur J Clin Invest. 1974;4:419–428. and cirrhosis. J Pediatric Surg. 1989;24:534–538.

26. Sokal E, Baudoux MC, Collette E, et al. Branched chain 29. Saner G, Süoğlu ÖD, Yiğitba M, Sökücü S, Elkabes B. Zinc
amino acids improve body composition and nitrogen balance nutrition in children with chronic liver disease. J Trace
in a rat model of extra hepatic biliary atresia. Pediatr Res. Elements in Exp Med. 2000;13:271–276.
1996;40:66–71. 30. Goulet OJ, de Ville de Goyet, Otte JB, Ricour C. Preoperative
27. Sokol RJ, Butler-Simon N, Conner C, et al. Multicenter trial nutritional evaluation and support of liver transplantation in
of d-alpha-tocopheryl polyethylene glycol 1000 succinate for children. Transplant Proc. 1987;19:3249–3255.
the treatment of vitamin E deficiency in children with chronic
cholestasis. Gastroenterology. 1993;104:1727–1735.
28. Gines P, Guevara M. Hyponatremia in cirrhosis: pathogen-
esis, clinical significance, and management. Hepatology.
2008;48:1002–1010.

27
Intestinal Failure
Robert H. Squires, Jr., MD

Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 311 1. Understand that while intestinal length is important, it
Definition of Intestinal Failure . . . . . . . . . . . . . . . . . . . . . 312 is not the only factor that determines a child’s ability to
Scope of the Problem reach enteral autonomy.
Etiology of Intestinal Failure. . . . . . . . . . . . . . . . . . . . . . . 313 2. Understand that the intestinal adaptive process takes
months and even years before enteral autonomy can, if
Intestinal Adaptation. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 313
ever, be achieved.
Management. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 313 3. Describe why enteral nutrition is necessary for intes-
Enteral Nutrition
Parenteral Nutrition tinal adaptation to occur.
Fluid Management 4. Explain how lipid-lowering strategies for soy-based
Medications lipid preparations or substitution with a fish-oil based
Non-Transplant Surgery lipid can improve serum aminotransferase levels and
General Principles reduce serum bilirubin.
Complications. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 316
Nutrition Deficiencies Introduction
Functional and Metabolic Complications
Liver Disease
Intestinal failure (IF) in infants and children is a devas-
Central Line Complications tating condition that can be broadly defined as the inability
Outcomes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 318 of the intestinal tract to sustain life without supplemental
Growth and Development parenteral nutrition (PN).1,2 Prior to PN, many infants died
Quality of Life as a consequence of insufficient bowel length or function.
Intestinal Transplant Infants found to have an “abdominal catastrophe” at lapa-
rotomy for conditions such as necrotizing enterocolitis
(NEC), volvulus, or gastroschisis were simply closed and
made comfortable to await the natural course of their tragic
circumstance. However, with the development of safe PN,
central line placement and care, improved medical and
surgical management, including intestinal transplanta-
tion, these infants now have an opportunity to survive with
a satisfactory or even excellent quality of life. The clinical
course for the child can be challenging and frustrating
to the family as well as those who provide medical care
and support. Intestinal adaptation, if it occurs at all, can
require months or years before the intestine can adequately
311
accommodate the growing child independent from PN. estimated the incidence of extreme SBS to be between 3 to
Along the way, the child is at risk for episodes of dehydra- 5 per 100,000 births per year.9 However, improvements in
tion, electrolyte imbalance, and macro- and micronutrient neonatal intensive care, anesthesia, and surgical techniques
deficiencies. More importantly, life-threatening complica- have improved survival of children who would have previ-
tions such as sepsis, end-stage liver disease, and vascular ously died, thus it is likely that the incidence and prevalence
thrombosis may occur. has increased in recent years.10 Other estimates suggest
Management of children with IF is best provided by an that at least 16,000 children are on home PN (HPN) in the
experienced multidisciplinary team that includes experts United States, but the precise number on PN for manage-
in pediatric gastroenterology, surgery, nutrition, nursing, ment of IF/SBS is unknown.11 More importantly, we have
social work, and feeding techniques. Most management no estimate of the number of children with SBS who have
strategies have not been rigorously investigated, leaving been weaned from PN but remain at risk for various nutri-
much to experience, tradition, trial and error, or “art” as tional and growth abnormalities as a consequence of their
most would prefer. The great majority of studies of children altered intestinal anatomy. The annual costs for managing a
with IF are single-site experiences, with small numbers of PN-dependent patient with IF/SBS are estimated to range
patients collected over many decades. 3–6 The goals of this between $100,000 and $150,000 with a mortality rate
brief chapter are to review the topic of intestinal failure and of approximately 30% at 5 years for those who cannot be
outline some strategies that might be useful in the care and weaned from PN.10
management of infants and children with intestinal failure.
Table 27-1 Causes of Intestinal Failure in Children
Definition of Intestinal Failure Prenatal Gastroschisis/Omphalocele
The small intestine almost doubles in length during the Intestinal atresia
last trimester with the normal full-term infant having 210 Total intestinal or very long-segment Hirschsprung’s
to 350 cm at birth.7 This fact makes defining residual bowel disease
Constitutive enterocyte disorders
length problematic when the resection and residual length Tufting enteropathy
measurements occur early in the third trimester. While the Microvillus inclusion disease
literature attempts to define short bowel syndrome (SBS) as Megacystis microcolon hypoperistalsis syndrome
the remnant intestine measuring less than 75 cm, a better Malrotation/Volvulus
approach was put forward by Teitelbaum and colleagues. 6 Bladder extrophy
They propose incorporating gestational age into the assess- Neonatal Necrotizing enterocolitis
ment and suggest that infants with less than 10% of their Vascular thrombosis
estimated bowel length are at increased risk of death than Desquamative enteropathy (Intracellular ß4
integrin mutation)
those with a longer residual bowel length.
Malrotation/Volvulus
Intestinal failure is a functional description indepen- Postnatal Complicated intussusception
dent of bowel length and better reflects the nature of the Trauma
clinical condition encountered in practice. It identifies Seat belt injury
a child whose loss of intestinal length or competence is Suction evisceration (eg, swimming pool drain)
Riding lawn mower injury
below the minimal amount necessary to maintain normal
Extensive vascular anomaly
digestion and absorption of nutrients and fluids for weight
Autoimmune/immune mediated enteropathy
gain and growth in children independent of PN. Such a Tumor
definition acknowledges children with conditions such as Fibroma
immune-mediated enteropathy, enteric myopathy, mito- Desmoid
chondrial disorders, intestinal pseudoobstruction, tufting Sclerosing encapsulating peritonitis (abdominal cocoon)
enteropathy, and microvillus inclusion disease who have Munchausen Syndrome by Proxy
Protracted diarrhea of infancy
a normal length of intestine but inadequate function to
Intestinal motility disorders
sustain life without PN. Mitochondrial defects/mutations
Intestinal pseudoobstruction
Scope of the Problem
Surprisingly, neither the incidence nor prevalence of IF/SBS
in the United States is well known.8 In 1992, Wallander et al

INTESTINAL FAILURE 313
Etiology of Intestinal Failure For example, disaccharides enhance adaptation more

Conditions associated with IF in infants and children are effectively than monosaccharides,19 and whole proteins
generally due to surgical short bowel syndrome (SBS), are more adaptogenic than protein hydrolysates. 20 Testing
motility disorders, or enterocyte abnormalities (Table these findings in the human have not been undertaken in
27-1).1 SBS is the underlying cause in the majority of these a rigorous fashion. Hormones and growth factors such
patients, the etiology of which may be congenital abnormali- as growth hormone, glucagon-like peptide 2, glutamine,
ties such as gastroschisis, intestinal atresia, malrotation with cholecystokinin, gastrin, insulin, peptide YY, and entero
volvulus, or acquired causes such as necrotizing enterocolitis glucagon, as well as dietary fiber and short-chain fatty acids
(NEC), vascular thrombosis, or trauma. Less commonly have been shown to be involved in the adaptive process,
seen are motility disorders such as total aganglionosis and but their clinical significance in humans remains unclear.18
chronic intestinal pseudoobstruction or enterocyte abnor- The functional capabilities of the remnant intestine also
malities such as microvillus inclusion disease and tufting impacts adaptation. For instance, complete absence of
enteropathy. the ileum precludes absorption of bile acids and vitamin
B12 . The absence of the ileal-cecal valve appears to have a
Intestinal Adaptation negative impact on intestinal adaptation for some, but not
Intestinal adaptation is a complex and incompletely under- all patients. 3–5,21,22 However, it is possible that the presence
stood process that ensues following significant bowel of a sufficient length of colon may be just as, if not more,
resection to compensate for the loss of intestinal surface important than the presence or absence of the ileal-cecal
area. It is characterized by both functional and morphologic valve.23,24 A biomarker for intestinal adaptation, such as
changes in the remnant bowel.12,13 Enteral nutrition (EN) is citrulline,25 would ideally reflect the quality and quantity of
necessary for adaptation. Clinical features associated with intestinal function, but its clinical usefulness is uncertain.
patients who are eventually weaned from PN include the Markers of hepatic function in patients with IF have not
absence of jaundice or cholestasis, a shorter duration of PN, been evaluated. Valid biomarkers are urgently needed so
the presence of the ileal-cecal valve, an intact colon, small that successful rehabilitation regimens can be objectively
bowel length greater than 15 cm, and placement of the small identified, and adaptation failure can be recognized earlier.
intestine in continuity with the colon. 5 The underlying Translational studies to identify potential genetic suscep-
physiologic mechanisms by which these clinical factors tibilities that would favor or impede intestinal adaptation
might directly impact the adaptive process in the human have not been performed.26
is incompletely understood. For instance, it is not clear
whether the ileal-cecal valve must be physically present or Management
whether its presence merely serves as a “marker” for a long
colon segment. Over time, the residual bowel lengthens and Enteral Nutrition
dilates and is thought to be a positive sign of adaptation. Enteral feeding is essential if intestinal adaptation is to
However, this anatomical change may be associated with occur. The 2 initial considerations are the type of formula
complications such as altered intestinal motility that can used and the manner in which it is provided. Breast milk
result in stasis of luminal contents and bacterial overgrowth is preferred and its use has been associated with decreased
which can negatively impact adaptation. Surgical techniques duration of PN. 3 The beneficial effects of breast milk are
aimed to improve intestinal function by increasing bowel attributable to its immunoprotective properties, effect on
length and reducing bowel diameter include the Bianchi postnatal development of intestinal flora, and its nutrient
procedure and Serial Transverse Enteroplasty (STEP).14,15 composition that includes long-chain triglycerides (LCTs),
The adaptive process occurs over many months or free amino acids, nucleotides, and growth factors as well
years. 5,16 Increased enteral intake, or hyperphagia, is asso- as complex protein and fat. 27 When breast milk is unavail-
ciated with intestinal adaptation in adults.17 The impact of able, however, formula choice is complicated by a variety of
luminal nutrients upon intestinal adaptation is complex, options that reflect differences in the desired complexity of
but likely involves a direct trophic effect on intestinal protein, fat, and carbohydrate. Complex nutrients, such as
epithelium, as well as stimulation of trophic hormones polysaccharides and whole protein, increase the functional
and pancreaticobiliary secretions.18 In animal models, it workload of the intestine, and as result, may stimulate adap-
appears that a more complex nutrient enhances adapta- tation.28 Unfortunately, studies to identify the ideal enteral
tion better than one that is simple or more “processed.” protein 29–31 and lipid32 have been plagued by insufficient

numbers of patients or have been extrapolated from animal based. It is administered to prevent essential fatty acid
models. deficiency and to provide an efficient, high-density caloric
A variety of methods are used to deliver enteral feed- source. An estimated 0.5 g/kg/d of intravenous lipid is the
ings to the intestinal lumen and include oral, gastric as minimal requirement to prevent deficiency.45 An intrave-
bolus or continuous, or jejunal which can only be given nous lipid preparation containing omega-3 fatty acids was
as a continuous feeding. Advantages of early oral feeding recently reported to reduce the incidence of PN-related
include stimulation of oral digestive enzymes and mainte- cholestasis,46 but it has not been rigorously studied in
nance of oral feeding skills to prevent oral aversion. 33 If the children. Similar reductions in serum bilirubin have been
patient is capable of oral feeding, but is incapable of taking achieved by limiting soy-derived lipid to 1 g/kg/d or less.
sufficient calories, supplemental direct enteral feeding is Serum electrolytes are monitored on a regular basis and
possible via a nasogastric tube, gastrostomy, or direct jejunal adjustments in electrolyte concentration are based on indi-
feeding. Continuous enteral infusion was found to be more vidual needs of the patient. Guidelines for pediatric vitamin,
beneficial in very low birth weight infants, 34 but studies in mineral, and trace element supplementation are available,
piglets suggest that bolus feedings are more advantageous. 35 but they are supported by a paucity of data. 37 While PN is
Continuous versus bolus feedings have not been thoroughly life saving in children with IF/SBS, long-term use of PN
studied in older infants and children. is often complicated by sepsis and liver disease which can
Clinical decisions to adjust the enteral feeding regimen become life threatening.
are determined by a number of factors, primarily stool or Given the host of potential complications associated
ostomy output, evidence of malabsorption, and other less with PN and IF/SBS, careful longitudinal monitoring
objective symptoms such as abdominal fullness, irritability, should be implemented to reduce complications and
and regurgitation. Currently, decisions related to advancing improve outcome. The frequency of monitoring will depend
enteral feeding, weaning PN, and long-term monitoring upon patient age, duration of PN, and acute changes in the
of patients at risk for growth failure are based almost clinical condition. Growth parameters (eg, height or length,
completely upon experience, tradition, and “art” rather than weight, head circumference) should be checked at each
evidence-based algorithms. However, the understanding of clinical visit. For infants and young children, monthly visits
the relative importance of these factors, how they are incor- are typical. For older children, on stable PN, visit frequency
porated into the daily management, and how they impact can be extended to every 3 to 4 months. Please see chapter
adaptation in patients with IF/SBS is critical if management on evaluation and monitoring (Chapter 36).
of infants with IF/SBS is to move beyond art and tradition
and into an evidence-based practice of medicine. Fluid Management
In addition to PN, children may also require supplemental
Parenteral Nutrition fluid management. This is particularly important for chil-
Parenteral nutrition (PN), first introduced in the late 1960s, dren with an ileostomy or those who are in continuity, but
is now an established life-saving treatment for children with with a short length of colon. These children are at increased
IF/SBS. 36–38 Components of PN include glucose, amino risk of developing salt and water depletion and should be
acids, lipids, electrolytes, vitamins, minerals, trace elements, monitored carefully.47 Unless the child’s fluid and electro-
and water. Glucose is the primary source of energy in PN, lyte requirements are very consistent day to day and week to
but glucose oxidation varies depending upon age and diag- week, supplemental fluids should be calculated and admin-
nosis. 39,40 Glucose infusion rates that are in excess of the istered separate from PN as this allows for more rapid,
patients’ oxidative capacity will promote fat deposition.41 and less expensive, adjustments in fluid and electrolyte
While glucose infusion rates vary, an intake greater than administration.
10 mg/kg/min may result in the conversion of glucose to
fat.42 An amino acid solution, ranging from > 2.5 g/kg/d for Medications
preterm infants to 0.75 g/kg/d for adolescents, is adminis- A variety of medications are used to manage symptoms and
tered to support protein metabolism.43 Amino acids are best complications associated with IF/SBS. It is important to
utilized when balanced with a proper proportion of non- know that not one of them has been studied in a random-
nitrogen calories. The ideal ratio of nitrogen:non-nitrogen ized fashion in an adequately powered study.
calories is estimated to be between 1:150 to 1:400.44 The Intestinal dysmotility is common in children with IF/
lipid source currently available in the United States is soy SBS. Anti-motility agents (eg, loperamide) are used in an

attempt to delay intestinal transit in hopes to provide a become an accepted technique at many intestinal failure
longer duration of contact between the intestinal mucosa centers. 52
and luminal nutrients. Children with gastroschisis are While there is a growing literature describing indi-
more likely to have problems with delayed gastric emptying vidual experiences with non-transplant surgery for children
and non-propulsive intestinal motility. In this setting, with IF/SBS, the relatively small numbers of patients, retro-
pro-motility agents (eg, metoclopramide, erythromycin, spective nature of data collection spanning many years, and
or amoxicillin-clavulanic acid) have been used to improve heterogeneous definitions and patient characteristics have
intestinal motility. Cisapride was removed from the market limited the ability to promulgate data-driven indications
in the United States due to its association with cardiac and timing for these techniques.
arrhythmias.
Anti-secretory agents are used to reduce fluid secretion General Principles
and stool output. Histamine-2 blockers and proton pump With the understanding that management of IF is highly
inhibitors might be useful during the early months following individualized and that evidence-based practice supported
massive intestinal resection. However, continued use, in by randomized, controlled trials is lacking, the following
the absence of clear benefit, may place the child at increased outline might serve as a “principled guide” to the manage-
risk for bacterial overgrowth or Candida esophagitis as ment of intestinal failure in children:
gastric acid serves a useful function in limiting fungal and 1. TPN
bacterial growth. a. Glucose infusion rate: < 15 mg/kg/min for the duration
Bile acid binding resins (eg, cholestyramine) have been of infusion.
tried in patients with little or no ileum when increased stool b. Protein: < 3 g/kg/d, closer to 3 for infants, lower for older
output is thought to be related to bile acid malabsorption. children.
These agents are not easily administered, have little or no c. Fat: In the first month, may need 1–2 g/kg/d; but after
palatability, and their efficacy in this clinical setting has not that, with an eye on the degree of cholestasis and total
been tested. caloric needs, would consider different strategies.
i. 1 g/kg/d given every other day; or MWF or M/Th.
Non-Transplant Surgery ii. Lipid reduction presumes that some enteral feeding
Half of children with SBS will have more than one abdom- is possible.
inal operation.48 Following the initial surgical intervention, iii. Follow essential fatty acids every 3 months.
subsequent surgeries often address complications such d. Fluid: Based on needs, it is hard to provide sufficient calo-
as stricture, intestinal dilation, and placement of invasive ries with less than 125 cc/kg/d; may need additional salt
feeding devices which are all considered standard of care.49 and water to support losses.
Longitudinal intestinal lengthening and tailoring 2. Enteral feeds
(LILT) and STEP represent advanced techniques that a. Use oral feeds if at all possible to maintain oral skills and
both taper dilated segments of bowel and increase intes- stimulate EGF, even if the child has a G-tube. 3–5 cc/feed
tinal length. Digestive function may improve not only and then gradually increase as one can.
because aboral flow is facilitated by a normalized luminal b. Breast milk is preferred and a casein hydrolysate/MCT-
caliber, but also because subsequent adaptation may containing formula is the author’s fallback, assuming that
lead to increased intestinal surface area. LILT was first intestinal adaptation is favored by a more complex enteral
described in 1980 by Bianchi,15 and has since been used diet; use of an amino acid-containing formula can be
at many centers.1 Criteria for using LILT vary, but gener- reserved for protein allergy.
ally require greater than 20 cm of symmetrically dilated c. J-tubes should be used rarely, as they further shorten the
intestine in the context of residual intestine > 40 cm.1 length of useable bowel length.
Standardized indications, contraindications, and surgical 3. Advancing feeds/reducing PN
guidelines have not been developed, which may explain a. The patient will tell you.
inconsistent results reported in literature. 50 STEP involves i. More concerned about the volume of stools than the
the application of a stapling device incompletely across number (which can be confused with “squirts”); so,
a dilated loop of intestine in serial fashion to create a for example, 10 stools per day may be “okay” if only
zig-zag pattern that results in a lumen both narrower and 3–4 or so are big enough to leave the diaper; if the
longer. Since its description by Kim et al 51 in 2003, it has bottom is not excoriated; if the family is comfortable; if
hydration is maintained.

ii. Aim for a rate of weight gain that follows the isopleth in Functional and Metabolic Complications
a box that surrounds the 5th percentile; adjust for SGA. Following massive bowel resection that alters normal intes-
Not trying to achieve weight gain at the 50th percentile, tinal physiology, a number of acute and chronic medical
although if one can with minimal PN support, that is complications develop that prompt an effort for medical
fine. The goal is to find the minimal amount of PN to interventions. Unfortunately, many interventions and
support reasonable weight gain and growth. treatments have not been adequately studied with sufficient
b. Once on < 25% total calories from PN, and reasonable numbers of patients.
stool output and satisfactory weight gain and growth Hypergastinemia develops shortly after small bowel
is established, one may consider a change from PN to resection and can reduce nutrient absorption by inacti-
D10 LR observe for 2–3 months; then hold the fluids for vating pancreatic enzymes, and precipitating bile salts,
2 months or so before pulling the line; unless the line is so thus leading to diarrhea as well as nausea and vomiting. 58–60
much trouble that keeping it in is too problematic. Small case series have reported mixed benefits of acid
4. Non-transplant surgery reduction to improve absorption. 61–64 However, there are
a. When to consider in a child with short bowel syndrome no large trials demonstrating a benefit to the use of these
i. A sufficient length of small bowel is dilated and medications in children with IF/SBS. Indiscriminate use of
1. Enteral feedings are not able to be advanced these medications may predispose patients to small bowel
2. The child is experiencing poor weight gain and/ bacterial overgrowth, calcium and iron malabsorption, or a
or growth heightened risk of Candida esophagitis or sepsis.65 Bile acid
b. What type of surgery? malabsorption as a consequence of ileal resection can result
i. May be surgeon specific; a learning curve is needed in a secretory diarrhea that complicates fat and fat-soluble
for both the STEP and Bianchi, but more so for the vitamin absorption.66 Rapid intestinal transit occurs
Bianchi following small bowel resection67,68 and is often managed
ii. You can STEP a STEP, and STEP a Bianchi, but you with the use of anti-motility agents such as loperamide
cannot Bianchi a STEP which have mixed effects on water and salt balance.69,70
Nephrolithiasis, when it occurs in the setting of IF/SBS, is
Complications typically due to either uric acid or calcium oxalate stones.71
Alterations in gastrointestinal motility, along with
Nutrition Deficiencies the use of acid blocking agents, may increase the bacte-
Deficiencies in vitamins, minerals, and trace elements rial content in the small intestine resulting in bacterial
are associated with IF/SBS. Malabsorption of fat-soluble overgrowth (BO). BO can deconjugate luminal bile acids
vitamins A, D, E, and K may result from an insufficient making them ineffective in micellar formation and can
intraluminal concentration of bile acids secondary to be associated with mucosal inflammation, nutrient defi-
excess fecal loss. 53 Surgical resections of the duodenum or ciencies (notably vitamin B12), D-lactic acidosis as well as
ileum, which have unique absorptive functions, add to the cramps, diarrhea, GI bleeding, and arthritis. The relation-
risk of developing nutrition deficiencies. The duodenum is ship between small bowel BO and systemic sepsis is not well
a primary site for iron and folate absorption and its resec- understood.72–75 BO is most often treated empirically with
tion can result in these micronutrient deficiencies. Absence intermittent oral doses of broad-spectrum antibiotics, and
of the ileum, with its unique ability to absorb vitamin B12 in some cases probiotics, but there are many varying prac-
and bile acids, places the patient at risk for fat-soluble tices for the frequency and duration of administration with
vitamin and vitamin B12 deficiency. Calcium and magne- no data available to evaluate relative efficacies.
sium deficiencies can result from binding to intraluminal D-lactic acidosis is a unique feature of patients with
long-chain fatty acid. 54,55 Deficiencies of other minerals and IF/SBS and was first described in children in 1983.76
trace elements such as zinc, riboflavin, thiamin, biotin, and The combination of a high anion gap acidosis and altered
also selenium can occur. 56 In addition, nutrient deficien- mental status that develops after a high carbohydrate
cies hinder intestinal adaptation further compounding the enteral feeding should prompt the clinical suspicion of
clinical impact. 57 D-lactic acidosis. Treatment involves discontinuation of
enteral feeding, selective bowel decontamination, and, if
needed, a surgical procedure aimed at decreasing intestinal
diameter and reducing bacterial overgrowth.77,78 Frequent

antibiotic therapy may, paradoxically, place the patient at disease develops, portal hypertension, variceal and stomal
risk for D-lactic acidosis by creating a selective advantage bleeding, infection, hypoglycemia, and hyperammonemia
for D-lactate producing bacteria.79 occur, making a combined liver-intestinal transplant the
only remaining life-saving measure.
Liver Disease
Liver disease is the most frequent complication of long-term Central Line Complications
PN with consequences that include cirrhosis, end-stage liver Maintaining central venous catheter (CVC) access is critical
disease, and even death.80 The incidence of IF/SBS-associ- in the long-term management of IF/SBS. Loss of vascular
ated liver disease (IFALD) is as high as 50% in infants who access can be fatal in this population and is an indication for
receive PN for 2 months with end-stage liver disease devel- intestinal transplantation. As a result, salvage of the CVC
oping in 90% of premature infants on PN for more than line is a strategy employed to preserve vascular access. In
3 months.81 Elevated serum transaminase and bilirubin addition, the advancement of newer approaches such as
levels are commonly observed in infants on PN, but these recanalization of a thrombosed vessel has been employed
levels can normalize and jaundice resolve with intestinal in selected patients when vascular sites are limited.95,96 The
adaptation and PN withdrawal. The long-term outcome threshold for removing CVC lines and referral to centers that
of IFALD in patients who adapt is unknown. The popula- perform recanalization is likely variable from both an insti-
tion currently thought to be at greatest risk for IFALD are tutional and physician standpoint. A greater understanding
premature infants with a birth weight < 1 kg and those with of the source of this variability will allow standardization to
IF/SBS resulting from surgical resection.82–84 The etiology of a “best practice” model and allow centers participating in
IFALD remains unknown but is likely multi-factorial with this collaborative to preserve access sites and better equip
prematurity, multiple abdominal surgeries, lack of enterally patients for long-term survival.
stimulated bile flow, bacterial sepsis, and components or Sepsis is an important cause of death in children with
deficiencies of PN infusates all potential contributors. IF/SBS. Accordingly, multiple factors contribute to the
Treatment of PN-associated liver disease is empiric and management of suspected sepsis in the patient with IF/SBS
imperfect. Current strategies to avert liver disease associ- including age and presence of a CVC. Catheter-associated
ated with long-term PN include employing a choleretic such bloodstream infections (CABSIs) are responsible for a
as ursodeoxycholic acid, 85 bowel “decontamination” to treat majority of the infectious morbidity. While the true inci-
bacterial overgrowth, 83,85 vigilant daily catheter care,86 and dence of CABSIs is unknown, IF/SBS patients constitute
modifying PN formulations. Infusing PN calories over less a high-risk group within the CVC population. Potential
than 24 hours, casually referred to as “cycling” PN, is thought risk factors include the proximity of fecal material to line
to improve cholestasis.87 The underlying mechanism for this entry sites and connections, frequent line access for labo-
action and effect is not clearly understood, but may involve ratory tests, and intestinal bacterial translocation. While
providing a metabolic “rest” from the continuous infusion translocation occurs in animal models, its proof in human
of calories, protein, and/or carbohydrate. Administration of populations is elusive.97 At the same time, several lines of
pediatric formulations of PN that include specific “targeted” evidence suggest a role for bacterial translocation in IF/
amino acids including taurine88 and limiting the infusion SBS. There is a greater incidence of enteric organisms
of dextrose so as to potentially decrease steatosis have also isolated in cultures from these patients compared to other
been utilized.89 Decreasing the aluminum and manganese populations with CVC lines.98 Furthermore, a comparison
content in PN may decrease hepatotoxicity.90,91 Decreasing of CVC isolates with fecal flora and mesenteric lymph node
the amount or altering the type of lipids administered may cultures were highly concordant.99 Finally, the incidence
improve serum transaminase levels, reverse PN-associated of infection has been demonstrated to be increased while
liver disease, or reduce lipid peroxidation.46,92,93 Recently, advancing enteral feeds.100
use of a fish oil-based intravenous lipid source was found to While CABSIs are of the greatest concern, patients
be associated with improvement of serum bilirubin in two with IF/SBS are also subject to numerous other central
children,46 although its long-term use in an animal model line-related complications. Of these, thrombosis and line
was associated with increased fibrosis.94 Unfortunately, breakage are the 2 most frequent. Fortunately, there is a
most of these interventions to reduce or prevent IFALD high salvage rate and treatment with thrombolytics or CVC
are employed empirically and lack significant clinical repair has been shown to result in a high CVC salvage rate.101
confirmation in large pediatric trials. Once end-stage liver The development of consensus guidelines based upon the

accrual of data across the population of IF/SBS is predicted posttransplant care and immunosuppression protocols,
to reduce CVC-associated complications as well as lengthen these outcomes have drastically improved. 2 More than
the life-span of each individual catheter and preserve access 900 intestinal transplants have now been performed in all
sites critical to survival and potential transplantation. age groups worldwide, with more than 500 in the pediatric
population.2,3 Five-year patient survival rates exceed 50%
Outcomes worldwide.4 Unfortunately, the indications for intestinal
transplant are broad and subject to a significant degree of
Growth and Development interpretation. There is a need for evidence-based parameters
Infants and children must digest and absorb sufficient that would improve the selection of patients for intestinal
calories, vitamins, minerals, and trace elements to gain transplant and determine optimal timing for transplant to
weight, grow, and develop. Children with IF/SBS are inca- maximize outcomes and minimize the need for combined
pable of sustaining adequate growth and development organ transplantation.
without supplemental PN. Successful intestinal adaptation A subset of patients with IF/SBS and associated liver
implies complete independence from PN while continuing disease may benefit from an isolated liver transplant.105–107
to demonstrate satisfactory growth and development. It has been postulated that IFALD may hinder bowel
However, there are no prospective studies available to adaptation and delay progression toward enteral feeding
address long-term growth and development in children tolerance.8 In fact, various authors have reported remark-
with IF/SBS following PN withdrawal. A recent retrospec- able bowel adaptation and feeding tolerance after isolated
tive study of 87 children identified over a period of 16 years liver transplant for severe IFALD.4,5,105
provides some insight into the long-term problems that
children with IF/SBS may face.16 The authors found that in Test Your Knowledge Questions
those children who achieved enteral autonomy, maximum 1. A 30-week infant with 35 cm of small bowel, an ileal-
weight gain and growth was achieved during the first 4 years cecal valve, and an intact colon has an advantage over a
after weaning PN. However, between 4 and 8 years post-PN, full-term infant with the same anatomy because:
weight gain and growth, expressed as a z score, appeared A. Etiologies for short bowel syndrome are different
to decline with the weight z score 8 years post-PN almost between the two groups.
identical to the weight at the time of weaning and height z B. Premature infants who survive are constitutionally
score slightly lower than the score at the time of weaning. stronger than full-term infants.
Interestingly, 21 children were noted to enter puberty at an C. The small intestinal length doubles in the last
age similar to their peers. trimester.
D. Complications associated with PN are less frequent
Quality of Life in the premature infant.
Studies in adult patients have identified reduced quality of 2. A clinical feature associated with enteral autonomy is:
life (QOL) scores in patients with SBS, which were further A. Being a female
reduced if the patient was on HPN. Interestingly, the pres- B. Small intestine in continuity with the colon
ence of a stoma did not appear to influence their quality C. Absent ileal-cecal valve
of life.102 Similarly detailed studies that address QOL and D. Having fewer than 10 stools per day
school performance have not been performed in children, 3. PN associated liver disease is caused by:
however, children on HPN appear to fare better than those A. Intravenous lipid
hospitalized for PN.103,104 B. Lack of enteral feeding
C. Recurrent infections
Intestinal Transplant D. Multiple factors, including all of the above
Intestinal transplant is reserved as the final life-saving 4. The best method to provide enteral feeding for children
procedure for patients with irreversible IF/SBS and life- with intestinal failure is via:
threatening complications of PN administration. In 1994, A. Gastrostomy
very few intestinal transplants were performed in the pedi- B. Nasogastric tube
atric population worldwide (approximately 25 according C. Jejunal feeding
to the Intestinal Transplant Registry), with unsatisfac- D. Oral feeding
tory outcomes in these early years.1 With advances in See p. 487 for answers.

19. Weser E, Babbitt J, Hoban M, Vandeventer A. Intestinal adap-

References tation. Different growth responses to disaccharides compared
1. Goulet O, Ruemmele F, Lacaille F, Colomb V. Irre-
with monosaccharides in rat small bowel. Gastroenterology.
versible intestinal failure. J Pediatr Gastroenterol Nutr.
1986;91(6):1521–1527.
2004;38(3):250–269.
20. Vanderhoof JA, Grandjean CJ, Burkley KT et al. Effect of
2. Kocoshis SA, Beath SV, Booth IW, et al. Intestinal failure
casein versus casein hydrolysate on mucosal adaptation
and small bowel transplantation, including clinical nutri-
following massive bowel resection in infant rats. J Pediatr
tion: Working Group Report of the Second World Congress
Gastroenterol Nutr. 1984;3(2):262–267.
of Pediatric Gastroenterology, Hepatology, and Nutrition. J
21. Wasa M, Takagi Y, Sando K, et al. Intestinal adaptation in
Pediatr Gastroenterol Nutr. 2004;39(Suppl 2):S655–S661.
pediatric patients with short-bowel syndrome. Eur J Pediatr
3. Andorsky DJ, Lund DP, Lillehei CW, et al. Nutritional and
Surg. 1999;9(4):207–209.
other postoperative management of neonates with short
22. Gambarara M, Ferretti F, Bagolan P. Ultra-short-bowel
bowel syndrome correlates with clinical outcomes. J Pediatr.
syndrome is not an absolute indication to small-
2001;139(1):27–33.
bowel transplantation in childhood. Eur J Pediatr Surg.
4. Goulet OJ, Revillon Y, Jan D, et al. Neonatal short bowel
1999;9(4):267–270.
syndrome. J Pediatr. 1991;119(1 ( Pt 1)):18–23.
23. Jeppesen PB, Mortensen PB. The influence of a preserved
5. Quiŕos-Teijeira RE, Ament ME, Reyen L, et al. Long-term
colon on the absorption of medium chain fat in patients with
parenteral nutritional support and intestinal adaptation in
small bowel resection. Gut. 1998;43(4):478–483.
children with short bowel syndrome: a 25-year experience. J
24. Nightingale JM, Lennard-Jones JE, Gertner DJ, et al.
Pediatr. 2004;145(2):157–163.
Colonic preservation reduces need for parenteral therapy,
6. Spencer AU, Neaga A, West B, et al. Pediatric short bowel
increases incidence of renal stones, but does not change high
syndrome: redefining predictors of success. Ann Surg.
prevalence of gall stones in patients with a short bowel. Gut.
2005;242(3):403–409; discussion 409–412.
1992;33(11):1493–1497.
7. Touloukian RJ, Smith GJ. Normal intestinal length in preterm
25. Luo M, Fernández-Estívariz C, Manatunga AK, et al. Are
infants. J Pediatr Surg. 1983;18(6):720–723.
plasma citrulline and glutamine biomarkers of intestinal
8. DeLegge M, Alsolaiman MM, Barbour E, et al. Short bowel
absorptive function in patients with short bowel syndrome? J
syndrome: parenteral nutrition versus intestinal transplanta-
Parenter Enteral Nutr. 2007;31(1):1–7.
tion. Where are we today? Dig Dis Sci. 2007;52(4):876–892.
26. Bernal NP, Stehr W, Zhang Y, Profitt S, Erwin CR, Warner
9. Wallander J, Ewald U, Lackgren G, et al. Extreme short bowel
BW. Evidence for active Wnt signaling during postresection
syndrome in neonates: an indication for small bowel trans-
intestinal adaptation. J Pediatr Surg. 2005;40(6):1025–1029;
plantation? Transplant Proc. 1992;24(3):1230–1235.
discussion 1029.
10. Schalamon J, Mayr JM, Hollwarth ME. Mortality and
27. Levy J. Immunonutrition: the pediatric experience. Nutrition.
economics in short bowel syndrome. Best Pract Res Clin
1998;14(7–8):641–647.
Gastroenterol. 2003;17(6):931–942.
28. Vanderhoof JA, Langnas AN. Short-bowel syndrome in chil-
11. Colomb V. Economic aspects of paediatric home
dren and adults. Gastroenterology. 1997;113(5):1767–1778.
parenteral nutrition. Curr Opin Clin Nutr Metab Care.
29. Ksiazyk J, Piena M, Kierkus J, Lyszkowska M. Hydrolyzed
2000;3(3):237–239.
versus nonhydrolyzed protein diet in short bowel syndrome in
12. Tavakkolizadeh A, Whang EE. Understanding and aug-
children. J Pediatr Gastroenterol Nutr. 2002;35(5):615–618.
menting human intestinal adaptation: a call for more clinical
30. Bines J, Francis D, Hill D. Reducing parenteral requirement
research. J Parenter Enteral Nutr. 2002;26(4):251–255.
in children with short bowel syndrome: impact of an amino
13. Drozdowski L, Thomson AB. Intestinal mucosal adaptation .
acid-based complete infant formula. J Pediatr Gastroenterol
World J Gastroenterol. 2006; 2(29):4614–4627.
Nutr. 1998;26(2):123–128.
14. Javid P, Kim H, Duggan C, Jaksic T. Serial transverse entero-
31. Taylor S, Sondheimer J, Sokol R, Silverman A, Wilson H.
plasty is associated with successful short-term outcomes
Noninfectious colitis associated with short gut syndrome in
in infants with short bowel syndrome. J Pediatr Surg.
infants. J Pediatr. 1991;119(1 ( Pt 1)):24–28.
2005;40(6):1019–1023; discussion 1023–1024.
32. Vanderhoof JA, Grandjean CJ, Kaufman SS, Burkely KT,
15. Bianchi A. Intestinal loop lengthening--a technique
Antonson DL. Effect of high percentage medium-chain trig-
for increasing small intestinal length. J Pediatr Surg.
lyceride diet on mucosal adaptation following massive bowel
1980;15(2):145–151.
resection in rats. J Parenter Enteral Nutr. 1984;8(6):685–689.
16. Goulet O, Gobet B, Talbotec C, et al. Outcome and long-
33. Blackman JA, Nelson CL. Reinstituting oral feedings in
term growth after extensive small bowel resection in the
children fed by gastrostomy tube. Clin Pediatr. (Phila)
neonatal period: a survey of 87 children. Eur J Pediatr Surg.
1985;24(8):434–438.
2005;15(2):95–101.
34. Dsilna A, Christensson K, Alfredsson L, et al. Continuous
17. Crenn P, Morin MC, Joly F, Penven S, Thuillier F, Messing B.
feeding promotes gastrointestinal tolerance and growth in
Net digestive absorption and adaptive hyperphagia in adult
very low birth weight infants. J Pediatr. 2005;147(1):43–49.
short bowel patients. Gut. 2004;53(9):1279–1286.
35. Shulman RJ, Redel CA, Stathos TH. Bolus versus contin-
18. DiBaise JK, Young RJ, Vanderhoof JA. Intestinal rehabilita-
uous feedings stimulate small-intestinal growth and
tion and the short bowel syndrome: part 1. Am J Gastroenterol.
development in the newborn pig. J Pediatr Gastroenterol Nutr.
2004;99(7):1386–1395.
1994;18(3):350–354.

36. Rhoads JE. The development of TPN: an interview with 54. Ament ME. Bone mineral content in patients with short
pioneer surgical nutritionist Jonathan E. Rhoads, MD. [Inter- bowel syndrome: the impact of parenteral nutrition. J Pediatr.
view by Carolyn T. Spencer and Charlene Compher]. J Am 1998;132(3 Pt 1):386–388.
Diet Assoc. 2001;101(7):747–750. 55. Fleming CR, George L, Stoner GL, et al. The importance of
37. Shulman RJ, Phillips S. Parenteral nutrition in infants and urinary magnesium values in patients with gut failure. Mayo
children. J Pediatr Gastroenterol Nutr. 2003;36(5):587–607. Clin Proc. 1996;71(1):21–24.
38. Dudrick SJ, Wilmore DW, Vars HM, Rhoads JE. Long-term 56. Buchman AL. Etiology and initial management of short bowel
total parenteral nutrition with growth, development, and syndrome. Gastroenterology. 2006;130(2 Suppl 1):S5–S15.
positive nitrogen balance. Surgery. 1968;64(1):134–142. 57. Ziegler TR, Evans ME, Fernández-Estívariz C, Jones DP.
39. Lafeber HN, Sulkers EJ, Chapman TE, et al. Glucose produc- Trophic and cytoprotective nutrition for intestinal adapta-
tion and oxidation in preterm infants during total parenteral tion, mucosal repair, and barrier function. Annu Rev Nutr.
nutrition. Pediatr Res. 1990;28(2):153–157. 2003;23:229–261.
40. Sheridan RL, Yong-Ming Y, Prelack K, Young VR, Burke 58. Buxton B. Small bowel resection and gastric acid hypersecre-
JF, Tompkins RG. Maximal parenteral glucose oxidation tion. Gut. 1974;15(3):229–238.
in hypermetabolic young children: a stable isotope study. J 59. Go VL, Poley JR, Hofmann AF, Summerskill WH. Distur-
Parenter Enteral Nutr. 1998;22(4):212–216. bances in fat digestion induced by acidic jejunal pH
41. Kalhan SC, Kilic I. Carbohydrate as nutrient in the infant due to gastric hypersecretion in man. Gastroenterology.
and child: range of acceptable intake. Eur J Clin Nutr. 1970;58(5):638–646.
1999;53(Suppl 1):S94–S100. 60. Williams NS, Evans P, King RF. Gastric acid secretion
42. Nose O, Tipton JR, Yabuuchi H. Effect of the energy source and gastrin production in the short bowel syndrome. Gut.
on changes in energy expenditure, respiratory quotient, and 1985;26(9):914–919.
nitrogen balance during total parenteral nutrition in children. 61. Cortot A, Fleming CR, Malagelada JR. Improved nutrient
Pediatr Res. 1987;21(6):538–541. absorption after cimetidine in short-bowel syndrome with
43. Safe Practices for Parenteral Nutrition Formulations. gastric hypersecretion. N Engl J Med. 1979;300(2):79–80.
National Advisory Group on Standards and Practice 62. Nightingale JM, Walker ER, Farthing MJ, Lennard-Jones JE.
Guidelines for Parenteral Nutrition. J Parenter Enteral Nutr. Effect of omeprazole on intestinal output in the short bowel
1998;22(2):49–66. syndrome. Aliment Pharmacol Ther. 1991;5(4):405–412.
44. Peters C, Fischer JE. Studies on calorie to nitrogen ratio for total 63. Tang SJ, Nieto J, Jenson DM, Ohning GV, Pisegna JR.
parenteral nutrition. Surg Gynecol Obstet. 1980;151(1):1–8. The novel use of an intravenous proton pump inhibitor in
45. Gutcher GR, Farrell PM. Intravenous infusion of lipid for a patient with short bowel syndrome. J Clin Gastroenterol.
the prevention of essential fatty acid deficiency in premature 2002;34(1):62–63.
infants. Am J Clin Nutr. 1991;54(6):1024–1028. 64. Malagelada JR. Pathophysiological responses to meals in the
46. Gura KM, Duggan CP, Collier SB, et al. Reversal of parenteral Zollinger-Ellison syndrome: 2. Gastric emptying and its effect
nutrition-associated liver disease in two infants with short on duodenal function. Gut. 1980;21(2):98–104.
bowel syndrome using parenteral fish oil: implications for 65. Chocarro MA, Galindo TF, Ruiz-Irastorza G, et al. Risk
future management. Pediatrics. 2006;118(1):e197–e201. factors for esophageal candidiasis. Eur J Clin Microbiol Infect
47. Schwarz K, Ternberg J, Bell M, Keating J. Sodium Dis. 2000;19(2):96–100.
needs of infants and children with ileostomy. J Pediatr. 66. Westergaard H. Bile acid malabsorption . Curr Treat Options
1983;102(4);509–513. Gastroenterol. 2007;10(1): 28–33.
48. Thompson JS. Reoperation in patients with the short bowel 67. Nightingale JM, Kamm MA, van der Sijp JR, et al. Disturbed
syndrome. Am J Surg. 1992;164(5):453–456; discussion gastric emptying in the short bowel syndrome. Evidence for a
456–457. ‘colonic brake’. Gut. 1993;34(9):1171–1176.
49. Wales PW. Surgical therapy for short bowel syndrome. Pediatr 68. Reynell PC, Spray GH. Small intestinal function in the rat after
Surg Int. 2004;20(9):647–657. massive resections. Gastroenterology. 1956;31(4):361–368.
50. Bianchi A. From the cradle to enteral autonomy: the role of 69. Nightingale JM, Lennard-Jones JE, Walker ER. A patient
autologous gastrointestinal reconstruction. Gastroenterology. with jejunostomy liberated from home intravenous therapy
2006;130(2 Suppl 1):S138–S146. after 14 years; contribution of balance studies. Clin Nutr.
51. Kim HB, Fauza D, Garza J, Oh JT, Nurko S, Jaksic T. Serial 1992;11(2):101–105.
transverse enteroplasty (STEP): a novel bowel lengthening 70. Rodrigues CA, Lennard-Jones JE, Thompson DG, et al.
procedure. J Pediatr Surg. 2003;38(3):425–429. The effects of octreotide, soy polysaccharide, codeine and
52. Modi B, Javid P, Jaksic T, et al. First Report of the Inter- loperamide on nutrient, fluid and electrolyte absorption
national Serial Transverse Enteroplasty Data Registry: in the short-bowel syndrome. Aliment Pharmacol Ther.
Indications, Efficacy, and Complications. J Am Coll Surg. 1989;3(2):159–169.
2007; 204(3):365–371. 71. Nightingale JM. Hepatobiliary, renal and bone complica-
53. Ohkohchi N, Andoh T, Izumi U, Igarashi Y, Ohi R. Disorder of tions of intestinal failure. Best Pract Res Clin Gastroenterol.
bile acid metabolism in children with short bowel syndrome. J 2003;17(6):907–929.
Gastroenterol. 1997;32(4):472–479.

72. Dibaise JK, Young RJ, Vanderhoof JA. Enteric microbial 90. Advenier E, Landry C, Colomb V, et al. Aluminum contamina-
flora, bacterial overgrowth, and short-bowel syndrome. Clin tion of parenteral nutrition and aluminum loading in children
Gastroenterol Hepatol. 2006;4(1):11–20. on long-term parenteral nutrition. J Pediatr Gastroenterol Nutr.
73. O’Keefe SJ. Bacterial overgrowth and liver complications 2003;36(4):448–453.
in short bowel intestinal failure patients. Gastroenterology. 91. Kafritsa Y, Fell J, Long S, Bynevelt M, Taylor W, Milla P.
2006;130(2 Suppl 1):S67–S69. Long-term outcome of brain manganese deposition in
74. Puwanant ML, Mo-Suwan, Patrapinyokul S. Recurrent patients on home parenteral nutrition. Arch Dis Child.
D-lactic acidosis in a child with short bowel syndrome. Asia 1998;79(3):263–265.
Pac J Clin Nutr. 2005;14(2):195–198. 92. Goulet O, de Potter S, Antébi H, et al. Long-term efficacy
75. Quigley EM, Quera R. Small intestinal bacterial overgrowth: and safety of a new olive oil-based intravenous fat emulsion
roles of antibiotics, prebiotics, and probiotics. Gastroenter- in pediatric patients: a double-blind randomized study. Am J
ology. 2006;130(2 Suppl 1):S78–S90. Clin Nutr. 1999;70(3):338–345.
76. Perlmutter DH, Boyle JT, Campos JM, Egler JM, Watkins 93. Cavicchi M, Crenn P, Beau P, Degott C, Boutron MC,
JM. D-Lactic acidosis in children: an unusual metabolic Messing B. Severe liver complications associated with long-
complication of small bowel resection. J Pediatr. 1983; term parenteral nutrition are dependent on lipid parenteral
102(2):234–238. input. Transplant Proc. 1998;30(6):2547.
77. Mayne AJ, Handy DJ, Pierce MA, George RH, Booth IW. 94. Kohl M, Wedel T, Entenmann A, et al. Influence of
Dietary management of D-lactic acidosis in short bowel different intravenous lipid emulsions on hepatobiliary
syndrome. Arch Dis Child. 1990;65(2):229–231. dysfunction in a rabbit model. J Pediatr Gastroenterol Nutr.
78. Hosie S, Loff S, Wirth H, Rapp HJ, von Buch C, Waag 2007;44(2):237–244.
KL. Experience of 49 longitudinal intestinal lengthening 95. Rodrigues AF, Van Mourik IDM, Sharif K, et al. Manage-
procedures for short bowel syndrome. Eur J Pediatr Surg. ment of end-stage central venous access in children referred
2006;16(3):171–175. for possible small bowel transplantation. J Pediatr Gastroen-
79. Coronado BE, Opal SM, Yoburn DC. Antibiotic-induced terol Nutr. 2006;42(4):427–433.
D-lactic acidosis. Ann Intern Med. 1995;122(11):839–842. 96. Lang EV, Reyes J, Faintuch S, Smith A, Abu-Elmagd K. Central
80. Goulet O, Ruemmele F. Causes and management of intes- venous recanalization in patients with short gut syndrome:
tinal failure in children. Gastroenterology. 2006;130(2 Suppl restoration of candidacy for intestinal and multivisceral trans-
1):S16–S28. plantation. J Vasc Interv Radiol. 2005;16(9):1203–1213.
81. Kelly DA. Liver complications of pediatric parenteral nutri- 97. Lichtman SN. Translocation of bacteria from gut lumen to
tion–epidemiology. Nutrition. 1998;14(1):153–157. mesenteric lymph nodes--and beyond? J Pediatr Gastroenterol
82. Teitelbaum DH. Parenteral nutrition-associated cholestasis. Nutr. 1991;13(4):433–434.
Curr Opin Pediatr. 1997;9(3):270–275. 98. Piedra PA, Dryja DM, LaScolea LJ Jr. Incidence of catheter-
83. Kelly DA. Intestinal failure-associated liver disease: what associated gram-negative bacteremia in children with short
do we know today? Gastroenterology. 2006;130(2 Suppl bowel syndrome. J Clin Microbiol. 1989;27(6):1317–1319.
1):S70–S77. 99. Kurkchubasche AG, Smith SD, Rowe MI. Catheter sepsis in
84. Beale EF, Nelson RM, Bucciarelli RL, Donnelly WH, Eitzman short-bowel syndrome. Arch Surg. 1992;127(1):21–24; discus-
DV. Intrahepatic cholestasis associated with parenteral nutri- sion 24–25.
tion in premature infants. Pediatrics. 1979;64(3):342–347. 100. Weber TR. Enteral feeding increases sepsis in infants with
85. Günsar C, Melek M, Karaca I, et al. The biochemical and short bowel syndrome. J Pediatr Surg. 1995;30(7):1086–1088;
histopathological effects of ursodeoxycholic acid and metron- discussion 1088–1089.
idazole on total parenteral nutrition-associated hepatic 101. Moukarzel AA, Haddad I, Ament M, et al. 230 patient years of
dysfunction: an experimental study. Hepatogastroenterology. experience with home long-term parenteral nutrition in child-
2002;49(44):497–500. hood: natural history and life of central venous catheters. J
86. Colomb V, Fabeiro M, Dabbas M, Goulet O, Merckx J, Ricour Pediatr Surg. 1994;29(10):1323–1327.
C. Central venous catheter-related infections in children 102. Carlsson E, Bosaeus I, Nordgren S. Quality of life and
on long-term home parenteral nutrition: incidence and risk concerns in patients with short bowel syndrome. Clin Nutr.
factors. Clin Nutr. 2000;19(5):355–359. 2003;22(5):445–452.
87. Burstyne M, Jensen GL. Abnormal liver functions as a result 103. Candusso M, Faraguna D, Sperli D, Dodaro N, et al. Outcome
of total parenteral nutrition in a patient with short-bowel and quality of life in paediatric home parenteral nutrition.
syndrome. Nutrition. 2000;16(11–12):1090–1092. Curr Opin Clin Nutr Metab Care. 2002;5(3):309–314.
88. Cooke RJ, Whitington PF, Kelts D. Effect of taurine supple- 104. Heine RG, Bines, JE. New approaches to parenteral nutri-
mentation on hepatic function during short-term parenteral tion in infants and children. J Paediatr Child Health.
nutrition in the premature infant. J Pediatr Gastroenterol Nutr. 2002;38(5):433–437.
1984;3(2):234–238. 105. Botha JF, Grant WJ, Torres C, et al. Isolated liver transplanta-
89. Bresson JL, Narcy P, Putet G, Ricour C, Sachs C, Rey J. tion in infants with end-stage liver disease due to short bowel
Energy substrate utilization in infants receiving total paren- syndrome. Liver Transpl. 2006;12(7):1062–1066.
teral nutrition with different glucose to fat ratios. Pediatr Res.
1989;25(6):645–648.

106. Diamond IR, Wales PW, Grant DR, Fecteau A. Isolated liver
transplantation in pediatric short bowel syndrome: is there a
role? J Pediatr Surg. 2006;41(5):955–959.
107. Horslen SP, Sudan DL, Iyer KR et al. Isolated liver transplan-
tation in infants with end-stage liver disease associated with
short bowel syndrome. Ann Surg. 2002;235(3):435–439.

28
Pulmonary Disorders
Allison Mallowe, RD, LDN, Suzanne Michel, MPH, RD, LDN, and Maria Mascarenhas, MBBS

Cystic Fibrosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 323 1. Understand the role of nutrition in lung disease.
Pathophysiology 2. Discuss nutrition as related to complications of cystic
Nutrition Assessment. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 325 fibrosis (CF).
Nutrition Recommendations . . . . . . . . . . . . . . . . . . . . . . . 325 3. List components of nutrition assessment for persons
Macronutrients with pulmonary disease.
Micronutrients 4. Understand micronutrient abnormalities that can
Minerals occur in CF.
Nutrition Support. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 329
Pancreatic Enzymes. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 330 Cystic Fibrosis
Eating Behaviors and CF. . . . . . . . . . . . . . . . . . . . . . . . . . 330
Pathophysiology
Nutrition-Related Cystic Fibrosis Complications. . . . . . . 331
Osteoporosis or Bone Disease Cystic fibrosis (CF) is a common autosomal recessive
CF-Related Diabetes genetic disorder that is most frequently seen in people of
Lung Transplantation northern European descent. In the United States CF occurs
Gastrointestinal in approximately 1 in 2,500 live births and affects approxi-
Other Chronic Lung Diseases . . . . . . . . . . . . . . . . . . . . . . 332 mately 30,000 Americans. The CF gene was isolated in
Overview and Pathophysiology 19891 and since then more than 1,500 mutations have been
Bronchopulmonary Dysplasia identified. The gene, which is localized on the short arm of
Asthma
Technology Dependent
chromosome 7, is called the cystic fibrosis transmembrane
Nutrition Assessment regulator (CFTR) and controls the flow of sodium and
Nutrition Recommendations chloride ions across the cell membrane. Mutations in the
Bone Health in Chronic Lung Disease gene result in abnormal epithelial ion transport in multiple
Summary. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 334 organs in the body. Clinical outcomes have been related to
the type of mutation. With the advent of almost universal
newborn screening programs in the United States, it is esti-
mated that the average life expectancy will increase from the
current median predicted life expectancy of 37.4 years. 2
Diagnosis during the newborn period by newborn
screening results in early nutrition intervention and
improved nutrition status, which may lead to better quality
of life and prolonged survival. (See Table 28-1 for clinical
features and diagnosis of CF.) Historically an abnormal
323
sweat test (chloride values > 60 mEq/L) was considered in a sustained host inflammatory response. Stimulated
diagnostic, but it is now recognized that this gold standard neutrophils release large amounts of oxidants and proteases
may not always be abnormal. Based on the severity of the including elastase which leads to increased mucus produc-
mutation, the clinical picture is variable and gene analysis, tion, bacterial trapping, and further lung damage.6 Clinical
nasal potential differences, and sputum cultures may be symptoms include cough, production of mucus, air trap-
required for the diagnosis of CF. 3 ping, and ultimately end-stage lung disease requiring lung
transplantation.
Table 28-1 Clinical Features and Diagnosis of Cystic Fibrosis In the pancreas there is accumulation of thick mucus
Clinical Features Manifested Clinical Features Manifested in the acinar glands leading to an obstruction of the ducts.
in Infants in the General CF Population Damage occurs in the glands due to the release of lytic
Meconium ileus Recurrent cough or wheeze enzymes resulting in chronic inflammation, fibrosis, fatty
Meconium peritonitis Clubbing of fingers and toes infiltration of the pancreas, and pancreatic insufficiency
Intestinal atresia Hyperinflation of chest (PI). These changes can occur in utero in patients with
Recurrent obstructive respiratory Cystic fibrosis-related diabetes severe mutations. PI is seen in about 70% to 80% of patients
disease/infections Chest wall deformities at diagnosis.7 Patients with adequate pancreatic function at
Rectal prolapse Nasal polyps diagnosis who are pancreatic sufficient (PS) may go on to
Failure to thrive Cirrhosis and portal hypertension develop PI over time, hence need to be monitored carefully.
Obstructive jaundice Recurrent pancreatitis Clinical symptoms of PI include malabsorption, diarrhea,
Hyponatremic dehydration Gallbladder disease weight loss, poor growth, vitamin deficiencies, increased
Malabsorption Focal biliary cirrhosis gas, and abdominal pain. Some patients may have a vora-
Salty taste in sweat (when Zinc deficiency & EFAD dermatitis
kissed)
cious appetite in an effort to ingest sufficient calories to
Fat-soluble vitamin deficiencies compensate for energy loss in their bowel movement from
Zinc deficiency
Hyponatremic deficiency without maldigestion and malabsorption. Approximately 5% to
Fat-soluble vitamin deficiency renal disease
15% of persons with CF will develop cystic fibrosis-related
EFAD: essential fatty acid deficiency.
diabetes (CFRD) and it is expected that this number will
Adapted from Gottschlich MM. Pulmonary disease. In: Gottschlich MM.
The Science and Practice of Nutrition Support: A Core-Based Curriculum. increase as life expectancy increases. 8
Dubuque, IA: Kendall/Hunt Publishing Co; 2001:501–516. Similar fluid and electrolyte disturbances occur in the
GI tract causing sticky mucus and stool accumulation which
Because the expression of the CF gene is limited to can result in meconium ileus in the newborn and distal
epithelial cells, the organs affected are primarily mucus- intestinal obstruction syndrome (DIOS) in older children
producing organs such as lungs, gastrointestinal (GI) tract, and adults. Meconium ileus, or the build-up of meconium
liver, pancreas, and sweat glands.4 The transport of sodium in utero, is the earliest manifestation of CF. Infants can be
and chloride across cell membranes is regulated by cyclic born with meconium plugs, intestinal obstruction, atresias,
adenosine monophosphate and calcium, both of which are volvulus, perforations, and meconium pseudocyst. DIOS is
controlled by CFTR. 5 The respiratory epithelial cells are the accumulation of sticky stool in the GI tract, primarily
impermeable to chloride ions which results in an increase in the terminal ileum and cecal area. It may occur in all
in airway sodium absorption. The movement of sodium persons who have CF (PI and PS). Predisposing factors are
into the cells results in the movement of water into the cell, decreased fluid intake, decreased salt intake, malabsorp-
leading to dehydration of the airway mucus and decreased tion, and decreased motility. Other changes in the GI tract
ciliary function. This results in viscous secretions in the include abnormal gastric and intestinal motility.
lung, liver, pancreas, and GI tract and in duct obstruction in In the liver CFTR is expressed in the biliary epithe-
sweat glands and elevated sweat chloride levels. lium, and similar abnormalities of ion transport occur. This
Pulmonary involvement is initially associated with results in the decreased flow of bile with secondary hepa-
infection with Staphylococcus aureus and later Pseudomonas tocyte damage, inflammation, fibrosis, and cirrhosis. In
aeruginosa. Chronic pulmonary damage, bronchiectasis, males, obstruction of the vas deferens results in infertility
fibrosis, and decreasing lung function occur over time. and in patients with mild mutations may be the presenting
Impaired gas exchange occurs secondary to airflow feature that leads to the diagnosis of CF.
resistance, hyperinflation, and uneven distribution of venti-
lation. Bacterial adherence and colonization both result

PULMONARY DISORDERS 325
Nutrition Assessment Table 28-2 Nutrition Assessment Parameters for Cystic Fibrosis
There is a strong correlation between pulmonary function Frequency of Assessment
Parameter
and nutritional status. In children, a body mass index (BMI) and Reassessment
at or above the 50th percentile has been associated with Anthropometrics
improved survival and optimal lung function. Associations Occipital-frontal head Measured only up to age 2 years
circumference
between deteriorating lung function and worsening nutri-
Body weight, height, length, Every 3 months
tion status have been noted.4,9 Malnutrition results from: head circumference
increased needs (increased metabolic rate,10 infections, MAMC, TSF Annually
work of breathing, cough); increased losses (malabsorption Nutritional Intake
due to pancreatic, liver, and intestinal disease; intestinal 24-hour recall Routine care and diagnostic
resection; vomiting; and CFRD); and decreased nutrient 3-day dietary fat balance Evaluate weight loss, growth,
intake (anorexia, gastroesophageal reflux disease (GERD), coefficient of diagnosis
eating disorders, abdominal pain, constipation, malaise, fat absorption < 93% or 85%
and medications). Aggressive nutrition intervention is often in infants
required to improve nutrition status. fecal elastase used to define
steatorhhea
Nutrition assessment is an important component
Biochemical
in the care of persons who have CF. Factors that affect
CBC with differential Routine care and diagnosis
nutrition status include maldigestion and malabsorption
Iron studies Diagnose iron deficiency anemia
of fat, protein, carbohydrates, and fat-soluble vitamins;
Fat-soluble vitamins Routine care and diagnosis
decreasing pulmonary function; chronic pulmonary infec-
Alpha-tocopherol
tions and increased oxidative stress; decreased energy
Serum plasma retinol
intake; increased energy requirements; and CFRD. A
25-OH vitamin D
comprehensive nutrition assessment must be performed
PIVKA II
at diagnosis and yearly. This consists of an assessment of
Essential Fatty Acid Deficiency
(1) growth including pattern of weight and height based
Ratio of triene to tetraene Diagnostic
on the growth curve, head circumference (as appropriate),
25-OH vitamin D Yearly
and BMI percentile; (2) biochemical indicators such as
MAMC: mid-arm muscle circumference; TSF: triceps skinfold; CBC:
vitamin and mineral levels; (3) nutrient intake; (4) eating complete blood count.
behavior and family eating patterns; (5) pancreatic enzyme Adapted from Gottschlich MM. Pulmonary disease. In: Gottschlich MM.
replacement therapy (PERT) management; (6) physical The Science and Practice of Nutrition Support: A Core-Based Curriculum.
activity; (7) severity of lung disease; (8) presence of any Dubuque, IA: Kendall/Hunt Publishing Co; 2001:501–516.
comorbidity such as CFRD, chronic infections, cirrhosis,
or bacterial overgrowth; and (9) factors which may impact
the patient’s ability to meet nutrition goals. Assessment of Nutrition Recommendations
bone health should be performed yearly and, as indicated,
growth parameters (height, weight, head circumference, Macronutrients
weight for length, or BMI percentile) should be assessed
and monitored at every visit. Arm anthropometrics can be Energy
measured as well. Based on the above information caloric As previously described, individuals who have CF have
requirements are calculated, vitamin and mineral prescrip- increased energy needs. Exact caloric prescriptions and
tion adjusted, and anthropometric goals calculated. formulas to calculate caloric need are difficult to provide
A nutrition screen must be performed at every visit so as due to individual patient variation11 but improved weight
to identify inadequate weight gain, weight loss, and faltering status has been found at intakes ranging from 110% to 200%
of linear growth. When these occur, a nutrition assessment of energy needs for the healthy population.12 Energy needs
must be performed, causes identified, and appropriate inter- of each patient should be assessed on an individual basis and
ventions implemented (Table 28-2). reflect the pattern of weight gain and fat stores.13 An estima-
tion of individual caloric need is based upon nutrition status,
growth pattern, fat stores, current dietary intake, degree of
fat malabsorption, clinical status (including pulmonary

function), level of activity, and incorporation of additional low-calorie, low-nutrient foods. Adding oil to commercial
requirements for nutrition repletion, weight gain, and/or jarred infant foods will increase calories; up to 1 teaspoon
catch-up growth.14 of oil to every 4 oz of baby food is suggested. Revised guide-
lines for infant feeding emphasize the safety and benefits
Fat of earlier introduction of meat for the energy, protein, zinc,
The energy goal can be best achieved by consuming a diet that and iron content for all infants.8 Parents who wish to prepare
contains 35% to 40% of calories as fat.13 Ongoing research homemade solids may require instruction. Positive feeding
suggests that a diet containing sources of linolenic acid (LA), behaviors should be encouraged throughout the feeding
such as flax seed, canola, and soy oils and cold-water marine experience.17
fish, may be beneficial for persons who have CF.15 Histori-
cally the amount but not type of fat has been emphasized. Micronutrients
Clinicians are encouraged to be aware of the symptoms of All persons with CF, both PI and using PERT and PS,18
essential fatty acid deficiency (EFAD). Most common symp- require supplementation with micronutrients. Deficiencies
toms of LA deficiency are poor growth and scaly skin lesions, of fat-soluble vitamins19 and zinc20 have been demonstrated
confirmed by an increase in triene-tetraene ratio of plasma in infants diagnosed through newborn screening and do
lipids.8 EFAD can occur not only in patients with severe not correct without appropriate supplementation and, if
lung disease, significant malabsorption, and/or cirrhosis but indicated, PERT. Children and adolescents are at risk for
also in patients with normal nutrition status. It is not known micronutrient deficiencies due to:14
whether the deficiency is due to a primary metabolic disorder • Inadequate intake
or due to malabsorption and increased oxidative stress.15 • Malabsorption possibly due to suboptimal PERT
• Malabsorption due to residual or incomplete bile salt
Protein absorption
Specific recommendations for protein intake in CF are • Poor clinical status and poor lung function
not available, although there is some evidence that protein • Increased utilization and reduced bioavailability
needs are met if a higher calorie diet is consumed14 and 15% • Liver disease
to 20% of total calories are from protein.16 • Bowel resection
• Late diagnosis of CF
Carbohydrate • Poor adherence to or inappropriate supplementation.
The diet should contain sufficient carbohydrate to meet
energy needs. As with persons who do not have CF, it is best Fat-Soluble Vitamins
if the source is from foods which contribute to the overall Multivitamins designed to meet the fat-soluble vitamin
nutrient intake, including fiber. needs of persons who have CF (CF-specific multivitamins)
are available in North America (Table 28-3). These vitamins
Infants contain fat- and water-soluble vitamins and zinc. The content
Infants require a diet that will promote optimal weight reflects the recommendations provided in the U.S. Pediatric
gain, and, when indicated, “catch-up” growth. Human milk Nutrition Consensus Report,13 the European Nutrition
or standard infant formula is recommended. When neces- Consensus Report,21 the U.S. Bone Consensus Report,22
sary, fortified human milk or calorically dense formula may and/or current research. Dosage and form of the CF-specific
be used to promote and/or maintain weight gain.17 Infants multivitamin supplementation is dependent on results of
with CF have specific sodium requirements (see section on laboratory evaluation of vitamin levels and the patient’s age.
Sodium Chloride). Infants may require 120 to 150 kcal/kg/d Patients may require additional single-nutrient supplements
to achieve catch-up growth.13 Hydrolyzed protein formulas (ie, vitamins A, E, D, K), if blood levels cannot be main-
containing medium-chain triglycerides (MCTs) are not tained on the CF-specific multivitamins. If the CF-specific
indicated in the absence of a medical reason, such as bowel multivitamin is unavailable, single-vitamin supplements are
surgery with significant bowel resection due to meconium necessary to make up the difference in content of traditional
ileus or liver abnormalities. Solids are added to the diet of multivitamins compared to recommendations.
infants who have CF on the same schedule used for non- For additional information specific to vitamins and
affected infants.8 Care must be taken when adding solids to CF the reader is referred to www.SourceCF.com for
avoid replacing nutrient- and energy-rich infant milks with newsletters.

Table 28-3 Fat-Soluble Vitamins and Zinc Content of Multivitamins1

SourceCF® Poly-Vi-Sol Drops®
CFF Consensus AquADEKs® Vitamax®
Age Drops, Chewables, ADEK Chewables® Centrum®
Report 2 Drops, Softgels Drops, Chewables
Softgels Chewable, Tablet
Vitamin A (IU) Retinol and Beta-Carotene (BC)
0–12 months 1,500 4627 (1 mL) 75% BC 5,751 (1 mL) 87% BC 3,170 (1 mL) 0%BC 1,500 (1 mL) 0% BC
1–3 years 5,000 9254 (2 mL) 75% BC 11,502 (2 mL) 87% BC 6,340 (2 mL) 0% BC 3,000 (2 mL) 0% BC
16,000 / chewable 9,000 / chewable Ages 4–10 yrs 18,167 5,000 / chewable 3,500 / chewable
4–8 years 5,000–10,000
88% BC 60% BC / 1 softgel, 92% BC 50% BC 29% BC
18,000 / 2 Ages 10 and up 10,000 / 2
32,000 / 2 softgels 7,000 / 2 tablets
9–18 years 10,000 chewables 36,334 / 2 softgels, chewables
88% BC 29% BC
60% BC 92% BC 50% BC
18,000 / 2 10,000 / 2
32,000 / 2 softgels 36,334 / 2 softgels 7,000 / 2 tablets
> 18 years 8000 chewables chewables
88% BC 92% BC 29% BC
60% BC 50% BC
Vitamin E (IU)
0–12 months 40–50 50 (1 mL) 50 (1 mL)3 50 (1 mL) 5 (1 mL)
1–3 80–150 100 (2 mL) 100 (2 mL)3 100 (2 mL) 10 (2 mL)
Ages 4–10 yrs: 150 /
4–8 100–200 200 / chewable 150 / chewable 200 / chewable 30 / chewable
1 softgel
Ages 10 and up: 300
9–18 years 200–400 400 / 2 softgels 300 / 2 chewables 400 / 2 chewables 60 / 2 tablets
/ 2 softgels
> 18 years 400 400 / 2 softgels 300 / 2 chewables 300 / 2 softgels 400 / 2 chewables 60 / 2 tablets
Vitamin D (IU)
0–12 months 4004 500 (1 mL) 400 (1 mL) 400 (1 mL) 400 (1 mL)
1–3 8004 1000 (2 mL) 800 (2 mL) 800 (2 mL) 800 (2 mL)
Ages 4–10 yrs: 800 /
4–8 years 800 1000 / chewable 400 / chewable 400 / chewable 400 / chewable
1 softgel
Ages 10 and up:
9–18 years 800 2000 / 2 softgels 800 / 2 chewables 800 / 2 chewables 800 / 2 tablets
1600 / 2 softgels
> 18 years 800 2000 / 2 softgels 800 / 2 chewables 1600 / 2 softgels 800 / 2 chewables 800 / 2 tablets
Vitamin K (mcg)
0–12 months 300–500 400 (1 mL) 400 (1 mL) 300 (1 mL) 0
1–3 300–500 800 (2 mL) 800 (2 mL) 600 (2 mL) 0
Ages 4–10 yrs: 700 /
4–8 years 300–500 800 / chewable 150 / chewable 200 / chewable 10 / chewable
1 softgel
Ages 10 and up:
9–18 years 300–500 1600 / 2 softgels 300 / 2 chewables 400 / 2 chewables 50 / 2 tablets
1400 / 2 softgels
> 18 years 1,000 1600 / 2 softgels 300 / 2 chewables 1400 / 2 softgels 400 / 2 chewables 50 / 2 tablets
Zinc (mg)
0–12 months 5 (1 mL) 5 (1 mL) 7.5 (1 mL) 0
1–3 years 10 (2 mL) 10 (2 mL) 15 (2 mL) 0
For 4–10 yrs:
4–8 years 15 / chewable 7.5 / chewable 7.5 / chewable 15 / chewable
10 / softgel
For Ages 10+:
9 years–Adult 30/ 2 softgels 15 / 2 chewables 15 / 2 chewables 22 / 2 tablets
20 / 2 softgels
1. The content of this table is as of December 2008. Products also contain a full range of water-soluble vitamins. Information not included in this table.
For a copy of the full table, go to: www.SourceCF.com.
2. Cystic Fibrosis Foundation. “Pediatric Nutrition for Patients with Cystic Fibrosis Consensus Conference Report” March 2001 (Table 7).
3. Also contains mixed tocopherols.
4. Based on “Guidelines to Bone Health and Disease in Cystic Fibrosis Consensus Conference Report” June 2002 (Figure 2).
5. ADEK® is registered trademark of Axcan Pharma Inc., AquADEKs® is a registered trademark of Yasoo Health Inc., Vitamax® is a registered trademark of
Shear/Kershman Labs. Inc., Poly-Vi-Sol Drops® is a registered trademark of Mead Johnson and Company, Centrum® is a registered trademark of Wyeth
Consumer Care.
Table reproduced with permission of SourceCF® Inc., a subsidiary of Eurand Pharmaceuticals, Inc.

Vitamin A Water-Soluble Vitamins

Vitamin A plays an important role in vision, immunity, lung Deficiency of water-soluble vitamins in CF is rare, but
health, and overall health, yet excessive intake of retinol can has been reported in patients not receiving multivitamins
cause liver and/or bone complications. Retinol is an acute and/or receiving medications interfering with B vita-
phase reactant and best measured when the patient is not ill. mins. 30 Over time, patients who have had a resection of the
Liver disease or zinc deficiency can cause low serum retinol terminal ileum will develop vitamin B12 deficiency requiring
levels. The total vitamin A content of CF-specific multivi- supplementation.14
tamins is based on both retinol and beta-carotene. The risk
of toxicity is avoided with a higher concentration of beta- Minerals
carotene.
Sodium Chloride
Vitamin E Persons who have CF lose excessive sodium in their sweat
Optimizing serum vitamin E will prevent the neurological and require supplementation throughout the year, especially
complications once seen in people who have CF. More in the summer months. Inadequate salt intake can be life
recently the role of vitamin E as an antioxidant in preserving threatening and/or result in poor appetite with subsequent
overall health in CF has been investigated.23 Vitamin E is poor growth. All infants who have CF and an elevated sweat
transported in the body with lipid, including cholesterol. test are to be supplemented with 12.6 mEq (1/8 teaspoon)
People who have CF often have low cholesterol levels, there- of salt daily from birth to 6 months of age at which time the
fore serum levels should be assessed as a ratio of vitamin E24 dose is increased to 25.2 mEq (1/4 teaspoon) daily.17 The
to total lipid 25 or to total cholesterol.25 Liver disease can salt is added in small, frequent amounts to baby formula or
cause low vitamin E levels. applesauce used to dose PERT until the daily dose is met.
Salt supplementation is continued until the child is eating
Vitamin D a diet rich in salt and added salt. Children and adolescents
Persons who have CF are at risk for low serum vitamin D. are to be counseled to consume salt, over and above their
Current repletion recommendations22 do not correct serum usual intake, when participating in physical activity. It may
levels in the majority of patients.26 Patients with liver disease be necessary to add salt to sports drinks to meet sodium
may have low vitamin D levels. Serum 25-hydroxyvitamin chloride needs (1/8 teaspoon to 12 oz). 31
D [25(OH)D] should be assessed annually, preferably in the
late fall and, if necessary, treated daily with D3-cholecalcif- Zinc
erol. The exact dose necessary for all patients is unknown at Pancreatic insufficient infants, prior to treatment with
this time; therefore dosage is based on individual need. PERT, lose excessive zinc in their stool. Acrodermatitis
enteropathica like rash, which resembles a severe rash in
Vitamin K the diaper area and the perioral area, is a clinical symptom
Vitamin K is essential for normal blood clotting and bone of zinc deficiency and is treated with PERT and zinc supple-
health. Persons who have CF are at risk for vitamin K defi- mentation. More subtle symptoms of zinc deficiency which
ciency due to fat malabsorption and routine use of antibiotics. can be seen at any age include lack of appetite, dysgeusia,
Additionally, any patient who has CF and liver disease is at poor growth, and compromised immunity. Laboratory
greater risk for vitamin K deficiency. Clotting time, or PT studies to determine zinc status are generally uninformative.
(prothrombin time), has been the standard test for assessing When zinc deficiency is suspected the usual supplemental
overall vitamin K nutrition, but a number of studies using dose is 1 mg elemental zinc per kilogram daily for 6 months
PIVKA II provided evidence that in CF, vitamin K deficiency in addition to that contained in the patient’s daily multivi-
exists in patients with normal PT.27–29 Over-the-counter tamin. Over-the-counter infant vitamin drops do not contain
multivitamins contain insufficient vitamin K to meet the zinc. Over-the-counter children’s chewable vitamins and
needs of persons who have CF. The vitamin K content of adult formulations contain zinc as do all of the CF-specific
CF-specific multivitamins is sufficient for the majority of multivitamins. When choosing a zinc preparation, it is
patients, although some people may require additional important to note which zinc salt is in the chosen product so
supplementation based on laboratory results. that the correct dose can be determined. For example, zinc
sulfate is 23% elemental zinc but zinc gluconate is only 14%
elemental zinc.

Iron Laboratory studies for individual micronutrients may be

Iron status in the general population is affected by a necessary when modifying the treatment care plan, such as
number of factors, including dietary intake, blood loss, and starting tube feeding.
medications. For persons with CF, all of these factors, plus
malabsorption, hemoptysis, short bowel syndrome, bacterial Nutrition Support
overgrowth, liver and renal diseases, and chronic inflamma- There is a positive correlation between pulmonary func-
tion contribute to altered iron status. Patients can have iron tion and weight.12 The CF Foundation recommends the
deficiency anemia, anemia of chronic disease or a combina- following nutrition goals:
tion of both. Prior to prescribing iron supplementation the • Infants: weight for length at the 50th percentile by 2
form of anemia must be defined. 32 Assessing iron status in years of age
CF is complicated by chronic inflammation. Serum ferritin, • Children 2 to 20 years of age: BMI percentile at or
an acute-phase reactant, may be falsely elevated in CF, thus above the 50th percentile
masking iron deficiency anemia. Measurement of soluble • Adults: BMI of 22 for women and 23 for men12
transferring receptor levels may be helpful in diagnosis. Additionally, children are expected to meet their
genetic potential for growth. Therefore, nutrition interven-
Calcium tions to reach and maintain weight and growth goals are
It is important to optimize the calcium intake of persons often necessary. Behavioral interventions for parents, care-
who have CF. In lieu of specific calcium recommendations givers, and patients may also help improve caloric intake,
for person who have CF, the RD should refer to those in the thus weight gain. 34 Weight percentiles are believed to be at
DRI. The CFF Bone Consensus Report may be referred their lowest during the first 2 years of life and early adoles-
to for more detail regarding bone health and CF. 22 At a cence therefore making aggressive nutrition intervention
minimum, the adequate intake levels should be achieved in important during these time periods. 35 For toddlers and
all patients. older children, initially using high-calorie oral supple-
ments or additives may be indicated. Infant formula can
Magnesium be concentrated or high-calorie modulars added to provide
Patients receiving aminoglycosides may require supple- adequate calories. However in some children this may not
mental magnesium. Blood levels should be monitored. 33 be sufficient to sustain a desired weight and growth status
and enteral feeding may be indicated. There are no specific
Fluoride guidelines regarding when to initiate enteral feeding in the
CF-specific vitamins do not contain fluoride; therefore the pediatric CF population. The CF Foundation Clinical Prac-
patient’s primary care physician may need to prescribe a tice Guidelines Subcommittee on Growth and Nutrition
supplement if local water is not fluoridated. has determined that for children with growth deficits, oral
or enteral supplements should be used to improve the rate
Assessment of weight gain.12 Enteral tube feeding can be via nasogastric
Blood levels of fat-soluble vitamins should be measured at tube, gastrostomy tube, or jejunostomy tube. The nasogas-
diagnosis for patients diagnosed greater than 1 year of age tric tube can be inserted and removed daily for short-term
and annually thereafter.13 For newly diagnosed infants, it is use. Adherence to this intervention may prove difficult. A
recommended that levels of vitamins E, A, and D be assessed gastrostomy tube may be more appropriate and allow for
1 to 3 months after starting supplementation and annually flexibility of feeding. Feeding via the gastrostomy tube can
thereafter.17 Prothrombin time is insensitive to vitamin K be intermittent, bolus, or continuous feeds. Continuous
deficiency in CF.27 PIVKA II provides a better indicator of feeds generally occur nocturnally. Nighttime feedings
vitamin K nutrition, but laboratory reference standards for allow for regular meal and snack pattern during the day.
full-term infants are not available, and therefore checking Enteral tube feeding may be complicated by early morning
PIVKA II levels is not recommended in the newborn period. fullness and vomiting, loss of appetite, and poor body image
Serum electrolytes and complete blood count is measured and self-esteem concerns. The reader is directed to papers
at 2 to 3 months of age and annually or as indicated.17 For related to these concerns. 35–37 It is important to strike a
children and adolescents assessment of fat-soluble vita- balance between initiation of enteral feeding and severity
mins, including PIVKA II and CBC with differential, is of lung disease to optimize the benefit of the intervention.
done at diagnosis and annually, unless otherwise indicated. Feeding via a jejunostomy tube is infrequent in patients

with CF and usually occurs in patients with significant lipase per gram of fat ingested, it is perhaps more practical
upper gastrointestinal dysmotility, failure of anti-reflux to use a dosing schedule with weight-adjusted guidelines. 39
procedures, intubated patients, and in some postoperative For children less than 4 years of age the recommendation
patients. Parenteral nutrition (PN) is considered a more is to began at 1,000 lipase units per kilogram per meal and
aggressive intervention and not routinely used in the daily over 4 years of age 500 lipase units per kilogram per meal.
management of CF. Dosing for snacks is routinely half of usual meal dose. The
recommendations are not to exceed a dose of 2,500 units of
Pancreatic Enzymes lipase per kilogram body weight per meal or 10,000 lipase
Persons who are pancreatic insufficient require PERT. units per kilogram per day and are based on a usual intake
Pancreatic damage and destruction occurs in utero or of 3 meals plus 2 snacks per day. 39
after birth, resulting in the absence of bicarbonate rich and Persons with CF should be viewed individually in
enzyme-containing pancreatic juice in the duodenum to help regards to dosing and response to PERT. Careful moni-
digest food. PERT has played a pivotal role in improving the toring of growth, stool pattern, and the absence or presence
care and outcome of persons with CF. 38 There are a variety of gastrointestinal symptoms is necessary to determine the
of enzymes available with subtle differences among brands adequacy of therapy. For infants and children unable to
and forms. As of this writing the most commonly used swallow enzyme capsules, the enzyme beads are removed
enteric-coated enzymes in the United States are: Creon® by from the capsule(s) and mixed with a small amount (1/8 to
Solvay; Pancrecarb® by Digestive Care; Zenpep by Eurand®; 1/2 teaspoon for infants, more for children) of applesauce
and Ultrase® by Axcan, Inc. Due to changes in PERT content and given at the time of each feeding.8 PERT is given at the
mandated by the Food and Drug Administration and to be beginning of the feeding or meal. If mealtime is more than
put in place by April 2010 the reader is referred to the manu- 30 minutes, then it is recommended that the dose be split
facturer’s Web site for details regarding enzyme content. and given at the beginning and halfway during the meal.
A non-enteric-coated form of enzyme, such as Viokase® For infants, to avoid mucosal erosion, the mouth should be
by Axcan, is subject to destruction by the acidic gastric envi- checked for beads following each feeding. The infant’s peri-
ronment.8 Microspheres and microtablets are enteric-coated anal area may require protection against enzyme excreted
to protect the enzyme from the acidic gastric milieu. The in the stool. Patients can be instructed to apply a thick layer
enteric coating allows for activation to occur in the alkaline of barrier cream to protect the skin around the anus.
pH of the duodenum, past the acidic gastric contents. If the Persons with CF who receive nasogastric tube, gastros-
pancreas is unable to deliver bicarbonate pancreatic juice to tomy tube, or jejunostomy tube feedings need PERT
the duodenum, gastric acid from the stomach is not neutral- supplementation. The amount and type of enzyme given
ized resulting in an acidic duodenal pH. Acidity in the depends on the type of formula and the ability of the patient
gastrointestinal tract may prevent or retard dissolution of to take enzymes orally. In general a meal dose of PERT is
enteric-coated pancreatic enzymes. 39 If activation does not given before and after night tube feeds when using an intact
take place in the small intestine, absorption of macro- and formula.13 Some patients may benefit from an additional dose
micronutrients cannot occur. Additional medications which midway during the feedings at night. During the day PERT
reduce or block acid production and raise the duodenal pH is best given before each bolus and this dose is dependent
may be needed to enhance PERT effectiveness. Even so, all on the amount and type of fat in the bolus. Enzymes can
nutrients may not be fully absorbed. If fat malabsorption be administered via the gastrostomy tube if the size of the
persists, consider lack of bile acids an etiology. bead is small enough to go through the tube and not cause
The pancreatic enzyme replacement products contain clogging. Pancrecarb®Four by Digestive Care contains
lipase, protease, and amylase for digestion of fat, protein, microspheres/microtabs that fit through a gastrostomy tube.
and carbohydrates, respectively. Enzyme activity or potency The reader is referred to the manufacturer’s Web site for more
is based on the amount of lipase per capsule or gel cap. For information.
example, for Creon 5® the 5 refers to 5,000 lipase units per
capsule. Creon 5® also contains 3,600 amylase units and Eating Behaviors and CF
200 protease units. The importance of nutrition in CF is recognized by the CF
PERT starting dose for infants of 2,000 to 4,000 units Care Team and by parents of children who have CF. Pres-
of lipase per 120 mL of formula or breast milk is recom- sure surrounding the importance of nutrition includes:
mended. 39 Though dosing is best calculated using units of improving and maintaining weight and adherence to PERT

and supplemental vitamins and/or minerals. As a result, levels, prolonged corticosteroid usage, delayed puberty,
mealtimes can become challenging. Parents of children low calcium intake, history of fractures, family history of
with CF commonly report mealtime behavior problems osteoporosis, significant lung disease, or liver disease. 22
including: poor appetite, avoidance of eating by talking, Normative data are available for DEXA scans for children
and spitting out food. 34 A negative correlation between the above 3 years of age. Treatment includes optimizing nutri-
children’s caloric intake and the number of problematic tion (calcium, vitamins D and K, and nutrition status),
mealtime behaviors has been identified.40 increasing physical activity, controlling underlying inflam-
Young children appear to be particularly at risk for mation, decreasing use of corticosteroids as indicated, and
behavioral difficulties at mealtime if their parents feel addressing any hormone deficiencies. In adults bisphos-
unusually concerned about their children’s health and phonates have been used in patients with osteoporosis and
caloric/food intake.40 For parents of infants with CF, the stress fractures, but in children there are limited data on
transition from formula to solids may present a challenge their safety.
and parents may need guidance surrounding positive
eating behaviors and high-calorie solids. The toddler stage CF-Related Diabetes
is typically characterized by changing food interests and CF-related diabetes (CFRD) shares features of both type
neophobia (fear of new foods), which for children with CF 1 and type 2 diabetes, but it is a distinct clinical entity.43
may complicate the selection of high-fat foods and food Diabetes occurs when people either are insulin deficient or
additives. 34 Parents may benefit from guidance to prevent insulin resistant. Individuals with CFRD are insulin defi-
and/or manage food refusal behaviors. Anticipatory guid- cient as a result of destruction by fibrosis or scarring of beta
ance might include education centered on avoidance of cells in the pancreas that produce insulin.44 Glucose metabo-
parental behaviors that may inadvertently reinforce non- lism is strongly influenced by factors unique to CF, including
eating behaviors and advice directed toward reinforcement undernutrition, chronic and acute infection, elevated energy
of desired behaviors through praise and limit setting.40 As expenditure, glucagon deficiency, malabsorption, abnormal
children become adolescents, a struggle for control and intestinal transit time, and liver dysfunction. These factors
independence may ensue. In this period, the challenge may are not static and may fluctuate over time in CF.43
be providing education and direction so that the child/ Retrospective studies have shown that pulmonary
adolescent makes appropriate choices that improve or decline and weight loss begin 2 to 4 years before diag-
maintain optimal nutrition status. Birch has stated that the nosis of CFRD.43 Symptoms of CFRD include polydipsia,
foundation for teen and adult eating styles is laid in child- polyuria, weight loss or inability to gain weight despite
hood as the parent and child work through issues of control aggressive nutrition intervention, poor growth, and poor
regarding feeding and eating.41 progression of puberty or unexplained chronic decline in
pulmonary function.43 Any patient with these symptoms
Nutrition-Related Cystic Fibrosis should be screened for CFRD using the CF Foundation
Complications recommendation.43
In the routine management of CF, casual glucose levels
Osteoporosis or Bone Disease are measured annually. If the person has a random blood
Bone disease is increasingly recognized in persons who glucose level of ≥ 126 mg/dL, further workup for CFRD
have CF. Decreased bone density, fractures, and kyphosis should be conducted. Tests include fasting blood glucose or
occur earlier in persons with CF than in healthy controls.42 2-hour oral glucose tolerance test (OGTT). The CF Foun-
The incidence of osteoporosis and fracture increases with dation assembled a consensus conference on CFRD and
increasing age and are prevalent in adult patients and in issued recommendations for monitoring glucose intoler-
those with end-stage lung disease. Predisposing factors ance; refer to these recommendations for further screening
include inflammatory cytokines, vitamin D deficiency, of CFRD.43
inadequate calcium intake, use of corticosteroids, delayed When discrepancies exist between the nutrition
puberty, short bowel syndrome, and liver disease. It is recommendations of the 2 diseases, the CFRD recom-
recommended that patients 8 years of age or older with mendations supersede those for type 1 and type 2 diabetes.
the following risk factors get a baseline dual energy X-ray The CF Foundation Consensus Statement on Diagnosis,
absorptiometry (DEXA) scan: small body size, low weight Screening, and Management of Cystic Fibrosis Related
for height, decreased physical activity, low vitamin D Diabetes Mellitus43 currently promotes these 2 principles

for nutrition management of CFRD: in the ileocecal junction resulting in abdominal pain and
• Achievement of optimal nutrition status through intake vomiting. Treatment/prophylaxis consists of optimizing
of sufficient calories is critical for survival in persons fluid and electrolyte intake, correction of any malabsorption
with CF. and the use of laxatives/stool softeners, such as polyeth-
• Near-normalization of blood glucose levels is necessary yleneglycol. Prevention is vital, and an attempt to find
to ensure optimal nutritional and metabolic status the precipitating factor for every episode should be made.
Diet guidelines for type 1 and type 2 diabetes are not Celiac disease, inflammatory bowel disease, eosinophilic
recommended for people who have CFRD.43 Ideally the esophagitis, and GI malignancies may also occur in CF.
person with CFRD is to maintain/achieve a healthy body Patients with pancreatic sufficiency are at risk for recur-
weight and is encouraged to continue a high-calorie, high- rent bouts of pancreatitis. Over time some of these patients
fat and high-sodium diet. Carbohydrate counting, meal may become PI. The most common liver lesion in patients
timing, and insulin therapy are significant interventions for with CF is fatty liver. Also seen are hepatitis, fibrosis, and
management of CFRD.16 cirrhosis with portal hypertension. Gallbladder dysfunction
is frequent and a non-functioning gallbladder or gallstones
Lung Transplantation can be seen on ultrasound examination. Biliary dyskinesia
Lung transplantation remains the most aggressive therapy can result in right upper quadrant abdominal pain. Some
for end-stage lung disease.45 Persons with CF are candidates patients with liver disease will progress to end-stage liver
for lung transplantation when they exhibit severely reduced disease and develop complications from cirrhosis (portal
lung function and progressive deterioration in their health encephalopathy and uncontrolled variceal bleeds) and
and quality of life.16 For children and adults, the largest require liver transplantation.
obstacle to long-term survival remains chronic allograft
rejection secondary to the development of bronchiolitis Other Chronic Lung Diseases
obliterans. Common weight criteria for adults are 80% to
130% IBW or BMI of 18.5 to 30 kg/m². There is no pediatric Overview and Pathophysiology
weight criterion. Further research in the area of weight and Chronic lung disease (CLD) is seen in premature infants
nutrition status is needed in the pediatric lung transplant who have significant respiratory disease, in infants and
population. children with congenital heart disease who need ventilator
support in the neonatal period, in patients with difficult-to-
Gastrointestinal manage asthma or reactive airways disease (RAD), and in
Gastrointestinal (GI) manifestations are frequently seen patients with chronic respiratory insufficiency requiring
in persons with CF and involve all parts of the GI tract.46 ventilator support.
Gastroesophageal reflux (GER) occurs at all ages and the
incidence varies between 25% and 100% depending on the Bronchopulmonary Dysplasia
study. Complications of GER include feeding disorders, Bronchopulmonary dysplasia (BPD) is a form of chronic
decreased caloric intake, failure to thrive, apnea in infants, lung disease that develops in preterm infants given positive
vomiting, esophagitis, worsening of lung disease, esopha- pressure ventilation and oxygen. The pathophysiology is
geal strictures, and Barrett’s esophagus. Reflux can be a complex and due to small airway damage, abnormal alveolar
significant problem in lung transplant recipients and is asso- development, and decreased surface area for gas exchange.48
ciated with rejection in the posttransplant period. Often a Additionally there is damage to small blood vessels in the
fundoplication is recommended in the pretransplant period. lungs and secondary damage to the heart and brain. BPD is
Gastroparesis and constipation can be seen in CF and the most commonly seen in preterm infants with a birth weight
latter may be 3 times more frequent than DIOS. Bacterial of more than 1250 g and 30 weeks gestational age. Males
overgrowth occurs in up to 60% of patients.47 Predisposing tend to be more affected. Surfactant therapy is used soon
factors include frequent antibiotic use, intestinal dysmo- after birth to prevent lung damage. Energy requirements
tility, history of previous GI surgery, and sticky intestinal are increased and are in the range of 125 to 150 kcal/kg/d.49
secretions that trap bacteria. DIOS is seen in all persons with Vitamin A supplementation is important and often used in
CF, not just in those with PI. Dehydration of the intestinal the neonatal intensive care unit to prevent BPD. Vitamin E
secretions, coupled with electrolyte imbalances and sticky supplementation is not helpful. These patients also have large
mucus, and poor motility lead to the accumulation of stool insensible water losses and need extra fluid which results in

opening of the patent ductus arteriosus and further stress on and omega-3 fatty acids has been associated with a reduc-
the lungs. Fluid restriction often results in inadequate nutrition in symptoms and reduced development of asthma in
tion intake. Calcium status is poor due to decreased intake those with atopy. 52 In children a linear association between
and increased losses from diuretics. Adequate intakes of obesity (increased BMI) and asthma has been noted with a
calcium and phosphorus, protein (3–3.5 g/kg/d), and anti- 6% increase in prevalence per unit increase of BMI. 53
oxidants (copper, zinc, and manganese) are required and it
is important to avoid excessive carbohydrate intake because Technology Dependent
it can impact on pulmonary function by altering the respira- Children with chronic respiratory failure may require
tory quotient. These patients often receive corticosteroids chronic ventilatory support. At-risk children include those
and diuretics for treatment of the lung disease often with with: neuromuscular dystrophy, spinal muscular atrophy,
significant consequences: increased sodium, potassium Duschenne’s muscular dystrophy, spinal cord injuries,
and magnesium losses, kidney stones, gallstones, and bone BPD, congenital diaphragmatic hernia, severe lung
disease. malformations, congenital hypoventilation syndrome,
Infants with severe BPD are at high risk for the following and myelomeningiocoele. From the above diagnoses, of
problems during the first 2 years of life: pulmonary infec- patients who require ventilator support, patients with
tions, frequent hospitalizations, RAD, and more frequent BPD and neuromuscular dystrophy are the most frequent.
visits to the doctor. These patients also may have develop- Respiratory support can be non-invasive (BIPAP) or inva-
mental delay, poor muscular development, poor feeding sive (tracheostomy and ventilator). The pathophysiology
skills, poor growth, and chronic lung disease. Infants with includes respiratory insufficiency (seen in BPD and pulmo-
BPD often have impaired weight for length and problems nary hypoplasia), secondary damage to the lungs from
with oxygen diffusion resulting in a chronic oxygen require- severe cardiac disease resulting in decreased surface area,
ment. Caloric needs are high because catch-up growth is decreased oxygen absorption, increased carbon dioxide
often a goal. The co-existence of reflux and BPD can exac- retention, poor lung development, small-volume lungs,
erbate poor oral motor function and can worsen feeding and insufficient vascular bed. There may also be decreased
problems in patients with developmental delay. Reflux can central drive for respiration as seen in persons with congen-
also worsen lung disease. Supplemental feeds are often ital central hypoventilation syndrome. Since these patients
required. have decreased work of breathing, their energy require-
ments are subsequently decreased. If careful attention is
Asthma not paid to their nutrition regimens, they can have exces-
Asthma or RAD is the most common cause of hospital sive weight gain which can further impact their respiration
admissions in children. It is a chronic pediatric lung status negatively. Often, in an attempt to decrease calories,
disease where there is chronic inflammation of the overall nutrient intake, especially protein and mineral
airways involving eosinophils, mast cells, T lymphocytes, intake, suffers. These patients may also be at risk for bone
macrophages, neutrophils, and epithelial cells. Additionally disease due to decreased weight bearing and micronutrient
there is variable air flow obstruction and increased bron- deficiency (vitamin D and calcium).
chial responsiveness to a variety of environmental stimuli.
The presence of airway edema and mucus contributes to the Nutrition Assessment
obstruction and bronchial reactivity that is seen. 50 Envi- For children with BPD and asthma it is best to monitor
ronmental triggers affect the normal development of the growth on a regular basis. Anthropometrics provide critical
respiratory and immune systems in genetically predisposed information regarding the growth of the infant or child. In
individuals. 51 Patients often require chronic inhaled or the infant with BPD, factors that may increase caloric require-
pulses of systemic corticosteroids. Excessive oral cortico ments include increased basal metabolic rate, increased
steroid use over time can result in growth failure, fluid and work of breathing, chronic illness or infections, and respira-
sodium retention, a voracious appetite, excessive weight tory distress or metabolic complications.54 The infant may
gain, hypertension, glucose intolerance, and obesity. There struggle with fluid sensitivity, which may limit the intake of
appears to be considerable variation in the side effects of calories and nutrients. Infants may have interrupted feeding
inhaled corticosteroids. Growth, puberty and bone health skill development, therefore may be poor oral feeders.54
can be affected depending on the duration and dose. 52
Early data suggest the use of antioxidants, Lactobacillus,

Nutrition Recommendations Test Your Knowledge Questions

In critically ill infants with BPD, efforts are made to prolong 1. Pancreatic enzymes are available in non-enteric-coated
life. Caloric provision is often relegated to secondary and enteric-coated form. How does the enteric coating
importance, compared to pulmonary edema, reduced help with nutrient absorption?
cardiac output, and electrolyte imbalance. 54 Please refer A. Enteric coating is subject to destruction by the
to the section on nutrition in the neonatal intensive care harsh acid-peptic gastric environment
unit for more detailed information on caring for the criti- B. Allows the enzymes to get through the build-up of
cally ill infant. As the infant’s condition improves, concerns thick mucus in the pancreatic ducts
regarding fluid overload and thermal losses remain. C. Allows for the activation to occur in the alkaline pH
Continued monitoring of intake, growth, and development of the duodenum, past the gastric contents of the
is essential. Individualizing macronutrient needs based on stomach
the patient’s growth in relation to the goal is best. Specific 2. Which fat-soluble vitamin blood levels should be
to the infant with BPD, calcium and phosphorous may be checked in persons with CF and why?
further compromised by diuretic therapy, steroid therapy, A. Vitamins A, D, K, and E and zinc. These are insensi-
long-term use of parenteral nutrition, and feeding delays. 54 tive markers in CF.
For further information on micronutrients, please refer to B. Vitamins A, D, E, and PIVKA II, to assure
the vitamin and mineral chapters (Chapters 6, 7, and 8). adequacy.
A diet providing appropriate amounts of macro- and C. Vitamins A, D, E, and PIVKA II. These are insensi-
micronutrients based on the U.S. Department of Agricul- tive markers in laboratory tests.
ture dietary guidelines for age is recommended. Increased 3. A baseline DEXA scan is recommended at the age of 8
appetite, abdominal fat accumulation, sodium and fluid years, especially if risk factors are present. Which of the
retention, and steroid-induced glucose intolerance are following set of risk factors are necessary to be aware of?
common side effects of oral corticosteroid therapy. Moni- A. Small body size, low weight for height, decreased
toring weight and linear growth on a regular basis is physical activity, low vitamin D levels, cortico
important. Nutrition support is discussed in Chapter 34. steroid usage, delayed puberty, low calcium intake,
history of fractures, family history of osteoporosis,
Bone Health in Chronic Lung Disease significant lung disease or liver disease
Pharmacologic therapy is an element in treating asthma. B. Increasing physical activity, large body frame,
The use of oral and high-dosed inhaled steroids has an effect asthma, low calcium intake
on nutrition status. Chronic corticosteroid use does induce C. Increasing physical activity, large body frame, low
osteoporosis. 54 Therefore, adequate amounts of calcium and weight for height, history of fractures, cortico
vitamin D supplementation are vital. To assess adequacy of steroid use, delayed puberty, liver disease
calcium and vitamin D include diet assessment, vitamin 4. In BPD, energy requirements are elevated. What other
D level, and DEXA scan. Normative data are available for nutrition treatments might be beneficial?
DEXA scans for children above 3 years of age. A. Optimize vitamin E in nutrition intake
B. Supplement vitamin A; provide appropriate fluid
Summary intake and adequate amounts of calcium, phospho-
Nutrition is an important part of the management of the rous, protein, and antioxidants; and avoid excessive
child who has chronic lung disease. In general the goal is intake of carbohydrates
normal growth and development and correction of nutri- C. Provide high levels of carbohydrates and fluids
tion abnormalities that result from the underlying medical
condition and the therapies used to treat the disease. Good See p. 487 for answers.
nutrition status has been associated with improved lung
function and outcomes in patients with cystic fibrosis. References
1. Riordan J, Rommens J, Kerem B, et al. Identification of the
cystic fibrosis gene: cloning and characterization of comple-
mentary DNA. Science. 1989;245(4922):1066–1073.
2. Cystic Fibrosis Foundation Patient Registry. 2007 Annual
data report to the center directors, Bethesda, MD.

3. Farrell PM, Rosenstein BJ, White TB, et al. Guidelines for 19. Feranchak AP, Sontag MK, Wagerner JS, Hammond KB,
diagnosis of cystic fibrosis in newborns through older adults: Accurso FJ, Sokol RJ. Prospective, long-term study of fat-
Cystic Fibrosis Foundation Consensus Report. J Pediatr. soluble vitamin status in children with cystic fibrosis identified
2008;153(2):S4–S14. by newborn screen. J Pediatr. 1999;135(5):601–610.
4. Amin R, Ratjen F. Cystic fibrosis: a review of pulmonary and 20. Krebs NF, Sontag M, Accurso FJ, Hambidge KM. Low plasma
nutritional therapies. Adv Pediatr. 2008;55:99–121. zinc concentrations in young infants with cystic fibrosis. J
5. Walker WA, Watkins JB, Duggan, C. Nutrition in Pediatrics: Pediatr. 1998;133(6):761–764.
Basic Science and Clinical Applications. 3rd ed. Hamilton, 21. Sinaasappel M, Stern M, Littlewood J, Wolfe S, Steinkamp G,
London: BC Decker Inc; 2003:672. Heijerman HGM. Nutrition in patients with cystic fibrosis: a
6. Tiddens H, Rosenfeld M. Respiratory manifestations of cystic European consensus. J Cyst Fibros. 2002;1:51–75.
fibrosis. In: Taussig LM, Landau LI, eds. Pediatric Respiratory 22. Aris RM, Merkel PA, Bachrach LK, et al. Consensus State-
Medicine. 2nd ed. Mosby Elsevier; 2008;871–887. ment: Guide to bone health and disease in cystic fibrosis. J
7. Gaskin K, Allen J. Exocrine pancreatic disease including Clin Endocrinol Metab. 2005;90:1888–1896.
cystic fibrosis. In: Walker WA, Watkins JB, Duggan C, eds. 23. Wood LG, Fitzgerald DA, Lee AK, et al. Improved antioxidant
Nutrition in Pediatrics. Hamilton, London: BC Decker Inc; and fatty acid status of patients with cystic fibrosis after anti-
2003:671–685. oxidant supplementation is linked to improved lung function.
8. American Academy of Pediatrics, Committee on Nutrition. Am J Clin Nutr. 2003;77:150–159.
Kleinman RE, ed. Pediatric Nutrition Handbook. 6th ed. Elk 24. Horwitt MK, Harvey CC, Dahm CH Jr, Searcy MT. Rela-
Grove Village, IL: The American Academy of Pediatrics; tionship between tocopherol and serum lipid levels for
2009. determination of nutritional adequacy. Ann NY Acd Sci.
9. Konstan MW, Butler SM, Wohl MEB, et al. Growth and 1972;203:223–236.
nutritional indexes in early life predict pulmonary function in 25. Huang SH, Schall JI, Zemel BS, Stallings VA. Vitamin E status
cystic fibrosis. J Pediatr. 2003;142:624–630. in children with cystic fibrosis and pancreatic insufficiency. J
10. Stallings VA, Tomezsko JL, Schall JI, et al. Adolescent devel- Pediatr. 2006;148:556–559.
opment and energy expenditure in females with CF. Clin Nutr. 26. Green D, Carson K, Leonard A, et al. Current treatment
2005;24:737–745. recommendations for correcting vitamin D deficiency in
11. Trabulsi J, Ittenbach RF, Schall JI, et al. Evaluation of formulas pediatric patients with cystic fibrosis are inadequate. J Pediatr.
for calculating total energy requirements of preadolescent chil- 2008;153:554–559.
dren with cystic fibrosis. Am J Clin Nutr. 2007;85:144–151. 27. Beker LT, Ahrens RA, Fink RD, et al. Effect of vitamin K1
12. Stallings VA, Stark LJ, Robinson KA, Feranchk AP, Quinton supplementation on vitamin K status in cystic fibrosis patients.
H; Clinical Practice Guidelines in Growth and Nutrition J Pediatr Gastroenterol Nutr. 1997;24:512–517.
Subcommittee (Ad Hoc Working Group). Evidence-based 28. Wilson DC, Rashid M, Durie PR, et al. Treatment of vitamin K
practice recommendations for nutrition-related manage- deficiency in cystic fibrosis: effectiveness of a daily fat-soluble
ment of children and adults with cystic fibrosis and pancreatic vitamin combination. J Pediatr. 2001;138:851.
insufficiency: results of a systematic review. J Am Diet Assoc. 29. Conway SP, Wolfe SP, Brownlee KG, et al. Vitamin K
2008;108:832–839. status among children with cystic fibrosis and its relation-
13. Borowitz D, Baker RD, Stallings V. Consensus report on ship to bone mineral density and bone turnover. Pediatrics.
nutrition for pediatric patients with cystic fibrosis. J Pediatr 2005;115:1325–1331.
Gastroenterol Nutr. 2002;35:246–259. 30. McCabe H. Riboflavin deficiency in cystic fibrosis: three case
14. Australasian Clinical Practice Guidelines for Nutrition and reports. J Hum Nutr Dietet. 2001;14:365–370.
Cystic Fibrosis, 2005. www.cysticfibrosis.org.au/pdf/CF_ 31. Kriemler S, Wilk B, Schurer W, Wilson W, Bar-Or O.
Nutrition_Guidelines.pdf. Accessed December 2008. Preventing dehydration in children with cystic fibrosis who
15. Maqbool A, Schall JI, Garcia-Espana JF, et al. Serum linoleic exercise in the heat. Med Sci Sports Exerc. 1993;31:774–779.
acid status as a clinical indicator of essential fatty acid status 32. Weiss G, Goodnough LT. Anemia of chronic disease. N Engl J
in children with cystic fibrosis. J Pediatr Gastroenterol Nutr. Med. 2005; 352:1011–1023.
2008;47(5):635–644. 33. vonVigier RO, Truttmann AC, Zindler-Schmocker K, et
16. Gottschlich MM. Pulmonary disease. In: Gottschlich MM. al. Aminoglycosides and renal magnesium homeostasis in
The Science and Practice of Nutrition Support: A Core-Based humans. Nephrol Dial Transplan. 2000;15:822–826.
Curriculum. Dubuque, IA: Kendall/Hunt Publishing Co: 34. Powers SW, Byars KC, Mitchell MJ, Patton SR, Schindler T,
2001:501–516. Zeller MH. A randomized pilot study of behavioral treatment
17. Borowitz D, Robinson KA, Rosenfeld M, et al. Management of to increase caloric intake in toddlers with cystic fibrosis. Chil-
infants diagnosed with cystic fibrosis: A Cystic Fibrosis Foun- dren’s Health Care. 2003;32(4):297–311.
dation workshop report. J Pediatr. Accepted for publication. 35. Erksine JM, Lingard C, Sontag M. Update on enteral nutrition
18. Lancellotti L, D’Orazio C, Mastella G, Lippi U. Deficiency of support for cystic fibrosis. Nutr Clin Pract. 2007;22:223–232.
vitamins E and A in cystic fibrosis is independent of pancreatic 36. Abbott J, Conway S, Etherington C, et al. Perceived body
function and current enzyme and vitamin supplementation. image and eating behavior in young adults with cystic fibrosis
Eur J Pediatr. 1996;155:281–285. and their healthy peers. J Behav Med. 2000;23:501–517.

37. Gilchrist FJ, Lenney W. Distorted body image and anorexia 46. Mascarenhas MR. Treatment of gastrointestinal prob-
complicating cystic fibrosis in an adolescent. J Cystic Fibros. lems in cystic fibrosis. Curr Trea Options Gastroenterol.
2008;7(5):437–439. 2003;6(5):427–441.
38. Littlewood JM. The historical development of nutritional and 47. Fridge JL, Conrad C, Gerson L, Cox K. Risk factors for small
dietetic management of cystic fibrosis. Based on a paper deliv- bowel bacterial overgrowth in cystic fibrosis. J Pediatr Gastro-
ered at the XIIIth International Cystic Fibrosis Congress. enterol Nutr. 2007;44(2):212–218.
Stockholm, Sweden; June 2000. Available from http://www. 48. Rajiah P. Bronchopulmonary dysplasia [emedicine website].
cysticfibrosismedicine.com. June 9, 2006. Available at http://emedicine.medscape.com/
39. Borowitz DS, Grand RJ, Drurie PR, et al. Use of pancreatic article/406564. Accessed December 2008.
enzyme supplements for patients with cystic fibrosis in the 49. Cox JH. Bronchopulmonary dysplasia. In: Groh-Wargo S,
context of fibrosing colonopathy. J Pediatr. 1995;127(68):1–4. Thompson M, Cox JH, eds. Nutritional Care for High-Risk
40. Crist W, McDonnell P, Beck M, Gillespie CT, Barrett P, Newborns. Chicago, IL: Precept Press Inc; 2000.
Mathews J. Behavior at mealtimes and the young child with 50. Morris MJ. Asthma [emedicine website]. July 10, 2008. Avail-
cystic fibrosis. J Dev Behav Pediatr. 1994;15(3):157–161. able at http://emedicine.medscape.com/article/29630.
41. Birch LL, Fischer JA. Appetite and eating behavior in children. Accessed December 2008.
Pediatr Clin North Am. 1995;42(4):931–953. 51. Sly PD. Asthma: Disease mechanisms and cell biology. In:
42. Henderson RC, Spector BB. Kyphosis and fractures in Taussig LM, Landau LI, eds. Pediatric Respiratory Medicine.
children and young adults in cystic fibrosis. J Pediatr. 2nd ed. Mosby Elsevier; 2008;791–804.
1994;25(2):208–212. 52. Landau LI, Martinez FD. Asthma: Treatment. In Pedi-
43. Moran A, Hardin D, Rodman D, et al. Diagnosis, screening atric Respiratory Medicine. 2nd ed. Mosby Elsevier;
and management of cystic fibrosis related diabetes mellitus: 2008:829–844.
a consensus conference report. Diabetes Res Clinical Practice. 53. Sithole F, Douwes J, Burstyn I, et al. Body mass index in child-
1999;45:61–73. hood: a linear association. Asthma. 2008;45(6):473–477.
44. O’Riordan S, Robinson P, Donaghue KC, Moran A. Manage- 54. Queen Samour P, King K. Pulmonary diseases. In: Queen
ment of cystic fibrosis-related diabetes. Pediatr Diabetes. Samour P, King K. Handbook of Pediatric Nutrition. 3rd ed.
2008;9(part I):338–344. Sudbury, MA: Jones and Bartlett Publication;2005:307–349.
45. Thiou TG, Cahill BC. Pediatric lung transplantation for cystic
fibrosis. Transplantation. 2008;86(5):636–637.

29
Organ Transplantation
Anita Nucci, PhD, RD, LD, Sharon Strohm, MBA, RD, LDN, Neelam Katyal, MS, RD, LDN, and Beth Lytle, RD, LDN

Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 337 1. Describe the indications for pediatric intestine, liver,
Indications for Organ Transplantation . . . . . . . . . . . . . . . 338 kidney, heart, and lung transplantation.
2. Describe the key nutrition factors that should be exam-
Nutrition Assessment Before Transplant . . . . . . . . . . . . . 339
Anthropometric Assessment ined prior to solid organ transplantation in children.
Physical Examination 3. Explain the posttransplant nutrition management
Biochemical Tests issues related to each of the following solid organs:
Macro- and Micronutrient Requirements intestine, liver, kidney, heart, and lung.
Feeding History 4. State the current outcomes, including morbidity and
Nutrition Management After Transplantation . . . . . . . . . 340 mortality, of childhood organ transplantation.
Intestine
Liver
Kidney
Introduction
Heart Transplantation of organs such as the liver, kidney, and
Lung heart has been performed successfully in children for
Food Safety. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 345 several decades and comprises 30%, 45%, and 16% of all
Current Status of Organ Transplantation in Children . . . 346 pediatric transplants, respectively.1 The number of intestinal
transplants performed annually has increased considerably
over the last 20 years and reductions in both morbidity
and mortality have been observed. However, neither the
number of children receiving a lung transplant (~2% of
all transplants in children) nor the survival rate after lung
transplantation has changed in the last decade.1
Despite differences between children and adults in the
causes of organ failure that result in organ transplantation,
and response to and complications associated with immu-
nosuppression, graft survival rates are similar.1 Advances
in surgical techniques and the emergence of tacrolimus
as the primary therapeutic immunosuppressive agent in
organ transplantation has improved survival.1–3 Even with
these improvements, postoperative nutrition management
remains challenging for some organ transplant recipients
as complications may result in the need for modifications
in nutrition therapy. Coordinated interdisciplinary team
337
management of the pediatric transplant patient is necessary ascites. Growth failure is also common.1 Approximately half
to address the many issues that may arise, including compli- of pediatric liver transplant recipients receive a standard
ance with medication and nutrition regimens. Long-term orthotopic liver transplant with a whole organ. Younger
outcomes such as adequate growth and development and children more often receive a split-liver transplant from a
improved quality of life are still being examined. deceased donor or a reduced size graft from a deceased or
living donor.
Indications for Organ Transplantation Kidney transplant is the most common of solid organ
The diagnoses that lead to the majority of intestine, liver, transplants. It is a reasonably safe and cost-effective treat-
kidney, heart, and lung transplants in children are shown ment for end-stage renal disease (ESRD). Optimal nutrition
in Table 29-1.1 Children with irreversible intestinal failure status prior to transplant correlates favorably with posttrans-
may be considered as candidates for intestinal transplanta- plant outcomes. ESRD in infants and young children is most
tion. Patients are considered to have intestinal failure when commonly due to congenital anomalies. Forty-five percent
fluid, electrolyte, and nutrition status cannot be maintained is related to renal hypoplasia or dysplasia, obstructive or
without parenteral nutrition (PN) and this dependence on reflux uropathy due to posterior urethral valves, agenesis
PN has led to complications that include catheter infections, or abdominal muscular defects (prune belly syndrome), or
sepsis, loss of venous access, cholestatic liver disease, and pyelonephritis. Renal failure in older children is generally
in some instances, liver failure.4,5 The initial evaluation of caused by acquired renal disease, known as glomerulone-
potential transplant candidates includes determination of phritis. In infants with ESRD, early transplantation should
venous access, functional status of the intestine (including be considered to avoid risks that can develop from chronic
motility studies), length of the intestine, degree of liver uremia and dialysis.6 In patients who are awaiting a renal
damage from PN, and the involvement of other organs transplant, there is a higher mortality rate for those who are
in the disease. This information helps the medical team on chronic dialysis than those who are not. Children with
to identify which type of allograft the patient will need. renal disease may receive a kidney transplant prior to the
Allograft options include an isolated small intestine, liver/ time when the disease becomes end-stage. Complications
small intestine, or a multivisceral graft (liver, stomach, from chronic renal insufficiency include failure to thrive,
duodenum-pancreas, and small bowel). delayed psychomotor development, hypervolemia, hyper-
kalemia, and metabolic bone disease. Children who have
Table 29-1 Diagnoses That Lead to the Majority of Intestine, Liver, Kidney, received a kidney transplant have improved survival as well
Heart, and Lung Transplants in Children as improved rehabilitation compared to children on chronic
Organ Diagnoses dialysis.7
Intestine Gastroschisis The majority of children undergoing orthotopic heart
Midgut volvulus transplantation have congenital heart disease. While
Necrotizing enterocolitis end-stage cardiomyopathy and congenital heart disease
Intestinal pseudoobstruction with ventricular failure are the primary reasons for trans-
Liver Biliary atresia plantation,1 a subset of children are transplanted due to
Acute hepatic necrosis protein-losing enteropathy (PLE) after a Fontan procedure.
Metabolic disease PLE eventually results in low serum blood protein with
Kidney Aplasia/hypoplasia/dysplasia subsequent ascites and edema as a result of the inability to
Obstructive uropathy maintain fluid within the vascular space of the abdomen
Focal segmental glomerular sclerosis and peripheral tissues, respectively. Other symptoms such
Heart Congenital disease
as diarrhea and malnutrition may also be present.
Cardiomyopathies
The primary reason for lung transplantation, particu-
Lung Cystic fibrosis
larly in children over the age of 1 year, is cystic fibrosis (CF)
Congenital heart disease (primarily those < 1 year of age)
followed by idiopathic pulmonary arterial hypertension.
Primary pulmonary hypertension
Heart-lung transplantation has become less common in
Liver transplantation is the only therapy available for recent years due in part to the decreased availability of both
children with end-stage liver disease. Complications while organs with the increased use of isolated heart transplants.
awaiting liver transplantation may include gastrointes- Additional reasons include improved surgical technique
tinal bleeding and encephalopathy, jaundice, pruritus, and for isolated lung transplantation and the recognition that

ORGAN TRANSPLANTATION 339
heart-lung transplants are not necessary for children with Physical Examination
these disorders. It is, however, indicated in situations where Along with anthropometric measurement, a child should
end-stage lung disease is coupled with severe dysfunction of also be given a physical examination. This preliminary look
the left ventricle.8 may then lead to more detailed evaluation, if necessary. Hair
that is sparse or easily breakable may indicate malnutrition.
Nutrition Assessment Before Transplant Dry skin may be a sign of vitamin A or folic acid deficiency
and skeletal changes may point to problems with vitamin D
Anthropometric Assessment or calcium metabolism.
A thorough nutrition assessment pretransplant is critical
to help maximize a child’s nutrition status and increase the Biochemical Tests
chance of a successful outcome after transplant. Anthropo- Monitoring of laboratory tests helps the clinician to adjust
metric measurement in children is a valuable tool because it the provision of nutrients and electrolytes in the diet,
is easily obtained and age-specific standards are available. enteral feedings, intravenous replacement fluids, and/or PN
Growth measures should be plotted and followed over time both pre- and posttransplant. Table 29-2 shows the basic
for all transplant candidates. These include weight, length biochemical tests that are often monitored before transplant
or height, weight for length or height, and occipital head by type of solid organ.9–13
circumference (if < 3 years of age). If the patient is > 2 years
of age, body mass index (BMI) should also be calculated and Macro- and Micronutrient Requirements
monitored. Adjustments in energy intake should be made to Calorie requirements for children on oral or enteral nutri-
maintain growth velocity, unless contraindicated due to the tion (EN) are usually assessed based on the dietary reference
child’s condition. Measurement of triceps skinfold thick- intakes (DRIs) for age with modifications made to maintain
ness and mid-arm circumference may also be followed. or accelerate growth and development.14 Indirect calorim-
However, it is important to use appropriate instruments, etry remains the best and most accurate way to assess basal
the same observer, and serial measurements to interpret metabolic requirements. However, this option is often not
these results. practical to perform, or it may produce unreliable results
Table 29-2 Biochemical Tests Monitored Before Transplant by Type of Solid Organ9–13
Biochemical Tests Intestine Liver Kidney Heart Lung
CBC with platelets X X X X X
PT/PTT X X X
Electrolytes X X X X X
CO2 X X
BUN and creatinine X X X X X
Calcium, phosphorous,
X X X X X
magnesium
Glucose X X X
Liver function tests X X X X
Alkaline phosphatase X X X
Amylase, lipase X
Albumin X X X X X
Triglyceride X X X
Vitamins A A A
E E E
D (25 and 1,25 OH) D (25-OH) if no renal impairment D (25-OH)
B12 D (1,25 OH) if renal impairment
RBC folate
Minerals Zn
Cu
Se
Mn
Other Carnitine PTH Glycosylated hemoglobin

if a child is mechanically ventilated and there are multiple weight, and growth status as well as pretransplant nutrition
air leaks. For children on both EN and PN, calorie require- state, ventilation status, wound healing, and the presence
ments are usually estimated at 5% to 10% less than the or absence of sepsis and rejection. Caloric requirements
estimate for oral/enteral intake alone. Calorie requirements may range from 70% to 120% of estimated requirements.
in those dependent on PN may be even lower. Overfeeding, Protein is generally provided at 150% of the estimated nutri-
particularly for those receiving PN, may enhance the tion need and may be adjusted if renal or liver dysfunction
onset of cholestatic liver disease in children with intestinal occurs.18 Additional zinc may be required in addition to any
failure.15 Malnutrition, if present, should be corrected if other micronutrient that was previously deficient.18
possible prior to transplant as it places the recipient at an
increased risk of infection, impaired wound healing, and Initial Enteral/Parenteral Nutrition Support
extended rehabilitation after transplant. Assessment of A continuous PN solution should be initiated in the early
macro- and micronutrient intake is needed to determine postoperative period. The length of time that the initial
need for supplementation or need to obtain nutrition lab nutrition support will need to be provided, or subsequently
values. Stool or ostomy output should be assessed to deter- resumed after discontinuation, depends upon the child’s
mine if stool studies are warranted or further nutrition lab ability to tolerate enteral feedings as well as the development
studies are needed or if medications should be considered. of complications (eg, rejection, sepsis, and pancreatitis). The
Protein requirements are generally estimated based volume and nutrient content of the solution should be deter-
on the DRI for age.16 Adjustments are made based on the mined by the child’s renal and cardiopulmonary function
child’s liver and renal function. and biochemical indices. Measures such as serum elec-
trolytes, glucose, blood urea nitrogen (BUN), creatinine,
Feeding History triglyceride, albumin, prothrombin time (PT) and partial
A complete nutrition assessment should also include a thromboplastin time (PTT), platelets, and liver function
history of enteral feeding tolerance and current eating tests should be monitored regularly to assess organ func-
habits. Children with chronic diseases have often tried tion and the need to modify the PN or intravenous (IV)
many different types of infant and enteral formulas before fluid solutions. An IV fluid solution of normal saline or
choosing the most tolerated option. It is important to note Lactated Ringer’s is provided immediately posttransplant
the type of formula and route and the percentage of calories to maintain fluid and electrolyte balance as well as replace
that are contributing to the child’s total calorie intake when ileostomy and gastric fluid losses.
providing both EN and PN. Upon the presence of ileostomy output or other evidence
Infants and children who receive long-term enteral of bowel function, enteral feedings should be started
feedings are also at risk for oral aversion due to the absence (generally on postoperative day 3 or 4). Feedings should
of oral feeding.9 Normal feeding and swallowing develop- be initiated continuously at a small volume and advanced
ment may have been missed. For children who can swallow, by small increments depending upon stoma output and
oral feeding of small amounts of varied food tastes and abdominal status. The choice of a starting feeding formula
textures is encouraged. Maintenance of oral stimulation as well as the route of administration (gastrostomy versus
may help in the posttransplant period when the patient is jejunostomy) varies from center to center. If stoma output
transitioning from enteral to oral feedings. Children with increases, formula advancement should be paused and fiber
oral aversion or other feeding issues should be referred to a supplements and/or antidiarrheal agents may be provided.
feeding clinic as soon as possible.17 A Video Feeding Study In addition, formula volume may also need to be reduced
may be needed to evaluate the safety of the child to take oral and fluid replacement increased. If a surgical jejunostomy
fluids and solids. is placed during surgery then feedings should be transi-
tioned from a jejunostomy to gastrostomy tube once the
Nutrition Management After Transplantation goal volume is reached.18
An oral diet of clear liquids may be initiated once
Intestine the child has been extubated and enteral tube feedings
have been initiated and tolerated. The oral diet should be
Nutrition Requirements advanced as tolerated but exclude foods high in simple
Protein and calorie requirements of the post-intestinal pedi- carbohydrates to control osmotic diarrhea. Some children
atric transplant patient will vary based on the child’s age, may also be sensitive to lactose-containing or high-fat

foods. As oral intake and absorption improves, continuous be made with a fecal fat test. Pancreatic enzyme therapy
enteral feedings should be cycled to overnight feedings in may be of benefit in patients with a quantitative fecal fat
an attempt to improve daytime oral intake. Children who > 20%.21
are orally aversive from years of dependency on PN may Growth and development should be monitored closely
require outpatient feeding therapy or an inpatient feeding after transplant. Studies have shown improved growth
program. velocity in recent years.22,23 Caloric requirements should be
based on growth as well as activity and absorption levels.
Advancement of Enteral/Oral Feeding and Factors that may affect growth include episodes of rejec-
Weaning of Parenteral Nutrition tion that necessitate corticosteroid usage and sepsis events
PN weaning should begin when the child is medically stable. that result in reduction or discontinuation of enteral/oral
PN should be gradually reduced by 2- to 4-hour increments feedings.
with a goal of a 12-hour infusion. Glucose levels should be
monitored regularly during the weaning process. Liver
Nutrition Management of Complications Nutrition Requirements

Immunosuppressive therapy posttransplant may result in Postoperative nutrition requirements for liver transplant
complications including hyperglycemia, hyperkalemia, recipients should be designed to provide sufficient calo-
hypertension, hypomagnesemia, and hyperlipidemia, ries to minimize catabolism and prevent complications
all of which may require changes in nutrition therapy. from pretransplant nutrition issues. Biochemical param-
Tacrolimus has been shown to cause hyperkalemia and eters should be monitored and nutrition therapy adjusted
hypomagnesemia.19 Potassium intake must be carefully as needed.24 A postoperative liver transplant patient may
monitored, and many patients require magnesium supple- require PN if he or she is malnourished, has had complica-
mentation. Corticosteroids are now reserved primarily tions, or if a lengthy recuperation is expected. During the
for rejection episodes but when used can cause hypergly- immediate postoperative period, PN should be infused
cemia. Insulin therapy may be necessary in the short term continuously.14 Guidelines for initiating postoperative PN
to control blood glucose levels. Corticosteroids and other are shown in Table 29-3.18,24,25
immunosuppressive drugs may also place patients at risk for A tube feeding may provide total enteral nutrition or be
hyperlipidemia. used in conjunction with the oral route if intake is subop-
Chylous ascites can be a complication post-intestinal timal. Breast milk is always preferred, if available. An intact
transplant due to lymphatic ducts being severed. Giving protein, age-appropriate formula should be used to start,
formula containing medium-chain triglyceride (MCT) with a change to a hydrolyzed protein or a free amino-acid
oil, which is water soluble and does not rely on this source hypoallergenic formula if an intolerance should occur. The
of transportation, will assist in the prevention of chylous caloric density of formulas may need to be manipulated
ascites. Should it occur, PN may be the primary or single depending upon fluid restrictions and caloric require-
source of nutrition until resolved. EN and an oral diet ments. Initially the tube feeding should run continuously
containing long-chain triglycerides (LCTs) can be slowly until the oral diet is advanced. As the oral diet is advancing,
reintroduced as tolerated. nocturnal enteral feedings or daytime bolus feedings may
Food allergies are not uncommon in children post-intes- need to be considered to support nutrition requirements. In
tinal transplant. Symptoms include increased stool output, addition, a daily multivitamin supplement for age should be
abdominal distention or pain, abdominal cramping, weight provided.24 The posttransplant oral diet may be described
loss, and failure to thrive.18 Milk-protein, wheat, peanuts, as a healthy diet for age with careful consideration of the
and egg allergies are the most commonly reported.20 Diag- current Food Pyramid as well as the 2005 Dietary Guidelines
nosis may be made by tissue eosinophilia on gastrointestinal for Americans.26,27 The protein, fat, and carbohydrate content
biopsy, a serum radioallergosorbent test (RAST®), or serum of the diet should follow these guidelines with additional
IgE. Generally, foods reported as a Class 3 or 4 allergen after consideration given for complications such as renal impair-
a RAST® should be restricted from the child’s diet.18 Some ment, hypertension, hyperkalemia, and diabetes mellitus.
intestinal transplant patients also experience fat malab- Calcium should be supplemented if intake is insufficient.
sorption. Symptoms include an increased stool output, oily
stool, weight loss, or abdominal cramping. Diagnosis may

Table 29-3 Guidelines for Initiating Parenteral Nutrition after Liver Transplant18,24,25
Nutrient Guidelines
Calories ■ Avoid overfeeding
■ Initially provide 120%–130% of resting energy expenditure to meet postoperative transplant needs
■ Pre-existing nutrition needs, surgical complications, wound healing, sepsis, and rejection may further necessitate additional calories
Protein ■ Provide 15%–20% of total calories as protein
Infants: 3–3.5 g/kg dry body weight
1–2 years: 2.5–3 g/kg dry body weight
3–13 years: 1.5–2.5 g/kg dry body weight
Adolescents: 1–1.5 g/kg dry body weight
■ Additional consideration should be given to renal function and wound healing
■ Trophamine® (B. Braun, Irvine, CA) is the preferred amino acid source due to its branched chain amino acid content and lower pH
for maximum solubility of calcium and phosphorus (cysteine is added only for children < 1 year of age)
Fat ■ Provide 30% of total calories as fat
■ 20% intravenous fat is preferred for its caloric density
Carbohydrate ■ Provide 50%–55% of total calories as carbohydrate
■ Begin at same concentration as the initial intravenous fluid and advance glucose as tolerated to a maximum of:
Term Infants: 14 mg/kg/min
1–10 years: 11 mg/kg/min
11–18 years: 8.5 mg/kg/min
Multivitamins ■ Provide standard intravenous multivitamin for age
Trace Minerals ■ Provide parenteral trace mineral solution based on weight
■ Provide full amount of trace minerals in patients without liver dysfunction
■ Provide ½ dose trace minerals + full amount of zinc with liver dysfunction secondary to cholestasis
■ Zinc should be supplemented at 1½ times the DRI for age if wound healing is an issue
Fluid ■ Based on weight, renal and cardiopulmonary function
■ Maintenance fluids:
1–10 kg dry body weight: 100 mL/kg/d
10–20 kg dry body weight: 1000 mL + 50 mL/kg for each kg over 10
20–30 kg dry body weight: 1500 mL + 20 mL for each kg over 20
Feeding Disorders calorie goals based on the DRI for height age.9 Those without
Advancement of the oral diet may be challenging in some growth delay may initially consume calories based on the
patients postoperatively. Oral aversion may occur in those DRI for age. Growth delay is common after liver transplant
who required long-term PN, EN, and mechanical venti- due to the nutrition impact of the original disease and use
lation. These patients may require consultation from of corticosteroids. Catch-up growth for weight occurs more
an occupational and/or speech therapist. Patients who rapidly than height.1,28,29 Linear growth and weight should
required special diet restrictions before transplant (eg, be monitored at primary care physician visits, and trans-
protein restriction) may continue to prefer the taste of their plant centers alerted for any change in growth velocity. 30
restricted diet. Temporarily, these patients may continue
their pretransplant medical nutrition enteral formulas until Kidney
they readily incorporate a variety of foods in their diet.
Nutrition Requirements
Growth and Development The nutrition recommendations for kidney transplant
Long-term goals for patients after liver transplant include patients immediately and later after transplant are shown in
nutrition and life-style factors. Optimization of linear Table 29-4. An age-appropriate oral diet can be started once
growth and physical development as well as socialization bowel function has resumed. An enteral tube feeding is
and participation in daily activities are desired. Calorie rarely needed after kidney transplant. However, for patients
requirements will vary with age, activity, and growth rate. who were fed via gastrostomy tube prior to transplant, it
Children who exhibit linear growth impairment will need may be necessary to continue tube feedings and gradually

Table 29-4 Nutrition Recommendations for Pediatric Kidney Transplant Recipients

Nutrient Immediately Posttransplant Later After Transplant
Calories DRI for height-age. May need additional calories if patient is DRI for height-age
underweight prior to transplant
Protein 125%–150% DRI for age DRI for age
Carbohydrates Avoid simple sugars Unrestricted unless obesity is present
Fat 30%–40% of total calories 30%–40% of total calories
Phosphorus May need higher intakes, provide supplements as necessary May need higher intakes, provide supplements as necessary
Calcium Unrestricted Unrestricted
Potassium Unrestricted unless necessary Unrestricted
Sodium Mildly restricted Unrestricted unless hypertension or edema is present
Iron Supplement as indicated by serum values Supplement as indicated by serum values
Fluids Unrestricted Unrestricted
Vitamins DRI. Supplementation usually not necessary unless severely DRI. Supplementation usually not necessary unless severely
malnourished prior to transplant, Vitamin D if indicated malnourished prior to transplant, Vitamin D if indicated
to transition over to oral feeds. Gastrostomy tubes should with anemia after transplant. 34
only be removed after fluid and caloric needs are met Excessive weight gain may result from an increased
orally. 31 PN is also rarely needed after kidney transplant calorie intake secondary to steroid therapy, fewer dietary
unless the patient has acute tubular necrosis, intractable restrictions, and improved feeling of well being as well as a
diarrhea, non-functional gastrointestinal tract, or small lack of exercise. Presence of bone disease may limit physical
bowel obstruction. Volume and nutrients are adjusted activity and decrease energy expenditure. Early counseling
based on urinary output and graft function. Long-term with a dietitian and repeated nutrition interventions are
nutrition goals after kidney transplant include promoting needed to promote a healthy lifestyle and initiate a regular
wound healing, promoting anabolism, preventing infec- exercise regimen. Steroid dosage should be decreased to
tion, promoting adequate growth, minimizing side effects the lowest amount possible without loss of graft function.
of medications, maintaining serum mineral and electrolyte Decreased bone mass, fragility, and fractures are a known
levels within normal limits, and maintaining blood pressure complication after transplant in adults. Alterations in bone
within appropriate limits for age. mass have been found in children and adolescents as well
with the greatest decrease in bone mineral density observed
Nutrition Management of Complications during the first 6 months after transplant. 35 Bone mineral
Hypertension can be caused by fluid overload, immunosup- density studies should be performed on a regular basis for
pressive agents, obesity, and/or a pre-existing condition of all children after transplant. Calcium, phosphorous, and
hypertension. Therapy may include a sodium-restricted vitamin D supplements are prescribed based on the patient’s
diet, diuretics, or hypertensive drugs. Hyperglycemia may intake and serum levels.
be caused by corticosteroid use. Simple sugars should be Adequate growth rate is directly related to age of
eliminated from the diet until glucose levels return to onset of disease and duration of disease and is assessed by
normal. The development of new onset insulin-dependent standard deviation scores or height deficit score (z score).
diabetes has been reported in a small percentage of recipi- Height potential is greatly reduced in children with chronic
ents. 32 Hyperlipidemia resulting from the use of medications kidney disease before age 2 because one-third of growth
(eg, corticosteroids, calcineurin inhibitors, and sirolimus) occurs during the first 2 years of life. Additional factors
as well as malnutrition and obesity should be evaluated and include metabolic acidosis, renal osteodystrophy, and
treated as it can hasten the progression of renal disease. 33 catabolic states associated with infection, corticosteroid
Lipid profiles should be monitored and patients placed on dosage, and renal function after transplant. 36 Newer induc-
a moderate-fat diet with emphasis on healthy fats such as tion protocols may allow steroid-free immunosuppressive
olive oil, fish, and nuts. Anemia is a complication of renal regimens that in turn may prevent obesity, hypertension,
failure but does not always resolve after transplantation. stunted growth, and non-compliance. 37 Use of recombi-
The presence of iron deficiency and dosage of immunosup- nant growth hormones during puberty has been found to
pressant have been identified as causative factors associated be effective in increasing height. 38 Physical adverse effects

such as cushingoid appearance, short stature, scars, obesity, Lung

hirsutism, and gum hyperplasia can cause lower self-esteem
and increased stress in adolescents. This may lead to non- Nutrition Requirements
compliance with medication therapy and an increased risk The post-lung transplant nutrition goals are to provide
of graft rejection. A social worker and child life specialist energy to prevent weight loss, promote healing, and prevent
can provide valuable insight and support in such situations. infection while minimizing gastrointestinal complications
and avoiding drug-nutrient interactions. Calorie needs are
Heart increased due to the body’s effort to fight infection and
promote wound healing. In contrast, the body uses less
Nutrition Requirements energy due to the decreased work of breathing and limited
The nutrition goals for posttransplant pediatric heart trans- activity level immediately posttransplant. Considering this
plant recipients include achieving and maintaining ideal combined effect, calorie requirements are typically 100% to
body weight, limiting sweets and foods high in concen- 120% of the DRI for age.14 Protein needs are elevated due
trated sugar, reducing foods high in fat and cholesterol, and to the healing process after surgery and are two times the
limiting salt.12 Most pediatric heart transplant recipients DRI.16
progress to a full oral diet within 4 days of transplant. 39–42
The exception are those orally aversive infants and children Enteral/Oral Supplementation
who were dependent on EN and/or total parenteral nutri- After transplant, the patient should be advanced to a regular
tion pretransplant. These patients may require additional diet as soon as tolerated. Oral nutrition supplements may
nutrition support while receiving intensive oral rehabilita- be encouraged to maximize energy intake. Initially the
tion therapy. patient may not be able to meet calorie needs from oral
intake because of side effects (ie, nausea and vomiting)
Dietary Modification from immunosuppressive medications. If the patient loses
Alterations in diet may be necessary due to side effects of 10% of his or her admission weight and is not able to meet
medications and immunosuppression therapy. Hyper- caloric needs orally then supplemental tube feeds should be
tension, hyperglycemia, and weight gain are common in recommended. Tube feedings have been shown to be more
posttransplant pediatric heart recipients.12 Lipid abnor- effective than oral intake for weight gain after transplant.46
malities have been reported at 1 year posttransplant.43 The patient often eats orally throughout the day and receives
Calcineurin inhibitors may create these elevated serum nocturnal tube feeds. For patients with CF and pancreatic
lipid levels, and a heart-healthy, low-cholesterol, low-satu- insufficiency, semi-elemental formula may be necessary. If
rated fat diet is recommended. 39 calorie and protein needs are not met by oral diet and/or EN
Osteoporosis is universal among pediatric posttrans- then PN should be initiated.
plant recipients. 39 The combined effects of nutrition status
before transplant along with calcineurin inhibitors and Pancreatic Enzyme Supplements/Vitamin-Mineral
steroids result in decreased calcium absorption and bone Supplementation
formation. Supplemental vitamin D (400–800 International Patients with CF and pancreatic insufficiency will continue
Units) and calcium (1200–1500 mg) are recommended. 39 to have pancreatic disease posttransplant. Pancreatic
In addition, an annual dual-energy x-ray absorptiometry enzyme therapy should resume with all meals and snacks.
(DEXA) scan may be warranted in some cases. There Previous vitamin and mineral supplementation should
are little data on the use of biphosphates, calcitonin, and continue. Patients with CF are at risk of developing high
hormone replacement therapy in the pediatric posttrans- vitamin A and vitamin E serum levels after transplant.
plant population. These levels should be monitored because adjustments are
Pretransplant growth parameters will impact the frequently required.47 Magnesium levels tend to be low after
amount of catch-up growth needed posttransplant.44–45 transplant and supplementation may be necessary.
Infants and children have demonstrated appropriate growth
velocity and weight gain posttransplant. Weight gain with Nutrition Management of Complications
lack of linear catch-up growth is characteristic of the adoles- Common complications after lung transplant that require
cent heart transplant population. 39 nutrition intervention include infection and rejec-
tion, diabetes, osteoporosis, renal complications, and

gastrointestinal complications. Infection and rejection are diet may be necessary based on abnormalities indicated in
significant obstacles that occur after lung transplantation. blood work.
Both problems are related to the immune system. Infec- Distal intestinal obstruction syndrome (DIOS) is a
tion can be a complication from oversuppression while common complication in CF transplant patients, with
rejection is a result of too little suppression. Immunosup- an estimate of 20% incidence in the early posttransplant
pressant drugs are medications given to prevent rejection period. 53 The combination of narcotics for pain manage-
of the transplanted organ and it is a difficult balancing act ment, inadequate intake food and fluid intake, and bed
to determine the correct amount of immunosuppression rest put these patients at extremely high risk of developing
required for each patient.48 Common immunosuppressive problems. Symptoms are characterized by abdominal pain,
medications include tacrolimus, cyclosporin, prednisone, abdominal distention, and vomiting. Some transplant
mycophenolate, rapamycin, and azathioprine. Medication centers give polyethylene glycol lavage solution as routine
doses are measured in the blood and adjustments are deter- care to prevent DIOS after surgery. 53 Recommendations
mined from these levels. Food can alter the absorption of for prevention of DIOS are to monitor bowel movements,
these drugs so it is important that patients take these medi- resume previous pancreatic enzyme regimen, encourage
cations either fasting or with meals on a consistent basis. It is adequate fluid intake, and use stool softeners as needed.
important to note any vomiting or diarrhea because this can Lung transplantation is an accepted treatment option
also influence the drug level. Other medications including for patients with various types of end-stage lung diseases.
antacids, antibiotics, and antifungals can interfere with There is currently a lack of research in the area of post-lung
immunosuppressant levels. Grapefruit, grapefruit juice, or transplant nutrition. Close monitoring of nutrition status is
juice that contains grapefruit juice is discouraged because it essential to improve patient survival. As the success rates
has also been shown to alter levels. improve, so will our understanding of both medical and
Impaired glucose tolerance and diabetes is relatively nutrition aspects of lung transplantation.
common after lung transplantation, especially in patients
with CF. Hyperglycemia is due to the use of high-dose pred- Food Safety
nisone posttransplant and has also been associated with Because most transplant recipients are receiving immuno-
the use of tacrolimus and cyclosporine. It is important to suppressive medications, they are particularly susceptible to
monitor metered blood glucose levels several times per day developing a foodborne illness caused by bacteria and other
and periodically check glycosylated hemoglobin levels. The pathogens that can contaminate food. The major pathogens
recommended treatment consists of diet modification and that can cause foodborne illness and the most common
insulin therapy.49 sources of contamination associated with these pathogens
Bone disease or osteoporosis is a problem generally are shown in Table 29-5. 54 The United States Department
seen in patients with various types of respiratory diseases of Agriculture, Food Safety and Inspection Service recom-
both before and after transplant. 50 Exposure to medications mends the following 4 basic steps to food safety: (1) clean
used after surgery, which includes long-term use of predni- hands and surfaces often as bacteria can be spread from
sone, cyclosporine, and tacrolimus, have all been associated surfaces to food; (2) separate meat, poultry, seafood, and
with bone loss. DEXA scans should be monitored annually eggs from ready-to-eat foods to avoid cross-contamination;
posttransplant to examine changes in bone density over (3) cook foods to proper temperatures; and (4) chill foods
time. Recommendations for management of bone health promptly. In addition, it is important to adhere to the manu-
include maintaining a normal weight, calcium and vitamin facturer “Sell-by” and “Use-by” dates when purchasing and
D supplementation, and routine exercise. 51 consuming perishable foods. When eating out, transplant
Renal function should be monitored closely after trans- recipients should avoid any food that contains uncooked
plant because immunosuppressant drugs used to prevent ingredients and speak to the food preparer to ensure that
rejection can cause renal impairment. Patients with CF are foods have been cooked to a proper minimum internal
at greater risk for renal insufficiency as compared to patients temperature. In general, buffets should be avoided. When
with other respiratory diseases. 52 Adequate amounts of traveling, gel packs should be used to keep food cold (40oF
fluids should be encouraged with alterations in electrolyte or below) as well as insulated containers to keep cooked
imbalances. It is especially important to increase oral fluids food hot (140oF or above). 54
when gastrostomy feeds are being decreased to make up the
difference of fluid loss from the tube feeds. Alterations in

Table 29-5 Major Foodborne Pathogens and Common Sources statistics but also discussions related to the achievement of
Pathogen Sources or return to physical, emotional, and social quality of life. 59
Bacteria Growth and development are important determinants
Campylobacter Raw and uncooked meat, poultry, milk, of quality of life. Impaired growth and development is a
and untreated water complication often experienced by pediatric transplant
Escherichia coli Undercooked or raw beef, contaminated patients. The presence or absence of impaired growth is
produce, raw milk, unpasteurized juices
and ciders affected by the length of illness and graft function, the use
Listeria monocytogenes Unpasteurized dairy products, sliced deli of corticosteroids, and development of infectious complica-
meats, deli-style prepared egg, ham, tions. 59 Quality of life after transplant often depends upon
seafood, and chicken salads the type of organ or organs received. Differences may also
Salmonella Raw and undercooked eggs, undercooked
poultry and meat, unpasteurized dairy
exist in perceived quality of life between the transplant
products or juice, contaminated produce recipient and his or her caregivers. Perceived physical and
Vibrio vulnificus Raw or undercooked fish or shellfish social function after pediatric intestinal transplant was
Viruses reported by recipients to be similar to other school children.
Norovirus Any food or water contaminated by However, their parents felt that their health and physical
someone who is infected with the virus abilities were less than normal.60 Children and adolescents
Protozoa who have had a kidney transplant have reported improved
Cryptosporidium Uncooked or contaminated food or water
quality of life in terms of physical and social well-being
Toxoplasma gondii Raw or undercooked meat or foods;
objects contaminated with cat feces
compared to children on dialysis.61 An early study on the
effect of heart or heart-lung transplantation on quality
of life in children showed improvement of quality of life
Current Status of Organ Transplantation within the early post-operative period.62 In another quality
in Children of life study completed with heart transplant recipients,
Survival rates have continued to improve for both patients adolescents perceived their quality of life and well-being
and organ grafts.1 The 1- and 5-year survival rates for liver as excellent compared to healthy controls.63 Finally, while
and heart transplant recipients are approximately 90% and greater quality of life has been reported after pediatric lung
85%, respectively.1,55 The 5-year survival rate for children transplantation, the development of complications such
who have received a kidney transplant has been reported as infection is more common in children than adults and
at 95%.1,56 A recent report on the current status of pedi- results in reduced perception of quality of life.64 While it
atric intestinal transplantation noted that the 1- and 5-year is difficult to measure quality of life in the pediatric popu-
patient survival rate at centers of excellence has reached lation, interest in the data is rising as life expectancy is
95% and 77%, respectively. 57 Patient survival for children increasing. 59
who have received a lung transplant has remained rela-
tively constant over the past decade with 5-year survival Test Your Knowledge Questions
at 50%. 58 Non-compliance with immunosuppressive treat- 1. Which of the following biochemical complications
ment regimens remains a problem, particularly in the may occur shortly after intestinal transplantation and
adolescent transplant population, and is one factor related require changes in nutrition therapy?
to graft failure.1 A. Hyperkalemia, hypermagnesemia, hyperglycemia,
Improvements with immunosuppressant treatment and hyperlipidemia
therapies and increases in survival rates have enlarged B. Hyperkalemia, hypomagnesemia, hypoglycemia,
the population of pediatric transplant recipients. Inter- and hyperlipidemia
disciplinary team management of the pediatric transplant C. Hyperkalemia, hypomagnesemia, hyperglycemia,
recipient is essential to assist with the complex medical and and hyperlipidemia
psychological issues that can result from chronic disease D. Hyperkalemia and hypermagnesemia
and the complications that can result from immunosuppres- 2. Common nutrition-related complications after kidney
sant therapy after transplant. In addition to medical issues, transplant include:
patients and families also need to adjust to the new life that A. Hyperlipidemia
transplantation has provided. In recent years, reported B. Obesity
outcomes after transplant have included not only survival C. Hyperglycemia
D. All of the above

3. Which of the following supplements are not recom- 14. Food and Nutrition Board, Institute of Medicine. Energy. In:
mended for children with cystic fibrosis and pancreatic Otten JJ, Pitzi Hellwig J, Meyers LD, eds. Dietary Reference
Intakes: The Essential Guide to Nutrient Requirements. Wash-
insufficiency after lung transplantation?
ington, DC: National Academy Press; 2006:625–651.
A. Pancreatic enzymes 15. Jeejeebhoy KN. Management of PN-induced cholestasis.
B. Standard enteral formula Pract Gastroenterol. 2005;24:62–68.
C. Parenteral nutrition 16. Food and Nutrition Board, Institute of Medicine. Protein
D. Vitamins and minerals and amino acids. In: Otten JJ, Pitzi Hellwig J, Meyers LD,
eds. Dietary Reference Intakes: The Essential Guide to Nutrient
Requirements. Washington, DC: National Academy Press;
See p. 487 for answers. 2006:740–772.
17. Byars KC, Burklow KA, Ferguson K, et al. A multicomponent
References behavioral program for oral aversion in children depen-
1. Sudan D, Bacha EA, John E, Bartholomew A. Childhood dent on gastrostomy feedings. J Pediatr Gastroenterol Nutr.
organ transplantation. Pediatr Rev. 2007;28(12):439–452. 2003;37(4):473–480.
2. Todo S, Tzakis A, Abu-Elmagd K, et al. Cadaveric small bowel 18. Phillips SK, McGhee B, Reyes J. Pediatric Liver, Intestine, and
and small bowel-liver transplantation in humans. Transplan- Multivisceral Transplantation: A Manual of Management and
tation. 1992;53(2):369–376. Patient Care. Hudson, OH: Lexi-Comp, Inc; 2003.
3. Grant D, Abu-Elmagd K, Reyes J, et al. 2003 report of the 19. Fung J, Allessiani M, Abu-Elmagd K, et al. Adverse
Intestine Transplant Registry: a new era has dawned. Ann effects associated with the use of FK506. Transplant Proc.
Surg. 2005;241:607–613. 1991;23:3105–3108.
4. Nucci A, Barksdale E, Beserock N, et al. Long-term nutritional 20. Koehler A, Yaworski J, Gardner M, et al. Coordinated interdis-
outcome after pediatric intestinal transplantation. J Pediatr ciplinary management of pediatric intestinal failure: a 2-year
Surg. 2002;37(3):460–463. review. J Pediatr Surg. 2000;35(2):380–385.
5. Kowalski L, Nucci A, Reyes J. Intestinal transplantation. In: 21. Strohm S, Koehler A, Mazariegos G. Nutrition manage-
Rolandelli RH, Bankhead R, Boullata JI, Compher CW, eds. ment in pediatric small bowel transplant. Nutr Clin Prac.
Clinical Nutrition Enteral and Tube Feeding. 4th ed. Philadel- 1999;14:58–63.
phia, PA: Elsevier Saunders; 2005:523–529. 22. Kowalski L, Nucci A, Perez G, Mazariegos G, Sindhi R. Nutri-
6. Khwaja K, Humar A, Najarian J. Kidney transplants for chil- tional outcomes after elimination of routine steroid therapy in
dren under one year of age – A single center experience. Pediatr pediatric intestinal transplantation [abstract]. World Trans-
Transplant. 2003;7(3):163–167. plant Congress; 2006.
7. Bartosh SM. Recipient characteristics: ESRD, chronic renal 23. Lacaille F, Vass N, Sauvat F. Long-term outcome, growth and
failure, glomerulonephritis. In: Fine RN, Webber S, Kelly digestive function in children 2 to 18 years after intestinal
D, Harmon W, Olthoff K, eds. Pediatric Solid Organ Trans- transplantation. Gut. 2008;57:455–461.
plantation. 2nd ed. Malden, MA: Blackwell Publishing; 24. Sutton MM. Pediatric liver transplantation. In: Hasse JM,
2007:146–152. Blue LS, eds. Comprehensive Guide to Transplant Nutrition.
8. MacLaughlin EF. Recipient characteristics: Lung transplan- Chicago, IL: American Dietetic Association; 2002:182–215.
tation, heart-lung transplantation, cystic fibrosis. In: Fine 25. The Nutrition Support Committee. In: Barksdale EM, Nucci
RN, Webber S, Kelly D, Harmon W, Olthoff K, eds. Pediatric A, Yaworski JA. Parenteral Nutrition Manual. 5th ed. Pitts-
Solid Organ Transplantation. 2nd ed. Malden, MA: Blackwell burgh, PA: Children’s Hospital of Pittsburgh; 2003.
Publishing; 2007:314–335. 26. Department of Health and Human Services. My Pyramid Food
9. Strohm S, Reyes J, Koehler A. Pediatric small bowel trans- Guidance System. Washington, DC: United States Department
plantation. In: Hasse JM, Blue LS, eds. Comprehensive Guide of Agriculture; 2005.
to Transplant Nutrition. Chicago, IL: American Dietetic Asso- 27. Department of Health and Human Services. Dietary Guide-
ciation; 2002:216–225. lines for Americans 2005. Washington, DC: United States
10. Sutton MM. Pediatric liver transplantation. In: Hasse JM, Department of Agriculture; 2005.
Blue LS, eds. Comprehensive Guide to Transplant Nutrition. 28. Alonso E. Growth and developmental considerations
Chicago, IL: American Dietetic Association; 2002:182–215. in pediatric liver transplantation. Liver Transplant.
11. Miller D, MacDonald D. Management of pediatric 2008;14:585–591.
patients with chronic kidney disease. Nephrol Nurs J. 29. Burra P, De Bona M. Quality of life following organ transplan-
2006;33(4):415–429. tation. Transpl Int. 2007;20:397–409.
12. Heart Transplant Team, Children’s Hospital of Boston. Pedi- 30. Balistreri W, Welch T, Daniels S. Care of children with solid-
atric heart transplantation: a practical parent guide. http:// organ transplants. In: McMillan J, Geigin RD, DeAngelis C,
www.experiencejournal.com/cardiac/clinic/htbook.shtml. Jones D. Oski’s Pediatrics. 4th ed. New York, NY: Lippincott
Accessed December 7, 2008. Williams & Wilkins; 2006:2606–2608.
13. Fulton JA, McKenna A. Pediatric lung transplantation. In: 31. Wong H, Mylrea K, Manion CA, Bass MI, Feber J, Filler G.
Hasse JM, Blue LS, eds. Comprehensive Guide to Transplant Caregivers attitudes towards gastrostomy removal after renal
Nutrition. Chicago, IL: American Dietetic Association; transplantation. Pediatr Transpl. 2005:9;574–578.
2002:153–171.

32. Furth S, Neu A, Colombian P, Plotwick L, Turner ME, 49. Moran A, Hardin D, Rodman D; and the Consensus
Flvush B. Diabetes as a complication of Tacrolimus (FK506) Committee. Consensus Document Diagnosis, Screening, and
in pediatric renal transplant patients. Pediatr Nephrol. Management of Cystic Fibrosis Related Diabetes Mellitus.
1996;10:64–66. Bethesda, MD: Cystic Fibrosis Foundation. 1999.
33. Saland JM, Ginsberg H, Fisher EA. Dyslipidemia in pediatric 50. Shane E, Papadopoulos A, Staron RB, et al. Bone loss
renal disease: epidemiology, pathophysiology and manage- and fracture after lung transplantation. Transplantation.
ment. Curr Opin Pediatr. 2002:14(2);197–204. 1999;68(2):220–227.
34. Kausman JY, Powell HR, Jones CL. Anemia in pediatric renal 51. Dosanijh A. A review of nutritional problems and the
transplant recipients. Pediatr Nephrol. 2004:19;526–530. cystic fibrosis lung transplant patient. Pediatr Transpl.
35. Feber J, Cochat P, Braillon P. Bone mineral density in 2002;6:388–391.
children after renal transplantation. Pediatr Nephrol. 52. Schindler R, Radke C, Paul K, Frei U. Renal problems after
2000;14:654–657. transplantation in renal patients. Nephrol Dial Transplant.
36. Fine RN. Management of growth retardation in pedi- 2001;16(7):1324–1328.
atric recipients of renal allografts. Nat Clin Pract Nephrol. 53. Gilljam M, Tullis E, Keshavjee S, Hutcheon M. GI complica-
2007;3:318–324. tions after lung transplantation in patients with cystic fibrosis.
37. Ellis D, Shapiro R, Moritz M, et al. Renal transplantation Chest. 2003;123:37–41.
children managed with lymphocyte depleting agents and low- 54. Food Safety and Inspection Service. Food Safety for Transplant
dose maintenance tacrolimus monotherapy. Transplantation. Recipients: A Need-to-Know Guide for Bone Marrow and Solid
2007:83(12);1563–1570. Organ Transplant Recipients. Washington, DC: United States
38. Hokken-Koelega AC, Stijnen T, de Ridder MA, et al. Growth Department of Agriculture. 2006.
hormone treatment in growth-retarded adolescents after renal 55. North American Pediatric Renal Transplant Cooperative Study
transplantation. Lancet. 1994;343:1313–1317. (NAPRTCS) 2006 Annual Report. Rockville, MD; 2006.
39. Blume E. Current status of heart transplantation in children: 56. Fricker FJ, Addonizio L, Bernstein D, et al. Heart trans-
Update 2003. Pediatr Clin North Am. 2003;50:1384. plantation in children: indications. Report of the Ad Hoc
40. Wagner K, Webber SA, Kurland G, et al. New onset diabetes Sub-committee of the Pediatric Committee of the Amer-
mellitus in pediatric thoracic organ recipients under ican Society of Transplantation (AST). Pediatr Transplant.
tacrolimus based immunosuppression. J Heart Lung Trans- 1999;3:333–342.
plant. 1997;16:275–282. 57. Mazariegos GV, Squires RH, Sindhi RK. Current perspectives
41. Chin D, Rosenthal D, Bernstein D. Lipoprotein abnormalities on pediatric intestinal transplantation. Curr Gastroenterol Rep.
are highly prevalent in pediatric heart transplant recipients. 2009;11:226–233.
Pediatr Transpl. 2000;4:193–199. 58. Marshall HI, Aurora P, Christie JD, et al. Registry of the Inter-
42. Penson MG, Winter WE, Fricker FJ, et al. Tacrolimus-based national Society of Heart and Lung Transplantation. J Heart
triple drug immunosuppression minimizes serum lipid eleva- Lung Transplant. 2008;27(9):937–983.
tions in pediatric cardiac transplant recipients. J Heart Lung 59. Burra P, De Bona M. Quality of life following organ transplan-
Transplant. 1999;18:707–713. tation. Transpl Int. 2007;20:397–409.
43. Pahl E. Heart transplantation: Literature review 2005-2006. 60. Sudan D, Horslen S, Botha J, et al. Quality of life after pedi-
Pediatr Transpl. 2007;11:709–715. atric intestinal transplantation: the perception of pediatric
44. Canter C, Shaddy R, Bernstein D, et al. Indications for recipients and their parents. Am J Transplant. 2004;4:407.
heart transplantation in pediatric heart disease. Circulation. 61. Rubik J, Grenda R, Jakubowska-Winecka A, Dabrowska A.
2007;115:666–667. Quality of life in children and adolescents with end-stage
45. Cohen A, Addonizio LF, Softness B, et al. Growth and skel- renal disease treated with dialysis and kidney transplantation.
etal maturation after pediatric heart transplantation. Pediatr Pol Merkuriusz Lek. 2000;8:280.
Transpl. 2004;8:126–135. 62. Wray J, Radley-Smith R, Yacoub M. Effect of cardiac or heart-
46. Fulton JA, Orenstein DM, Koehler AN, Kurland G. Nutrition lung transplantation on the quality of life of the paediatric
in pediatric double lung transplant patient with cystic fibrosis. patient. Qual Life Res. 1992;1:41–46.
NCP. 1995;10:67–72. 63. Pollock-BarZiv SM, Anthony SJ, Niedra R, Dipchand AI,
47. Robert R, Durie P, Verjee Z, Chaparro C, Corey M, Tullis West LJ. Quality of life and function following cardiac trans-
E. Increased vitamin A and E levels in adult cystic fibrosis plantation in adolescents. Transplant Proc. 2003;35:2468.
patients after lung transplantation. Transplantation. 64. Mallory GB, Spray TL. Pediatric lung transplantation. Eur
2005;79(5):613–615. Respir J. 2004;24:839.
48. Visner GA, Goldfarb SB. Posttransplant monitoring of
pediatric lung transplant recipients. Curr Opin Pediatr.
2007;19:321–326.

30
Oncology, Hematopoietic Transplant,
and Survivorship
Nancy Sacks, MS, RD, LDN, Elizabeth Wallace, RD, CNSC, LDN, Seema Desai, MS, RD, LDN, CNSD, Vinod K. Prasad, MD, MRCP
(London), David Henry, MS, BCOP, Virginia Guzikowski, MSN, CRNP, Liesje Nieman Carney, RD, CNSD, LDN, Beth Bogucki Wright, MS,
RD, CSP, LDN, and Susan Rheingold, MD

General Oncology Overview. . . . . . . . . . . . . . . . . . . . . . . . 349 1. Evaluate the nutrition status of the pediatric oncology
Hematopoietic Transplant. . . . . . . . . . . . . . . . . . . . . . . . . 354 patient and determine the caloric, macronutrient, and
micronutrient needs of the patient.
Late Effects of Treatment for
Survivors of Childhood Cancer . . . . . . . . . . . . . . . . . . . . . 362 2. Identify the common nutrition issues for children
undergoing hematopoietic stem cell transplantation.
Appendix 30-1: Algorithm For Nutritional
Intervention In The Pediatric Oncology Patient. . . . . . . . 365 3. Choose the most effective mode of nutrition support
and monitor its tolerance in the pediatric oncology
Appendix 30-2: Algorithm for Nutritional Intervention
and Categories of Nutritional Status in the Pediatric population.
Oncology Patient — References and Resources . . . . . . . 366 4. Identify the nutrition and activity goals for survivors of
Appendix 30-3: Categories of Nutritional Status childhood cancer.
for the Pediatric Oncology Patient. . . . . . . . . . . . . . . . . . 367 5. Become more knowledgeable regarding types of medi-
Appendix 30-4: Gastrointestinal Supportive cation used to alleviate gastrointestinal problems.
Care Medications . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 368
General Oncology Overview
Pediatric cancer is the leading cause of death by disease in
children under the age of 15 years. It is estimated that 1 in
475 children will develop cancer by age 15 years, accounting
for more than 13,000 new cases of pediatric cancer a year
in the United States (ages 0–19 years). As a result of multi-
modal therapy, the 5-year survival has improved from less
than 50% in the 1970s to almost 80% today. Although the
cure rate varies, it is estimated that by the year 2010 that
1 out of 250 young adults will be a survivor of childhood
cancer.1 The type of cancer and treatments utilized adversely
impact nutrition status of the child with cancer during and
following therapy; therefore, it is essential to maximize
nutrition status at diagnosis, throughout therapy, and after.
Nutrition Aspects: Diagnoses and Malnutrition

The risk of malnutrition is a significant concern during
pediatric cancer treatment. Due to the increased nutrition
needs for growth and development during childhood, and
349
the metabolic stress of cancer, malnutrition is a frequent Radiation Therapy

treatment complication. Between 6% and 50% of children Radiation therapy is a treatment used independently or in
will present with acute malnutrition at diagnosis.2–5 Higher conjunction with surgery and chemotherapy. Radiation
incidence of malnutrition may be related to delay in diag- destroys the genetic material within the cell, thereby killing
nosis, extent of disease, and location of the tumor. During the malignant cell.14 Complications arise from radiation
the course of therapy, malnutrition is observed in 8% to therapy because healthy cells in the radiation field are inevi-
32% of children.6 Higher incidences of malnutrition have a tably damaged during treatment. The area most susceptible
direct correlation with more intensive courses of treatment, to nutrition effects of radiation is the GI tract.15 Mucosa
often including transplant. Younger children may be at from the mouth to the anus can be damaged causing malab-
particularly higher risk of acute malnutrition due to limited sorption of nutrients, diarrhea, and severe pain both with
nutrient stores and increased demand for growth. and without oral intake. In adults, the effect on appetite is
Nutrient needs may not be met due to increased meta- dependent on the involved radiation field, total dose of radi-
bolic demands, depleted stores, or inadequate intake.7,8 ation, and number of fractions received.16 Acute side effects
Inadequate nutritional intake is common during therapy, of radiation may begin as early as 1 week from the initia-
which can result in acute and long-term malnutrition. tion of radiotherapy, and last several weeks after the final
Nutrition status should not be assessed by weight or appear- fraction. Patients receiving cranial radiation can develop
ance alone as large tumor burdens may disguise the loss of postradiation somnolence syndrome 6 to 8 weeks after
adipose and lean muscle mass, thereby making it difficult to completion of radiation, causing severe lethargy and flu-like
assess nutrition status at diagnosis. symptoms. Expected side effects based upon the location of
Certain diagnoses are more likely to result in nutri- the radiation field are found in Table 30-1.
tion problems due to altered metabolism, physiological
changes, and effects of antineoplastic therapy.9 Children Table 30-1 Nutrition-Related Side Effects of Radiation Therapy
with sarcomas, neuroblastoma, and brain tumors typically Location Adverse Reaction
present at diagnosis with protein depletion and weight Central Nervous System Nausea/Vomiting
loss.10,11 Other diagnoses that are at high risk for nutrition Brain and Spinal Cord Fatigue
Loss of Appetite
complications include advanced stage Wilms’ tumor and Alterations in Pituitary Functions
acute myelogenous leukemia (AML). Growth Failure
Head and Neck Xerostomia
Multimodal Treatment and the Effects on Nutrition Tongue, Larynx, Pharynx Sore Mouth/Throat
Oropharynx, Tonsils, Dysphagia
Salivary Glands Mucositis
Surgery Altered Taste and Smell
Surgical intervention is necessary for most solid tumors. Fatigue
Nausea, vomiting, fatigue, altered bowel motility, and Loss of Appetite
Abdomen and Pelvis Nausea/Vomiting
decreased appetite pre- and postoperative are complications GI Tract, Reproductive Organs, Diarrhea
that can impact the ability to meet nutrient requirements. Rectum, Colon, Testicles Abdominal Cramping
Solid tumors involving the gastrointestinal (GI) tract can Bloating
cause changes in absorption and nutrient delivery, and Gas
Enteritis and Colitis
affect digestion and absorption prior to surgical resection.12 Lactose Intolerance
Postoperative complications from GI tract or intraperito- Fatigue
neal organ surgery can include impaired swallow function, Loss of Appetite
decreased gastric capacity or emptying, ileus of the small
bowel, and altered bowel length and integrity. Children Chemotherapy
malnourished at the time of surgery have been found to Classic cytotoxic chemotherapy works by inhibiting the
have compromised wound healing and an increased risk of division of rapidly dividing cells.17 Although cancer cells
morbidity and mortality, whereas well-nourished patients are the main target, rapidly dividing normal cells including
have fewer surgical complications.13 those of the GI tract, taste buds, hair, and bone marrow are
equally affected. The effect of chemotherapy on the patient’s
nutrition status is associated with the exact medication used,
dose, route of administration, and length of treatment.

ONCOLOGY, HEMATOPOIETIC TRANSPLANT, AND SURVIVORSHIP 351
The most common nutrition-related side effect of Table 30-2 Role of Cytokines and Hormones in Cancer Cachexia
cytotoxic drugs is nausea and vomiting, but with modern Cytokine Effect on nutrition
anti-emetics the degree of emesis is much less severe. Loss Tumor Necrosis Factor (TNF) Suppresses lipoprotein lipase20
of taste buds can make familiar foods unpalatable and cause Increases cortocotropin-releasing
decreased appetite. All of these, along with anticipatory hormone which suppresses food
intake27
effects, lead to anorexia. Some chemotherapy agents have
Interleukin-1 (IL-1) Blocks neuropeptide Y induced
the side effects of diarrhea, others constipation, and many feeding; increases corticotropin-
lead to mild-to-severe mucositis due to slow replacement releasing hormone27
growth of the mucosa. These all can significantly alter the Interleukin-6 (IL-6) Induces cachexia and acute
digestion and absorption of nutrients.17,18 Narcotic pain phase proteins in animal
models20,28
medication and anti-emetics can cause drowsiness and
Interferon (INF)-g Induces cachexia; INF-g
increase sleep time, leading to a secondary anorexia. antibodies reversed wasting27
Peptide YY (PYY) Levels increased with greater
Nutrition Aspects of Cancer disease burden; inverse
correlation with BMI24
Ghrelin Low values associated with
Metabolic greater disease burden24
Cancer cachexia is defined as a “state of malnutrition char-
acterized by anorexia, weight loss, muscle wasting, asthenia,
depression, chronic nausea, and anemia and results in Physiological
physiological distress, changes in body composition and The toxicity of chemotherapy can cause changes in organ
alterations in carbohydrate, lipid, and protein metabo- function resulting in altered nutrient metabolism and excre-
lism.”19,20 These metabolic alterations result in weight loss tion. Cisplatin and cyclophosphamide can cause electrolyte
from muscle and adipose tissue, which compounds the wasting by the kidneys that can last for weeks after the
effects of inadequate intake and anorexia. Cytokines are agent is given. Mild to moderate transaminitis and hyper-
substances made by the cells of the immune system that bilirubinemia are common side effects of chemotherapy,
mediate cell and tissue function and assist in regulating demonstrating direct effects on hepatic function. Tumors
satiety signals and gastric emptying.21,22 Elevated cytokine of the nasopharynx, neck, mediastinum, and GI tract and
levels are found in patients with cancer, likely contributing organs can cause direct obstruction and lead to decreased
to the complex metabolic response of cancer cachexia. 23,24 oral intake. Other side effects of therapy leading to subop-
Table 30-2 outlines the role of selected cytokines in nutri- timal intake are described in detail above.
tion and cachexia. Research has demonstrated that changes
in glucose, protein, and lipid metabolism in cancer patients Psychological
cause weight loss even before the patient experiences Emotional well-being is essential to achieving and main-
decreased appetite and oral intake.24–26 taining physical health, including an optimal nutrition
Energy utilization in the body can range from hypo- to status. Depression and anxiety affects up to 20% of all
hypermetabolism.29 Tumor cells use glucose as their main patients diagnosed with cancer and one study in children
energy source, as well as anaerobic metabolism and amino with cancer found that 59% had mild psychological prob-
acids for tumor cell growth.26,30 Inefficient energy utiliza- lems. 33 While anxiety appears to affect younger children,
tion by the tumor causes increased activity of the Cori cycle and depression older, both can lead to inactivity, loss of
to produce lactic acid to be converted to glucose. Gluconeo- appetite, self-criticism, and hopelessness. Self-image and
genesis, the production of glucose from the breakdown of self-esteem, including perception of weight status and phys-
fat and protein stores, aids in glucose homeostasis. 31 Despite ical appearance, are important to monitor in the pre-teen
the increased demand for glucose, patients frequently and teenage population. Learned food aversions due to fear
exhibit relative glucose intolerance and insulin resistance. 32 from eating and vomiting seem to affect toddlers and young
An increase in lipolysis and decrease in lipogenesis allows children. A specialized feeding program may be necessary
for large losses in fat mass in oncology patients. Muscle to help overcome food aversions and resume normal oral
protein synthesis is reduced, and acute phase protein intake and eating patterns during or after completion of
production in the liver is increased, leading to the risk of treatment.
muscle catabolism.

Evaluation of Nutrition Status and Determination oped by the American Academy of Pediatrics (AAP) and
of Nutrient Requirements modified by Andrassy and Chwals4,41 as well as the Cancer
Control Nutrition Sub-Committee of The Children’s
Energy and Protein Oncology Group (Appendix 30-2).
Determining nutrition status at diagnosis and potential
for malnutrition is necessary for good supportive care.19 Outcomes Measures
Although no specific nutrition protocols exist for pediatric
oncology, it is recommended that a patient’s nutrition status Biochemical Evaluation
be categorized using guidelines developed by The Chil- Laboratory tests should be closely monitored from initial
dren’s Oncology Group (COG), Cancer Control Nutrition nutrition assessment through repletion. One should assess
Sub-Committee (Appendix 30-1). The American Dietetic basic electrolytes (sodium, potassium, chloride, bicar-
Association (ADA) has developed adult nutrition protocols bonate), glucose, renal function (creatinine, blood urea
for medical, surgical, and radiation oncology patients that nitrogen), minerals (calcium, phosphorus, magnesium),
may serve as a resource for the pediatric population, and for liver function tests (alkaline phosphatase, serum amin-
the adolescents and young adults frequently treated in pedi- otransferases, gamma glutamyl transferase (GGT), total
atric oncology centers. 34,35 Table 30-3 contains accepted bilirubin), triglycerides, and cholesterol. Serum albumin
subjective and objective measures commonly used to eval- and prealbumin values may reflect protein stores.
uate pediatric nutrition status.
Caloric and protein needs are difficult to assess in the Table 30-3 Components of Nutrition Assessment
pediatric oncology population, and are affected by current Medical History Diagnosis stage and date
nutrition status, disease state, and therapy protocols. Past medical history
Medication history
Appendix 30-2 contains formulas to assist in estimation Anticipated therapy protocol
of caloric and protein needs. An activity/stress factor may Anthropometics* Weight history
BMI/Weight-for-age
need to be utilized with these formulas; however, recent Height-for-age
literature reports that weight loss may be better correlated Recent growth trends
to decreased oral intake and not increased energy expendi- % Ideal body weight
% Usual body weight
ture. 36 Serum albumin and prealbumin values may indicate % Diagnosis weight
depleted protein stores, although these values can be influ- Mid-arm circumference
Triceps skinfold
enced by hydration status, stress, and liver function and Dietary Intake Current intake (amounts, stage, feeding times)
should be interpreted based on clinical status. 37 Evaluation Usual intake
Feeding behavior
Modified oral intake
Growth and Development Tube feeds
The goal of nutrition intervention for the child with cancer Parenteral nutrition
Vitamin/Mineral supplementation
is to provide adequate nutrients for growth and develop- Gastrointestinal Nausea
ment, and reverse protein-calorie malnutrition. Optimal Symptoms/Side Vomiting
growth and weight gain in pediatric patients is essential for Effects Constipation
Diarrhea
maximizing physical tolerance to treatment and decreasing Dry mouth
the amount of treatment delays. 8,38,39 Strategies for nutrition Taste changes
Mouth sores
intervention for specific symptoms should be implemented Difficulty swallowing
in all patients. Table 30-4 provides general recommenda- Early satiety
tions for nutrition intervention during therapy.40 Laboratory Electrolytes
Assessment Blood glucose
Nutrition support should be individualized for each Serum proteins
child, with the development of a nutrition plan based upon Absolute neutrophil count
Complete blood count
the patient’s nutrition assessment, disease type and stage, Liver function tests
treatment, and quality of life considerations. Studies show Quality of Life Activity level
that pediatric patients who receive intervention from a Family support system
Depression/Anxiety
registered dietitian during active treatment have improved Pain
weight status through therapy.40 Guidelines for nutrition Treatment plan
Resources
intervention for pediatric cancer patients have been devel- * Refer to Appendix 30-1, Algorithm for Nutritional Intervention and Appendix
30-2, Categories of Nutritional Status in the Pediatric Oncology Patient.

Table 30-4 Nutrition Strategies for Symptom Management adolescents with leukemia. Suboptimal nutrition prior to or
Symptom Dietary Intervention Strategies while receiving therapy for acute lymphoblastic leukemia
Nausea/Vomiting Small frequent meals, high carbohydrate content, (ALL) resulted in longer duration of treatment, prolonged
non-acidic beverages, cold clear foods and hospitalization, higher infection rate, increased mortality
beverages, avoid extreme temperatures and highly
seasoned items, avoid high-fat content items
during the first 2 phases of treatment, and lower rate of
Anorexia Small frequent meals, nutrient-dense foods and 5-year survival.46–48
supplements, carbohydrate and protein modulars,
create a pleasant atmosphere, dine with the child, Tolerance to Treatment
vary colors/flavors/textures of foods
Tolerance to treatment and delays in treatment are associ-
Diarrhea Low fat, cold, or room temperature foods, avoid
caffeine, encourage adequate fluid intake ated with nutrition status and disease. Patients treated for
Dysgeusia Herbs, spices, and marinades, cold non-odorous stage IV neuroblastoma who were malnourished at diag-
foods, fruit-flavored beverages, good oral hygiene, nosis or who had weight loss early in treatment had increased
mint mouthwashes, lemon-flavored beverages delays in therapy. 38,44 Malnourished patients with ALL or
and sour candies
Wilms’ tumor were more likely to require a reduction in
Mucositis Soft diet, smooth bland moist foods, frozen
slushes/ices/ice cream, high-calorie liquid drug therapy relative to their better-nourished peers. 8,39,49
beverages Patients who developed anthracycline-associated cardio-
Xerostomia Moist foods, encourage liquids with meals, add myopathy were more likely to be malnourished at initiation
sauces/gravy/butter/broth, add vinegar and of therapy. 50
lemons to stimulate saliva, good oral hygiene
Selection of Nutrition Support Route

Anthropometric
Physical examination is an important piece of the nutrition Oral Nutrition
evaluation. Promoting consistent growth along chart curve Oral nutrition is important to continue to promote normal-
percentiles is essential for long-term assessment. Growth ized and developmentally appropriate feeding for children
should be plotted and monitored for each patient monthly and should be encouraged as much as is medically reason-
on weight-for-age, length/height-for-age, body mass index able. Patients and families should be educated on the
(BMI)-for-age (> 2 years), weight-for-length (< 2 years), appropriate strategies to alter nutrient intake using modulars
and head circumference (< 3 years of age). Measurement of and supplements. Unfortunately many pediatric patients
triceps skinfold thickness and mid-arm circumference for on oral diet alone have significant weight loss and muscle
assessment of fat and muscle stores may be beneficial when wasting51,52 and need to be supported by other means.
unable to obtain accurate weights (eg, critically ill patients,
fluid retention).42 Enteral Tube Feeding
Enteral tube feeding (TF) may significantly enhance a
Disease Outcome child’s nutrition status during cancer therapy. 52–54 Selection
Though it cannot be used as an independent marker of of the correct formula must be determined in order to maxi-
mortality, more severe malnutrition is frequently related to mize nutrient intake. Though no large clinical trials have
a worse prognosis. 39,43,44 Several studies in pediatric solid been conducted, research suggests that a calorie concen-
tumors have shown a correlation between outcome and trated formula may be more beneficial to malnourished
nutrition status. 39,43,44 There is a direct correlation between patients receiving TF. 53 Preliminary evidence regarding
outcome and nutrition status in localized solid tumors, but the use of TF as supplementation or full calories, prior to
not in patients with metastatic disease. 2 Decreased relapse developing weight loss, shows an overall improvement in
rates have been correlated with improved nutrition status the patient’s nutrition status at the end of therapy. 55 Tube
in children with localized solid tumors and lymphomas, but feedings can be provided enterally via nasogastric (NG),
not with advanced disease at diagnosis.2 Children with stage nasojejunal (NJ), or a percutaneous endoscopy gastrotomy
IV neuroblastoma who were malnourished at diagnosis had (PEG) tube. Benefits of a PEG tube include a one-time
a significantly higher incidence of disease recurrence and placement in a location that is not apparent, especially in
death 1 year into treatment.45 an appearance-conscious adolescent. It also bypasses the
Similar results have been published associating poor issue of tube displacement with emesis and traumatic tube
survival outcomes in malnourished and obese children and replacement during periods of mucositis. The placement of

a prophylactic PEG tube prior to the initiation of radiation infections.23,60 Infections also induce a release of cytokines
for head and neck cancers in adults has resulted in decreased IL-1, IL-6, and TNF, further compounding the cancer
incidence of morbidity related to weight loss. 5 This practice cachexia phenomenon.61 Nutrient metabolism and absorp-
should be considered for pediatric patients as many radiation can also be altered during an infection due to increased
tion side effects that affect adults also affect children. The production of catecholamines, cortisol, glucagons, and
disadvantage of a PEG tube is the requirement for surgical growth hormone.
placement and a risk of cellulitis at the incision site. Mucositis, the inflammation of mucosal membranes
lining the digestive tract, is a side effect of many chemo-
Parenteral Nutrition therapy agents and radiation. Mucositis can range in severity
Parenteral nutrition (PN) support has been documented from mild erythema to extensive mucosal sloughing at any
to increase a patient’s overall nutrition status, weight, and location in the GI tract. Oral mucositis can severely impact
anthropometric measurements, but has not improved oral intake and limit the placement of NG tubes secondary to
clinical outcomes.45,56 Though PN can provide short- pain. Some research suggests that supplementing the patient
term improvement, the effects often subside when the PN with oral glutamine may help to prevent and decrease the
is discontinued. 57 Appendix 30-1 outlines intervention severity of mucositis.62
considerations for oral, enteral, and parenteral nutrition. Diarrhea causes a loss of fluids and electrolytes, as well
as nutrient malabsorption, and can be linked directly to
Complementary and Alternative Medicine specific chemotherapies, radiation to the abdominal and
Patients and families with chronic diseases often look to pelvic areas, and abdominal surgery. Other potential causes
resources outside of conventional medicine for treatment. for diarrhea during therapy include primary and secondary
Complementary medicine is used in conjunction with infections, antibiotics, adverse drug effects, and stress.
conventional medicine, while alternative medicine replaces Malabsorption complicates the use of some nutrition
the westernized approach. An increasing number of patients interventions such as oral and TF. When combined with
are using complementary and alternative medicine (CAM). limited nutrient intake, malabsorption can contribute to
The use of CAM in pediatrics has been reported in up to severe weight loss in a short period of time. Surgery may
84% of patients in recent years. 58 The AAP has developed a cause altered nutrient transit time, limiting the ability for
task force to review issues and develop resources for patients intestinal absorption. Chemotherapy induces vomiting,
and health care practitioners. 59 diarrhea, mucositis, and enteritis, and radiation can cause
Limited clinical trials exist on the use of CAM in the malabsorption throughout the entire GI tract. A decreased
pediatric oncology population. Children should not be production in saliva during and postradiation to the head
placed on adult dosages of nutrition-related supplements and neck causes a decrease in oral enzymes, while abdom-
due to differences in metabolism and concerns of drug inal and pelvic radiation can cause enteritis and diarrhea.
interactions and toxicity. Further evaluation and clinical Late effects of radiation may include mucosal inflammation
trials need to be conducted before CAM can be routinely and intestinal fibrosis after an extended period posttherapy
recommended to patients. which may not be reversible.15
Additional complications including dysgeusia, anos-
Complications of Cancer Treatment mia, and xerostomia can significantly alter oral intake
Anorexia or loss of appetite is a common side effect of cyto- because of decreased palatability or decreased tolerance
toxic therapy. Though typically seen as an independent of certain textures. Though these complications generally
symptom, there are many variables that can cause anorexia. subside, they can create long-standing food aversions.
Weight loss, cachexia, dehydration, persistent vomiting, and
early satiety can all cause anorexia in children. Anorexia may Hematopoietic Transplant
be perpetuated by continuous cycles of chemotherapy and Hematopoietic stem cell transplantation (HSCT) is per-
other treatments. formed to replace diseased and defective bone marrow and
Children receiving chemotherapy are at an increased restore hematopoietic and immunologic function. It is a
risk of developing infections. Per data in adults, it is under- broad category and encompasses bone marrow transplan-
stood that malnutrition can increase that risk by 15% to 20%, tation (BMT), peripheral blood stem cell transplantation
and it likely translates to pediatrics.22 Energy requirements (PBSCT), and umbilical cord blood transplantation
may increase by 30% in patients fighting viral or bacterial (UCBT) depending on the source of hematopoietic stem

cells. HSCT is a treatment option for children with a variety chemotherapy and/or radiation and therefore causes
of potentially fatal diseases including malignancies, immu- less toxicity and can be used in patients with comorbidi-
nodeficiency syndromes, severe aplastic anemia, Fanconi’s ties. These transplants are also called “mini” or “reduced
anemia, and inherited metabolic disorders like Krabbe’s dis- intensity” transplants. However, risk of relapse is higher
ease and Hurler syndrome. Pediatric malignancies treated following non-myeloablative transplants.
with HSCT include acute myeloid and lymphoblastic leu- 2. Infusion. After the completion of conditioning and
kemia, Hodgkin’s disease and non-Hodgkin’s lymphoma, usually a day or 2 of rest, the stem cells are infused
myelodysplastic syndrome, and some solid tumors (eg, via an intravenous catheter. It can take 30 minutes to
high-risk neuroblastoma). HSCT offers the only curative 4 hours to infuse the cells depending on the type of
option for many of these children. donor source and whether the product required any
HSCT can be autologous (the patient receives his or her manipulation (eg, volume depletion, red blood cell
own stem cells); allogeneic (the patient receives cells from (RBC) depletion, or T-cell depletion).
another person who may be a sibling, or parent (haplo) or 3. Pancytopenia. The conditioning regimen leads to
an unrelated donor); or syngeneic (when an identical twin suppression or ablation of the bone marrow causing
is the cell donor). Donors are selected on the basis of many a decrease in white blood cells (WBCs), platelets,
factors including the level of human leukocyte antigen and RBCs. This period usually lasts for 2 to 4 weeks
(HLA) matching. HLAs are genetically defined proteins or depending on the donor source, cell dose, and many
antigens that are highly polymorphic and are encoded by other factors. During this period of pancytopenia,
the major histocompatibility complex (MHC). Class I HLA patients have no white cell count and are at increased
(-A, -B, and -C) antigens are expressed on almost all nucle- risk of infections. Antimicrobial prophylaxis is
ated cells of the body. Class II proteins (-DR, -DQ , and commonly used in this period. The patients also
-DP) are mainly expressed on hematopoietic cells (B cells, require blood and platelet transfusions.
dendritic cells, and monocytes). Currently HLA typing 4. Engraftment. Engraftment is confirmed when absolute
is performed by DNA-based methods. While full HLA neutrophil count (ANC) is > 500 per cubic mm for 3
matching is preferred, mismatched donors are appropriate consecutive days. Sometimes, it may take many weeks
in certain situations, especially if the graft source is a cord for cells to engraft. During this process, some patients
blood unit. Donor availability and clinical requirements may develop hyperacute graft versus host disease
determine the source of the stem cells. The donors may be (GVHD) which is also called engraftment syndrome
related or unrelated to the patient. and is characterized by fever, rash, weight gain, and
in some cases severe capillary leak and pulmonary
Transplantation Process edema.
1. Conditioning. The purpose of the conditioning regimen 5. Post-engraftment. In this period of continuing recovery
is to destroy the defective or diseased marrow, kill patients are vulnerable to many complications like
cancerous cells, create space for donor cells, and prevent acute GVHD, graft failure, organ toxicity, drug-related
rejection of donor cells by neutralizing the patient’s adverse reactions, and infections.
immune system. Conditioning therapy (also known 6. Long term. While most patients recover very well
as cytoreduction or preparative regimen) consists of a without major complications, they are at risk for a
combination of chemotherapy drugs with or without number of long-term problems including delayed and
radiation and is given over a number of days prior to slow growth and development, organ dysfunction,
transplant. There are 2 types of conditioning regimen: neurocognitive issues, endocrine problems, chronic
(1) myeloablative and (2) non-myeloablative. Myeloab- GVHD, avascular necrosis, secondary malignancy,
lative, also known as conventional conditioning and others.
regimen, uses high-dose chemotherapy and/or total
body irradiation that destroys or “myeloablates” the Nutrition Evaluation and Nutrient Requirements
bone marrow. The high-dose chemotherapy and radia- Children undergoing HSCT are at increased risk of malnu-
tion causes acute and long-term toxicities including trition and it is critical to assess their needs, anticipate
severe mucositis, myelosuppression, nausea, vomiting, problems, and institute appropriate preventive nutrition
liver function abnormalities, and cardiotoxicity. The support in a timely manner. The toxicity of conditioning
non-myeloablative conditioning uses a milder form of regimen affects the integrity of the GI tract causing

mucositis, nausea, vomiting, and diarrhea. These symptoms intake and fluid balance are critically important and useful.
may be further exacerbated by posttransplant complica- Weekly measurement of mid-arm circumference should be
tions like GVHD, infections, use of multiple antibiotics, considered.
and immunosuppressive medications. These and other
complexities of HSCT are important to understand. The Energy and Protein Needs
nutrition status in some patients may be suboptimal due to Patients undergoing HSCT show changes in energy require-
previous treatments, prolonged hospitalizations, and other ments throughout the process.64–66 During this period,
problems that have affected their ability to eat or drink well. patients are in a hypermetabolic state with increased catab-
Certain diagnoses are more likely to be associated with olism due to mucositis, fever, tissue repair, and marrow
malnutrition at the time of diagnosis and during therapy (eg, regeneration. Increase in the metabolic rate can also be
acute myelogenous leukemia and high-risk neuroblastoma) caused by the conditioning regimen, fevers, and posttrans-
which require much more intense initial chemotherapy plant complications.64 As a result, the caloric needs of the
before they are even referred for HSCT. Fifty-four percent HSCT patient have been reported to be as high as 150% of
of pediatric patients undergoing HSCT were reported to the basal metabolic rate (BMR) of non-stressed well-nour-
have suboptimal nutrition status pretransplant.42 Impaired ished patients and 180% to 200% of BMR of malnourished
pretransplant nutrition status was found to be a negative patients.67–69 On the other hand, Duro et al observed
prognostic factor leading to delayed engraftment.42 Preven- significant decreases in resting energy expenditure (REE)
tion of malnutrition and preservation of nutrition status is following allogeneic stem cell transplant in patients with
vital for better transplant outcomes. A complete nutrition leukemias and aplastic anemia, with return of energy
assessment should be performed at the time of hospital expenditure to pretransplant levels after engraftment. REE
admission. Nutrition status and nutrient needs continue decreased by 4% to 7% per week posttransplant as measured
to change throughout the transplant process, therefore by indirect calorimeter.66 Duggan et al also reported signifi-
continued assessment and evaluation is important during cant decline in REE after HSCT in pediatric patients. Some
the transplant process (refer to Table 30-3 for components of the decrease in REE is being attributed to decrease in
of nutrition assessment). Physiological and psychological lean body mass.65 Studies assessing energy requirements
complications affecting nutrition status during therapy are in HSCT are limited and equivocal. Further studies are
discussed in depth in the General Oncology section of this needed to better determine the caloric needs of pediatric
chapter and thus will not be addressed here. patients during transplant and posttransplant. Based on
current literature, indirect calorimetry for assessing caloric
Anthropometric Assessment requirement is the gold standard. In absence of indirect
Height, weight, and BMI are good indicators of nutri- calorimetry one should use clinical judgment while using
tion status. These should be measured at the time of the calorie calculation formula and continue to assess for
admission and throughout the recovery process. Serial potential overfeeding/underfeeding. Protein require-
anthropometric measurements over a period of time are a ments are increased to minimize loss of lean body mass
good measure of long-term nutrition status. Growth charts and promote tissue repair. Table 30-5 provides caloric and
should be maintained to help assess the growth velocity. protein requirements of HSCT pediatric patients.
However, during early posttransplant stage, one should be
careful about using weight and BMI as the sole criteria to Table 30-5 Caloric and Protein Requirements of Pediatric HSCT
assess changes in nutrition status. Body weight and BMI Patients67,69,71
are affected by hydration. Cheney et al observed fluid shifts Age Calories Protein (g/kg/d)
during the first 4 weeks after transplant and concluded that 0–12 mo BMR* x 1.6–1.8 3
the change in body weight did not correlate with the body 1–6 y BMR x 1.6–1.8 2.5–3
cell mass or fluid volume changes.63 Importantly, calculated 7–10 y BMR x 1.4–1.6 2.4
11–14 y BMR x 1.4–1.6 2
arm muscle area correlated well (p < 0.05) with changes in
15–18 y BMR x 1.5–1.6 1.8
body cell mass and is a better reflection of nutrition status.
> 19 y BEE**x 1.5 1.5
BMI has been reported to be a poor predictor of nutri-
*For BMR equation, refer to Appendix 30-2.
tion status when compared with body cell mass.42 Despite **BEE equations:
these limitations, serial height, weight, and BMI measure- Male: 66 + (13.7 x wt in kg) + (5 x ht) – (6.8 x age)
ments combined with assessment of caloric and protein Female: 665 + (9.6 x wt in kg) + (1.7 x ht) – (4.7 x age)

Fluid Needs supplemented. For further information on bone health, see

In general, daily fluid needs can be assessed using the Late Effects of Treatment in Survivorship in this chapter.
Holliday-Segar method.70 However, one must take into
consideration the various factors that impact daily fluid Provision of Nutrition Support
balance. For example, fluid need is increased with fever, GI
losses (eg, vomiting, diarrhea), mucositis, open skin wounds, Oral Route
and other factors.67 Liver and kidney dysfunction may lead High-dose chemotherapy and posttransplant complications
to fluid retention and may require fluid restriction. In addi- lead to anorexia, mucositis, nausea, vomiting, and diarrhea,
tion to the total parenteral nutrition, and oral or enteral causing poor oral intake and malabsorption. Chemotherapy
intake, patients receive additional fluid with medications drugs like busulfan, melphalan, cyclophosphamide, metho-
and blood products and these must be taken into account. trexate, carboplatin, and most others can cause taste changes.
Therefore, close monitoring of fluid status is important. The etiology of taste changes in HSCT may be multifacto-
rial including mucositis, hyposalivation, and side effects of
Vitamin and Mineral Needs medications like antibiotics, antihypertensives, and antide-
Vitamin and mineral requirements for patients undergoing pressants.72 About a third of patients receiving chemotherapy
HSCT have not been determined. The nutrition support and/or radiation demonstrate food aversion. Patients learn
regimen should meet 100% of the dietary reference intake to avoid foods that remind them of uncomfortable feelings
(DRI) of vitamins and minerals. If oral intake or enteral of nausea and vomiting.73 Oral intake and appetite in HSCT
nutrition support does not meet the vitamin and mineral patients does not return to a normal state until they are 4
needs, then an iron-free multivitamin and mineral supple- to 6 weeks posttransplant.74 Severity of oral mucositis and
ment should be provided. Generally, iron supplementation GVHD are the most significant factors affecting return
is not required in HSCT patients because they receive of oral intake.68 Appetite stimulants may be useful to help
frequent blood transfusions and supplemental iron can stimulate appetite in patients who have engrafted and
result in iron overload. The risk of vitamin and mineral do not have GVHD. Sometimes, even after return of oral
deficiency is particularly higher if the patient has diarrhea, intake and absence of GVHD, oral feeding may be difficult
vomiting, and malabsorption. Thiamin, vitamin K, vitamin due to malabsorption. At this time a complete GI workup
D, calcium, or zinc deficiencies have been seen in some to rule out fat and carbohydrate malabsorption, pancreatic
patients. Vitamin K deficiency as determined by PIVKA- insufficiency, and bacterial overgrowth may be warranted.
II level was seen in 31% of pediatric patients undergoing In infants and toddlers with food aversion, feeding therapy
HCST and was attributed to use of phenytoin, inadequate with the help of speech and occupational therapy should be
intake, or malabsorption. 54 The investigators did not find a considered. Refeeding a child after HSCT is a slow process
direct correlation between prothrombin time and vitamin and needs careful monitoring of symptoms and frequent
K status. However, in clinical practice prothrombin time assessment.
is a good indicator of significant vitamin K deficiency
and can guide vitamin K therapy. Antibiotic use has been Diet Restrictions
shown to decrease the production of vitamin K in the body. Most institutions prescribe a neutropenic or low bacteria
HSCT patients receive multiple antibiotic treatments post- diet in the posttransplant period. In addition, a low-lactose
transplant; therefore, vitamin K supplementation of 1 mg/ diet may also be recommended. The goal of a neutropenic
kg should be provided weekly.67,71 In patients with severe diet is to restrict foods that are believed to contain large
chronic diarrhea, zinc losses may be significant and supple- amounts of potentially pathogenic bacteria, which can
mentation may be necessary. cause infections in the immuno-compromised patient.
Patients undergoing HSCT often receive multiple Such food items include non-pasteurized dairy products;
agents that alter bone metabolism as part of their treatment. aged cheeses; fresh fruits and vegetables; deli meats and
These include methotrexate, steroids, cyclosporine, and cheeses; deli-type salads (eg, potato salad, egg salad, tuna
total body irradiation. For many patients, physical activity salad, and pasta salads); undercooked meat, poultry, egg,
and exposure to sun is limited and can lead to additional fish, and seafood; food with visible mold; salad dressings
nutrition problems like osteopenia, vitamin D deficiency, made with egg and moldy cheeses; and bakery food prod-
and eventually poor bone health. Therefore, serum ucts.69 Listeria monocytogenes, Escherichia coli, Salmonella,
vitamin D and calcium should be routinely monitored and Cryptosporidium parvum, and Campylobacter are the most

common pathogens that cause food-borne illness. Signs or survival rates. However Roberts et al74 in 2005 reported
and symptoms of a food-borne illness include stomach no difference in length of stay, engraftment time, days to
ache, abdominal pain, diarrhea, nausea, vomiting, head- resume oral intake, and rate of infection in patients who
ache, fever, and chills.75 Studies have shown inconsistent received PN versus patients on oral diet. They concluded
results regarding the effect of dietary modification on the that prophylactic use of PN results in improved nutrition
incidence of food-borne illness.76,77 Current A.S.P.E.N. status and does not affect the time to resume oral intake.
guidelines for HSCT adult patients state that until further Reported benefits of PN include reversal of protein
research is available it seems prudent to restrict high-risk energy malnutrition, restoration of immune-competence,
foods, as described above, during neutropenia.78 It is impor- and enhanced tolerance to anti-neoplastic therapy. 69
tant to encourage patients and caretakers to practice safe However, use of PN is associated with increased risk for
food handling. several complications including line infections, hyper
glycemia, hypertriglyceridemia, and cholestasis.67 Patients
Enteral Nutrition who present with compromised nutrition status prior to
Benefits of enteral nutrition (EN) in protecting the gut transplant are at risk of refeeding syndrome (Chapter 19).
integrity, preventing bacterial translocation, and being If a patient is at high risk for refeeding syndrome, nutrition
cost-effective are well known. However, enteral feeding support should be slowly advanced to meet goal energy
has not been the norm for most pediatric HSCT patients requirements.85,86 As with any patient receiving PN, the
mainly because of risk of bleeding with tube placement patient should be monitored closely and the nutrition
in the presence of pancytopenia and mucositis and due to support regimen adjusted accordingly. Since most studies
concerns about delayed gastric emptying and malabsorp- are done on heterogeneous patient populations with regards
tion of nutrients.68,79 In 2 small studies involving a total to type of transplant, diagnosis, kind of conditioning, age,
of 49 patients, enteral feeding was found not only to be and pretransplant nutrition status and the small sample
feasible and cost-effective but also to be as successful as PN size, there are no established criteria as to when PN should
in preserving the nutrition status of children undergoing be initiated. Based on our clinical experience PN should be
allogeneic HSCT.80,81 In an earlier study, Papadopoulo et al initiated after transplant for pediatric patients who receive
reported that EN, when tolerated, is beneficial and prevents myeloablative conditioning regimen, who are expected to
the deterioration of nutrition status of pediatric patients have severe mucositis, or patients with poor nutrition status
undergoing HSCT.82 EN may be attempted if there is no prior to transplant. However patients with non-myeloabla-
active pathology in the GI tract and continued if the patient tive conditioning regimen, with minimal or no mucositis,
is able to tolerate it. In case of intolerance, it may be possible and adequate nutrition status prior to transplant may be
to modify the formula and tube placement. For example, placed on oral or enteral nutrition. Clinical judgment about
nasoduodenal (ND) or nasojejunal (NJ) tubes may have a the type of nutrition support should not only include the
lower risk of causing vomiting and aspiration. 83 Refer to the specifics of patient population but also the risk and benefits
Algorithm (Appendix 30-1) in making decisions regarding of PN.
type of tube, delivery system, and formula selection.
Nutrition Monitoring During HSCT
Parenteral Nutrition Monitoring and evaluating the efficacy of nutrition support
In the setting of severe regimen-related GI toxicities leading in patients undergoing HSCT is very important and a
to poor oral intake and intolerance to EN, PN has been complex process. However, there is a paucity of data to
historically used to support patients after HSCT. There are support the use of a single specific test or a battery of tests
mixed studies regarding the benefits and indications of PN that could be used broadly in most clinical situations. This
use in HSCT patients. In 1987, Weisdorf and colleagues84 section will examine the published data on various measures
demonstrated that prophylactic use of PN in previously of nutrition assessment.
well-nourished HSCT patients was associated with positive
outcomes. In 1997, Charuhas et al71 reported that patients Fluid and Electrolyte
who were randomized to PN resumed PO intake 6 days Multiple factors, including the type and quantity of feeding,
later than an intravenous (IV) hydration group, and even impact fluid and electrolyte status. Decisions about the
though the IV hydration group experienced 1.14% weight volume and composition of total parenteral nutrition as
loss there was no difference seen in re-admission, relapse, well as of the type and amount of enteral formula must be

Table 30-6 Side Effects of Some of the Drugs Commonly Used During HSCT
Drug Usage Side effect
Steroids Immunosuppressive Hyperglycemia, weight gain, osteoporosis, fluid and sodium retention, cardiomyopathy,
hypercholesterolemia, hypertriglyceridemia, gut infection
Methotrexate Immunosuppressive Mucositis, nausea, vomiting, diarrhea, hepatic and renal toxicities
Cyclosporine Immunosuppressive Hypertension, nephrotoxicity, significant hyperkalemia, hypomagnesemia, hepatotoxicity,
hyperglycemia, hyperlipidemia, hypercholesterolemia, nausea, vomiting
Tacrolimus Immunosuppressive Hypertension, nephrotoxicity, hyperkalemia, hypomagnesemia, hyperbilirubinemia, hypercalcemia,
hypercholesterolemia, hyperglycemia, hyperlipidemia, hyperphosphatemia, hypocalcemia,
hypokalemia, hypomagnesemia, hyponatremia, hypophosphatemia, elevated hepatic enzymes,
nausea/vomiting, anorexia, diarrhea
Sirolimus Immunosuppressive Edema, hyperlipidemia, hypercholesterolemia
Cellcept Immunosuppressive Nausea, vomiting, diarrhea, anorexia, renal impairment, neutropenia
Antithymoocyte Immunosuppressive Infusion reactions, increased infection risk, hypotension, nausea, vomiting
globulin (ATG)
Acyclovir Antiviral Nephrotoxicity, anorexia, nausea, vomiting, diarrhea, elevated hepatic enzymes, hyperbilirubinemia
Cefepime Antibiotic Nausea, vomiting, diarrhea
Amikacin Antibiotic Nephrotoxicity
Gentamicin Antibiotic Nephrotoxicity
Voriconazole Antifungal Hepatotoxic, skin rash, visual problems
Amphotericin Antifungal Nephrotoxicity
Micafungin Antifungal Hepatotoxic
Source: Clinical Pharmacology [database online]. Tampa, FL: Gold Standard, Inc; 2009. http://www.clinicalpharmacology.com. Accessed December 2009.
based on the state of fluid and electrolyte balance which Table 30-7 Suggested Schedule for Monitoring Blood Biochemical and
must be monitored daily and carefully. Mucositis, diar- Other Indices During Early Stages of HSCT
rhea, vomiting, excessive salivation, fever, and other factors Lab Frequency
increase fluid losses. However, fluid retention is commonly Sodium, potassium, chloride, Every day until stable on total
carbonate, BUN, creatinine, parenteral nutrition (TPN), then
seen at the time of engraftment. Other problems including calcium, magnesium 3 times per week while on long-
sinusoidal obstruction syndrome (SOS) (formerly known term TPN
as veno-occlusive disease (VOD)) and renal insufficiency Phosphorus 3 times per week until stable on
may also cause fluid retention. In addition, they lead to TPN, then weekly
electrolyte problems. Severe inflammatory reaction in the Ionized calcium With consistent low-serum
calcium
posttransplant period may lead to capillary leak and “third-
LFTs, albumin, total bilirubin 3 times per week until Day +30,
spacing” of fluids. In such a situation the weight may be high then weekly while on TPN
but the intravascular compartment is depleted. Many drugs Prothrombin time Weekly while on multiple
like tacrolimus, cyclosporine, amphotericin, vancomycin, antibiotics
and ifosfamide can cause increased urinary losses of elec- Vitamin D (25 OH D2+D3) Pretransplant; then every 3
trolytes requiring increased supplementation. Table 30-6 months until 1 year
Zinc When increased losses suspected
shows side effects of some of the drugs commonly used
Manganese, copper, selenium Monthly when on long-term TPN
in HSCT. In general one should monitor basic biochem- (4–6 weeks)
ical indices like sodium, potassium, chloride, blood urea Triglycerides Weekly while on intravenous lipid
nitrogen, creatinine, glucose, calcium, phosphorus, and emulsion
magnesium. See Table 30-7 for a suggested schedule for Weights Daily while inpatient, then with
monitoring of biochemical indices. every outpatient visit
Input/output Daily while inpatient

Triglycerides and Liver Function Tests posttransplant.89 The same study showed that triceps skin-
Fasting triglyceride levels should be obtained prior to fold (TSF) measurements and midarm circumference
administration of intravenous fat emulsion (IVFE), and then also decreased. Therefore, TSF measurements should be
weekly for the duration of the IVFE therapy. Cyclosporine, obtained and monitored. Fluid shifts will not affect skin-
corticosteroids, tacrolimus, and sirolimus can all result in fold measurement.89 Bone growth can be monitored by
elevated triglyceride levels. Serum triglyceride levels should obtaining a dual-energy x-ray absorptiometry (DEXA) scan
be monitored weekly if a patient is receiving any of the medi- bi-annually.90
cations listed.67,71,79 During the first 4 weeks posttransplant,
patients are at risk for SOS. Liver function tests (LFTs) HSCT Complications Impacting Nutrition
should be monitored at least 3 times a week. If increasing Pediatric patients undergoing HSCT are at significant risk
levels are noted, more frequent LFTs may be necessary. for developing many complications that may have direct and
indirect impact on the nutrition status. The most important
Micronutrients are described below.
Copper, selenium, and manganese levels should be moni-
tored monthly if a patient has been receiving PN for more Mucositis
than 1 month, or in the presence of hyperbilirubinemia.67,71,87 Mucositis, or inflammation and breakdown of the mucosal
If zinc supplementation is implemented, zinc levels (ie, lining of the mouth and gut, may occur in up to 100% of
serum or plasma zinc) should be monitored. However, zinc patients undergoing HSCT with high-dose chemotherapy.91
levels in blood are adversely affected by inflammation or Severity depends on many factors including the dose inten-
infection so this should be taken into account when inter- sity of chemotherapy and use of concomitant radiation.
preting results. Clinical discretion should be used when Moderate to severe mucositis often requires IV narcotics.
evaluating zinc levels, keeping in mind that zinc levels in In the presence of moderate and severe mucositis oral
blood do not reflect tissue stores. intake is nearly impossible and PN is the only option. Severe
mucositis also predisposes to infections.92
Other Biochemical Indices
Low serum albumin is predictive of an increase in mortality, Graft versus Host Disease
poor outcome, complication rate, and length of stay and may GVHD is caused by an immunologic reaction in which
be low in severe and chronic malnutrition, but it is not a good donor-derived T-cells recognize the host cells as foreign
marker of acute nutrition status. 37 Nitrogen balance may be and attack them. Generally, acute GVHD occurs before
useful to assess protein status but the accuracy of the calcu- 100 days posttransplant and chronic GVHD develops after
lation is compromised in patients with vomiting, diarrhea, more than 100 days from transplant. This definition/clas-
and renal insufficiency. Also, a 24-hour urine collection sification is being replaced with the new classification by
in pediatric patients may be difficult. Serum transferrin, the National Institutes of Health that includes late-onset
prealbumin, and retinol binding protein are also not good acute GVHD (after day 100) and an overlap syndrome with
indicators of nutrition status. 37 During inflammatory states, features of both acute and chronic GVHD.93,94 Immuno-
their hepatic synthesis is decreased by as much as 25% and suppressive drug combinations are used to prevent GVHD.
their intravascular concentration is reduced due to capillary Calcineurin inhibitors, cyclosporine, and tacrolimus are
leak.88 Other factors like hydration, infection, and liver and generally used with methotrexate, mycophenolate, steroids,
renal insufficiency also affect their levels. or sirolimus. High-dose steroids are used to treat acute
GVHD.95 For treating chronic GVHD, steroids with or
Growth without calcineurin inhibitors are used.96
Weight trends should be monitored daily, as well as intake
and output, throughout the entire transplant period.67 Acute GVHD
Length should be monitored monthly but one should be The organs most commonly affected in acute GVHD are the
mindful that critically ill transplant patients will likely skin (81%), gut (54%), and liver (50%).97 Skin is usually the
not attain age-expected linear velocity, despite provision first organ to be involved. Symptoms of acute gut GVHD
of optimal nutrition support. Although weight fluctuates include nausea, vomiting, loss of appetite, abdominal pain,
with fluid shifts, one study revealed that weight decreased and diarrhea, which is secretory in nature and is voluminous
overall and height increased slowly (1.7 cm/mo) 4 months (> 2 L/d in severe cases).98 Gut GVHD most commonly

Table 30-8 Staging and Grading of Acute GVHD

Stage Skin* Liver bilirubin Gut^#
+ Maculopapular rash < 25% body surface 2–3 mg/dL Diarrhea, 500–1000 mL/d or persistent nausea
++ Maculopapular rash 25–50% body surface 3–6 mg/dL Diarrhea, 1000–1500 mL/d
+++ Generalized erythroderma 6–15 mg/dL Diarrhea, > 1500mL/d
++++ Desquamation and bullae > 15 mg/dL Abdominal pain with or without ileus
*Use “rule of nines” or burn chart to determine extent of rash.
^ Diarrhea volumes apply to adults.
# Persistent nausea requires endoscopic biopsy evidence of GVHD histology in the stomach or duodenum.
Overall Grade Skin Liver Gut Functional Impairment
0 (none) 0 0 0 0
I (mild) + to ++ 0 0 0
II (moderate) + to +++ + + +
III (severe) ++ to +++ ++ to +++ ++ to +++ ++
IV (Life threatening) + to ++++ ++ to ++++ ++ to ++++ +++
Reprinted with permission from Sullivan KM. Graft-vs-host disease. In: Blume KG, Forman SJ, Appelbaum F, eds. Thomas’ Hematopoietic Cell
Transplantation. 3rd ed. Oxford: Blackwell Publishing; 2004:635–664.
affects the lower GI tract causing severe, high-output diar- diarrheal output worsens with ingestion of food and EN.
rhea associated with bleeding and cramping abdominal
pain.99 GVHD of the upper GI tract causes decreased appe- Pancreatic Insufficiency
tite, nausea, and vomiting.79 Active GVHD leads to mucosal If diarrhea continues in absence of GVHD, patients should
degeneration, malabsorption, and protein loss. Liver GVHD be evaluated for pancreatic insufficiency.105 Of pediatric
is characterized by cholestatic hyperbilirubinemia, however patients undergoing HSCT, 4.9% were found to have acute
it can be difficult to differentiate other causes of liver func- pancreatitis.102
tion impairment; the differential diagnosis includes SOS,
infection, sepsis, drug effects, iron overload, or PN-induced Bacterial Overgrowth
cholestasis.98 Acute GVHD is graded based on the extent of Bacterial overgrowth has not been well studied and defined
skin, liver, and gut involvement (see Table 30-8 for staging in this group of patients. However, based on clinical reports,
and grading). Long-term survival (5 years) for grade III if diarrhea continues after GVHD and infection and pancre-
is 25% and grade IV is 5%.100 Prevalence of acute GVHD atic insufficiency is ruled out, patients should be worked up
varies from 35% to 45% in full matched sibling donors to for bacterial overgrowth. Long-term use of antibiotics and
60% to 80% in patients with 1 antigen HLA mismatched patients’ inability to take oral diets for prolonged periods
transplant.101 With the same degree of HLA mismatch, after HSCT can alter the type and quantity of bacterial flora
patients receiving umbilical cord blood transplant have similar to short gut.
lower frequency of acute GVHD (35% to 65% compared to
60% to 80% in patients receiving unrelated donor graft).102 Infection
The immuno-suppressed patient is highly susceptible to
Chronic GVHD bacterial, viral, and fungal infections. C. difficile infection is
Chronic GVHD involves skin, gut, liver, lungs, eyes, mouth, one of the common infections identified in the transplant
and bone marrow. Risk factors for development of chronic population.106 Some of the viral infections known to cause
GVHD include the age of the patient and history of acute diarrhea in HSCT patients are adenovirus, cytomega-
GVHD. About 22% to 29% of pediatric patients undergoing lovirus, astrovirus, and rotavirus.107 Infections affecting
HSCT will develop chronic GVHD.103 In adult patients, the GI tract can lead to intolerance of oral intake and EN.
chronic GVHD ranges from 30% to 50% in HLA-matched Antiviral, antifungal, and antibiotic medications can cause
sibling transplant.104 loss of appetite, nausea, vomiting, diarrhea, and malabsorp-
A low-fiber, low-lactose, low-fat, bland diet may be tion. Antibiotic medications may also decrease the amount
necessary during periods of acute GVHD, but use of this of lactase enzyme in the intestine; if symptomatic, these
dietary modification is not the norm.69 PN is warranted when patients may benefit from a low-lactose diet.108,109

Hemorrhagic Cystitis Risk factors for late effects can be due to tumor, from
High-dose cyclophosphamide can lead to hemorrhagic direct tissue effects, tumor-induced organ dysfunction, and
cystitis, a complication characterized by bloody urine. mechanical effects. The multimodal treatment used during
Fluid intake may need to be twice the maintenance needs in treatment can also be responsible for many late effects. The
order to irrigate the blood clots in the bladder. Viral infec- Children’s Oncology Group Long-Term Follow-Up Guide-
tions unique to the immuno-compromised patient, which lines for Survivors of Childhood, Adolescent, and Young
include adenovirus and BK virus, can also lead to hemor- Adult Cancers (COG-LTFU Guidelines)115 extensively
rhagic cystitis.67,87,108 review late effects of treatment used. Genetic predisposi-
tion, capacity for normal tissue repair, organ function not
Sinusoidal Obstruction Syndrome affected by treatment, developmental status, and pre-morbid
SOS is usually seen between 1 to 4 weeks posttransplant state can influence development of late effects.114,116
and reflects regimen-related toxicity.110 Injury to the
endothelial cells of the sinusoids, thickening of the hepatic Long-Term Follow-Up Guidelines
venules due to edema, and deposition of fibrin, factor VII, The COG-LTFU Guidelines115 are clinical practice guide-
and blood cell fragments leads to narrowing and increased lines used in screening and management of late effects that
resistance to the blood flow through the venules. This causes can result from therapy used during treatment for pediatric
hepatic congestion and portal hypertension.111 Weight gain, malignancies. The guidelines are evidence-based (utilizing
hyperbilirubinemia, ascites, right upper-quadrant pain, established associations between therapeutic exposures and
and hepatomegaly are the clinical symptoms associated late effects to identify high-risk categories) and grounded in
with SOS. Severe SOS can lead to liver failure, hepatorenal the collective clinical experience of experts (matching the
syndrome, portal hypertension, and multiorgan failure. magnitude of the risk with the intensity of the screening
Pre-existing liver dysfunction, previous transplantation, recommendations). These guidelines are appropriate for
abdominal irradiation, conditioning regimen, adrenoleu- survivors of childhood, adolescent, or young adult cancers
kodystrophy, and neuroblastoma are some of the risk factors 2 or more years following the completion of cancer therapy.
for SOS.112 The incidence of SOS in children after HSCT Given the wide age range, some guidelines may not be appli-
ranges from 5% to 40%,112 and the mortality rate in severe cable (ie, limiting alcohol intake in a 10-year-old); therefore,
SOS has been reported to be as high as 47%.113 clinicians must be guided by the age of the patient and the
relevance of the guidelines. References related to each late
Conclusion effect and patient education materials on a variety of topics
Nutrition assessment, support, and monitoring during are also included in the guidelines.115
the transplant process are critical parts of patient manage- When determining guidelines for cancer survivors it is
ment. These measures are even more important in pediatric important to use traditional assessment/recommendations
patients because of small size, need for continuing growth taking into account the age of the survivor and his or her
and development, and the potential for rapid deterioration. pertinent clinical history. Suggestions are geared toward
Comprehensive assessment may include information about leading a healthy lifestyle and include nutrition and activity
anthropometrics, food intake, appetite, presence of infec- guidelines. The recommendations for cancer survivors is
tion, organ dysfunction, wounds, nausea, vomiting, diarrhea, that they adopt the prevention guidelines.
and mucositis amongst others. Good clinical judgment is
critical and decision making should be individualized in an Gastrointestinal (GI) Problems in Survivors117
effort to provide optimal nutrition management. Treatment for childhood cancer can result in chronic prob-
lems of the intestine or other parts of the GI system including
Late Effects of Treatment for Survivors of bowel obstruction, gallstones, esophageal stricture, hepatic
Childhood Cancer fibrosis, colorectal cancer, and chronic enterocolitis.
The 5-year survival rate for pediatric cancer has improved Treatments that increase risk for having GI problems
and is about 80% for some diagnoses, although many patients include:
experience late effects or long-term health-related outcomes • Radiation – doses of 30 Gy (3000 cGy/rads) or higher
that can result in organ dysfunction, second malignant to the chest, neck, pelvis, or abdomen
neoplasms, and adverse psychological sequelae.114 • Surgery in the pelvis or abdomen

• Other risk factors include a family history of gallstones, lowering medication (cholestyramine) and high-dose
colorectal or esophageal cancer, patient history of bowel heparin for prolonged periods are risk factors.
adhesions (scarring) or bowel obstruction (blockage), 3. Suggestions for decreasing risk of osteoporosis include
use of tobacco, or chronic GVHD activity with weight-bearing (walking, dancing) and
Possible symptoms of GI problems can include chronic resistance (light weight lifting) exercises.
nausea, vomiting, acid reflux, constipation or diarrhea, pain General guidelines for calcium requirements are 1000 to
(with swallowing or abdominal), change in appetite, weight 1500 mg/d (elemental calcium), but may vary based on age,
loss, black tarry stools or blood in stool, abdominal disten- clinical history, and results of DEXA scan. Food sources
tion, and jaundice. Suggestions for managing GI problems include dairy products (milk, cheese, yogurt) and non-dairy
include118: sources (ie, salmon, collards, broccoli, white beans, fortified
1. Eat 5 or more servings of fruits and vegetables daily. foods such as orange juice and some cereals).
2. Choose a variety of foods from all food groups. Calcium is found in supplements as a salt and is bound
3. Include high-fiber foods in diet (eg, whole grain breads, to carbonate, gluconate, citrate, or lactate. The recom-
cereal). mendations are based on elemental calcium. Calcium
4. Avoid foods high in sugar (eg, candy, soda). carbonate is the most prevalent form of calcium supple-
5. Choose low-fat milk and dairy products. ment on the market and should be taken after meals as it
6. When eating meats, choose leaner cuts and broil or boil requires stomach acid for better absorption. It provides
when preparing. more elemental calcium (40% elemental) than calcium
7. Decrease high-fat foods (potato chips, french fries). citrate; therefore, not as many tablets are required.
8. Limit the use of alcohol. Calcium citrate is the best absorbed supplemental form of
9. Do not smoke or use tobacco and avoid second-hand calcium. It does not require extra stomach acid for absorp-
smoke. tion; therefore, it may be taken any time during the day,
even on an empty stomach.
Bone Health115 Some brands list total weight of calcium salt, not the
Bone is a living growing tissue (206 bones in the body) made amount of elemental calcium. Generic brands are less expen-
up of calcium, phosphorus, magnesium, vitamin D, and sive, but they may not meet United States Pharmacopeia
fluoride. All of these nutrients are important in the develop- (USP) standards for quality and purity. It is best to avoid
ment and maintenance of bone and other calcified tissues. A oyster shell, bone meal, or dolomite as they may contain
consequence of childhood cancer treatment is a decrease in lead, mercury, or arsenic. The Nutrition Facts Label should
peak bone mass from normal levels and an increased loss of state the Percent Daily Value (%DV) based on 1000 mg of
calcium from the bones. Survivors are at increased risk for elemental calcium. It is necessary to individualize calcium
osteoporosis, a result of poor bone formation or too much requirements based on age and clinical history.
bone loss; therefore fractures may occur as bones become Vitamin D is needed to absorb calcium and is generally
weaker. Osteoporosis is diagnosed by an X-ray technique, found in dairy products that are fortified. It is recommended
known as DEXA, which measures bone density or bone that supplementation not exceed 800 International Units
mass and takes less than 20 minutes to complete. per day, but should be based on age and clinical history.
Risk factors for osteoporosis are as follows: Although we are able to make Vitamin D through sun expo-
1. General risk factors include female, family history of sure, it is felt that most people do not make enough due to
osteoporosis, Caucasian or Asian, older age, small/thin the use of sunscreens and limited sun exposure.
frame, smoking, diet low in calcium, increased amounts
of alcohol, caffeine or soda, lack of weight-bearing exer- Heart Health after Treatment for Childhood Cancer119
cise and diet that is high in salt. Cancer treatments that can cause heart problems include
2. Risk factors in survivors of childhood cancer include chemotherapy (anthracyclines) and radiation to the heart
anti-cancer treatment utilizing methotrexate or corti- or surrounding tissues. Types of heart problems that can
costeroids as well as radiation to weight-bearing bones. occur after treatment include left ventricular dysfunction,
Other medical treatments such as anticonvulsants cardiomyopathy, arrhythmias, valvular stenosis or insuf-
and medication used to treat early puberty and endo- ficiency, pericardial fibrosis, and coronary artery disease.
metriosis (Lupron) can affect bones. Drugs including Risk factors for developing heart problems can be due to
aluminum-containing antacids (Maalox®), cholesterol- other medical conditions (obesity, high blood pressure,

diabetes, elevated cholesterol or triglycerides). Aerobic 9. Do not smoke or chew tobacco.

exercise is generally safe and healthy for the heart, but some 10. Handle food safely (immune system may be affected in
forms of exercise can be stressful to the heart (eg, wrestling survivors – risk for food-borne illness).
and heavy weight lifting). Survivors who might be at risk for 11. Rethink the pattern of eating with two-thirds of a meal
having heart problems should check with their health care comprising vegetables, fruits, whole grains, and beans
provider before starting an exercise program. and one-third coming from cheese or animal foods.
Tests that are done to monitor heart function include Maximize the variety of vegetables and fruits eaten
electrocardiogram (ECG), echocardiogram, or MUGA as they contain phytochemicals (plant compounds
scan and should be recommended by a health care provider that have been shown to act as antioxidants, boost the
if appropriate. In order to prevent problems with the heart it immune system, have anti-inflammatory, antiviral, and
is best to stay at a healthy body weight, limit fat intake to no antibacterial effects, and aid in cellular repair).
more than 30% of calories, exercise moderately for at least Nutrients should be provided in the diet from a variety
30 minutes on most days, and avoid smoking. of sources. Protein is needed for growth, repair of body
tissue, and assistance with maintaining immune function.
Diet and Physical Activity for Survivors119 Carbohydrates and fats are the body’s major energy (calorie)
American Institute for Cancer Research Recommendations sources. Vitamins and minerals are essential for proper
for Cancer Prevention118 include the following: growth and development and are needed to utilize the
1. Be as lean as possible (not underweight). energy in food. Water is important to prevent dehydration,
2. Be physically active (30 minutes on most days). which may cause a person to feel listless or dizzy. Benefits
3. Avoid sugary drinks. Limit intake of processed foods of regular exercise and good nutrition for childhood cancer
high in fat and/or added sugar, or low in fiber. survivors include promoting healing of tissues/organs
4. Eat a variety of vegetables, fruits, whole grains, and damaged by cancer and treatment, building strength and
legumes (beans). endurance, reducing risk of certain types of adult cancers
5. Limit consumption of red meat (beef, pork, lamb). and diseases (eg, diabetes, heart disease), decreasing stress,
Avoid processed meats. and providing a feeling of well-being.
6. If consumed, limit alcoholic drinks to 2 for men and 1 Although late effects can occur in survivors of pediatric
for women per day. cancer, a healthy lifestyle including proper diet and phys-
7. Limit consumption of salty foods and foods processed ical activity are important to maximize quality of life and
with salt (sodium). prevent the incidence of certain chronic diseases.
8. Do not use supplements to protect against cancer.

Appendix 30-1: Algorithm For Nutritional Intervention In The Pediatric Oncology Patient
Identify appropriate category: Age > 2 years choose either BMI (Body Mass Index) or IBW (Ideal Body Weight)
Age < 2 years choose WT/LT (Weight for Length) or IBW (Ideal Body Weight)
Categories for Nutritional Status

Underweight Normal Risk of Overweight / Overweight*
BMI < 5th % ile 5-85th % ile > 85-95th % ile > 95th % ile
WT/LT < 10th % ile 10-90th % ile > 90th % ile
IBW < 70% Severe > 90-110 % > 110-120% > 120%
> 70-80% Moderate
> 80-90% Mild
*Evaluate for weight gain or loss
> 5 % wt loss from Usual Body Weight (UBW) or during therapy

or
Crossing > 2 percentile channels
NO
Meeting > 80 % estimated nutritional needs through

oral intake (food and supplements)
YES
YES
NO
Encourage oral intake/supplements and monitor NO Will impending treatment adversely affect nutritional status
weight/adequacy of diet once a month. and ability to meet needs orally?
YES
NO
Oncologic prognosis warrants TPN (Total Parenteral Nutrition) or TF (Tube Feeding)
YES
Can patient safely tolerate/absorb nutrients via GI tract?
NO YES
Is expected need for nutritional Is patient a candidate

support > 5 days? for tube feeding?
YES NO
Can intolerance be alleviated by changing formula or

NO TPN until GI tract can be using antiemetics/motility agents YES
safely used
NO YES
Monitor and intervene as needed TPN High risk of pulmonary aspiration or excessive emesis
NO YES
NO Gastric feeds Post-pyloric feeds
Can tolerance be alleviated by changing formula, method Tube feedng required for > 3 months
of administration or adding medication?
NO YES
YES
Nasoenteric tube feeding Enterostomy tube feeding (PEG vs.G-Tube)
Implement necessary changes Nasogastric (NG) Gastrostomy (GT)
NO Nasoduodenal (ND) Jejunostomy (JT)
Nasojejunal (NJ) Gastro-Jejunostomy (G-JT)
Provide tube feedings as tolerated and wean when Can patient tolerate feedings in strength and
oral consumption is > 50% estimated needs YES amounts necessary to meet estimated needs?
©Children’s Oncology Group, Cancer Control Nutrition Sub-Committee 10/04. Reprinted with permission.

Appendix 30-2: Algorithm for Nutritional Intervention and Categories of Nutritional Status in
the Pediatric Oncology Patient — References and Resources

Appendix 30-2, continued
Appendix 30-3: Categories of Nutritional Status for the Pediatric Oncology Patient
Identify appropriate category: Age > 2 years choose either BMI1 (Body Mass Index) or IBW2 (Ideal Body Weight)
Age < 2 years choose WT/LT3 (Weight for Length) or IBW2 (Ideal Body Weight)
» Weight loss/gain may or may not be present
Underweight Normal Risk of Overweight / Overweight*

BMI < 5th % ile 5-85th % ile > 85-95th % ile > 95th % ile
WT/LT < 10th % ile 10-90th % ile > 90th % ile
IBW < 70% Severe 70-80% Moderate > 90-110 % > 110-120% > 120%
> 80-90% Mild
BMI - Body Mass Index (percentile)

1
Hammer LD, Kraemer HC, Wilson DM, Ritter PL, Dornbusch SM. Standardized percentile curves of body-mass index for children
and adolescents. American Journal of Disease of Child. 145:259–263, 1991.
Pietrobelli A, Faith MS, Allison DB, Gallagher D, Chiumello G, Heymsfield, SB. Body mass index as a measure of adiposity
among children and adolescents: A validation study. Journal of Pediatrics. 132:204–210, 1998.
IBW - Ideal Body Weight for height or length (percentage)
2
Waterlow JC. Classification and definition of protein-calorie malnutrition. British Medical Journal 3: 566-569, 1972.
WT/LT - Weight for Length (percentile)
3
Motil KJ. Sensititve measures of nutritional status in children in hospital and in the field. International Journal ofCancer:
Suppl. 11: 2-9, 1998.

Appendix 30-4: Gastrointestinal Supportive is on metoclopramide. Other drugs such as tacrolimus and
Care Medications cyclosporine may have increased absorption when a patient
Nutrition support efforts in pediatric and adult cancer is on metoclopramide.123 Doses of metoclopramide should
patients are often complicated by problems with gut motility, be reduced in patients with renal dysfunction.
hyperacidity, nausea and vomiting, loss of appetite, and
treatment-induced mucositis. This appendix discusses some Erythromycin
of the medications available to help treat these conditions. This drug is a macrolide antibiotic, but it also is a motilin
receptor agonist that increases proximal gut motility.120,124
Motility Agents (Metoclopramide, Prokinetic effects are evident at doses as low as 4 to 12
Erythromycin) mg/kg/d as compared to the 30 to 50 mg/kg/d used for
These agents have numerous uses, including to aid naso- antimicrobial effects. Numerous studies suggest activity
gastric intubations, and for gastroparesis, gastroesophageal of erythromycin for improving feeding tolerance in chil-
reflux, and intolerance to feedings. dren.120,124 Typical problems with antimicrobial doses of
erythromycin include gastrointestinal upset, diarrhea, and
Metoclopramide/Reglan™ inhibition of P450 1A2 and 3A4 enzymes causing drug
This drug blocks dopamine and at higher doses, 5 HT3 interactions. These effects are less likely at the lower doses
(serotonin) receptors. Its effects on motility may involve used for motility. Although rare, there are some concerns
increased release of acetylcholine in the gut. The effect on about adverse effects such as hepatotoxicity, ototoxicity,
the gut is increased forward peristalsis in the stomach and cardiac arrhythmias, and pyloric stenosis.124 The latter has
duodenum. Metoclopramide has been used for the indi- been reported mostly in infants less than 2 weeks old. A
cations listed above as well as for chemotherapy-induced theoretical concern is the potential for low-dose antibiotics
nausea and vomiting. The latter use typically requires higher to stimulate resistance among bacteria. This has not been
doses. Data confirming the clinical utility vary with the indi- documented with the use of erythromycin for motility and
cation. For chemotherapy-induced nausea and vomiting, thus is an unknown. Caution should be used in patients with
combinations of high-dose metoclopramide with dexam- hepatic impairment, largely due to the potential of erythro-
ethasone and either diphenhydramine or lorazepam were mycin to cause hepatotoxicity.
demonstrated to be effective in the 1980s, but serotonin
receptor antagonists such as ondansetron have been shown Acid-Blocker Medications
to be superior. Metoclopramide is typically effective in H2 receptor antagonists and proton pump inhibitors have
aiding intubations for patients with slow gastric motility and been used mostly for ulcers or gastroesophageal reflux
for gastroparesis. Data proving utility in pediatric patients disease in adults. They may be useful in children in situations
with gastroesophageal reflux or feeding intolerance are where blocking acid secretion is helpful. Although antacids
harder to find.120 Children are more sensitive to extrapyra- or sucralfate may be reasonable for short-term use in pediat-
midal side effects of dopamine blockers. Diphenhydramine rics, the aluminum that can be absorbed from sucralfate and
(Benadryl™) is effective at preventing or treating dystonias, some antacids contraindicates any longer term use.
while lorazepam is often more effective at reducing akath-
isias.121 While akathisias and dystonias are generally easily H2 Receptor Antagonists (Famotidine/Pepcid™,
reversed, there are a few reports of tardive dyskinesias Ranitidine/Zantac™, Nizatidine/Axid™, Cimetidine/
causing long-term movement disorders.120 In February 2009, Tagamet™)
the Food and Drug Administration (FDA) announced it was These drugs block histamine-induced acid secretion.
requiring a “boxed warning” in the labeling regarding the Higher doses of H2 receptor antagonists block acid secre-
risk of tardive dyskinesia with higher doses or longer-term tion better than lower doses, although proton pump
use of metoclopramide. Manufacturers must implement a inhibitors block acid secretion better than high doses of
risk evaluation and mitigation strategy to ensure patients H2 receptor antagonists.125–127 Some data support the use
receive a medication guide discussing the risk.122 The major of H2 receptor antagonists for gastroesophageal reflux
drug interactions involving metoclopramide relate to its disease in infants and young children, although a potential
ability to speed transit through the gut. Drugs that are limitation to chronic use is the development of tolerance to
designed for sustained release or that have slow dissolution the acid neutralization.128 Adverse effects are uncommon
and absorption may have reduced absorption while a patient but include headaches, sedation, and gastrointestinal side

effects. Cimetidine may inhibit the metabolism of some antagonists and dopamine blockers are generally useful for
drugs, but other H2 receptor antagonists are not likely to all 3 causes. Other drugs discussed here are mostly used
affect drug metabolism. Any of these drugs may alter the for chemotherapy-induced nausea and vomiting. The most
absorption of other drugs that are sensitive to higher gastric recent American Society of Clinical Oncology antiemetic
pH (eg, ketoconazole, itraconazole, ampicillin, iron). All guidelines include suggestions regarding radiation-induced
4 of these drugs require reduced doses in patients with emesis.121 The National Comprehensive Cancer Network
renal impairment. H2 receptor antagonists are available in publishes emesis guidelines (updated annually) on its Web
nonprescription formulations. site, and the Multinational Association of Supportive Care
in Cancer also has published guidelines on the Internet.
Proton Pump Inhibitors (Omeprazole/Prilosec™, All of these guidelines currently divide chemotherapy
Lansoprazole/Prevacid™, Pantoprazole/Protonix™, drugs into classes that are high, moderate, low, or minimal
Esomeprazole/Nexium™, Rabeprazole/Aciphex™) likelihood of causing emesis. Combinations of a serotonin
These drugs block hydrogen/potassium ATPase (the receptor antagonist with a steroid and aprepitant (Emend™)
“proton pump”), effectively blocking acid secretion induced are recommended for highly emetogenic chemotherapy
by virtually all stimuli. Proton pump inhibitors have shown regimens by all guidelines. Combinations of a serotonin
good activity in adults with GERD and hypersecretory receptor antagonist and a steroid are generally recom-
syndromes, and there is some evidence for efficacy in chil- mended for moderately emetic regimens, a single agent
dren with gastroesophageal reflux disease.128 As with H-2 (often steroids) for low emetogenicity, and antiemetics only
receptor antagonists, adverse effects are rare but include “as needed” for minimally emetic regimens.
headaches and gastrointestinal effects such as abdominal
pain, constipation, or diarrhea. Altered absorption of other Serotonin Receptor (5HT3 or 5-hydroxytryptamine-3)
drugs can occur due to elevated gastric pH, and omepra- Antagonists (Ondansetron/Zofran™, Granisetron/
zole may inhibit some hepatic P450 enzymes, reducing Kytril™, Dolasetron/Anzemet™, Palonosetron/Aloxi™)
metabolism of some drugs such as warfarin.128 Proton These drugs block the effects of serotonin at the 5HT3
pump inhibitors work best when administered 15 to 30 receptors in the gut and the chemotherapy receptor trigger
minutes before a meal.129 Administration of lansoprazole zone. They are generally better at reducing vomiting than at
or omeprazole through an NG tube is best accomplished by reducing nausea.132 Used in equivalent doses, there are few
either using the lansoprazole Oral Disintegrating Tablet, or differences between these agents, although palonosetron
mixing the enteric coated granules from the lansoprazole has a longer duration of activity, apparently due to its tighter
or omeprazole capsule or packet for suspension in 8.4% binding to receptors and longer half-life. Palonosetron may
sodium bicarbonate solution (1 mEq/mL parenteral solu- be better at preventing delayed nausea and vomiting due
tions are generally used for this).130,131 These formulations to this activity, although most studies have compared it to
are less viscous and appear to go through tubes better. An a single dose of the shorter acting agents, which are more
alternative is mixing the contents with an acidic fruit juice, likely to be used daily. In this class of drugs, the oral route of
which preserves the enteric coating until the granules administration is equally effective as intravenous, as long as
reach the alkaline contents of the small intestine. Another the patient is not actively vomiting. Recently, all antiemetic
alternative may be the intravenous formulations available guidelines have dropped serotonin receptor antagonists
for pantoprazole and lansoprazole. Mixing enteric-coated from their recommended drugs to treat delayed nausea and
granules in water for administration results in a more vomiting (more than 24 hours after chemotherapy) due to the
viscous solution that does not go through enteric tubes as minimal evidence for their efficacy.133 The most likely adverse
well. Dosaging guidelines are not available, but doses may effects with serotonin receptor antagonists are headaches,
need to be reduced in patients with significant hepatic and constipation with multiple-day use.132 Prolongation of
impairment. Omeprazole is available as a nonprescription the QTc interval has been reported with this class of drugs,
drug. although it is generally not thought to be clinically signifi-
cant. However, the dolasetron package insert does contain a
Antiemetics warning regarding use in patients at increased risk of arrhyth-
Antiemetics in pediatric hematology/oncology patients mias, and dolasetron is not approved for use in children
are used primarily for nausea and vomiting due to chemo- in Canada due to reports of cardiovascular adverse effects
therapy, radiation, and surgery. Serotonin receptor (arrhythmias, cardiovascular arrest).134 Patients who have

received therapy with anthracyclines (doxorubicin, dauno- or metoclopramide, but can be used as single agents for mildly
rubicin, idarubicin, epirubicin, mitoxantrone, cisplatin, or emetic regimens. Glucocorticoids have a long list of adverse
ifosfamide) are at the greatest risk for cardiovascular side effects, but the ones most commonly seen with short-term
effects. The latter 2 can cause electrolyte abnormalities due use are hyperglycemia, gastrointestinal upset, hypertension,
to renal tubular losses of calcium, magnesium, potassium, and mental or behavioral changes. Doses should be reduced
phosphate, and bicarbonate. These losses may require supple- when used with aprepitant, as mentioned above.
mentation, and oral supplementation generally tastes bad and
is poorly absorbed. Anthracyclines and mitoxantrone cause Phenothiazines (Prochlorperazine/Compazine™,
damage to cardiac myofibrils that may result in heart failure Promethazine/ Phenergan™, Chlorpromazine/
for some patients. This is most common when young children Thorazine™) and Butyrophenones (Haloperidol/
receive the drug, and at lifetime doses above 300 mg/m2 for Haldol™, Droperidol/Inapsine™)
younger children and 450 to 550 mg/m2 for older children These drugs block dopamine receptors in the vomiting
and adults. Ondansetron has a prolonged half-life in patients center and chemotherapy-receptor trigger-zone. These
with severe liver impairment and doses should be reduced. agents are currently recommended mostly for acute nausea
Palonosetron, dolasetron, and granisetron do not need dose and vomiting from mildly to moderately emetic chemo-
adjustments in renal or hepatic dysfunction.134 therapy regimens, or for breakthrough nausea and vomiting.
Prochlorperazine and promethazine have been used for
Aprepitant (Emend™ and Fosaprepitant, delayed nausea and vomiting with some success. Potential
the Intravenous Emend™) side effects include sedation, anticholinergic effects such
This drug is a neurokinin-1 receptor antagonist (its ligand is as urinary retention or constipation, and alpha-adrenergic
Substance P) that has been found to produce a small reduc- blockade effects such as hypotension. However the major
tion in acute nausea and vomiting, but a larger reduction in adverse effects are extrapyramidal effects: akathisias
delayed nausea and vomiting. The FDA-approved dosing is (restlessness) and dystonias (muscle contraction) such as
for the first 3 days of the chemotherapy regimen, combined trismus and torticollis. These effects occur more frequently
with a serotonin receptor antagonist and a steroid, but not in children and many pediatric practitioners limit the use
as a single agent. Until 2008, only the oral formulation was of dopamine blockers due to these side effects. Diphenhy-
available and therefore there was not an easy way to admin- dramine (Benadryl™) will generally reverse extrapyramidal
ister this drug to most children. Although adolescents are effects within 30 to 60 minutes, and has often been used
often large enough to be dosed as adults, children have gener- prophylactically to reduce the risk of extrapyramidal reac-
ally not been treated with aprepitant. A potential problem tions. Also of note are specific issues with 2 of these drugs.
with aprepitant is its ability to inhibit P450 microsomal First, droperidol is either not used or dose-limited in many
enzymes and reduce metabolism of other drugs. Dexa institutions due to its ability to lengthen the QTc interval
methasone doses of approximately 12 mg with aprepitant and cause arrhythmias. Second, IV promethazine can be
are equivalent to 20 mg without aprepitant. Warfarin doses very irritating on injection, and if injected into an artery
will generally require reduction also. There is concern that can cause significant tissue damage. Many institutions are
some chemotherapy drugs may have reduced clearance limiting its use to low doses or oral administration. Risk
when patients take aprepitant, but currently there are little may be minimal if central lines are available for adminis-
data suggesting clinical problems with this potential inter- tration, which is commonly the situation in children with
action. Regardless, it is important to only use aprepitant cancer. Additionally, promethazine has a boxed warning
for highly emetic regimens as indicated in current practice in the package insert against using it in patients less than 2
guidelines, and to use caution when concomitant chemo- years old, due to reports of fatal respiratory depression.
therapy agents are known to be metabolized by hepatic
P450 enzymes. Cannabinoids (Dronabinol/Marinol™, Nabilone/
Cesamet™)
Glucocorticoids (Dexamethasone/Decadron™, These drugs have been used mostly for patients who have
Methylprednisolone Sodium Succinate/Medrol™) not responded well to more typical antiemetics. These drugs
These drugs have been used as antiemetics since the early are synthetic versions of THC (tetrahydrocannabinol),
1980s, but it is still not clear how they work. They are used the psychoactive component of marijuana. Early studies
mostly in combinations with a serotonin receptor antagonist suggested these agents were most effective in younger adult

patients, patients who had smoked marijuana, and patients the drugs tried, only progestins and glucocorticoids showed
who developed euphoria while taking them. While many a benefit in cancer-induced anorexia and weight loss. There
pediatric institutions have some experience using these are doubts about even these drugs, as the weight gain from
agents in children, there are little data published on use in progestins such as megestrol may consist more of fat and
children, and most of those data are with nabilone. Recom- water than lean body mass136 and glucocorticoids have
mended doses of dronabinol are very high; some patients negative anabolic effects that result in muscle weakness
tolerate the drug better when lower doses are used and over time.
started prior to the chemotherapy. Adverse effects are the Studies have shown at least some increased appetite and
same as for marijuana, including euphoria or dysphoria, weight gain benefit from methylprednisolone (Medrol™),
hypotension, tachycardia, increased appetite, dry mouth, dexamethasone (Decadron™), and prednisone. In addition
and occasionally hallucinations. to the short-term side effects discussed above in the anti-
emetic section, glucocorticoids have numerous long-term
Atypical Antipsychotics (Olanzapine/Zyprexa™) side effects that include osteoporosis, aseptic necrosis, cata-
These drugs are similar to the dopamine blockers discussed racts, easy tearing of the skin, and loss of muscle strength.
above, but are less likely to cause extrapyramidal side Perhaps the best use of these agents for increasing appetite
effects. Very few studies have been published, but there are is in hospice patients where the longer term adverse effects
several case reports and small studies showing efficacy of are of less consequence.
olanzapine in adult patients who have not responded well
to more standard antiemetics.132 Adult recommended doses Megestrol/Megace™ and Medroxyprogesterone/
are 5 to 10 mg per day, with 2.5 to 5 mg per day being used Provera™
in case reports in children. Other than sedation, few side These drugs are progestins that have an effect of increasing
effects have been reported with short-term use. appetite and causing weight gain. Most studies of megestrol
have involved only adults, but one pediatric study used
Antihistamines (Diphenhydramine/Benadryl™) and megestrol in a few patients for whom cyproheptadine (see
Benzodiazepines (Lorazepam/Ativan™) below) did not work. Five of 7 children responded with
These drugs have been used as adjunctive agents for che- weight gain.137 As noted above, there is some doubt about the
motherapy-induced nausea and vomiting. Neither has nature of the weight gained (fluid retention or fat versus lean
good activity on its own as an antiemetic for chemotherapy, body weight), but there are numerous studies documenting
although the sedation they cause may help the patient sleep the weight gain.135 Potential adverse effects of significance
and have less nausea and vomiting. Diphenhydramine has include thrombophlebitis, photosensitivity, impotence in
good anticholinergic activity in the brain, and is therefore men, and Cushing’s syndrome with adrenocortical suppres-
able to reduce and/or treat extrapyramidal reactions from sion and the potential for Addisonian crisis.134,138
dopamine blockers. Likewise, lorazepam is beneficial in
reducing or treating akathisias caused by dopamine block- Dronabinol/Marinol™ (But Not Nabilone)
ers. Lorazepam’s activity as an antianxiety medication and This drug has been studied for weight gain in adults, and
its ability to cause anterograde amnesia in some patients may is FDA approved for treating anorexia in AIDS patients.
help reduce anticipatory nausea and vomiting. Some pediat- Little data are available on use in cancer patients with
ric patients develop paradoxical reactions to these agents, anorexia or in pediatrics. While it does stimulate appetite
becoming agitated instead of sedated. This appears to be for periods of at least 5 months, there is minimal evidence
more common in younger patients and with higher doses. for efficacy in causing weight gain or reducing weight loss in
Additionally, some pediatric patients become weepy or have cancer patients.134,135,138,139 As noted above in the antiemetic
hallucinations, limiting the usefulness of lorazepam. section, there are many potential adverse effects associated
with dronabinol, however the doses used for appetite stim-
Appetite Stimulants ulation are lower (2.5 mg twice daily) than those used for
Weight loss in cancer patients may be due to numerous antiemesis, so there may be fewer adverse effects.
factors, as described in detail in the prior sections. Appetite
stimulants have been used in attempts to counter weight Cyproheptadine/Periactin™
loss in cancer patients, but studies have had mixed results. This drug is a serotonin antagonist and antihistamine that
A review of adult studies by Yavuzsen135 suggests that of all has been studied as an appetite stimulant in cancer patients.

An earlier study in adults showed increased appetite to maintain oral intake. Opioids can be very helpful, but
but no less weight loss than with a placebo in adults with frequently subject the patient to constipation and some-
advanced malignancies.140 A recent study in children with times to nausea and vomiting, itching, or when dosed
cancer found that many did respond with weight gain, with excessively, respiratory depression. A number of drugs have
drowsiness as the only common side effect.137 Studies with been used in attempts to reduce the frequency and severity
this agent are ongoing in children. Doses may need to be of mucositis (prevention).
reduced in patients with hepatic impairment.
Chlorhexidine/Peridex™
Medications for Mucositis Chlorhexidine/Peridex™ has antiseptic-type effects, and
Mucositis consists of inflammatory ulcerations in the mouth since mucositis can result from fungal or viral mouth infec-
and gut that usually result from chemotherapy, radiation, tions, this product might help. However there is minimal
or the conditioning regimens for HSCT. Mucositis occurs evidence for benefits in preventing or treating mucositis
inconsistently after chemotherapy regimens outside of the with chlorhexidine. Recent guidelines from the Multina-
transplant setting, and the time course after chemotherapy tional Association of Supportive Care in Cancer (MASCC)
generally parallels that of neutropenia. These features make do not recommend its use for either prophylaxis or treat-
it difficult to study since it occurs erratically and resolves ment.141 Since most chlorhexidine-containing products also
with or without therapy. Medications used for mucositis fit contain alcohol, they may elicit pain in patients who already
into two categories: prevention or treatment. Treatments have mucositis.
treat symptoms, having little if any effect on the healing
rate of the mucositis. When mucositis is seen in the mouth, Glutamine
presumably it is occurring throughout the gut, including Glutamine is an amino acid that is thought to be espe-
the stomach. Administration of acid-blocking drugs is cially important to cells of the gut. Studies in the past have
commonly thought to help, although data on the value of suggested that it might help maintain the integrity of the gut
this treatment are scarce. Medications used to treat symp- in patients receiving long-term total parenteral nutrition, or
toms of mucositis include drugs such as “Magic Mouthwash” may help prevent chemotherapy-induced mucositis. Studies
combinations, Gelclair™, and opioids. have suggested reductions in mucositis for autologous stem
cell transplant patients, but there also has been a suggestion
Magic Mouthwash of increased relapses.141–143 The most recent MASCC guide-
This usually contains viscous lidocaine, diphenhydramine, lines do not recommend the use of glutamine, but there is
and an antacid or nystatin. Lidocaine is a strong local anes- enough interest that studies of specialized formulations of
thetic, diphenhydramine is a weak local anesthetic, and the glutamine are in clinical trials.
antacid may help neutralize acid in the stomach, although
the dose is probably too low to effectively raise gastric pH. Palifermin/Kepivance™
Nystatin is in combinations at some institutions because Palifermin/Kepivance™ is a recombinant human kerati-
mucositis may cause or be caused by Candida infections nocyte growth factor. It is approved and used for reducing
(thrush). There are little if any published data on the effi- mucositis in patients with hematologic malignancies
cacy of these combinations, but they relieve symptoms in receiving hematopoietic stem cell transplants. Use in solid
some patients. Combinations containing viscous lidocaine tumors is considered contraindicated by many practitio-
have been reported to cause systemic lidocaine toxicity if ners due to the potential for stimulating epithelial cells (and
used in relatively high or frequent doses, especially in small perhaps the cancers); however, studies in solid tumors in
children or infants. Doses should be limited if the medica- patients receiving standard chemotherapy are in progress.
tion is to be swallowed. This is not a problem if it is swished Palifermin is expensive and does cause some side effects
and spit out. Gelclair™ is a polymer-type combination of such as “thick tongue,” altered taste, and rashes. Palifermin
polyvinylpyrrolidone, hyaluronic acid, and glycyrrhetinic has been demonstrated to reduce the duration and severity
acid. It coats the mucosa of the mouth, protecting it from of oral mucositis as well as the use of opioids in patients
air and irritants that elicit pain. It is suggested not to eat or receiving autologous HSCT for hematologic malignancies.
drink for an hour or more after using the Gelclair™. Some There are less data for allogeneic transplants.
patients seem to benefit from this product. Opioids are used The MASCC guidelines mention numerous other
when less potent treatments fail, and may allow the patient products (favorably or unfavorably), most of which are

not currently used in pediatrics. Slurries or suspensions of 5. Survivors of childhood cancer can be at greater risk for
sucralfate (Carafate™) have been used in children with oral osteoporosis due to:
mucositis, but there is a lack of efficacy data in general, plus A. History of corticosteroid use
several negative studies in adults with radiation-induced B. Methotrexate containing regimen
oral mucositis.141 Another product that is being studied C. Use of anticonvulsants
currently in children is Traumeel S™. It is a homeopathic D. All of the above
mixture of approximately a dozen herbals or supplements
that is not thought to have side effects, although allergies See p. 487 for answers.
to ingredients would be a possibility. One study in children
and young adults receiving stem cell transplants showed References
favorable results and further studies are ongoing.144 1. National Cancer Institute, Surveillance Epidemiology and
End Results. SEER Cancer Statistics Review, 1975-2006.
http://seer.cancer.gov/csr/1975_2006. Accessed December
Test Your Knowledge Questions 3, 2009.
1. Mucositis is one of the complications affecting the 2. Donaldson SS, Wesley MN, DeWys WD, Suskind RM, Jaffe
nutrition status of the pediatric oncology patient. N, van Eys J. A study of the nutritional status of pediatric
Which chemotherapy agent is most likely to lead to the cancer patients. Am J Dis Child. 1981;135:1107–1112.
development of mucositis? 3. Coates TD, Rickard KA, Grosfeld JL, Weetman RM. Nutri-
tion support of children with neoplastic diseases. Surg Clin
A. Methotrexate
North Am. 1986;66:1197–1212.
B. Cyclophosphamide 4. Mauer AM, Burgess JB, Donaldson SS, et al. Special nutri-
C. Cytarabine tional needs of children with malignancies: a review. J Parenter
D. Carboplatin Enteral Nutr. 1990;14(3):315–324.
2. One of the leading causes of death within the first 2 5. Cady J. Nutritional support during radiotherapy for head and
months post-hematopoietic transplant is sinusoidal neck cancer: the role of prophylactic feeding tube placement.
Clin J Oncol Nurs. 2007;11(6):875–880.
obstruction syndrome. Which of the following are 6. Han-Markey T. Nutritional considerations in pediatric
symptoms associated with the development of SOS? oncology. Semin Oncol Nurs. 2000;16(2):146–151.
A. Nausea, vomiting, bloody urine 7. Rickard KA, Gosfeld JL, Kirksey A, Ballantin TV, Baehner RL.
B. Weight gain, ascites, hyperbilirubinemia, hepatomegaly Reversal of protein-energy malnutrition during treatment of
C. Pruritic rash, diarrhea, protein losing enteropathy advanced neoplastic disease. Ann Surg. 1979;190(6):771–781.
8. Lahorra JM, Ginn-Pease ME, King DR. The prognostic signi
D. Dysgeusia, mouth sores, nausea
ficance of basic anthropometric data in children with advanced
3. The use of EN in hematopoietic transplant is commonly solid tumors. Nutr Cancer. 1989;12(4):361–369.
discouraged because of: 9. Cancer Therapy Evaluation Program. Common Toxicity
A. The need of frequent tube replacement Criteria Document for Adverse Events, Version 3.0. DCTD,
B. Risk of excessive bleeding with tube placement due NCI, NIH, DHHS. http://ctep.cancer.gov. Accessed
to mucositis November 19, 2008.
10. Carter P, Carr D, van Eys J, Coody D. Nutritional parameters in
C. Dislodgement of the feeding tube children with cancer. J Am Diet Assoc. 1983;82(6):616–622.
D. All of the above 11. Smith DE, Stevens MC, Booth IW. Malnutrition at diagnosis
4. Which is TRUE regarding agents used to enhance gut of malignancy in childhood: common but mostly missed. Eur
motility? J Pediatr. 1991;150(5):318–322.
A. Use of erythromycin to enhance gut motility 12. Donaldson SS, Wesley MN, Ghavii F, Shils ME, Suskind
RM, DeWys WD. A prospective randomized clinical trial of
increases resistance among susceptible bacteria.
total parenteral nutrition in children with cancer. Med Pediatr
B. Children are more susceptible to the extrapyra- Oncol. 1982;10(2):129–139.
midal side effects of both metoclopramide and 13. Barrera R. Nutrition support in cancer patients. J Parenter
erythromycin than are adults. Enteral Nutr. 2002;26(Suppl 5):S63–S71.
C. Case reports of tardive dyskinesias with the use of 14. National Cancer Institute. Nutrition in Cancer Care (PDQ ).
metoclopramide are too infrequent to be consid- http://www.cancer.gov/cancerinfo/pdq/supportivecare/
nutrition/healthprofessional. Accessed November 1, 2008.
ered clinically important. 15. Unsal D, Mentes B, Akmansu M, et al. Evaluation of nutri-
D. Motility-enhancing agents may increase or decrease tional status in cancer patients receiving radiotherapy: a
the absorption of other drugs. prospective study. Am J Clin Oncol. 2006;29(2):183–188.

16. Ogama N, Suzuki S, Umeshita K, et al. Appetite and adverse 33. National Cancer Institute. Nutrition in Cancer Care (PDQ ):
effects associated with radiation therapy in patients with head Depression. Supportive Care. http://www.cancer.gov/cancer-
and neck cancer. Eur J Oncol Nurs. 2009;Sep 4 [Epub ahead topics/pdq/supportivecare/depression/healthprofessional.
of print]. Accessed March 20, 2009.
17. Wilkes C, Ingwersen K, Barton-Burke M. Oncology Nursing 34. Gilbreah J, Inman-Felton A, et al. Medical Nutrition Therapy
Drug Handbook. Sudbury, Mass: Jones & Bartlett Publishers; Across the Continuum of Care-Client Protocols. 2nd ed. Chicago,
2003. IL: The American Dietetic Association; 1998.
18. Baltzer CL, Haywood R. Oncology Pocket Guide to 35. Ladas EJ, Sacks N, et al. Standards of nutritional care in
Chemotherapy. 5th ed. Philadelphia, PA: Mosby Medical pediatric oncology: results from a nationwide survey on
Communications/Elsevier Science; 2002. the standards of practice in pediatric oncology. A Chil-
19. Tyc VL, Vallelunga L, Mahoney S, Smith BF, Mulhern RK. dren’s Oncology Group study. Pediatr Blood Cancer.
Nutritional and treatment-related characteristics of pedi- 2006;46(3):339–344.
atric oncology patients referred or not referred for nutritional 36. Green GJ, Weitzman SS, et al. Resting energy expenditure
support. Med Pediatr Oncol. 1995;25(5):379–388. in children newly diagnosed with stage IV neuroblastoma.
20. Barber MD, Ross JA, Fearon KC. Cancer cachexia. Surg Oncol. Pediatr Res. 2008;63(3): 332–336.
1999;8(3):133–141. 37. Fuhrman MP, Charney P, et al. Hepatic proteins and nutrition
21. National Cancer Institute. Dictionary of Cancer Terms. http:// assessment. J Am Diet Assoc. 2004;104(8):1258–1264.
www.nci.nih.gov/Templates/db_alpha.aspx?CdrID=44111. 38. Rickard KA, Detamore CM, et al. Effect of nutrition staging
Accessed November 29, 2008. on treatment delays and outcome in Stage IV neuroblastoma.
22. Martindale RD, Shikora SA, Nishikawa R, et al. The metabolic Cancer. 1983;52(4):587–598.
response to stress and alterations in nutrient metabolism. In: 39. Lobato-Mendizabal E, Ruiz-Arguelles GJ, et al. Leukaemia
Shikora SA, Martindale RG, Schwaitzberg SD, eds. Nutri- and nutrition. I: Malnutrition is an adverse prognostic factor in
tional Consideration in the Intensive Care Unit. Silver Spring, the outcome of treatment of patients with standard-risk acute
MD: American Society for Parenteral and Enteral Nutrition; lymphoblastic leukaemia. Leuk Res. (1989);13(10):899–906.
2002:11–19. 40. Charuhas PM. Introduction to marrow transplant. American
23. Jones MO, Pierro A, Hammond P, Lloyd DA. The meta- Dietietics Association, Oncology Nutrition Dietetic Practice
bolic response to operative stress in infants. J Pediatr Surg. Group Newsletter. 1994;2:2–9.
1993;28(1):1258–1263. 41. Andrassy RJ, Chwals WJ. Nutritional support of the pediatric
24. Moschovi M, Trimis G, et al. Serial plasma concentrations ocology patient. Nutrition. 1998;14(1):124–129.
of PYY and ghrelin during chemotherapy in children with 42. White M, Murphy AJ, et al. Nutritional status and energy
acute lymphoblastic leukemia. J Pediatr Hematol Oncol. expenditure in children pre-bone-marrow-transplant. Bone
2008;30(10):733–737. Marrow Transplant. 2005:35(8):775–779.
25. Ovesen L, Allingstrup L, et al. Effect of dietary coun- 43. Reilly JJ, Odame I, et al. Does weight for height have prognostic
seling on food intake, body weight, response rate, survival, significance in children with acute lymphoblastic leukemia?
and quality of life in cancer patients undergoing chemo- Am J Pediatr Hematol Oncol. 1994;16(3):225–230.
therapy: a prospective, randomized study. J Clin Oncol. 44. Pedrosa F, Bonilla M, et al. Effect of malnutrition at the time
1993;11(10):2043–2049. of diagnosis on the survival of children treated for cancer in
26. Cravo M L, Gloria LM, et al. Metabolic responses to tumour El Salvador and Northern Brazil. J Pediatr Hematol Oncol.
disease and progression: tumour-host interaction. Clin Nutr. 2000;22(6):502–505.
2000;19(6):459–465. 45. Rickard KA, Foland BB, et al. Effectiveness of central parenteral
27. Argiles JM, Moore-Carrasco R, Busquets S, Lopez-Soriano nutrition versus peripheral parenteral nutrition plus enteral
FJ. Catabolic mediators as targets for cancer cachexia. Drug nutrition in reversing protein-energy malnutrition in children
Discov Today. 2003;8(18):838–844. with advanced neuroblastoma and Wilms’ tumor: a prospec-
28. Dunlop RJ, Campbell CW. Cytokines and advanced cancer. J tive randomized study. Am J Clin Nutr. 1983;38(3):445–456.
Pain Symptom Manage. Sep 2000;20(3):214–232. 46. Viana MB, Murano M, Ramos G, et al. Malnutrition as a
29. Bosaeus I, Daneryd P, et al. Dietary intake, resting energy prognostic factor in lymphoblastic leukemia: a multivariate
expenditure, weight loss and survival in cancer patients. J analysis. Arch Dis Child. 1994;71(4):304–310.
Nutr. 2002;132(11 Suppl):3465S–3466S. 47. Mejia-Arangure JM, Fajardo-Gutierrez A, Reyes-Ruiz NI,
30. Eden E, Edstrom S, et al. Glucose flux in relation to energy et al. Malnutrition in childhood lymphoblastic leukemia: a
expenditure in malnourished patients with and without predictor of early mortality during the induction to remission
cancer during periods of fasting and feeding. Cancer Res. phase of treatment. Arch Med Res. 1999;30(2):150–153.
(1984) 44(4):1718–1724. 48. Hafitz MG, Mannan MA. Nutritional status at initial
31. National Cancer Institute. Dictionary of Cancer presentation in childhood acute lymphoblastic leukemia
Terms. http:w w w.nci.nih.gov/Templates/db_a lpha. and its effect on induction of remission. 2007;17(2
aspx?CdrlD=44111. Accessed November 29, 2008. (supplemental)):S46–S51.
32. Lelbach A, Muzes G, et al. Current perspectives of cata-
bolic mediators of cancer cachexia. Med Sci Monit.
2007;13(9):RA168–173.

49. Halton JM, Scissons-Fisher CC. Impact of nutritional status 66. Duro D, Bechard LJ, et al. Weekly measurements accurately
on morbidity and dose intensity of chemotherapy during represent trends in resting energy expenditure in children
consolidation therapy in children with acute lymphoblastic undergoing hematopoietic stem cell transplantation. J Parenter
leukemia (ALL). J Pediatr Hematol Oncol. 1999;21:317. Enteral Nutr. 2008;32(4):427–432.
50. Obama M, Cangir A, van Eys J. Nutritional status and 67. Charuhas PM, Lipkin A, et al. Hematopoietic stem cell trans-
anthracycline cardiotoxicity in children. South Med J. plantation. In: Merritt RJ, DeLegge M, Holcombe B, et al,
1983;76(5):577–578. eds. The A.S.P.E.N. Nutrition Support Practice Manual. 2nd
51. Hays DM, Merritt RJ, et al. Effect of total parenteral nutri- ed. Silver Spring, MD: American Society for Parenteral and
tion on marrow recovery during induction therapy for acute Enteral Nutrition; 2005.
nonlymphocytic leukemia in childhood. Med Pediatr Oncol. 68. Bechard LJ, McCarthy TC. Oncology and stem cell trans-
1983;11(2):134–140. plantation. In: Baker SS, Baker RD, Davis AM. Pediatric
52. Bakish JD, Hargrave, et al. Evaluation of dietetic intervention Nutrition Support. Sudbury, MA: Jones and Bartlett Publishers;
in children with medulloblastoma or supratentorial primitive 2007:433–445.
neuroectodermal tumors. Cancer. 2003;98(5):1014–1020. 69. Charuhas PM. Nutrition management of oncology and
53. den Broeder E, Lippens RJ, et al. Effects of naso-gastric tube marrow/hematopoietic stem cell transplantation. In:
feeding on the nutritional status of children with cancer. Eur J Amorde-Spalding K, Nieman L, eds. Pediatric Manual of Clin-
Clin Nutr. 1998;52(7):494–500. ical Dietetics. 2nd ed. Update. Chicago, IL: American Dietetic
54. Barron MA, Duncan DS, et al. Efficacy and safety of radio- Association; 2008:175–184.
logically placed gastrostomy tubes in paediatric haematology/ 70. Bunting D, D’Souza S. Texas Children’s Hospital Pediatric
oncology patients. Med Pediatr Oncol. 2000;34(3):177–182. Nutrition Reference Guide. 8th ed. 2008.
55. Sacks N, Lange B, et al. Pilot study of proactive enteral tube 71. Charuhas PM, Gautier ST. Parenteral nutrition in pediatric
feedings in children receiving chemotherapy for newly diag- oncology. In: Chernoff R, Baker RD, Baker SS, Davis AM.
nosed AML/MDS, CNS, and high-risk solid tumors. Neuro Pediatric Parenteral Nutrition. New York, NY: Chapman and
Oncol. 2008;10(3):458. Hall; 1997.
56. Rickard KA, Becker MC, et al. Effectiveness of two methods 72. Wickham RS, Rehwaldt M, et al. Taste changes experienced
of parenteral nutrition support in improving muscle mass of by patients receiving chemotherapy. Oncol Nurs Forum.
children with neuroblastoma or Wilms’ tumor. A randomized 1999;26(4):697–706.
study. Cancer. 1989;64(1):116–125. 73. Capra S, Ferguson M, et al. Cancer: impact of nutrition inter-
57. Donaldson SS. Effects of therapy on nutritional status of the vention outcome--nutrition issues for patients. Nutrition.
pediatric cancer patient. Cancer Res. 42(2 Suppl)729s–736s. 2001;17(9):769–772.
58. Kelly KM, Jacobson JS, et al. Use of unconventional therapies 74. Roberts S, Thompson J. Graft-vs-host disease: nutri-
by children with cancer at an urban medical center. J Pediatr tion therapy in a challenging condition. Nutr Clin Pract.
Hematol Oncol. 2000;22(5):412–416. 2005;20(4):440–450.
59. Kemper KJ, Vohra S, et al. American Academy of Pediatrics. 75. Centers for Disease Control and Prevention. Food Safety.
The use of complementary and alternative medicine in pediat- http://w w w.cdc.gov/foodsafety/disease.htm. Accessed
rics. Pediatrics. 2008;122(6):1374–1386. November 20, 2008.
60. Chwals WJ, Letton RW, et al. Stratification of injury severity 76. Moody K, Finlay J, et al. Feasibility and safety of a pilot
using energy expenditure response in surgical infants. J Pediatr randomized trial of infection rate: neutropenic diet versus
Surg. 1995;30(8):1161–1164. standard food safety guidelines. J Pediatr Hematol Oncol.
61. Btaiche IF, Marik P, et al. Nutrition in Critical Illness, 2006;28(3):126–133.
Including Immunonutrition. The A.S.P.E.N. Nutrition Support 77. VanTiel FH, Harbers MM, et al. Normal hospital and low-
Practice Manual. 2nd ed. Silver Spring, MD: American Society bacterial diet in patients with cytopenia after intensive
for Parenteral and Enteral Nutrition; 2002:263–270. chemotherapy for hematological malignancy: a study of safety.
62. Choi K, Lee SS, et al. The effect of oral glutamine on 5-fluo- Annals of Oncology. 2007;18(6):1080–1084.
rouracil/leucovorin-induced mucositis/stomatitis assessed 78. August DA, Huhmann MB. A.S.P.E.N. clinical guidelines:
by intestinal permeability test. Clin Nutr. 2007;26(1):57–62. nutrition support therapy during adult anticancer treatment
63. Cheney CL, Abson KG, et al. Body composition changes in and in hematopoietic cell transplantation. J Parenter Enteral
marrow transplant recipients receiving total parenteral nutri- Nutr. 2009;33(5):472–500.
tion. Cancer. 1987;59(8):1515–1519. 79. De Santas K, Vlachos A. Care of the hematopoietic stem
64. Ringwald-Smith K, Williams R, et al. Determination of cell transplant patient after leaving the transplant center. In:
energy expenditure in bone marrow transplant patient. Nutr Altman, AJ. Supportive Care of Children with Cancer: Current
Clin Pract. 1998;13(5):215–218. Therapy and Guidelines from the Children’s Oncology Group.
65. Duggan C, Bechard L, et al. Changes in resting energy 3rd ed. Baltimore, MD: The Johns Hopkins University Press;
expenditure among children undergoing allogeneic stem cell 2004:286–333.
transplantation. Am J Clin Nutr. 2003;78(1):104–109. 80. Hopman GD, Pena EG, et al. Tube feeding and bone marrow
transplantation. Med Pediatr Oncol. 2003;40(6):375–379.
81. Hastings Y, White M, et al. Enteral nutrition and bone marrow
transplantation. J Pediatr Oncol Nurs. 2006;23(2): 103–110.

82. Papadopoulou A, Nathavitharana K, et al. Diagnosis and 99. Przepiorka D, Weisdorf D, et al. 1994 Consensus Confer-
clinical associations of zinc depletion following bone marrow ence on Acute GVHD Grading. Bone Marrow Transplant.
transplantation. Arch Dis Child. 1996;74(4):328–331. 1995;15(6):825–828.
83. Sefcick A, Anderton D, et al. Naso-jejunal feeding in alloge- 100. Cahn JY, Klein JP, et al. Prospective evaluation of 2 acute
neic bone marrow transplant recipients: results of a pilot study. graft-versus-host (GVHD) grading systems: a joint Societe
Bone Marrow Transplant. 2001;28(12):1135–1139. Francaise de Greffe de Moelle et Therapie Cellulaire (SFGM-
84. Weisdorf SA, Lysne J, et al. Positive effect of prophylactic total TC), Dana Farber Cancer Institute (DFCI), and International
parenteral nutrition on long-term outcome of bone marrow Bone Marrow Transplant Registry (IBMTR) prospective
transplantation. Transplantation. 1987;43(6):833–838. study. Blood. 2005;106(4):1495–1500.
85. Dunn RL, Stettler N, et al. Refeeding syndrome in hospital- 101. Petersdorf EW, Longton GM, et al. The significance of
ized pediatric patients. Nutr Clin Pract. 2003;18(4):327–332. HLA-DRB1 matching on clinical outcome after HLA-A, B,
86. Tresley J, Sheean PM.Refeeding syndrome: recognition is DR identical unrelated donor marrow transplantation. Blood.
the key to prevention and management. J Am Diet Assoc. 1995;86(4):1606–1613.
2008;108(12):2105–2108. 102. Barker JN, Wagner JE. Umbilical-cord blood trans-
87. Stern J M. Oncology fluid and electrolyte disorders. Support plantation for the treatment of cancer. Nat Rev Cancer.
Line. 2005;27:19–27. 2003;3(7):526–532.
88. Gabay C, Kushner I. Acute-phase proteins and other 103. Zecca M, Prete A, et al. Chronic graft-versus-host disease
systemic responses to inflammation. N Engl J Med in children: incidence, risk factors, and impact on outcome.
1999;340(6):448–454. Blood. 2002;100(4):1192–1200.
89. Rodgers C, Wills-Alcoser P, et al. Growth patterns and 104. Atkinson K. Chronic graft-versus-host disease. Bone Marrow
gastrointestinal symptoms in pediatric patients after Transplant. 1990;5(2):69–82.
hematopoietic stem cell transplantation. Oncol Nurs Forum. 105. Akpek G, Valladares JL, et al. Pancreatic insufficiency in
2008;35(3):443–448. patients with chronic graft-versus-host disease. Bone Marrow
90. Wasilewski-Masker K, Kaste SC, et al. Bone mineral Transplant. 2001;27(2):163–166.
density deficits in survivors of childhood cancer: long-term 106. Barker CC, Anderson RA, et al. GI complications in
follow-up guidelines and review of the literature. Pediatrics. pediatric patients post-BMT. Bone Marrow Transplant.
2008;121(3):e705–713. 2005;36(1):51–58.
91. Rubenstein EB, Peterson DE, et al. Clinical practice guidelines 107. Chakrabarti S, Collingham KE, et al. Isolation of viruses from
for the prevention and treatment of cancer therapy-induced stools in stem cell transplant recipients: a prospective surveil-
oral and gastrointestinal mucositis. Cancer. 2004;100(9 lance study. Bone Marrow Transplant. 2000;25(3):277–282.
Suppl): 2026–2046. 108. Wingard JR. Opportunistic infections after blood and marrow
92. Classen DC, Burke JP, et al. Streptococcus mitis sepsis in transplantation. Transpl Infect Dis. 1999;1(1):3–20.
bone marrow transplant patients receiving oral antimicrobial 109. Burgunder MR, Dickson BJ. Hematopoietic stem cell trans-
prophylaxis. Am J Med. 1990;89(4):441–446. plantation. In: Kogut VJ, Luthringer SL. Nutritional Issues
93. Filipovich AH, Weisdorf D, et al. National Institutes of in Cancer Care. Pittsburgh, PA: Oncology Nursing Society;
Health consensus development project on criteria for clinical 2005:253–263.
trials in chronic graft-versus-host disease: I. Diagnosis and 110. Richardson PG, Elias AD, et al. Treatment of severe veno-
staging working group report. Biol Blood Marrow Transplant. occlusive disease with defibrotide: compassionate use results
2005;11(12):945–956. in response without significant toxicity in a high-risk popula-
94. Griffith LM, Pavletic SZ, et al. Chronic graft-versus-host tion. Blood. 1998;92(3):737–744.
disease–implementation of the National Institutes of Health 111. Kumar S, DeLeve L, Kamath P, Tefferi A. Hepatic veno-
Consensus Criteria for Clinical Trials. Biol Blood Marrow occlusive disease (sinusoidal obstruction syndrome) after
Transplant. 2008;14(4):379–384. hematopoietic stem cell transplantation. Mayo Clin Proc.
95. MacMillan ML, Weisdorf DJ, et al. Response of 443 patients 2003;78:589–598.
to steroids as primary therapy for acute graft-versus-host 112. Cesaro S, Pillon M, et al. A prospective survey on incidence,
disease: comparison of grading systems. Biol Blood Marrow risk factors and therapy of hepatic veno-occlusive disease
Transplant. 2002;8(7):387–394. in children after hematopoietic stem cell transplantation.
96. Koc S, Leisenring W, et al. Therapy for chronic graft- Haematologica. 2005;90(10):1396–1404.
versus-host disease: a randomized trial comparing 113. Song JS, Seo JJ, et al. Prophylactic low-dose heparin or prosta-
cyclosporine plus prednisone versus prednisone alone. glandin E1 may prevent severe veno-occlusive disease of the
Blood. 2002;100(1):48–51. liver after allogeneic hematopoietic stem cell transplantation
97. Martin PJ, Schoch G, et al. A retrospective analysis of therapy in Korean children. J Korean Med Sci. 2006;21(5):897–903.
for acute graft-versus-host disease: initial treatment. Blood. 114. National Cancer Institute. Nutrition in Cancer Care (PDQ ).
1990;76(8):1464–1472. http://www.cancer.gov/cancerinfo/pdq/supportivecare/
98. Ferrara JL, Levine JE, et al. Graft-versus-host disease. Lancet nutrition/healthprofessional. Accessed November 1, 2008.
2009;373(9674):1550–1561.

115. Children’s Oncology Group. Long-term Follow-up Guide- 133. Geling O, Eichler HG. Should 5-hydroxytryptamine-3
lines for Survivors of Childhood, Adolescent and Young receptor antagonists be administered beyond 24 hours after
Adult Cancers. Version 3.0. Last updated March 2008. http:// chemotherapy to prevent delayed emesis? Systematic re-eval-
www.survivorshipguidelines.org/pdf/LTFUGuidelines.pdf. uation of clinical evidence and drug cost implications. J Clin
Accessed November 26, 2008. Oncol. 2005;23:1289–1294.
116. Schwartz CL. Late effects of treatment in long-term survivors 134. Taketomo CK, Hodding JH, et al. Pediatric Dosage Handbook.
of cancer. Cancer Treat Rev. 1995;21(4):355–366. Hudson, Ohio: Lexicomp; 2007.
117. Castellino S. GI Health - Gastrointestinal Health after Child- 135. Yavuzsen T, Davis MP, et al. Systematic review of the treat-
hood Cancer. Health Link - Healthy living after treatment for ment of cancer-associated anorexia and weight loss. J Clin
childhood cancer GI health, Version 3.0 - 10/08; 2008. Oncol. 2005;23(33):8500–8511.
118. AICR. Nutrition and the Cancer Survivor, Special Population 136. Loprinzi CL, Schaid DJ, et al. Body-composition changes in
Series. Washington, D.C.: American Institute for Cancer patients who gain weight while receiving megestrol acetate. J
Research; 2001. Clin Oncol. 1993;11(1):152–154.
119. Friedman D, Hudson MM, Landier W. Heart Health – 137. Couluris M, Mayer JL, et al. The effect of cyproheptadine
Keeping Your Heart Healthy after Treatment for Childhood hydrochloride (periactin) and megestrol acetate (megace) on
Cancer. Health Link – Healthy living after treatment for weight in children with cancer/treatment-related cachexia. J
childhood cancer Version 3.0 - 10/08; 2008. Pediatr Hematol Oncol. 2008;30(11):791–797.
120. Chicella MF, Batres LA, et al. Prokinetic drug therapy in 138. Jatoi A, Windschitl HE, et al. Dronabinol versus megestrol
children: a review of current options. Ann Pharmacother. acetate versus combination therapy for cancer-associated
2005;39(4):706–711. anorexia: a North Central Cancer Treatment Group study. J
121. Kris MG, Hesketh PJ, et al. American Society of Clinical Clin Oncol. 2002;20(2):567–573.
Oncology guideline for antiemetics in oncology: update 2006. 139. Strasser F, Luftner D, et al. Comparison of
J Clin Oncol. 2006;24(18):2932–2947. orally administered cannabis extract and delta-9-
122. Food and Drug Administration. U.S. Food and Drug Admin- tetrahydrocannabinol in treating patients with cancer-
istration. 2009. http://www.fda.gov. related anorexia-cachexia syndrome: a multicenter, phase III,
123. Food and Drug Administration. Metoclopramide boxed randomized, double-blind, placebo-controlled clinical trial
warning announcement. http://www.fda.gov/NewsEv- from the Cannabis-In-Cachexia-Study-Group. J Clin Oncol.
ents/Newsroom/PressAnnouncements/ucm.149533.htm. 2006;24(21):3394–3400.
Accessed September 1, 2009. 140. Kardinal CG, Loprinzi CL, et al. A controlled trial of cypro-
124. Curry JI, Lander TD, et al. Review article: erythromycin as heptadine in cancer patients with anorexia and/or cachexia.
a prokinetic agent in infants and children. Aliment Pharmacol Cancer. 1990;65(12): 2657–2662.
Ther. 2001;15(5):595–603. 141. Keefe DM, Schubert MM, et al. Updated clinical practice
125. Cuttica CE, Chicella MF, et al. Comparison of pantoprazole, guidelines for the prevention and treatment of mucositis.
omeprazole and ranitidine in children requiring acid suppres- Cancer. 2007;109(5):820–831.
sion: a prospective pilot study. J Pediatr Pharmacol Ther. 142. Anderson PM, Ramsay NK, et al. Effect of low-dose oral
2004;9:198–201. glutamine on painful stomatitis during bone marrow trans-
126. Khan S, Shalaby TM, et al. The effects of increasing doses of plantation. Bone Marrow Transplant. 1998;22(4):339–344.
ranitidine on gastric pH in children. J Pediatr Pharmacol Ther. 143. Cockerham MB, Weinberger BB, et al. Oral glutamine for
2004;9(4):259–264. the prevention of oral mucositis associated with high-dose
127. Wedlake LJ, Loader G. Cancer therapy-induced mucositis: paclitaxel and melphalan for autologous bone marrow trans-
Where are we now? Clin Nutr Highlights. 2007;3:2–9. plantation. Ann Pharmacother. 2000;34(3):300–303.
128. Whitworth J, Christensen ML. Clinical management of 144. Oberbaum M, Yaniv I, et al. A randomized, controlled
infants and children with gastroesophageal reflux disease. J clinical trial of the homeopathic medication TRAUMEEL
Pediatr Pharmacol Ther. 2004;9(4):243–253. S in the treatment of chemotherapy-induced stomatitis
129. Hatlebakk JG, Katz PO, et al. Proton pump inhibitors: better in children undergoing stem cell transplantation. Cancer.
acid suppression when taken before a meal than without a 2001;92(3):684–690.
meal. Aliment Pharmacol Ther. 2000;14(10):1267–1272.
130. Woods DJ, McClintock AD. Omeprazole administration. Ann
Pharmacother. 1993;27(5):651.
131. Olabisi A, Chen J, et al. Evaluation of different lansoprazole
formulations for nasogastric or orogastric administration.
Hosp Pharm. 2007;42(6):537–543.
132. Schwartzberg LS. Chemotherapy-induced nausea and
vomiting: which antiemetic for which therapy? Oncology
(Williston Park). 2007;21(8):946–953; discussion 954, 959,
962 passim.

31
Trauma and Burns
Arlet G. Kurkchubasche, MD

Nutrition Considerations in the 1. Understand the components of the stress response and
Pediatric Trauma Patient . . . . . . . . . . . . . . . . . . . . . . . . . 378 how these contribute to hypermetabolism in trauma
General Background on Trauma in Childhood and burn patients.
Closed Head Injuries/Traumatic Brain Injury 2. Identify childhood conditions that place patients at
Spinal Cord Trauma
Blunt Abdominal Trauma/Solid Visceral Injuries
risk for trauma and child abuse as well as nutrition
Blunt Abdominal Trauma/Hollow Visceral Injuries impairment.
Thoracic Injuries 3. Understand the injury pattern seen in blunt trauma and
Summary on Pediatric Trauma how it impacts the ability to use enteral nutrition.
Pediatric Burns. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 383 4. Understand limitations of methods for predicting
Features Specific to the Pediatric Patient energy needs in pediatric patients with significant burn
Energy Estimates in Burn Injury injury.
Clinical Example 1. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 384
Answer/Considerations Nutrition Considerations in the
Clinical Example 2. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 385 Pediatric Trauma Patient
Answer/Considerations Trauma, burn injury, and surgery are known stressors
Clinical Example 3. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 385 resulting in hormonal, metabolic, and immune derange-
Answer/Considerations ments. The initial physiological response to these events
is well studied and is generally described in terms of the
hormonal and cytokine responses. These responses include
the centrally mediated release of adrenocorticotropic
hormone (ACTH), which stimulates cortisol release from
the adrenal glands. This augments the action of epinephrine
and norepinephrine, which are released from the adrenal
medulla via sympathetic stimulation and impact the cardio-
vascular response. Glucagon is responsible for mobilizing
glucose availability via glycogenolysis and gluconeogenesis.
During the initial resuscitation, tissue perfusion is reduced
and there is an overall (transient) reduction in metabolic rate.
This is promptly followed by the hypermetabolic/catabolic
phase of injury, which is mediated by the hypothalamic-
pituitary axis and the proinflammatory cytokines (ie, tumor
necrosis factor, interleukin-6). This phase is characterized
378
TRAUMA AND BURNS 379
by changes in glucose homeostasis, with insulin promoting elimination of multiple vascular access sites and provision
lipolysis and proteolysis to generate glucose, while relative of nutrients via the intact intestinal system. The patient with
insulin resistance contributes to elevated serum glucose blunt abdominal trauma and an extensive pancreatic injury
levels during this acute phase. may not be able to tolerate gastric feedings and should be
Trauma and burn injury have provided good clinical considered for jejunal feeding if such access is possible. In
models for studying these responses because they are “quan- the interim, provision of energy needs should occur by the
tifiable” injuries in terms of trauma scores and extent of burn parenteral route.
injury. The physiological responses in the pediatric patient
are fundamentally no different than in the adult. The focus General Background on Trauma in Childhood
of nutrition management is aligned with the fundamentals Trauma accounts for significant morbidity, mortality, and
of critical care, which attempt to optimize all organ function long-term disability in children. The patterns of pediatric
by optimizing perfusion and tissue oxygenation. Support of trauma are both age and gender related. Mechanisms for
this hypermetabolic state, with an aim to control the resul- injury in children in the first 3 years of life include falls,
tant hyperglycemia and to limit the extent of proteolysis, poisoning (including caustic ingestions), transportation-
becomes the focus of nutrition interventions. The specific related injuries, foreign body aspiration or ingestion, burn
nutrient requirements and whether certain micronutrients injuries, assault/neglect, and submersion/drowning mecha-
either become conditionally essential or can impact the nisms. With the older child, falls and bicycle/pedestrian and
elaboration of pro- and anti-inflammatory cytokines and transportation-related injuries assume a greater frequency.
other agents such as nitric oxide have been the subject of These primarily blunt mechanisms are accompanied later
intense research. in adolescence by an increasing number of penetrating
The premise of this chapter on trauma and burns is that injuries. The specific organ injuries are broadly classified as
the nutrition support of the child in the critical care unit neurotrauma (closed head injury/traumatic brain injury and
follows clinical guidelines that parallel those of the child spinal cord injury), thoracic trauma (chest wall, pulmonary,
presenting with shock and sepsis or respiratory failure. and cardiac), abdominal-pelvic trauma (solid and hollow
Distinguishing this “surgical scenario” is that appropriate visceral, genitourinary), and musculoskeletal injuries (long
consideration must be given to the actual physical and phys- bone and pelvic fractures, craniofacial injuries). An anatom-
iological insult. These patients generally require a much ical classification system allows for injury severity scoring,
higher consideration of pain-related issues because of the which has a strong relationship with outcomes including
associated tissue damage than in the non-physically injured morbidity, mortality, and length of stay.
child. While the use of narcotic and non-narcotic medica- While most children are generally healthy prior to
tions contributes to an amelioration of metabolic demands, their acute injury, others have underlying diagnoses such as
it also promotes intestinal dysmotility and ileus and thereby neuro-developmental delay, disorders on the autism spec-
impacts enteral feeding tolerance. The use of agents such as trum, or attention deficit disorder. These conditions not only
propofol, which are solubilized in a lipid solution, requires modify their risk-taking behaviors and place them at risk for
reconsideration of the nutrient allocation by parenteral injury but also potentially contribute factors that may result
nutrition. in nutrition depletion over a shorter period of time than
Because of the nature of organ and skin injury, there are expected. On the opposite end of the spectrum, children
more frequent interruptions of nutrient delivery as a conse- injured as passive bystanders/occupants of a vehicle may
quence of surgical interventions. As a result, many patients also present with significant issues related to overweight/
remain undernourished in this acute phase of injury when obesity.1 These issues may complicate their acute manage-
reliance is placed on enteral feedings alone and frequent ment and impact their nutrition support in the acute phase.
periods of non-feeding are necessary for procedures under The sections below provide brief descriptions of the most
conscious sedation and general anesthesia. In this set of common forms of pediatric trauma and serve to provide a
patients, the goals of energy provision are estimated to be perspective on when, in the course of injury, enteral nutri-
130% to 160% of resting energy expenditure (REE) with tion is feasible and when there should be an anticipation of
an expectation to initiate this by day 3 and consistently prolonged non-enteral nutrition.
deliver this by 7 days postinjury. The route of administra-
tion is dependent on patient-specific factors. For instance,
the patient with extensive burn wounds is best served by

Closed Head Injuries/Traumatic Brain Injury includes the acute use of steroids in those with “incomplete”
The brain has an inordinately high metabolic demand and injury as well as hypothermia protocols. The nutrition
under normal circumstances brain metabolism and cere- assessment of these patients becomes a very individualized
bral blood flow are generally tightly regulated. When there task due to variability in neuromuscular deficit and meta-
is a traumatic brain injury there is frequently a change in bolic demand despite ongoing perfusion.6,7
cerebral perfusion as a consequence of intracranial pressure
changes.2 Despite this, the brain remains critically depen- Blunt Abdominal Trauma/Solid Visceral Injuries
dent on the uninterrupted delivery of both oxygen and Solid organ injuries are some of the most frequent inju-
glucose. Failure to support the brain adequately during this ries encountered in the pediatric patient. In contrast to
period likely impacts long-term outcomes. Hypothermia the adult population, these injuries are frequently isolated
protocols in pediatric traumatic brain injury aim to reduce and can be managed non-operatively. Despite their preva-
the metabolic needs during periods of relative hypoperfu- lence, there has been no universally accepted algorithm
sion. Clearly the nutrition support of such a severely injured for their management. While radiographic parameters
patient will require assurance of glucose provision, however permit grading of injuries to indicate severity of injury, it
the concomitant use of medications such as glucocorti- is the hemodynamic response to injury that determines
coids and development of diabetes insipidus (DI) place this the immediate course of action. Operative intervention is
patient at risk for hyperglycemia. Furthermore, sodium and reserved for those with profound or persistent hemody-
water balance are affected by the syndrome of inappropriate namic instability. Simple immobilization with bed rest may
antidiuretic hormone secretion (SIADH) and DI, as well as be sufficient in most patients to permit intrinsic mechanisms
by administration of resuscitative fluids which may include for hemostasis to result in formation of a stable hematoma.
hypertonic saline. These electrolyte and fluid balance issues Since the stomach is intricately associated with the spleen
may impact the ability to provide proteins, which along with via the short gastric vessels, it is usually decompressed or
lipids remain essential during the catabolic phase. Once enteral feedings are at least withheld for 24 hours to avoid
neuro recovery is underway, maintenance of muscular tone gastric distention and retching. If there has been a signifi-
for adequate respiratory function and physical rehabilitation cant amount of blood in the abdomen, this not only creates
is critical. The use of immune-enhancing diets containing abdominal pain but also is responsible for a transient ileus.
omega-3 fatty acids, branched-chain amino acids, and The period of observation with bed rest is variable and is
nucleotides has been evaluated in head injury patients and generally related to the degree of injury. Hemodynamic
has not shown benefit over the use of standard nutritional instability despite transfusion is the predominant factor
formulations. 3 in determining whether non-operative management will
With a transition into rehabilitation facilities, nutrition be successful. With hemodynamically unstable splenic
management is still tightly regulated, because these patients injuries, splenic salvage can be attempted operatively or
often have impaired swallowing and airway protection. Esti- splenectomy may become necessary. Given the role of the
mating caloric needs is difficult and there are many studies spleen in the immunocompetency of the child, every effort
documenting a difference between the calculated needs of is made to avoid splenectomy.
the predictive equations and actual needs based on nitrogen Hepatic injuries rarely require operative interven-
balance studies.4,5 The concern is that overfeeding will lead tion. In the most severe instances an avulsion of the liver
to hyperglycemia for the reasons mentioned above and an off the retrohepatic vena cava occurs, and these injuries are
excessive respiratory quotient (RQ ) which will impact the generally immediately fatal. Parenchymal injuries are best
patient’s ventilatory management. managed non-operatively especially if Glisson’s capsule
is intact. The abdominal wall provides some compression
Spinal Cord Trauma and containment, which is lost with laparotomy. When
This constellation of injuries more often affects the adoles- hemodynamic instability mandates exploration, the liver
cent in the context of sports injuries, diving, and motor is packed with laparotomy sponges to compress the injured
vehicle crashes. Depending on the level of spinal cord tissues, arterial inflow can be reduced by occluding the
injury, the patient may become dependent on mechanical hepatic artery manually, and either injured segments can
ventilation and lose the use of all truncal and extremity be compressed with large sutures or resected. Control of
musculature. The peri-injury protection of the spinal cord hemorrhage is as much a surgical as medical event in that
remains a topic of active research and controversy and hypothermia and coagulopathy can rapidly obviate any

surgical advances. In the patient who is or becomes stable, delayed for 4 to 6 weeks to allow the cyst wall to “mature.”
postoperative management will assess bilirubin levels This allows the cyst content of pancreatic secretions to drain
which may become elevated for a number of reasons (shed into the intestinal tract with ultimate expectation that the
blood, biloma formation, biliary ascites). Intestinal bleeding ductal defect will heal and that the pseudocyst involutes.
may be from hemobilia in which a fistula forms from the The extent of nutrition support depends on the physi-
vascular system into the biliary ductal system. Depending ological impact of this traumatic pancreatitis. When jejunal
on the degree of shock, the liver parenchyma may exhibit access can be safely established, it is reasonable to use this
some degree of hepatic dysfunction which should be taken route once there is evidence of return of intestinal motility.
into account when selecting medications. With restora- In the most severely injured, with ongoing pancreatitis and
tion of adequate perfusion, this is usually only a transient perhaps complications such as tissue necrosis and infection,
phenomenon. These solid organ injuries are rarely associ- parenteral nutrition (PN) is likely essential in the early post-
ated with significant gastrointestinal dysfunction and oral injury period.
diets are resumed within several days of injury. Depending
on the severity of injury and on whether there are additional Renal Trauma
injuries, these patients may benefit from caloric supplemen- Injuries to the kidneys are typically unilateral, and assess-
tation. This is because these children may not demonstrate ment must include evaluation of the ureter and bladder.
a normal appetite and may develop constipation due to the Typically, delayed phase images on CT scan will identify
lack of physical activity. urinary extravasation. In the absence of urine extravasa-
tion, renal injuries are primarily managed non-operatively.
Pancreatic Trauma Patients remain at bed rest until the hematuria subsides. If
The pancreas is typically injured as a consequence of a urinary extravasation occurs it is classified as contained or
compression force to the mid-abdomen. This may be a free. The former may permit ongoing non-operative manage-
bicycle handlebar or another object striking the epigas- ment although placement of a ureteral stent or percutaneous
trium or it can be the consequence of a deceleration injury drainage would be advised in the latter. In rare cases a
associated with the use of a seatbelt. Child abuse must primary nephrectomy is performed. Late consequences
always be considered when the mechanism is otherwise not of renal injury include the development of renovascular
obvious. Complete fractures of the pancreas occur over the hypertension. These patients generally experience a tran-
neck of the organ where it crossed the spinal column. Initial sient ileus and then are able to resume an enteral diet. There
laboratory assessment in the trauma room has been found are rarely concerns of renal insufficiency that would lead to
to be inadequate for detection of this injury. Amylase and consideration of special diets.
lipase levels rise typically 8 hours after injury. Computed
tomography (CT) scan of the abdomen is the typical study Adrenal Hemorrhage
that raises concern, but it may not be sufficiently sensitive. The adrenal glands have an exuberant blood supply from
While adult trauma protocols would mandate operative multiple sources. While generally protected in the retro-
exploration, there are series in pediatric patients in which peritoneum, they are at risk for direct injury, but rarely as
the injury is managed non-operatively with the use of endo- an isolated organ. Injury is generally evident as adrenal
scopic retrograde cholangiopancreatography (ERCP) for hemorrhage but does not necessarily portend adrenal insuf-
stenting of the ampulla and even across a major ductal injury. ficiency, even when bilateral. When isolated, these injuries
These cases are controversial and the most “conservative” have minimal impact on the overall nutrition management
approach may indeed be exploration with resection of the of the patient.
tail of the pancreas, thereby eliminating the ongoing leak of
pancreatic enzymes. Resections at this level of the pancreas Blunt Abdominal Trauma/Hollow Visceral Injuries
are not expected to affect glucose homeostasis, although
there are some reports of late pancreatic exocrine insuffi- Duodenal Injuries
ciency, which present with malabsorption as evidenced by Duodenal hematoma and perforation are not infrequently
diarrheal stools. encountered in pediatric trauma. They occur with blunt
The patient who develops a pancreatic pseudocyst as force trauma to the epigastrium (ie, bicycle handlebar
a consequence of the trauma can be managed with laparo- injury, non-accidental trauma). While most duodenal hema-
scopic, open, or endoscopic cyst gastrostomy. This is usually tomas are dealt with non-operatively, duodenal perforation

is a significant injury that demands prompt operative inter- parenchyma, resulting in pulmonary injury which most
vention to avoid morbidity and even mortality. Duodenal often consists of contusion rather than overt tissue disrup-
hematomas become symptomatic when extraluminal blood tion. Similarly the pliability of the intrathoracic vessels
impacts on the luminal caliber, resulting in gastric outlet results in fewer great vessel injuries than seen in the adult
obstruction. Passage of a transduodenal feeding tube is population. Blunt cardiac trauma is also well-compensated
almost always possible, either by radiographic guidance or for with the capacity to offset contractility compromise
endoscopically. This allows the patient to receive enteral with an increased heart rate response. When intrathoracic
nutrition despite the proximal obstruction, which may injuries occur that require operative intervention, recovery
require decompression with a concomitant nasogastric tube. is supported by the generally healthy state of these organs.
Operative intervention is rarely indicated in this injury. Often these injuries occur in the setting of multiple traumas
Pancreatic injury may be concomitant so it is wise to check and then require mechanical pulmonary support. When in
for chemical pancreatitis before initiating feeds. Resolution isolation, they are usually of minimal consequence to nutri-
of the obstruction can occur within 10 to 14 days of injury tion management.
as evidenced by improved gastric emptying.
Duodenal perforation is a much more significant injury Pelvis and Extremity Trauma
which, depending on its extent, will require either primary When long bone fractures and pelvic fractures occur in
repair with drain placement or sometimes more compli- multiply injured trauma patients these injuries contribute to
cated surgical solutions to protect the duodenal repair from the injury severity score and consequently to the nutrition
leakage (ie, pyloric exclusion with gastrojejunostomy). and metabolic demands of the patient. When these bony inju-
Typically the pyloric channel will open 4 to 6 weeks later, ries are associated with overlying open soft tissue wounds
which prompts the gastrojejunostomy to close spontane- the risk for infection is increased. Operative management
ously. These patients will often require parenteral nutrition for limiting the extent of contamination and fixation of the
support in the early postoperative phase until the gastro- fracture are routine measures. Even simple immobilization,
jejunal anastomosis becomes functional. whether of a long bone fracture or the pelvis, has metabolic
consequences to the patient. The importance of providing
Small Intestine and Colon Injuries adequate vitamin D and calcium is emphasized in the
Jejunoileal perforations or mesenteric injuries resulting in current literature. The focus of the American Academy of
devascularized segments of small intestine are frequently Pediatrics consortium on calcium was to limit the fracture
associated with seatbelt injuries and other mechanisms risk for young children and adolescents.8,9
resulting in deceleration forces on the abdomen. These are In the skeletally immature pediatric patient, the
most commonly identified in the first 24 hours, however, consequences of growth plate fractures, non-union of frac-
later strictures from ischemic injury without perforation tures, and subsequent growth impairment are critical to
can cause late (> 4 weeks) symptoms of enteral intolerance. address. In the absence of multiple organ injury involving
Unless there is an extensive delay in diagnosis, most of these the abdomen, these patients rapidly resume enteral intake.
injuries can be treated with resection and anastomosis. Targets for caloric intake should include consideration of
When peritoneal contamination is extensive, the patient’s level of activity.
hemodynamic status is not optimal, and the perfusion of Facial trauma constitutes a specific subset of musculo-
the involved segment is questionable, it is often prudent to skeletal trauma but has the added concerns for impacting
proceed with stomal diversion. These same principles apply enteral alimentation when the mandible and maxilla are
to colon perforation, which is rare and more commonly involved.
encountered in penetrating mechanisms of injury. These
injuries require a brief period of non-enteral feeding, but Summary on Pediatric Trauma
then permit rapid reinstitution of normal dietary habits. While much pediatric trauma is of a minor and ambulatory
nature, those children with major single-system injuries or
Thoracic Injuries multiply injured pediatric trauma patients require early and
Thoracic injuries in children may be remarkably unassoci- intense evaluation for nutrition support. After restoration
ated with chest wall signs of trauma. The bony thoracic of vital organ perfusion, consistent nutrition support is a
case is sufficiently pliable in the young child to permit critical intervention to assure meeting the high metabolic
complete transduction of the impact energy to the lung demands imposed by injury.10

Pediatric Burns Use of the intestinal tract for alimentation has been
Burn trauma encompasses injuries that occur as a result of promoted for burn injuries in particular. Concerns about
flame, thermal and chemical exposure, inhalation of smoke, mucosal atrophy and impairment of the gut-associated
and electrical contact. These continue to inflict significant immune defenses as a consequence of non-use have been
morbidity and mortality on patients at the extremes of age. key motivators. While enteral feeding may frequently
Young children are particularly vulnerable to both acci- require administration via nasoenteric tubes, often oral
dental and non-accidental burn injuries. The management supplementation is well received by young children. At
of burns has evolved dramatically in the past 30 years with a times, simple nighttime supplementation to reach target
centralization of care for the more severely injured patients. caloric goals is sufficient. Choice of formula is typically
This has allowed for more concentrated experiences as well based on calculated caloric needs with special emphasis on
as focused clinical trials. The result of these data has been protein content. Early enteral feeding has not shown the
significantly improved outcomes, with decreased mortality benefit demonstrated with delayed enteral feeding and risks
attributable to shock and wound sepsis. These patients, using an underperfused intestinal tract, thereby subjecting
however, require extensive and chronic support from a the patient to additional morbidity.16,17 The use of pharma-
multidisciplinary team to return to optimal functional cologic agents such as growth hormone, oxandrolone (a
status. With a better understanding of the metabolic conse- testosterone analog), and insulin-like growth factor results
quences of burn injury on both the animal research as well in decreased catabolism, but it is unclear how this ultimately
as on the clinical research front, the consistent emphasis on will affect clinical course and outcomes. The use of low-dose
the importance of nutrition support has persisted as one of insulin has been described as a useful intervention, which
the hallmarks of burn care.11 may be a consequence of control of hyperglycemia in a state
of relative insulin resistance.18
Features Specific to the Pediatric Patient Inhalation injury also has a greater potential for
Children, as compared to adults, will have deeper burn complications in the young child as a consequence of the
injuries for a given injury mechanism as a consequence of decreased luminal diameter of the trachea and bronchi with
the thinner dermal structure and architecture. In contrast a propensity for formation of obstructive casts and secretion
to the older patient, their thermal injury occurs as a conse- plugs. Early intubation and respiratory toilet are important
quence of contact with hot liquids in 70% of cases, rather especially in those with associated facial burn injury, given
than flame burn. The percent total body surface area (TBSA) the rapid and dramatic swelling associated with third-
involvement by second- and third-degree burns remains space extravasation of resuscitative fluids. These patients
a critical determinant of mortality. An understanding remain at risk for prolonged respiratory support and venti-
of individualized burn resuscitation, guided by %TBSA lator-associated pneumonias which further impact their
involvement, has led to virtual elimination of burn shock as hypermetabolic state.19 Recent studies document that the
a cause of immediate death. With injuries involving > 20% highest mortality is encountered in children under 4 years
of TBSA there is an associated stress response which leads of age with TBSA > 30% and inhalation injury.20
to the hypermetabolic state that has been well described
with burn injury. It is less clear how TBSA impacts the Energy Estimates in Burn Injury
severity of the stress response invoked when greater areas Children start off with greater metabolic and specific
are involved,12 although TBSA > 30% to 40% results in nutrient demands (greater caloric demand per kilogram) as
tenfold elevations of urinary catecholamines.13 Attempts compared to their adolescent and young adult counterparts,
to modulate the severity of this response have been diverse a demand that is amplified by the injury. They generally
and have included wound management strategies, enteral have lower energy stores, which are more rapidly depleted.
feeding strategies, and the use of pharmacologic agents. Their propensity toward fevers, despite the absence of infec-
Current therapies that employ early burn wound excision tion, further compounds their energy demands. Despite
and grafting have had a significant impact in reducing the ubiquitous use of the Harris Benedict equation and
wound infections, reducing transdermal losses of fluid and other variants to estimate caloric needs for these patients,
protein, and achieving earlier healing and rehabilitation. these remain very rudimentary tools and there are data that
The improved technologies for coverage of burn wounds they do not accurately reflect actual needs as measured by
with reduced frequency of painful dressing changes also indirect calorimetry.21 Providing excess calories will not
will reduce metabolic demands.14,15 obviate the proteolysis accompanying the hypermetabolic

response, but likely contributes to hyperglycemia. How aggressive enteral feeding leading to luminal obstruction
hyperglycemia specifically impacts the incidence of wound and perforation.27 PN support retains a critical role in those
infection in burn patients is not known; however, there is patients with a prolonged ileus or persistent systemic and
enough suggestive evidence from other models of critical visceral hypoperfusion.
illness to avoid blatant overnutrition. On the opposite end, Laboratory evaluation using the standard visceral
we know that undernutrition negatively impacts wound proteins is limited in the immediate/acute injury period
healing and maintenance of lean body mass. Muscle catabo- and may be more useful as a predictor of outcomes, rather
lism, particularly involving the muscles of respiration, leads than as a measure of visceral protein status. The degree of
to functional debilitation which can be measured in terms hypoalbuminemia observed in early burn injury is attribut-
of prolonged respiratory support; however, physical reha- able to the losses via the burn wound. Further complicating
bilitation of the core muscles and extremities is similarly their interpretation is that albumin therapy is prevalent in
impacted in the later stages of therapy. Despite the consis- burn resuscitation and does not reflect intrinsic production.
tent recommendation to assess these patients with indirect Weight and other anthropometrics are also invalidated in
calorimetry, in general, a target of 120% to 130% of REE is the early resuscitative phase given the rapid expansion of
believed to be appropriate.22 the extravascular space. Trends in prealbumin and other
The composition of the energy sources is primarily carbo- visceral proteins as well as weight changes once the acute
hydrate (up to 60% of calories) but with maximum glucose resuscitative phase is complete are reasonable to monitor.
load limited to 7 mg/kg/min to not only avoid hyperglycemia,
but also to limit lipogenesis which results in increased oxygen Clinical Example 1
consumption and carbon dioxide elaboration which raises A morbidly obese 14-year-old is transported to the trauma
the RQ. Lipids should initially deliver between 12% to 15% center after being involved in a multi-vehicle collision as
of total non-protein calories. This lower proportion has been a restrained passenger. Although alert and oriented she is
associated with improved clinical outcomes as compared to dyspneic and is found to have a pneumothorax. She has a
the higher lipid-containing diets (35% calories from fat) in significant air leak, suggesting a bronchial injury. She is
a randomized clinical trial.23 The use of omega-3 containing intubated and undergoes bronchoscopy with subsequent
fatty acids is theoretically beneficial from the standpoint of thoracotomy for repair of a proximal airway injury. Her
reducing the precursors for prostaglandin E2 and leukot- initial abdominal exam was unremarkable but limited by
rienes, thereby limiting further immunosuppression. The obesity. Focused Assessment with Sonography for Trauma
protein needs are exacerbated in burn patients because of (FAST) exam was not possible and the urgent intervention
the additional losses via the open wounds in addition to the for her airway delayed further evaluation. She develops
standard urine losses and the gluconeogenesis as seen in abdominal tenderness which prompts CT evaluation and
other instances of hypermetabolism. Daily intake of 2.5 g/ subsequent laparotomy for a left hepatic duct avulsion with
kg/d and up to 4 g/kg/d may be necessary and is limited by ischemia to the left lobe of the liver. What are her require-
the patient’s state of hydration and renal function. Specific ments for energy support in this phase of her acute illness?
“immune-enhancing” diets which contain high protein loads, How are they best met?
omega-3 fatty acids, and branched-chain amino acids and
nucleotides have not been shown to be superior to standard Answer/Considerations
high-protein diets.24,25 The energy assessment of the overweight and morbidly
The preferred route of nutrition support remains obese teenager who requires critical care support is extraor-
enteral feedings and these should be instituted as soon as dinarily difficult. In this time of metabolic stress, the goal
it is deemed safe to use the intestinal tract. In some insti- should not be weight management, but preservation of
tutions the early use of postpyloric feedings is encouraged, protein status. Estimates for caloric intake are best derived
and techniques have been developed to safely place these from assessment of metabolically active tissues and these
devices at the bedside.26 Although initial studies suggested are more closely related to ideal body weight than actual.
that early feeding would be beneficial, no clear benefit Not only will this patient need to heal her traumatic injuries
has been demonstrated in terms of decreased length of but she now has two additional wounds (thoracotomy and
stay, morbidity, or mortality.17 As with any other invasive laparotomy) to heal. Indirect calorimetry will likely provide
procedure, the risks and benefits must be considered when the best guidance in this scenario. Given the intra-abdom-
initiating enteral feeds. There are case reports of early inal injuries one would expect a period of ileus to follow

and thus provision of nutrients should not be delayed and and protein can be started early via this route. At the time of
initially can occur by parenteral route. operation it would be ideal to have a nasoenteral tube placed
for subsequent enteral feeding access. Energy requirements
Clinical Example 2 are notoriously difficult to predict and indirect calorimetry
A 12-year-old equestrian sustained a kick to her stomach remains the most accurate tool.
while grooming her horse. Her initial abdominal CT shows
a hematoma over the neck of the pancreas. There is no free Test Your Knowledge Questions
fluid in the abdomen. She is nauseated and a nasogastric 1. Blunt abdominal trauma with injury to the liver:
tube evacuates bilious fluid. Over the next 24 hours she A. Requires prolonged support on parenteral
continues to complain of abdominal pain and her amylase nutrition
rises to 950. Do you advise nutritional supplementation at B. Requires specialized formulas to account for hepatic
this point? insufficiency
It is now 5 days later, an ERCP has been done, and there C. Rarely requires operative intervention
is no major ductal injury. Her abdominal pain is improved D. Is rare in the pediatric patient
and amylase is 200. What do you expect her ability to eat 2. Pancreatic trauma may result in all except:
will be within the next 48 hours? A. Chemical pancreatitis
B. Prolonged intestinal ileus
Answer/Considerations C. Clinical features of pancreatic insufficiency
Pancreatic injuries, despite non-operative management, can D. Diabetes mellitus
lead to significant metabolic stress as a consequence of the 3. Closed head injury patients unequivocally benefit from
inflammatory nature of the retroperitoneal injury (hema- provision of immuno-nutrients.
toma) which is further exacerbated by release of pancreatic A. True
enzymes. While we can expect this patient to have been B. False
active and healthy from a nutrition standpoint, we would 4. Total burn surface area (TBSA) is most predictive of:
anticipate a return to GI function within perhaps 5 days. A. Mortality
The information related to the ERCP would suggest that B. Metabolic stress
cautious introduction of enteral feeds would be acceptable C. Energy needs
and that her response to enteral stimulation of pancreatic D. None of the above
secretions must be monitored. Should she develop recur-
rent pain and pancreatitis with oral intake, institution of See p. 487 for answers.
PN until such time as a jejunal feeding tube can be placed
would be appropriate. References
1. Rana AR, Michalsky MP, Teich S, Groner JI, Caniano
Clinical Example 3 DA, Schuster DP. Childhood obesity: A risk factor for
injuries observed at a level-1 trauma center. J Pediatr Surg.
A 2-year-old is brought to the trauma/burn unit with 35% 2009;44(8):1601–1605.
TBSA injury from a hot oil burn to his face, trunk, and lower 2. Philip S, Udomphorn Y, Kirkham F, Vavilala M. Cerebrovas-
extremities. Within 24 hours, he has developed anasarca, cular pathophysiology in pediatric traumatic brain injury. J
but is hemodynamically stable and making urine at 1 mL/ Trauma. 2009;67(2 Suppl):S128.
kg/h. He is scheduled to undergo burn wound excision on 3. Briassoulis G, Filippou O, Kanariou M, Papassotiriou I,
Hatzis T. Temporal nutritional and inflammatory changes in
the following day. When do you consider starting nutrition
children with severe head injury fed a regular or an immune-
support? How do you best determine his caloric needs? enhancing diet: a randomized, controlled trial. Pediatr Crit
How do you initiate caloric intake? Care Med. 2006;7(1):56.
4. Havalad S, Quaid M, Sapiega V. Energy expenditure in chil-
Answer/Considerations dren with severe head injury: Lack of agreement between
This child has sustained a significant injury and is expected measured and estimated energy expenditure. Nutr Clin Pract.
2006;21(2):175.
to exhibit a stress response leading to catabolism. Nutrition 5. Joffe A, Anton N, Lequier L, et al. Nutritional support
support will become essential to re-establishing a positive for critically ill children. Cochrane Database Syst Rev.
nitrogen balance. Given the extent of injury this child will 2009(2):CD005144.
likely have central venous access and provision of glucose

6. Patt P, Agena S, Vogel L, Foley S, Anderson C. Estimation of 18. Schulman C, Ivascu F. Nutritional and metabolic conse-
resting energy expenditure in children with spinal cord inju- quences in the pediatric burn patient. J Craniofac Surg.
ries. J Spinal Cord Med. 2007;30(Suppl 1):S83. 2008;19(4):891.
7. Brown RL, Brunn MA, Garcia VF. Cervical spine 19. Palmieri T, Warner P, Mlcak R, et al. Inhalation injury in chil-
injuries in children: a review of 103 patients treated consec- dren: a 10 year experience at Shriners Hospitals for children. J
utively at a level 1 pediatric trauma center. J Pediatr Surg. Burn Care Res. 2009;30(1):206.
2001;36(8):1107. 20. Sheridan RL, Schnitzer JJ. Management of the high-risk pedi-
8. Baker SS, Cochran WJ, Flores CA, et al. American Academy atric burn patient. J Pediatr Surg. 2001 8;36(8):1308–1312.
of Pediatrics. Committee on Nutrition. Calcium require- 21. Suman OE, Mlcak RP, Chinkes DL, Herndon DN. Resting
ments of infants, children, and adolescents. Pediatrics. energy expenditure in severely burned children: analysis
1999;104(5):1152. of agreement between indirect calorimetry and prediction
9. Goulding A. Risk factors for fractures in normally active chil- equations using the Bland-Altman method. Burns. 2006
dren and adolescents. Med Sport Sci. 2007;51:102. 5;32(3):335–342.
10. Hasenboehler E, Williams A, Leinhase I, et al. Metabolic 22. Chan MM, Chan GM. Nutritional therapy for burns in chil-
changes after polytrauma: an imperative for early nutritional dren and adults. Nutrition. 2009 3;25(3):261–269.
support. World J Emerg Surg. 2006;1:29. 23. Garrel DR, Razi M, Larivire F, et al. Improved clinical status
11. Purdue G. American Burn Association presidential address and length of care with low-fat nutrition support in burn
2006 on nutrition: yesterday, today, and tomorrow. J Burn patients. J Parenter Enteral Nutr. 1995;19(6):482.
Care Res. 2007;28(1):1. 24. Saffle JR, Wiebke G, Jennings K, Morris SE, Barton RG.
12. Atiyeh B, Gunn SWA, Dibo S. Metabolic implications of severe Randomized trial of immune-enhancing enteral nutrition in
burn injuries and their management: a systematic review of burn patients. J Trauma. 1997;42(5):793–800.
the literature. World J Surg. 2008;32(8):1857. 25. Marin V, Rodriguez-Osiac L, Schlessinger L, Villegas J, Lopez
13. Chan M, Chan G. Nutritional therapy for burns in children M, Castillo-Duran C. Controlled study of enteral arginine
and adults. Nutrition. 2009;25(3):261. supplementation in burned children: impact on immunologic
14. Saba S, Tsai R, Glat P. Clinical evaluation comparing the and metabolic status. Nutrition. 2006;22(7-8):705.
efficacy of aquacel ag hydrofiber dressing versus petrolatum 26. Cone L, Gilligan M, Kagan R, Mayes T, Gottschlich M.
gauze with antibiotic ointment in partial-thickness burns in a Enhancing patient safety: the effect of process improvement
pediatric burn center. J Burn Care Res. 2009;30(3):380. on bedside fluoroscopy time related to nasoduodenal feeding
15. Saffle JR. Closure of the excised burn wound: temporary skin tube placement in pediatric burn patients. J Burn Care Res.
substitutes. Clin Plast Surg. 2009;10;36(4):627–641. 2009;30(4):606.
16. Venter M, Rode H, Sive A, Visser M. Enteral resuscitation and 27. Scaife CL, Saffle JR, Morris SE. Intestinal obstruction
early enteral feeding in children with major burns—effect on secondary to enteral feedings in burn trauma patients. J
McFarlane response to stress. Burns. 2007 6;33(4):464–471. Trauma. 1999;47(5):859.
17. Peck M, Kessler M, Cairns B, Chang Y, Ivanova A, Schooler
W. Early enteral nutrition does not decrease hypermetabolism
associated with burn injury. J Trauma. 2004;57(6):1143.

32
Surgery
Arlet G. Kurkchubasche, MD

General Nutrition Considerations in 1. Identify factors that impact the nutrition requirements
Pediatric Surgery. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 387 associated with the acute metabolic changes in the
General Nutrition Considerations in Neonatal Surgery pediatric and neonatal surgical patient.
Surgical Considerations in Infants with 2. Identify methods for optimizing nutrition support
Congenital Disorders . . . . . . . . . . . . . . . . . . . . . . . . . . . . 393 along the entire perioperative period by utilizing
Proximal Intestinal Obstruction clinical assessment, laboratory analysis, and bedside
Distal Intestinal Obstruction
Abdominal Wall and Diaphragm
calorimetry.
Hepatobiliary Disorders 3. Provide a basis for determining when to initiate and
Other (Non-GI) Malformations . . . . . . . . . . . . . . . . . . . . . 400 progress enteral feeding in a core group of neonatal
surgical conditions.
Nutrition Support in Infants with
Acute GI-Related Disorders. . . . . . . . . . . . . . . . . . . . . . . . 401 4. Delineate the strategies to limit the progression of
Necrotizing Enterocolitis cholestatic jaundice in the postoperative infant with
Isolated Intestinal Perforation intestinal dysfunction.
Intestinal Malrotation and Midgut Volvulus
Pyloric Stenosis General Nutrition Considerations in
Nutrition Support in Children and Pediatric Surgery
Adolescents Requiring Operation. . . . . . . . . . . . . . . . . . . 403 The metabolic consequences of surgical stress have been
General Principles
extensively studied and show a characteristic/stereotypic
Feeding Access in Pediatrics
Insertion of Gastrostomy response in terms of hormone and cytokine elaboration. The
resultant hypermetabolic state during the phase of injury
and recovery has been the focus of nutrition support. In
pediatrics, the challenge is not only to provide those nutri-
ents to support the immediate metabolic needs but also to
avert catabolism of limited stores of protein and fat, while
providing substrate for growth and development.
In the surgical patient, wound failure, infection, and
mortality are primary outcome measures that have been
related to the perioperative nutrition condition. The disci-
pline of surgical nutrition arose at a time when nutrition
support was often unavailable to those in the immediate
postoperative period because of a lack of enteral tolerance.
The institution of parenteral nutrition (PN) changed the face
387
of postoperative care for this subset of patients. Malnutrition and pediatric patient in response to altered metabolic
and consequent complications were the cause of demise for demands as a consequence of operation. Patients who expe-
many neonatal patients with disorders which nowadays one rience similar stresses as a consequence of trauma or burn
is hard-pressed to consider lethal. As the ability to provide injury are discussed elsewhere (Chapter 31). The second
PN support has improved, an awareness of its potential for section focuses on nutrition support strategies specific to
adverse effects has become apparent, specifically the unique the various congenital, typically anatomic, gastrointes-
problem of cholestasis in the pediatric population. tinal (GI) disorders encountered in the neonatal pediatric
With further advances in the science of intestinal physi- surgery patient.
ology, our appreciation for the complexity of the intestinal Surgical care of the newborn infant and extending to
tract in terms of its role in water, electrolyte, and nutrient the skeletally mature adolescent requires a fundamental
assimilation as well as immune sampling functions became knowledge of the physiological changes that occur with
evident. Provision of appropriate nutrition held the promise growth and maturation. Based on the underlying condition,
of enhanced immune function, fewer complications related these patients will have variable impairments of GI function
to catabolism, and overall improved outcomes. Studies on that may be related to intestinal motility, surface absorptive
immunomodulatory agents provided either parenterally or capacity, and immune function. The perioperative state is
enterally in clinical sepsis have been conducted on adults and a dynamic phenomenon and as the patient’s clinical status
pediatrics alike. In the pediatric literature the focus came evolves, constant reassessment and redirection of nutri-
to rest on the components of breast milk, which appeared tion care must occur. Because these patients also represent
beneficial in averting gut-derived sepsis.1 The limitations a spectrum of acute and chronic disease and/or disability,
of clinical research in pediatrics are evident when it comes one uniform set of standards for nutrition care can be diffi-
to studies requiring repeated blood sampling and invasive cult to generate.
procedures; however, there is reason to believe that the find- The principles upon which guidelines are established
ings from adult clinical trials can be applied to the pediatric should focus on and correspond to the general American
patient. There is a wealth of knowledge from observational Society for Parenteral and Enteral Nutrition guidelines for
studies in pediatrics about the growth needs for all age nutrition assessment in pediatrics. These include:
groups and many congenital/heritable conditions, but these 1. Individualized assessment of nutrition status to deter-
studies are generally careful to exclude the more complex mine urgency and extent of patient support needs.
surgical patient. The best quantitative neonatal and pedi- 2. Consideration of the timing of onset of postopera-
atric data related to the effects of the metabolic response to tive nutrition support and the appropriate use of total
stress are derived from studies of a relatively homogenous parenteral nutrition when the alimentary tract is
group of infants who undergo cardiopulmonary bypass for compromised, with consideration for provision of
repair of congenital cardiac disease or who require extra- either enteral or parenteral nutrition support within 3
corporeal membrane oxygenation (ECMO) for pulmonary days of hospitalization.
support.2,3 These infants, however, cannot represent the 3. Provision of nutrition in a manner (enteral or paren-
entire spectrum of pediatric surgical conditions and much teral) most consistent with safe clinical practice.
work remains to be done. 4. Avoidance of potential complications by continuous
Nutrition assessment and support of the pediatric reassessment of individual risk/benefit ratios including
surgical patient requires consideration of the acute impact determining optimal timing for alimentary tract
of surgical intervention as well as the more chronic conse- challenge.
quences of operation. Potential postoperative complications, 5. Employing methods for determining the adequacy of
as well as the underlying congenital disorder, may further nutrition support.
contribute to persistent impairment of intestinal function.
Associated conditions, such as cholestatic jaundice, which General Nutrition Considerations in Neonatal Surgery
may be related to the primary problem or occur as a conse-
quence of sepsis or prolonged total parenteral nutrition Neonatal Assessment, Nutrient Composition, and Targets for
exposure, further compromise the recovery of the patient.4 Nutrition Support in the Early Postoperative Period
The first section of this chapter will focus on peri- Infants with congenital disorders of the abdomen and
operative nutrition support and the general concept of especially the intestinal tract have fluid and nutrition
adjustments in the nutrition considerations of the neonatal requirements that require frequent reassessment in the

SURGERY 389
immediate perioperative period. The excess fluid demands C-reactive protein (CRP)), and retinol-binding protein.
to restore or maintain vital organ perfusion in the periop- These function as the measures of protein anabolism after
erative period are not necessarily accompanied by a greater the acute phase of injury and are difficult to interpret earlier.
demand for caloric provision. 5–7 It is important to consider Whereas one strives for meeting the metabolic needs and
these requirements separately and avoid the potential for accomplishing weight gain and growth in the healthier
overfeeding and hyperglycemia. There are many factors infant, the short-term goals in the postoperative patient
in the postoperative patient that impact the energy esti- are targeted to provide for sufficient substrate to prevent
mates; these include the use of mechanical ventilation, catabolism and allow for anabolism in the context of wound
the provision of external heat support, the use of sedating healing. Often, non-protein in an amount of 60 to 80 kcal/
agents, and neuromuscular blockers. Pain control has a kg/d, perhaps even less, will be sufficient to meet these
tremendous impact on the perioperative hormonal stress initial goals in the neonate.11
response. Preemptive analgesia, local block, and caudal It has been documented that preterm neonates often
blocks all contribute to reducing the stress response and require a generous protein supply, perhaps as high as 4 g/
are part of current surgical practice. For instance, in infants kg/d, which primarily serves to provide substrate for tissue
undergoing patent ductus arteriosus (PDA) ligation it repair and does not independently prevent catabolism of
was demonstrated that a fentanyl anesthetic resulted in the existing muscle mass. By counting this protein delivery
improved protein metabolism. 8,9 as energy-yielding caloric intake, this may result in inad-
While the assessment of volume status can be quanti- equate caloric provision. This is the basis for calculating and
fied using weight, fluid balance records, and occasionally targeting non-protein calories in the acute perioperative
invasive monitoring with central venous pressures, this setting. In order to provide an optimal substrate for nutrient
process is not as straightforward when assessing metabolic assimilation, a non-protein calorie-to-nitrogen ratio of
demands. Unless nitrogen balance studies are readily acces- 130:1 to 210:1 is generally recommended as the target total
sible, the best estimates for caloric provision are made on parenteral nutrition solution. Whereas the calculation of
the basis of the infant’s gestational age and formulas for the caloric targets in terms of non-protein calories may be
resting energy expenditure (REE) of the infant in the acute important in the early perioperative phase, this should again
phases as well as in the recovery phase, which is best modi- convert to total caloric intake once the acute wound-healing
fied with estimated stress factors. demands return toward baseline. The time for this transi-
Unfortunately the impact of nutrition interventions is tion is perhaps best estimated by normalization of the CRP
measured in intervals approaching weeks rather than days and should correspond to clinical indicators such as wound
and is generally based on the infant’s ability to demonstrate status, return of intestinal function, and lack of infectious
anticipated rates of growth and other anthropometric complications.
measures. Ideally, one would be able to assess parameters
consistently, such as the infant’s glucose homeostasis, and Cholestasis: PN-Associated and of Other Origins
verify adequate glycogen stores and a positive nitrogen In contrast to the adult experience with overfeeding
balance along with the anticipated weight gain. However, resulting in steatosis, cholestasis is a significant problem
these are impractical goals in the immediate postoperative in pediatric surgical patients, who frequently require
period; therefore one must focus on maintaining eugly- prolonged PN support and are at further risk for hepatic
cemia and avoiding hyperlipidemia and azotemia/uremia, injury by virtue of their non-enteral feeding status and
while providing an escalating amount of balanced macro- susceptibility to sepsis. The generally accepted measure
nutrients in the form of carbohydrate, lipid, and protein. of significant cholestasis is the direct bilirubin exceeding
Laboratory parameters are used to assess nutrition 2 mg/dL.
status; however, these must be used as trends rather than For those patients anticipated to have a prolonged
as absolute measures in the infant, for whom there are often dependence on total parenteral nutrition ( > 1 month) this
no gestationally appropriate controls.10 In the acute hyper- author’s institution initiates cycling of PN when the clin-
metabolic phase there is whole-body proteolysis to provide ical condition permits, usually after the first month of life
not only substrate for gluconeogenesis but also for protein (term gestation infant) when it is predicted that glycogen
synthesis of necessary enzymes and other acute phase reac- stores are adequate and the infant perhaps is receiving
tants. Principal laboratory markers include total protein, some enteral feedings. Cycling off glucose infusion requires
albumin, prealbumin (evaluated in the context of a normal that the patient can maintain euglycemia to prevent the

development of hypoglycemia. Seizures as a consequence of Initiation and Choice of Enteral Alimentation

hypoglycemia carry the most profound risk for neurological Enteral nutrition is incrementally introduced when there
devastation. The procedure for cycling involves reducing the is evidence of GI tract motility and assurance that anas-
rate of total parenteral nutrition infusion to 50% for 1 hour tomoses, if performed, have achieved satisfactory healing.
prior to discontinuing infusion and reinitiating the next bag General principles in managing postoperative patients
of PN at a 50% rate for 1 hour before achieving the goal rate include a conceptual understanding of normal postop-
(see Figure 32-1) The targets for cycling on neonates are 4 erative events including paralytic ileus, delayed gastric
to 6 hours off infusion; however, this must include consid- emptying, the effect of narcotic analgesics, and the peri-
eration of glucose infusion rates, which may be significantly anastomotic edema that may impede transit during the
higher with consolidation of total parenteral nutrition. The first 48 hours postoperation. General guidelines for deter-
author’s institution provides lipid infusions as 24-hour infu- mining the ability to initiate feeding include an assessment
sions, which helps maintain patency of the catheters without of (1) gastric output both in terms of quality (bilious vs.
the need for additional fluid infusions when heparin locking gastric or even salivary content) and volume; (2) physical
might not be desirable because of multiple entries into the examination for evaluation of abdominal distention and
catheter hub. Both components are cycled when the patient the presence of bowel sounds; and (3) assessment of output
is discharged to home on total parenteral nutrition and the whether by stoma or per rectum, remembering that motility
catheter can be heparin locked for an extended period. recovers first in the distal intestine and therefore that occa-
Other considerations to limit PN-associated cholestasis sional stool output is not an assurance of actual GI transit.
for those infants on complete parenteral nutrition involve The recognition of potential intestinal complications such
maintaining relative ratios between macronutrients. as anastomotic leak, intraabdominal sepsis, wound failure
Examples of this include targeting a non-protein calorie- at the level of the abdominal wall closure, and even stoma-
to-nitrogen ratio of approximately 180:1, and the provision related problems (eg, stomal stenosis or prolapse) is critical
of lipid calories not exceeding 30% of total non-protein to those managing these patients.
calories. The role of lipids with a more anti-inflammatory The timing of initiation of feeds therefore depends on
profile (eg, omega-3 fatty acids) is not yet clear and, in the an assessment of the risks and benefits of providing enteral
absence of a diverse assortment of lipid sources, it may be nutrients. Choice and mode of feeding are often predicated
wise to use Intralipid® (a soy-based and omega-6 fatty acid by the infant’s gestational maturity, the history of mucosal
based solution) judiciously.12,13 Limitation of lipid calories injury/disruption, effectiveness of motility, urgency to tran-
may, however, necessitate pushing the glucose infusion rate sition off PN, and the presence of gastroesophageal reflux
(GIR) as high as 15 mg/kg/min to achieve caloric goals. (GER). In general, breast milk should remain the first choice
Clearly the initiation of enteral feeds is one of the most for all of its innate qualities in optimizing gut mucosal func-
critical steps14 in this process, and cycling nonabsorbable tion and immunity. Although donor breast milk will lack
enteral antibiotics may additionally be instituted to limit some of the immune benefits, it remains a desirable nutrient
the potential for bacterial overgrowth and enteral-derived source. When commercial formulas are necessary, infants
sepsis which would further compound the cholestatic injury who have no history of a compromised intestinal wall
to the liver. The use of ursodeoxycholic acid is beneficial (mucosal damage, transmural edema/fibrosis) can be started
when the terminal ileum is in continuity or proximal to a on standard hydrolyzed whey-based formulas for gesta-
stoma. tional age, whereas those infants who have a positive history
As the infant enters the phase of recovery, absent any should be started on a more elemental substrate to optimize
infectious or wound-healing complications, the focus absorption in the presence of a compromised mucosal
changes toward the more typical pediatric goals of nutrition barrier. Casein hydrolysates (Pregestimil®, Alimentum®)
support covering the acute needs as well as those demanded are common choices for the surgical infant and the specific
for growth and development. Here the documentation formula is often based on the fat composition and osmotic
of weight gain, resolution of the acute phase reactants load. However, these specialized formulas only provide a
(eg, CRP), and establishment of a trend of increasing preal- fraction of the calcium and phosphorus needs for a preterm
bumin values become the primary outcome measures for infant, and this must be taken into consideration with supple-
the efficacy of nutrition support. As mentioned above, the mentation, when possible. More elemental, extensively
focus on providing protein purely for wound-related anabo- hydrolyzed formulas (Neocate®, EleCare®), which consist
lism is reduced at this point. of amino acids and peptides and were designed to obviate

SURGERY 391
Figure 32-1

protein allergies, may in some instances be better tolerated The limits of “tolerance” are probably best defined by evalu-
in those with compromised motility as well. Theoretically ating the volume and nature of the output. Because stool
they reduce the luminal content of nutrients reaching the output is not measured in terms of frequency of stools with
distal intestine and perhaps limit bacterial overgrowth and a stoma, the guideline to be used is that output should not
carbohydrate fermentation, which result in excess reducing exceed one-third of total enteral intake. Other formulas
substances being excreted along with luminal fluids in the include the assessment of normal stoma output on the basis
form of diarrhea or frequent loose stools. As the patient’s of weight, with expected output estimated at 1 mL/kg/h
intestinal tract recovers, transition to a more complex and and tolerable amount to allow progression of enteral feeds
age-appropriate formula can be accomplished in a gradual set at either 30 mL/kg/d or 2 mL/kg/h.15 Excess outputs
manner. In contrast, infants with congenital disorders serve as indicators of inadequate absorptive capacity and
that do not affect the intestine itself, such as infants with osmotic fluid losses and should be further evaluated with
omphalocele, congenital diaphragmatic hernia, malrotation the content of reducing substances and stool pH. Reducing
without volvulus, pyloric stenosis, and thoracic conditions, substances will shed light on carbohydrate malabsorption
should be able to tolerate standard formulas. with contents of 1% or greater in the presence of loose stools
Guidelines for caloric estimates in critically ill surgical constituting an indication for intervention, depending on
infants requiring respiratory support are difficult to estab- the type of enteral intake. Stool pH will reflect whether
lish, but are best assessed using a metabolic cart.6 Whereas there are organic acids generated by unabsorbed sugars, and
the acutely, short-term ventilated patient probably does not this can happen independent of the presence of reducing
require a major revision in energy provision, this is countered substances.
by those infants who are chemically relaxed and actively Ideally a target caloric goal is established for each patient
ventilated and not participating in their work of breathing. and EN is pushed to the limit of tolerance with PN providing
Most of the recent publications have focused on the subset the balance of calories necessary to achieve weight gain and
of neonatal cardiac surgery patients2,3 who can be analyzed laboratory goals. While consistently pushing the limits
as a reasonably cohesive group. In between this spectrum of the intestinal tract, it is important not to have frequent
are the infants with congenital diaphragmatic hernia who, setbacks which ultimately delay operation to restore conti-
while intubated, are variably assisted in ventilation and nuity and thereby compromise the best case scenario for
require attention to avoid an inappropriate respiratory complete adaptation. The use of distal refeeding provides
quotient (RQ ) which might adversely impact their ability a valuable adjunct in these situations, at least contributing
to eliminate CO2 . Clearly, each of these patients is unique to restoring a complete enterohepatic pathway for bile if the
and generic formulas cannot be applied. These issues are distal ileum has been retained.16 The benefits are, however,
more extensively discussed in chapters on critical care and counterbalanced by the often arduous contraptions that
specific consideration must additionally be placed given the have to be created to collect and reinfuse the stoma output
surgical patient’s underlying condition. and the risk of perforating the distal intestine with repeated
The goal is to have a patient who is in optimal nutrition catheterization. The decisions involved in these complicated
shape. To the surgeon this is a multifactorial evaluation, cases require that all care providers reach consensus on the
which hopefully indicates that the infant has an appro- short- and long-term plans for the patient. Only then can the
priate weight gain of 1% to 2% of body weight per day and is ideal nutrition support plan be instituted.
demonstrating appropriate somatic growth in length, head All surgical patients must be monitored carefully for
circumference, and triceps skinfold measurement. Further- the onset of jaundice. Often the default reason for the onset
more, based on laboratory parameters, the child will either of direct hyperbilirubinemia is the use of PN; however,
have achieved a serum albumin within normal limits or at surgical patients can develop intestinal obstruction whether
least show a trend of progressively escalating prealbumin it be at the level of an anastomosis, at the level of a proximal
values. A multifactorial assessment is particularly impor- stoma, or at a random site due to peritoneal adhesions. These
tant when contemplating a secondary surgical intervention, conditions must remain in the foreground as correctable
such as a stoma closure. To achieve these goals one can causes of obstructive jaundice. Others conditions include
ideally provide a balanced enteral and parenteral regimen. drug-related cholestasis (seen with cephalosporins), low-
Sufficient enteral nutrition (EN) (trophic or greater) should grade sepsis, and even secondary disorders such as biliary
be provided to stimulate the mucosa and maintain its health, tract disease (gallstones and sludge) or pyloric stenosis.
promote motility, and avoid recurrent luminal obstruction.

SURGERY 393
Surgical Considerations in Infants with reconstruction/repair at a later date, or to those infants who
Congenital Disorders are expected to have poor oral-motor skills or other feeding
dysfunction based on concomitant disorders (trisomy,
Proximal Intestinal Obstruction retrognathia, etc). Given the reliance on total parenteral
A congenital proximal intestinal obstruction is usually nutrition for a period of 7 days or more, most neonatal
recognized antenatally or immediately postnatally and typi- centers will either place central venous access preopera-
cally prompts urgent operative intervention. While these tively (PICC line) or surgically place access at the time of
conditions can be temporized with effective nasogastric reconstruction. Because these considerations for alimenta-
suction, delay of operation is reserved for those infants with tion are not based on technique, there is no difference in the
suspected congenital heart disease who will require further postoperative management in thoracoscopic or open repair
evaluation (ie, patients with esophageal atresia and duodenal of esophageal atresia.
atresia) or would benefit from a stabilization of their transi- After the esophageal anastomosis is verified to be free
tional circulation changes before undergoing anesthesia and of leak with a contrast esophagram, the contrast is followed
operative stress. Although unusual, the concern for the pres- through the duodenum primarily to establish the absence
ence of an underlying non-survivable metabolic disorder or of malrotation. Duodenal stenosis due to annular pancreas
lethal chromosomal disorder constitutes a second justifica- and an even duodenal atresia can co-exist with esopha-
tion for delaying surgical intervention. geal atresia. This will not be apparent at operation because
the abdominal cavity is not entered. Enteral feeds can be
Esophageal Atresia commenced, preferably by mouth, to avoid repeated instru-
The most complex decision making involves infants who mentation of the esophagus. It must be kept in mind that
have esophageal atresia, and are significantly preterm there will be esophageal dysmotility based on the lack of a
and/or low birth weight. Operation may safely be delayed progressive peristaltic wave down the esophagus and based
1 to 2 days while postnatal circulation stabilizes and the on the perhaps more capacious proximal pouch that empties
child undergoes screening evaluations for disorders in as much by gravity as by propulsive esophageal wall activity.
the VACTERL association (vertebral, anorectal, cardiac, Delayed emptying through the anastomosis will result in
tracheo-esophageal, renal, and limb). During this time prompt oral regurgitation but also will result in tracheal
most neonates will be started on at least peripheral total compression which becomes evident as desaturation with
parenteral nutrition with a plan to escalate to central total feeds. These events are expected even in the absence of a
parenteral nutrition once appropriate venous access has stricture, and are only further accentuated by any luminal
been established, either via a temporary umbilical venous compromise. Infants must be maintained with the head of
catheter, peripherally inserted central catheter (PICC) line, the bed elevated and should be fed as upright as possible.
or surgically placed central venous line inserted at the time The goal of oral feeding should be to allow the infant to
of operative repair. The expectation is that the infant will practice frequently with low-volume amounts (5–10 mL
not be able to utilize the intestinal tract until approximately every 3 hours). Once these are tolerated, the progression of
7 days postoperatively when the esophageal anastomosis is feeds should be gradual, but should remain on a frequent
evaluated for patency and absence of leak. basis (every 3 hours) as the next barrier to reaching full
Many surgeons will not place a trans-anastomotic feeds will be GER. When breastfeeding is initiated it should
feeding tube at the time of operation, because gastric feed- similarly be limited in time, and this interval for feeding is
ings will likely be associated with a significant incidence of progressed as the infant tolerates. Although it is difficult
GER (on the basis of probable anatomic distortion of the to measure intake, reports of weighing the infant pre- and
angle of His) and this should be avoided until the esophageal postfeed suggest that this may be a method to quantitate
anastomosis is shown to be without leak. The association of intake.
trans-anastomotic tubes with anastomotic complications The stomach capacity will increase with time; however,
remains speculative, but unsubstantiated in the literature.17 any acid reflux is detrimental to the anastomosis and
When there is a leak, the period of non-enteral alimenta- can result in stricture formation. These infants therefore
tion may extend for another 5 to 7 days, since there is no should be placed on acid reduction therapy immediately
safe esophageal access to the stomach or beyond. The use postoperatively, and this therapy is usually maintained
of gastrostomy tubes generally has been limited to those for 6 to 12 months. The addition of metoclopramide may
infants with long-gap atresia who will undergo esophageal be helpful when feeds are first initiated, so as to promote

gastric emptying. Optimally the infant will progress to anticipated need for PN in the pre- and perioperative period
full feeds over a period of 5 to 7 days, although it is not while awaiting healing of the anastomosis, resolution of any
unusual for those infants who are more symptomatic with peri-anastomotic swelling, and onset of effective peristalsis
tracheomalacia to take longer. These infants may require in the dilated proximal duodenal segment. While most
repeated intubation for mechanical ventilatory support infants can undergo this reconstructive operation within
or they may require support with high-flow nasal cannula 48 hours of birth, there are some in whom the management
oxygen which compromises their ability to tolerate gastric of prematurity and congenital heart disease will dictate
feeds. In these instances it may be advisable to place a trans- the timing of operation and the provision of total paren-
pyloric feeding tube to enable the infant to take EN and be teral nutrition will be prolonged in duration. Based on the
weaned off PN, while his or her airway disability is being specific functional cardiac defect, a decision can be made
addressed. In severe cases, this may constitute an indication with the cardiologists to proceed early with abdominal
for placement of a gastrostomy tube. The current reluctance operation before the pulmonary pressures rise significantly
to place a gastrostomy is that the physical distortion of the and impact the perioperative fluid and cardiac management.
stomach as a result of a gastrostomy may further negatively This would reduce the cholestatic consequences of the
impact GER, which in turn may adversely affect healing combination of anatomic obstruction with prolonged PN, a
of the anastomosis. Surgical therapy of GER, while neces- combination which may become detrimental with time. For
sary in a subset of infants, is avoided due to (1) the inherent anatomic reasons, the repair of duodenal atresia involves
dysmotility of the esophagus which may not be able to no resection, but creates an anastomosis joining the dilated
overcome any level of obstruction distally and (2) anatomi- proximal segment to a segment of the tiny, previously unused
cally by the shortened length of the esophagus. While these duodenum. At operation an assessment is made of the distal
concerns can be taken into account surgically with a less bowel to assure that there are no further sites of atresia, the
tight fundoplication and esophageal lengthening proce- duodenum is assessed in terms of its caliber and contractility
dures such as the Collis gastroplasty, these are best avoided, for possible tapering duodenoplasty, and the overall situa-
unless a recalcitrant esophageal stricture forms.18 tion is assessed for the potential need for prolonged gastric
During infancy, the choice of infant formula should be decompression via gastrostomy. In a child who requires a
based on gestational age. There are no specific intestinal duodeno-duodenostomy, has a reasonable caliber anas-
absorptive defects to prompt the use of more elemental tomosis, and a not overly dilated proximal pouch, enteral
formulas. Caloric concentration of infant formulas is often feeds can generally be started after the fifth postoperative
necessary and advisable to accomplish achieving nutri- day. Duodenal leak can be a catastrophic complication due
tion goals, given the propensity for reflux. Long-term to the leakage of activated pancreato-biliary secretions.
nutrition problems in esophageal atresia relate to ongoing Often a contrast study for anatomic and functional evalua-
problems with GER and proximal strictures. Surveillance tion is requested in these infants prior to commencing feeds.
esophagrams are sometimes indicated and mechanical or In contrast to most postoperative patients, the assessment
hydrostatic fluoroscopic dilatation is usually effective in for when to start feeds has less to do with the bilious aspi-
treating strictures. With progression to solid foods, these rate from the nasogastric (NG) tube or drainage from the
children must be coached to chew well and to consume gastrostomy feeding tube (G-tube) than to do with volume.
liquids with their meals to overcome any potential residual Because of the congenital obstruction, the pylorus is often
esophageal dysmotility. It is not unusual for overly large incompetent and bile will flow retrograde into the stomach.
pieces of food to become lodged at the level of anastomosis The progressive decrease in output, however, indicates
and result in esophageal obstruction. This problem tends forward peristalsis through the anastomosis and is the best
to resolve with age, the increasing caliber of the esophagus, indication that it is safe to start enteral feeds. When breast
and maturity of the child. milk is not available, the choice of infant formula is based on
gestational age. There are no predictable associated absorp-
Duodenal Atresia tion disorders to require specialized formulas. The mode of
Infants with duodenal atresia are most often identified feeding again is dependent on the child’s anatomic and func-
antenatally and parents can be advised about their antici- tional considerations. While intermittent oral feeds may be
pated perinatal course in a prenatal consultation. The focus a successful strategy, often a more rapid transition from PN
of these discussions from a pediatric surgical standpoint is to EN is achieved with continuous gastric feeds which are
the operative management of the anatomic defect and the then transitioned to bolus and oral feeds. Certainly oral

SURGERY 395
feeds can be added on top of continuous feeds to allow the either leak or obstruction as a consequence. Surgical clinical
infant to acquire oral motor skills. The more complicated judgment will dictate what is reasonable to salvage.21,22
infants have greater duodenal dysmotility and may have In the most complex variant of jejunoileal atresia, the
required a tapering enteroplasty. These infants often have a “apple peel deformity,” there is a complex malformation
G-tube inserted to facilitate gastric decompression, thereby of the proximal intestine along with preservation of the
protecting the anastomosis and allowing the infant greater distal ileum on a vascular pedicle that provides retrograde
success in extubating from mechanical ventilation without perfusion for a variable length of intestine. The particular
a nasogastric tube in place. Given the potentially complex anatomic appearance of the twisted intestine, “may-poled”
and prolonged postoperative course in this disorder, PN is around the single vascular trunk originating from the distal
started routinely and converted to central formulation once ileal arcade, is important to recognize such that inadvertent
central venous access has been established. further vascular compromise is avoided by torque from a
poorly aligned enteric anastomosis. Furthermore, careful
Jejunoileal Atresia perioperative fluid management is essential to preserve
As the anatomic site of obstruction extends further distally, adequate perfusion to the distal most intestine. Hypotension
the immediate postoperative problems related to provi- will result in splanchnic vasoconstriction compromising
sion of EN generally are less frequent and less severe. These mucosal flow to particularly this section of bowel.
proximal obstructions can occur in isolation as well as in Nutrition considerations in these infants focus on the
various constellations of increasing complexity, culminating provision of adequate PN calories via central access, with
with the type IV apple peel deformity. In the simple mucosal early consideration of techniques to limit cholestatic disor-
web or single transmural atresias, operative considerations ders since the process to complete conversion to enteral
are relatively simple if the infant has normal overall intes- feeds may be prolonged by dysmotility and complications
tinal length. A resection of the abnormally dilated jejunal such as necrotizing enterocolitis (NEC). With the intent to
segment and primary anastomosis to the distal unused bowel gradually stimulate the bowel for adaptation, continuous
results in the least size discrepancy between adjacent limbs of feeds are most often initiated and the infants who often
intestine and predictably has the least common incidence of have G-tubes to facilitate this are allowed to sham-feed by
peri-anastomotic obstruction and dysmotility. These infants mouth and eventually are later converted to full bolus feeds
would be anticipated to tolerate the onset of enteral feed- by mouth or G-tube.23
ings once bilious NG output has resolved and volumes have
decreased in concert with the passage of bile-pigmented stool Distal Intestinal Obstruction
output. This can occur 5 to 10 days after operation and there- Distal intestinal obstruction usually involves the terminal
fore mandates use of PN in the interim. Infants with multiple ileum and beyond. These infants will present with
intestinal atresia are likely to have compromise of the overall abdominal distention which is not relieved with naso-
bowel length, and operative methods to salvage length gastric decompression. Distal ileal atresia or obstruction
must be considered in relation to the infant’s gestational from inspissated meconium can result in volvulus of the
age and how this relates to ongoing longitudinal growth of distended, fluid-filled segment and cause ischemic necrosis
the intestine during the third trimester. Infants delivered at of more extensive regions of the intestine. In the absence
term and diagnosed with multiple intestinal atresia have less of significant intestinal loss, these conditions are unlikely
opportunity to compensate for lost intestinal length. The to require more than conventional perioperative nutrition
most proximal segment of intestine will be the only segment support. Resection of the right colon including the ileocecal
dilated, and length can be preserved by performing a stan- valve is usually well tolerated. The need for replacement of
dard longitudinal tapering enteroplasty. Only in the event of vitamin B12 must be considered at a later time (age 2 years)
severe congenital short bowel should more novel techniques if a significant portion of terminal ileum accompanies the
such as the serial transverse enteroplasty procedure (STEP) or resection. More extensive colon resections, as might be
Bianchi be considered to optimize salvage of mucosal surface encountered in Hirschsprung’s disease, have more signifi-
area while promoting intestinal contractility.19 As many as cant effects on resorption of water and electrolytes. Patients
possible of the subsequent atretic portions of intestine should with Hirschsprung’s disease and anorectal malformations
be salvaged using a “shish-kebab” technique in which conti- require long-term dietary management with the focus on
nuity is created over a device such as a broviac catheter.20 The achieving optimal evacuation of stool.
calculated risk, however, is the non-union of segments with

Colon Atresia diverting stoma becomes necessary with staged explora-

Colon atresia is a rare condition, accounting for only 10% tion and restoration of continuity at a later date. If the distal
of all intestinal atresia. Most common is a vascular defect end of the bowel can be identified this is helpful in trying
at the level of the middle colic artery resulting in an inter- to prepare it for the subsequent operation and for consider-
ruption of continuity at the mid-transverse colon. The right ation of distal refeeding of proximal stoma output (see later
colon becomes massively distended since a competent section in this chapter).
ileocecal valve may not allow for distribution of the enteric Nutrition management of these infants requires consid-
contents into the terminal ileum. Operatively there are eration of the likely underlying diagnosis of CF, which must
several solutions for this condition. An extended right hemi- be verified by testing. While in the past it was taught that EN
colectomy with anastomosis of the ileum to the transverse with a protein hydrolysate formula or breast milk did not
colon results in permanent loss of a significant surface area require provision of pancreatic enzymes, common practice
for nutrient and water absorption. Fortunately the left colon now is to provide these enzymes nevertheless, to optimize
can compensate for the water absorption with adaptation whatever enteral intake is available for absorption. This has
and the patient should not have persistent watery stools. to be balanced with the past concerns for mucosal damage
More complicated solutions focus on preserving the right from specific formulations of enzyme dosing. This infant
colon with a proximal diverting stoma in the hopes that it with a diverting stoma is a classic example of the nutrition
will decompress and regain its normal caliber and motility. decision-making involved with a child who will require a
The nutrition considerations in these patients are generally second, complicated operation, 6 weeks or more in the future
simple and are impacted by whether a second reconstruc- (see section on management of stoma output). Cholestatic
tive operation is necessary. jaundice is based not only on total PN exposure, but also
on potentially underlying liver disease associated with CF.
Meconium Ileus and Variants Once intestinal continuity to a stoma or the rectum is estab-
This is a condition usually associated with cystic fibrosis lished postoperatively the goal is to wean total PN support
(CF), resulting in distal ileal obstruction as a consequence expeditiously while recognizing that these infants tend to
of the abnormal luminal contents which become inspissated. have a higher than usual caloric requirement.
Meconium ileus may be complicated further by either (1)
perforation of the obstructed bowel resulting in meconium Hirschsprung’s Disease
peritonitis or (2) volvulus of the distended bowel resulting Hirschsprung’s disease is a consequence of the absence of
in ischemia and stricture formation which may appear iden- the ganglion cells from the rectum and distal-most colon,
tical to an atresia. While simple meconium ileus, in which typically involving the rectosigmoid. The enteric ganglion
there is only luminal inspissation, can be decompressed with cells are essential to receptive relaxation of the intestine and
sequential gastrograffin enemas, operation is sometimes their absence results in a functional obstruction of the colon
necessary. In the process of attempting to decompress the with remarkable dilation of the normal colon proximal to
obstructed segment with saline or N-acetylcysteine irriga- the transition zone beyond which these neural crest cells
tion, it is possible to perforate or excessively traumatize the failed to migrate during the embryonic period. The conse-
intestine. Often the safest choice is placement of a T-tube quence is a functional obstruction at the level of the absence
that provides access for continued postoperative irrigation of ganglion cells (aganglionosis). Hirschsprung’s disease
and gradual resolution of the obstruction. In the event of most often affects term or near-term infants and is unusual
complicated meconium ileus due to luminal discontinuity, in preterm infants. The newborn who is diagnosed and
a resection and primary anastomosis may be possible, but promptly undergoes reconstructive operation—whether it
because of the risk of recurrent distal obstruction, creating be an open operation, laparoscopic assisted, or transanal—
a “vented” anastomosis (Bishop Koop or Santulli stoma) is likely to be able to start normal EN within 5 days of
provides the greatest assurance of success. This allows operation. Therefore the provision of even peripheral total
the enteric contents to evacuate per stoma should distal PN, during the first few days of life, once the child has been
obstruction re-occur and provides direct access to the diagnosed, is probably sufficient. This scenario, however,
distal bowel to treat with 3% N-acetylcysteine solution. The changes with a late diagnosis of Hirschsprung’s disease,
most difficult variant to deal with operatively is meconium which is often associated with significant failure to thrive,
peritonitis, in which the site of perforation may be unable enterocolitis, and long-segment disease. These situations are
to be identified or mobilized to create a stoma. A proximal independent predictors of a difficult postoperative course

SURGERY 397
and therefore surgeons will often choose not to operate Beckwith-Wiedemann syndrome is diagnosed when ompha-
immediately and instead to manage these patients medically locele is associated with macroglossia, hypoglycemia, and
(with irrigations if the transition zone is distal) or perform a hemihypertrophy. This is a transient metabolic condition
stoma at the point where ganglion cells are present. Failure with no long-term implications for glycemic control, but
of the initial reconstruction potentially leads to a lifetime places the patient at risk for solid organ tumors. Associated
of anorectal disability. Once diverted, or established on an congenital heart disease may involve various intracardiac
effective irrigation program, the alimentary tract can again defects or a constellation of defects involving the heart,
be challenged with nutrients and should be able to function pericardium diaphragm, and sternum which are referred to
appropriately, allowing the infant to thrive. The infant with as the Pentalogy of Cantrell. Depending on the size of the
total colon aganglionosis is essentially diverted at the level of abdominal wall defect, the liver and intestine are typically
the terminal ileum. He or she may require total PN support extra-abdominal, and reconstruction can be accomplished
transiently until such time when adaptation has occurred. in one vs. several stages.
The rare infant with aganglionosis extending into the small A small omphalocele can be closed within days after
intestine often will suffer from severe short bowel syndrome birth once associated anomalies have been excluded. The
(SBS) and must be managed accordingly. child is typically kept NPO preoperatively, although this
may not strictly be necessary, but convenient for the preop-
Anorectal Malformations erative evaluations. Once a small omphalocele is closed,
Children with isolated anorectal malformations generally enteral alimentation can be commenced as soon as there
have no specific nutrition requirements. Their anorectal is evidence of GI motility/function. While there are no
defect will either respond to progressive dilation allowing for predictable GI problems, extrinsic gastric compression from
a delayed operative intervention or will require a diverting the oversized liver and GER are not uncommon and may
colostomy. These children grow and develop normally in require transient postpyloric feeding. In the more compli-
the absence of associated disorders. cated giant omphaloceles, PN is commonly started to bridge
After reconstruction, children with Hirschsprung’s the child’s nutrition needs while multiple operative proce-
disease and low variants of imperforate anus will have issues dures interfere with consistent EN. Ethical considerations
related to stooling, with some developing severe functional arise when an infant with omphalocele is diagnosed with
constipation which may progress to overflow incontinence. a lethal chromosomal disorder such as trisomy 18. Often
Children with high imperforate anus tend to have problems the surgical condition can be managed in a non-operative
with fecal incontinence either due to absence of the sphincter manner and EN can be delivered in a relatively non-invasive
complex or deficient innervation. Appropriate dietary manner via a nasogastric feeding tube if the child will not
management along with a supervised bowel management feed by mouth.
program are essential to the well being of children with this The outcomes of omphalocele should be excellent but
spectrum of disease. Dietary considerations include provi- for the most complex disorders.
sion of sufficient non-absorbable fiber intake along with
sufficient liquid intake to assure daily evacuation. Gastroschisis
Gastroschisis is frequently the more complex defect from
Abdominal Wall and Diaphragm the standpoint of operative interventions and providing
optimal nutrition support. This abdominal wall defect is
Omphalocele typically a relatively small full-thickness aperture to the
Omphalocele and gastroschisis are two very distinct right of the umbilical cord insertion. Much of the GI tract
congenital disorders with completely different consider- is extruded through this defect and is bathed in amniotic
ations in terms of their postnatal GI function. While both fluid through pregnancy. The exposed intestine is at risk
conditions involve the presence of an abdominal wall defect, for torsion, vascular impairment from a tight fascial defect
the intestine is protected within a membrane in patients which remains fixed as the intestine and its mesentery
with omphalocele and is not subject to the fascial constric- enlarge, and is subject to serosal irritation and trauma by
tion and amniotic exposure encountered in gastroschisis. virtue of its extraperitoneal location. Immediate postnatal
Omphalocele can be associated with genetic disorders as coverage of the intestine is accomplished by either primary
well as renal and cardiac defects and it is typically these abdominal closure or more commonly by placement of a
conditions that determine the outcome of these patients. temporary “silo.” This sterile silastic tube accommodates

the intestine and is secured via a flexible but reinforced known interventions that lead to a more rapid resolution
ring at its open end, which slides under the abdominal wall of wall edema. In general these infants require a generous
fascia, thereby creating a covered extension of the peritoneal amount of intravenous fluid support in the first few days
cavity. Gradual compression of the silo from the top down as they are projected to be relatively volume depleted on
forces the intestine into the gradually expanding abdominal presentation and continue to require good vascular perfu-
space and allows for the ultimate abdominal wall closure. sion of the intestine. The peripheral edema which may appear
Although there are multiple variations in the technique to occurs on a different basis than that of the intestine, which
achieve reduction and closure, there do not appear to be likely happens as a consequence of vascular and lymphatic
any remarkable differences in outcome in terms of time to congestion at the level of the fascial ring defect. In contrast
full feeds and hospital discharge.24 Non-operative, bedside to the peripheral edema, it is unlikely that diuresis affects
closure with simple coverage using the umbilical remnant this visceral edema in the early phases.
has also been described and is being evaluated for its long- The onset of intestinal feeding must coincide with
term outcomes. evidence of effective full intestinal peristaltic activity as
The most important predictor of outcomes appears to evidenced by decreasing NG outputs and onset of stooling.
be the original condition of the intestine. The intestinal Early feeding into a dysmotile and transmurally altered
surface in gastroschisis has a variable appearance and ranges intestine likely accounts for the higher incidence of NEC in
from non-edematous, pliable, and virtually normal intes- gastroschisis than any other gestational age-matched infant
tine without surface adhesions to stiff, edematous bowel population. While bolus feedings have benefit in stimulating
whose contour and continuity cannot be assessed visually hormonally regulated secretions from the pancreatobiliary
or even by palpation. Further complicating the presenting tract, they are limited by virtue of the initially small capacity
features is the tendency for these children to have a shorter of the stomach. Because cholestasis is common in these
than normal length of intestine. Fortunately some of these infants, there is a desire to wean them off PN expeditiously;
changes will resolve with time; however, the period of time however, this is best achieved not by starting feeds prema-
to normal intestinal peristalsis can be quite variable. After turely, but by providing continuous enteral stimulation via
an extended period of observation of 4 to 6 weeks, without continuous drip feeds, once motility is evident. These can
evidence of bowel continuity, contrast studies are indicated certainly be augmented by interval bolus feeds which allow
to evaluate whether there is an intestinal atresia present. the child to develop the necessary oral feeding skills and
Evaluation much earlier is without benefit, as the abdomen may stimulate the GI hormones. Vigilance is essential as
will be quite hostile to exploration. the enteral component is advanced. Guidelines for advance-
An interesting situation arises when an atretic segment ment of feeds should take into account the frequency of
is recognized at birth. Although the intuitive response stools as well as the pH and reducing substances as these
would be to divert at that level to allow for some enteral may indicate poor absorption and/or an excessive osmotic
stimulation, this is not generally advisable. There is limited load. Because of the perceived fragility of the intestine,
abdominal wall surface area for a stoma and the edema of this author’s practice is generally to use a more elemental
the intestine rarely allows it to reach the abdominal wall in formula and limit the osmolality of the formula, trying not
an orientation that is feasible for creation of a stoma. It is to increase the caloric density of feeds until the child is
currently considered best practice to close the abdomen and nearly fully established on EN.
correct the atresia at a second operation.25,26 Setbacks relate to septic events concerning the central
Given the primary dysfunction of the intestine on line, which are usually gram negative in etiology and reflect
multiple levels, these infants may require an extended the ongoing reduced mucosal barrier defense in the intes-
period of PN support. During the initial few weeks, the tine. Given the combination of cholestasis and poor motility,
infant remains decompressed with a nasogastric tube. these patients are great candidates for cycled enteral antibi-
Again, in contrast to other children who may require otics to obviate bacterial overgrowth and its complications.
prolonged decompression, there is a reluctance to perform Gastroschisis is one of the more common causes of neonatal
any visceral procedure, even a gastrostomy, due to abdom- SBS. The etiologies involve congenital torsion or ischemic
inal wall constraints and the altered surface characteristics necrosis of entire segments of intestine, simple atresias, and
of the GI tract. Unless these children are extremely preterm, postnatal loss of intestine due to poor perfusion, NEC, or
they usually have an uneventful perioperative course with surgical catastrophes. Caloric estimates for the needs of
a short duration of mechanical ventilation. There are no these infants depend on their phase of recovery. In the initial

SURGERY 399
postnatal period there appears to be an intense inflamma- Infants with CDH and severe cardiopulmonary
tory state as evidenced by elevated CRP which resolves as compromise requiring inotropic support and other medica-
the bowel recovers. The incidence of cholestatic jaundice is tions such as nitric oxide for stabilization of the pulmonary
likely multifactorial in this population.26 hypertension present challenges to the provision of even a
fraction of the targeted caloric requirements. The assess-
Congenital Diaphragmatic Hernia ment of caloric needs is especially difficult because there
Congenital diaphragmatic hernia (CDH) involves a hetero- are so many confounding factors such as level of sedation,
topic location for the viscera within either chest cavity possible chemical muscular relaxation, degree of mechan-
as well as associated developmental defects in lung and ical respiratory support, and level of temperature support
pulmonary vascular development and maturation. While provided. During this phase the goal of nutrition support
the former is a surgically correctable defect, the second is to provide those essential components to allow for basic
component determines the child’s clinical course and ulti- metabolic needs and repair of tissues. Calories earmarked
mate prognosis. Infants with CDH therefore fall into several for growth and development become priorities as the
categories. There are those with a diaphragmatic defect, infant’s clinical condition improves. When these patients
usually first detected postnatally, in whom there is little require cardiopulmonary support on ECMO , the assump-
hemodynamic and pulmonary compromise; they tolerate tion was that just as the lungs were being “rested,” the
the operation well and can relatively quickly be transi- metabolic demand would decrease. This has been shown
tioned to enteral feedings. Infants in whom the defect was to be an incorrect assumption; these patients continue to
identified early in gestation tend to have a greater degree exhibit the hypermetabolic response, and this even persists
of pulmonary hypoplasia and more difficulty with pulmo- after decannulation.29,30 In the past there has been debate as
nary hypertension. These infants may require cardiac and to the safety of administering lipids to an infant on ECMO.
pulmonary support via ECMO. Nutrition support in this The consensus now is that they can safely be administered
disorder therefore spans the whole spectrum and must be via a central line separate from the ECMO circuit, whereas
individualized. The GI tract, although displaced initially, is the dextrose and amino acid solution is typically adminis-
fundamentally normal in terms of its motility and absorp- tered via the cannulae and in this situation only, can safely
tion capacity. As such there are no specific recommendations exceed dextrose concentrations greater than 20% since
for the type of enteral alimentation. Consideration will there are sufficiently high flow rates directly into the atrium.
need to be given to the fact that total fluid provision will Provision of high glucose loads along with insulin therapy
likely be restricted in the postoperative patient as he or has been shown to be beneficial in this population in terms
she is weaned off ventilatory support. While it is enticing of limiting protein catabolism. 31,32
to provide highly concentrated formulations, this has to be
balanced with the potential for mucosal damage leading to Hepatobiliary Disorders
enteric-derived sepsis in vulnerable infants who likely have
multiple vascular access points. Provision of adequate calo- Biliary Atresia
ries will likely be best accomplished by this means once the Infants presenting with direct hyperbilirubinemia are
infant has tolerated enteral feedings and becomes limited promptly evaluated for surgically correctable biliary tract
in the amount of volume that can be delivered for reasons disorders such as biliary atresia and choledochal cyst.
of gastric capacity and emptying. All children with CDH While other conditions such as neonatal hepatitis also lead
have some degree of foregut dysmotility, which renders to similar laboratory presentations, they, as well as a host of
them at risk for GER.27,28 The risk of reflux with aspiration infectious disorders and enzymatic defects, require medical
is particularly pronounced in these patients who already support only. Biliary atresia most often becomes evident at 1
have a compromised pulmonary system, given the nature month of life and the infant may have experienced failure to
of the congenital defect. This forms the basis for providing thrive of unknown etiology. Hallmarks of clinical diagnosis
continuous feeds initially to full enteral needs and then include jaundice, acholic stools, and dark urine. Ultrasound,
transitioning them to bolus feeds. Again, the provision of HIDA scan, and percutaneous liver biopsy should confirm
continuous enteral feedings should not be a disincentive to the diagnosis. Once established, preoperative administra-
allow for oral feeds. This can be structured to be the volume tion of vitamin K is one of the standard recommendations to
of feeds targeted to be delivered over 1 hour or even more as optimize coagulation parameters. The diagnosis is further
the child tolerates. confirmed intraoperatively by demonstrating lack of the

extrahepatic ductular system. Reconstruction involves by routine postoperative guidelines and have no special
creation of a jejunal limb that is anastomosed to the portal nutritional considerations, other than those imposed by
plate, the region of the liver where the hepatic ducts would virtue of prolonged ventilatory support and concern for
be presumed to originate from the liver parenchyma. In reflux with aspiration. Many of these operations can now
fortunate situations, there is early evidence of bile flow with safely be achieved with minimally invasive techniques
resolution of the hyperbilirubinemia. Postoperative steroids further reducing the surgical stress, postoperative pain
are frequently used as a choleretic and to reduce the paren- response, and minimizing wounds to heal. Infants born
chymal inflammation within the liver. This postoperative with chylothorax, or those who develop it as a consequence
course is typically a period of 5 days of non-enteral alimenta- of perioperative complications, are managed depending on
tion to allow for healing of the intestinal anastomosis with the amount of daily chylous output with gut rest with PN
subsequent initiation of enteral feedings. With the frequent support and the subsequent introduction of enteral feeds
delay in diagnosis to 2 months of age, some infants will be with high MCT oil concentration.
in very poor nutrition condition. On preoperative assess-
ment, some surgeons will opt to place central venous access Urologic, Neurosurgical, and Orthopedic
at the time of operation, to provide the debilitated child Infants born with complex urological defects such as bladder
with some nutrition in the interim so as to optimize healing exstrophy and cloacal exstrophy will certainly require a
and prevent further weight loss. There is no indication for number of staged surgical interventions by various special-
preoperative nutrition repletion because decompression ists. The intestinal tract is intact and generally normal in
of the obstructed biliary tract is the most important goal. bladder exstrophy whereas there is imperforate anus with
Postoperative feedings are generally breast milk if available, exteriorization of the hindgut between two bladder halves
or a protein hydrolysate formula with approximately 50% in cloacal exstrophy. This portion of the hindgut will need
medium-chain triglyceride (MCT) oil to provide MCTs to be tubularized to create a distal stoma or require prox-
which are more easily absorbed by the infant with liver imal diversion. Hydronephrosis, prune belly syndrome,
disease. These children have impaired ability to digest fats and other congenital renal anomalies may have evidence of
and require supplementation of the fat-soluble vitamins A, renal insufficiency or failure that will require adjustments
D, E, and K. There are reports of these infants requiring to the infant’s nutrient intake as discussed in other chapters.
a disproportionately larger caloric intake than for others Congenital neurosurgical and orthopedic interventions
their size. generally do not involve the peritoneal cavity or even the
More on the nutrition support of the child with surgically retroperitoneum and therefore do not impact enteral feeding
non-correctable liver disease is discussed elsewhere. 33,34 status. Depending on the extent of operation and metabolic
stress, adjustments primarily affect caloric goals and will
Choledochal Cyst need to be individualized. A thoughtful consideration of
Infants with this congenital disorder may present during the impact of general anesthesia, which is virtually uniform
the neonatal period or later, but generally before age 5 years. in neonatal patients undergoing surgery, will suggest that
The acute presentation may include pancreatitis in addition resumption of enteral intake occur in a slightly delayed
to hyperbilirubinemia. These children rarely have chronic manner.
malnutrition despite complaints of abdominal pain. Subse-
quent to resection of the choledochal cyst, which involves Neonatal Airway Disorders
variable portions of the extrahepatic ductal system, and Infants who require interventions on their airway frequently
reconstruction of biliary outflow with a standard roux-en-Y have associated aerodigestive disorders that may extend to
hepaticojejunostomy, these patients will be able to consume foregut dysmotility syndromes. Reconstructive interventions
a normal diet and in the absence of significant underlying for laryngomalacia, subglottic stenosis, and tracheomalacia
liver disease do not need special nutritional formulations. require protection of the airway from GER. Often tracheo-
stomy can be averted by appropriate management of enteral
Other (Non-GI) Malformations feedings along with pharmacologic interventions to limit
exposure of the glottic structures to acid gastric contents.
Thoracic Disorders This may require insertion of a postpyloric feeding tube
Children who require thoracic operations for congenital to assure continued nutrition support without the risk of
lung lesions or even foregut duplications can be treated reflux. If chronic in nature, then early consideration for a

SURGERY 401
Nissen fundoplication is appropriate. Infants with airway stage 1 NEC). Altered perfusion may be the consequence
compromise have an increased work of breathing and may of primary cardiac events (congenital heart disease, PDA),
exhibit failure to thrive even despite mechanical feeding. pulmonary compromise with consequent hypoxia and
Once supported with a tracheostomy, the infant will often resultant shunting away from the viscera, and other events
show rapid catch-up growth and can sustain a reduction in such as hemorrhage (pulmonary, intraventricular). Beyond
what is normally considered caloric goals. It is important to the mucosal border the immaturity of the host immune
remember that despite the presence of a tracheostomy, the system is overcome due to limited phagocytic and bacteri-
airway is not completely protected from either GER or aspi- cidal activity of neutrophils and other components of the
ration salivary secretions because the pediatric airway often gut-associated lymphoid tissue (GALT). These speculated
does not require a cuffed tracheostomy, and every conscious factors would all contribute to facilitating an enteric source
effort is made to preserve some airflow past the cords to of sepsis. Needless to say the etiology of NEC is manifold
prevent progressive subglottic stenosis. and complex. The radiographic hallmarks are pneumatosis
intestinalis and portal venous gas, both of which portend
Nutrition Support in Infants with that there has been transgression of the mucosa by gas-
Acute GI-Related Disorders producing organisms. If the sepsis can be controlled and
the intestine is able to maintain its integrity, no operative
Necrotizing Enterocolitis intervention is necessary (Bell stage 2 NEC). However, if
NEC remains one of the most frequent indications for evidence of perforation becomes evident or the abdominal
emergency operation on preterm neonates. Although the sepsis fails to come under control, operative intervention
mortality has decreased over time and management of becomes mandatory (Bell stage 3 NEC). The options are
intestinal dysfunction has improved, this remains a diag- often dictated by the infant’s size and degree of clinical insta-
nosis with a significant morbidity and mortality. Although bility. In the smallest and most unstable infant, placement
this is not to be an exhaustive summary on the pathophysi- of a peritoneal drain may be all that can be safely offered
ology of NEC, it is important to understand some of the while in larger or more stable infants a limited laparotomy
mechanisms thought to be responsible for its development at the bedside or in the operating room may allow for more
as these influence the way surgeons treat infants who have definitive therapy. At operation the extent of intestinal
experienced and may be at further risk for mucosal injury. involvement becomes apparent. In the least severe circum-
NEC is best considered a consequence of exposure stances, a limited segment of intestine has transmural
of an immature and naïve intestinal tract with potentially gangrene or has perforated. Resection and diversion with
compromised perfusion to pathogenic organisms, which stoma versus primary anastomosis are decided upon based
traverse the intestinal barrier to initiate the gut-derived on the patient’s overall condition and specifically the condi-
sepsis syndrome. The gut mucosal barrier is compromised tion of the intestine. In infants with more extensive and
on several levels in the premature infant. 35 The normally acid even skip involvement, proximal diversion and only exci-
environment of the stomach serves as an initial barrier to sion of those areas of definite gangrene become the guiding
microbes, yet acid production is often immature and is often principles so as to preserve as much intestinal length as
altered iatrogenically by providing acid-suppressing medi- possible. Despite optimal management, these affected areas
cations, in the hopes of avoiding gastritis and ulceration. may progress to full-thickness gangrene or heal as fibrotic
Other factors include the limited supply of luminal protec- strictures, further compromising residual length and poten-
tive factors such as the lectins and IgA provided by maternal tially resulting in SBS. Survival is only possible if the sepsis
milk. Structurally the mucosal surface provides oppor- is controlled. 36
tunities for attachment of bacteria via a decreased mucus The acute management focuses on providing adequate
barrier, tight junctions which may not be as tight as in older, perfusion to the residual intestine in order to allow it to
term infants, and active translocation mechanisms which recover from the initial insult. This results in the generous
optimally are suited for sampling a safer environment than provision of intravenous fluids early on and the restriction
that provided in a neonatal intensive care unit (NICU). The of fluids upon resolution of the sepsis in order to optimize
mucosal integrity may become further compromised with pulmonary function. This compromises the ability to
decreased visceral perfusion. The mucosa is at greatest risk provide optimal nutrition in a consistent manner. Enteral
with hypoperfusion, and mucosal sloughing as evidenced by feeding would be considered no earlier than 7 days of thera-
bloody stools is an early indication of potential NEC (Bell py. As in other complex GI disorders a coherent plan has to

be generated by the managing teams so as to best utilize a of antibiotic therapy apply as they do in NEC infants. From
combination of EN and PN. Recurrent sepsis and progres- a nutrition standpoint one assumption to be made is that the
sive cholestatic jaundice are the predictors of mortality. All remainder of the GI tract will not have experienced the same
techniques available to limit these complications should be generalized mucosal insult as encountered in NEC and that
utilized in these patients. Reconstitution of the full GI tract enteral feedings and rehabilitation should be achievable with
is accomplished after 6 weeks to limit operative complica- greater success rates.
tions and to have given sufficient time for strictures to form
and to be identified such that they can be treated at the same Intestinal Malrotation and Midgut Volvulus
operation. 37 Even in those infants managed without opera- Midgut volvulus as a consequence of intestinal malrotation
tive intervention, the clinicians must maintain suspicion for can occur at any age, having been described both prenatally
developing strictures, particularly if the colon was involved, and in adult patients. The first month of life is, however,
which can be difficult to tell non-operatively. Aggressive the most common time of presentation. The infant who is
feeding of an infant with a distal bowel obstruction will born with intestinal malrotation and experiences a midgut
only lead to recurrence of NEC. 38 While the specific amino volvulus can be severely compromised. With timely diag-
acid composition of neonatal total parenteral nutrition is ad- nosis and intervention, the midgut (proximal jejunum to
dressed in other sections, much attention had been focused mid-transverse colon) should be salvageable. At opera-
on the utility of providing glutamine to this population with tion the abdomen may be filled with chylous ascites as a
a compromised gut mucosal barrier; however, this does not consequence of obstruction and rupture of the mesenteric
appear to be an effective strategy. 39,40 lymphatics. Untwisting of the mesenteric pedicle will
Infants who survive the early postoperative course restore venous drainage and allow for improved arterial
associated with NEC are among the highest risk infants inflow. Resection is only considered if there are regions of
for intestinal dysfunction, SBS, and cholestasis. All nutri- complete necrosis. Any intestinal segment with border-
tion techniques described earlier in relation to initiation of line perfusion is retained and reassessed at 24 hours with
trophic feedings, enteral antibiotics, and cycling of modu- a second-look laparotomy to avoid unnecessary resection
lation of total parenteral nutrition should be applied in leading to SBS. Depending on the extent of the intestinal
this context. The optimal timing of refeeding and stoma injury, these infants must initially be fed cautiously to avoid
closure remain topics of controversy and are often individu- a “second hit” to a compromised bowel. The perioperative
ally determined or institutional preferences rather than nutrition support team again must target metabolic needs
evidence-based protocol-driven events. as well as protein substrate for tissue repair. In the absence
of any significant intestinal resection, there should be no
Isolated Intestinal Perforation ongoing considerations. The management of the child who
This is a condition that closely mimics NEC in that it presents suffers massive intestinal loss is covered in the chapter on
with evidence of visceral perforation, usually pneumoperito- intestinal failure (Chapter 27). As with NEC these infants
neum in the absence of pneumatosis, or portal venous gas and are the most likely to have lost the terminal ileum and will
thus requires some surgical intervention. The infants affected likely require vitamin B12 supplementation in the future.
with this disorder are usually extremely low-birth-weight
infants (< 750 g), in their first week of life, and may never have Pyloric Stenosis
been fed. Often the diagnosis remains speculative since many Infants with pyloric stenosis primarily require rehydration
are treated with peritoneal drainage only and isolated involve- and correction of electrolytes preoperatively but then can
ment of only a small intestinal segment cannot be verified be relied upon to resume a normal infant diet. How this is
other than by operation. These infants are generally thought initiated varies by institution. In general, no postoperative
to have a better prognosis because of limited colonization of feeding tubes are placed as these put the exposed pyloric
the GI tract during the first week of life, better source control channel mucosa to the risk of perforation. The infants are
of sepsis once the abdomen has been drained, a self-sealing typically hungry and have good feeding skills. In this author’s
perforation site, and consequently a less profound sepsis institution, our feeding protocol was developed to provide a
syndrome. The initiating events remain elusive, but may be consistent algorithm that allows the vast majority of infants
related to focal perfusion defects or focal luminal injury by to be discharged to home within 24 hours of operation. We
medications such as indomethacin. The same concerns for hold oral feeds for 6 hours, and then test the stomach with 2
indications for laparotomy, length of NPO status, and length small-volume (15 mL) Pedialyte® feeds 2 hours apart. If the

SURGERY 403
child experiences no vomiting, then formula or breast milk of these chronic conditions can be the consequence of
is offered at 30-mL volumes every 3 hours and advanced by neonatal interventions with adapted SBS, late stenosis,
15 mL every second feed to a maximum of 60 mL, which and dysmotility in the atresia (duodenal and jejunoileal)
provides the necessary volumes for the average 3 to 3.5 kg patients. Malignancies affecting the GI tract are generally
infant with pyloric stenosis. At this point the infant can be rare and most frequently involve lymphomas, although
discharged home and feedings are advanced as tolerated carcinoid tumors, desmoid tumors, and other solid visceral
by the parents with the proviso that individual volumes tumors will impact the GI tract. Abdominal visceral trans-
should not be excessive so as to minimize reflux. Recur- plantation is yet another surgical intervention in which
rent vomiting will always raise the spectre of recurrent specialized focus on nutrition management must occur.
stenosis or of an incomplete operation, both of which are These more complex topics of irritable bowel syndrome,
rare events in experienced hands. The infant’s stomach is malignancy, and transplantation are addressed in individual
capacious given the preoperative obstruction, but more chapters elsewhere.
frequent limited volume feeds will assure retention of feeds The nutrition management of the acutely ill surgical
and optimal absorption. All parents are amazed by the patient is generally focused on resumption of enteral intake
infant’s persistent need to feed within the first month post- and, when this becomes delayed beyond 5 to 7 days, consid-
operation. This resolves spontaneously as the child achieves eration is given to PN support. There is evidence from the
“catch-up” growth. Persistent vomiting should prompt critical care literature to indicate that many of these acutely
consideration of gastroesophageal reflux, which can be ill patients are significantly undernourished while in the
ameliorated with antacid therapy including even a dose of ICU. There is also evidence that simple calculation of REE
sodium bicarbonate, which may also act to help disintegrate without accounting for physical activity underestimates
a mucus plug in the pyloric channel. More serious consid- caloric requirements.42,43 While there is a consistent attempt
erations should include the potential for an intraoperative to provide medical patients and traumatized patients in the
bowel injury or wound/fascial dehiscence. Typically these ICU setting with early enteral feedings, these principles
infants will have other symptoms in addition to persistent cannot be applied to the surgical patient who likely is at
vomiting. If ranitidine was provided perioperatively it can higher risk for anastomotic breakdown, abdominal sepsis,
usually be discontinued at the follow-up visit 3 to 4 weeks and the development of complications such as surgical site
later. Most of these infants have undergone multiple formula infections, fascial dehiscence, and enterocutaneous fistulae
changes prior to their diagnosis; we reassure parents that which then further complicate clinical and nutrition
the formula is now less important and that they should use management. Despite these surgical concerns, the initia-
what they have at home and what is most accessible.41 tion of enteral feedings should be a clinical goal to allow
At other institutions the interval of time to feeding may transition off PN support at the earliest feasible time. The
differ as will the protocol, even to the point of providing the ability to handle complex wound failure has been markedly
infant with improvised feeds. The technique (laparoscopic improved with advances in enterostomal care and with the
or open) of pyloromyotomy does not have an impact on use of negative pressure wound devices that contribute to
tolerance of feeds or time to discharge. more rapid closure of open wounds and even enterocuta-
neous fistulae. The earlier control of fluid and protein losses
Nutrition Support in Children and Adolescents from these wounds should impact overall protein balance in
Requiring Operation a favorable manner.
The subset of children who present the highest risk for
General Principles emergency operation are those with chronic malnutrition.
In the older child and adolescent, many of the surgical Examples include children with failure to thrive on the basis
interventions for GI problems are of an acute nature (ie, of congenital heart disease or developmental delay resulting
appendicitis, Meckel’s diverticulum, duplications of the GI in inadequate oral intake, and children with spine deformi-
tract, and intestinal obstruction due to hernia) where there ties (severe kyphosis and scoliosis) who are at risk for the
are typically no premorbid nutrition impairment concerns. superior mesenteric artery (SMA) syndrome in which
Those children presenting with more chronic disorders, there is duodenal obstruction as a consequence of extrinsic
such as inflammatory bowel disease, polyposis syndromes, compression of the third portion of the duodenum between
and chronic GER require a closer evaluation of their nutri- the SMA and the vertebral column. Children with spastic
tion status before elective surgery is contemplated. Some quadriplegia and seizure disorders may have a limited

gastric capacity and poor gastric emptying with a tendency within 24 hours of operation. With open and laparoscopic
to reflux, which thereby has limited their enteral intake. techniques there may be some initial postoperative ileus;
Children with malignancies often are nutritionally depleted however, the main reason for decompressing the stomach
as a consequence not only of the disease process but also the or at least avoiding exogenous input is to allow a seal to
therapies applied. At children’s hospitals we have become form between the gastrostomy and the abdominal wall so
much more attuned to the preoperative nutrition evaluation that with retching and vomiting there is no extravasation
of these patients in an effort to optimize surgical outcomes between these structures into the peritoneal cavity.
from often extensive surgical interventions. Much of the How the enteral feedings are provided depends on the
focus therefore becomes provision of feeding access for child’s underlying situation. If the enteral feedings are for
nutrition support. supplementation of oral feeds, then oral intake can certainly
be started and G-tube feeds given as small bolus volumes
Feeding Access in Pediatrics which are increased according to tolerance. In children
Many children are referred for placement of enteral feeding with neurological deficits/developmental delay, initia-
devices. If access is required for more than a temporary tion of G-tube feeds may be best assessed by open vented
situation, the options include the various techniques of feeds. Rapid egress of formula from the feeding bag into
gastrostomy placement (percutaneous endoscopic gastros- the stomach with no regurgitation into the tube suggests
tomy (PEG), laparoscopic G-tube, open G-tube), insertion a large-capacity stomach that will accommodate addi-
of a gastrojejunal device, and direct jejunal feeding tubes. tional volumes, whereas slow evacuation into the stomach
Despite their seemingly simple and innocuous nature, these suggests a smaller stomach capacity or increased resistance
interventions have the potential for complications and because of abdominal wall contraction, possibly due to pain
morbidity.44,45 or spasticity. In this latter situation it may turn out to be
When placing a gastrostomy, consideration should be more efficient to provide feeds initially as slow continuous
given to the potential for promoting increased reflux on drips rather than bolus volumes. Closed infusion of feeds
the basis of anatomic alterations. Children who have typi- certainly is the least cumbersome but risks GER with
cally only consumed small amounts of food may not have potential for aspiration, or requires communication from
evidence of reflux until larger volumes are directly admin- the patient that the stomach is full. This may be exhibited
istered into the gastric lumen. A preoperative evaluation as retching, or visceral pain initiated by overdistention.
should be conducted to assess the risks, particularly when In some children with significant reflux there may be
these children are developmentally delayed and at risk for various concerns about proceeding with a fundoplication.
aspiration. The concomitant construction of a fundopli- Perhaps the child is so nutritionally depleted that the risks
cation may become necessary. Anatomic evaluation will are not in favor of proceeding with a major operation. In this
also determine whether there are impediments to proper situation a gastrostomy tract can become the conduit for a
gastric emptying that may be amenable to correction at the gastrojejunostomy tube which allows for gastric decom-
same operation. The principal diagnosis to be considered is pression and jejunal feedings. The disadvantage to the
malrotation with partial duodenal obstruction on the basis commercially available tubes is that they have a minimum
of Ladd’s bands. Typically a pH study or impedance study size of 16 French and therefore are excessively large and stiff
is conducted to address the former question and an upper for infants, but become usable at a patient size of about 10
GI study is performed to exclude all forms of distal obstruc- kg. In smaller patients other devices can be jury-rigged to
tion. If consideration is given to an antireflux operation, achieve the same tasks. These tubes are meant as transient
a nuclear medicine gastric emptying scan can be useful. feeding support devices, and repeated insertion by required
These tests can also provide information regarding reflux fluoroscopy is not ideal in the pediatric patient. The author’s
although less quantifiable than those noted above. Gastric institution uses them as a bridge to help the patient achieve
outlet procedures (eg, pyloromyotomy and pyloroplasty) an improved nutrition state, thereby becoming a better
are occasionally considered in those patients with increased candidate for fundoplication.
concern for early failure of a fundoplication. Children with neurodevelopmental impairment, spas-
ticity, and seizures often have a higher risk for disruption of
Insertion of Gastrostomy their fundoplication and the option of avoiding this opera-
When a gastrostomy tube is inserted for the sole purpose of tion by the use of jejunal tubes is often enticing. Discussions
providing enteral access, enteral feedings can be commenced with their family and caretakers should evaluate not only

SURGERY 405
the child’s operative risk but also whether continuous feeding 4. Which clinical diagnosis is expected to have impair-
via a GJ tube or J tube will interfere with their daily activity ment of intestinal motility and may require prolonged
schedule. These tubes do not allow for bolus feedings other total PN support?
than through the gastrostomy limb. Often the ability to A. Gastroschisis
provide intermittent bolus feeds is a significant improve- B. Omphalocele
ment in quality of life for both the child and family.46 With C. Hirschsprung’s disease
the advent of the laparoscopic fundoplication, there is less D. Malrotation without midgut volvulus
surgical impact in terms of abdominal wall wound healing
and pain, although early studies showed that surgical stress See p. 487 for answers.
in terms of hormone release was not altered. With excellent
short-term results this operation has gained favor; however, References
the long-term efficacy of this operation, especially in the 1. Barlow B, Santulli T, Heird W, Pitt J, Blanc W, Schullinger J.
higher risk populations, is still under evaluation.47 An experimental study of acute necrotizing enterocolitis - the
importance of breast milk. J Pediatr Surg. 1974;9(5):587.
Primary jejunostomy tubes have been avoided in all but 2. Nydegger A, Bines JE. Energy metabolism in infants with
the most chronic and perhaps institutionalized patients since congenital heart disease. Nutrition. 2006 8;22(7-8):697–704.
they represent a long-term commitment to continuous enteral 3. Owens J, Musa N. Nutrition support after neonatal cardiac
feedings. Operatively a tract is developed through the abdom- surgery. Nutr Clin Pract. 2009;24(2):242.
inal wall and an imbricated jejunal limb before the tube enters 4. Vaidyanathan B, Radhakrishnan R, Sarala D, Sundaram K,
Kumar R. What determines nutritional recovery in malnour-
the jejunal lumen. This establishes a relatively long tract for
ished children after correction of congenital heart defects?
reliable replacement of the tube in the correct orientation and Pediatrics. 2009;124(2):e294.
minimizes risk of leakage. These tubes certainly have their 5. Jaksic T, Shew SB, Keshen TH, Dzakovic A, Jahoor F. Do criti-
role in the management of complex surgical patients. cally ill surgical neonates have increased energy expenditure?
When preoperative nutrition repletion is not feasible J Pediatr Surg. 2001 1;36(1):63–67.
before an urgent surgical intervention, the focus must then be 6. Garza JJ, Shew SB, Keshen TH, Dzakovic A, Jahoor F, Jaksic
T. Energy expenditure in ill premature neonates. J Pediatr
on providing early nutrition support, which may require the Surg. 2002 3;37(3):289–293.
placement of central venous access or reliable enteral access 7. Pierro A, Eaton S. Metabolism and nutrition in the surgical
for this purpose at the time of operation. neonate. Semin Pediatr Surg. 2008 11;17(4):276–284.
8. Gruber EM, Laussen PC, Casta A, et al. Stress response in
Test Your Knowledge Questions infants undergoing cardiac surgery: a randomized study of
fentanyl bolus, fentanyl infusion, and fentanyl-midazolam
1. Which of the following strategies are considered bene-
infusion. Anesth Analg. 2001 April 1;92(4):882–890.
ficial in reducing cholestasis? 9. Shew SB, Keshen TH, Glass NL, Jahoor F, Jaksic T. Ligation of
A. Provision of > 40% of calories as lipid emulsion a patent ductus arteriosus under fentanyl anesthesia improves
B. Maintaining GIR > 15 mg/kg/min protein metabolism in premature neonates. J Pediatr Surg.
C. Continuous provision of PN 2000 9;35(9):1277–1281.
D. Initiation of enteral feedings 10. Hulst JM, van Goudoever JB, Zimmermann LJI, Tibboel
D, Joosten KFM. The role of initial monitoring of routine
2. Which is a contraindication to commencing enteral biochemical nutritional markers in critically ill children. J
feedings? Nutr Biochem. 2006 1;17(1):57–62.
A. Bilious nasogastric output in jejunoileal atresia 11. Reynolds RM, Bass KD, Thureen PJ. Achieving positive
B. Contrast extravasation on postoperative day 7 after protein balance in the immediate postoperative period in
esophageal atresia repair neonates undergoing abdominal surgery. J Pediatr. 2008
1;152(1):63–67.
C. Abdominal distention with lack of stoma output
12. de Meijer VE, Gura KM, Le HD, Meisel JA, Puder M. Fish
D. All of the above oil-based lipid emulsions prevent and reverse parenteral
3. On a 3-kg infant status post stoma closure after resec- nutrition-associated liver disease: The Boston experience. J
tion for NEC, when should enteral feedings be limited? Parenter Enteral Nutr. 2009 Sept 1;33(5):541–547.
A. Number of bowel movements exceeds 8 over 13. Lee SI, Valim C, Johnston P, et al. The impact of fish oil-based
24-hour period lipid emulsion on serum triglyceride, bilirubin, and albumin
levels in children with parenteral nutrition-associated liver
B. Reducing substances < 1/2% disease. Pediatr Res. Aug 14 [Epub ahead of print] 2009.
C. Fecal pH > 7
D. Mucoid stools

14. Javid PJ, Collier S, Richardson D, et al. The role of enteral 31. Agus MSD, Javid PJ, Ryan DP, Jaksic T. Intravenous
nutrition in the reversal of parenteral nutrition-associ- insulin decreases protein breakdown in infants on extra-
ated liver dysfunction in infants. J Pediatr Surg. 2005 corporeal membrane oxygenation. J Pediatr Surg. 2004
6;40(6):1015–1018. 6;39(6):839–844.
15. Boarini JH. Principles of stoma care for infants. J Enterostomal 32. Hulst JM, van Goudoever JB, Zimmermann LJ, Hop WC,
Therapy. 1989;16(1):21–25. Büller HA, Tibboel D, et al. Adequate feeding and the useful-
16. Al-Harbi K, Walton JM, Gardner V, Chessell L, Fitzgerald ness of the respiratory quotient in critically ill children.
PG. Mucous fistula refeeding in neonates with short bowel Nutrition. 2005 2;21(2):192–198.
syndrome. J Pediatr Surg. 1999;34(7):1100. 33. Willot S, Uhlen S, Michaud L, Briand G, Bonnevalle M, Sfeir
17. Alabbad SI, Ryckman J, Puligandla PS, Shaw K, Nguyen LT, R, et al. Effect of ursodeoxycholic acid on liver function in
Laberge J. Use of transanastomotic feeding tubes during esoph- children after successful surgery for biliary atresia. Pediatrics.
ageal atresia repair. J Pediatr Surg. 2009 5;44(5):902–905. 2008;122(6):e1236.
18. Goyal A, Jones MO, Couriel JM, Losty PD. Oesophageal 34. DeRusso P, Ye W, Shepherd R, Haber B, Shneider B, Whit-
atresia and tracheo-oesophageal fistula. Arch Dis Child Fetal ington P, et al. Growth failure and outcomes in infants with
Neonatal Ed. 2006;91(5):F381. biliary atresia: A report from the biliary atresia research
19. Ching YA, Fitzgibbons S, Valim C, Zhou J, Duggan C, Jaksic consortium. Hepatology. 2007;46(5):1632.
T, et al. Long-term nutritional and clinical outcomes after 35. Petrosyan M, Guner Y, Williams M, Grishin A, Ford H.
serial transverse enteroplasty at a single institution. J Pediatr Current concepts regarding the pathogenesis of necrotizing
Surg. 2009;44(5):939. enterocolitis. Pediatr Surg Int. 2009;25(4):309.
20. Yardley I, Khalil B, Minford J, Morabito A. Multiple jejunoileal 36. Hall NJ, Peters M, Eaton S, Pierro A. Hyperglycemia is
atresia and colonic atresia managed by multiple primary anas- associated with increased morbidity and mortality rates in
tomosis with a single gastroperineal transanastomotic tube neonates with necrotizing enterocolitis. J Pediatr Surg. 2004
without stomas. J Pediatr Surg. 2008 11;43(11):e45–e46. 6;39(6):898–901.
21. Piper HG, Alesbury J, Waterford SD, Zurakowski D, Jaksic 37. Al-Hudhaif J, Phillips S, Gholum S, Puligandla PP, Flageole H.
T. Intestinal atresias: Factors affecting clinical outcomes. J The timing of enterostomy reversal after necrotizing entero-
Pediatr Surg. 2008 7;43(7):1244–1248. colitis. J Pediatr Surg. 2009 5;44(5):924–927.
22. Wales PW, Dutta S. Serial transverse enteroplasty as primary 38. Bohnhorst B, Müller S, Dördelmann M, Peter CS, Petersen
therapy for neonates with proximal jejunal atresia. J Pediatr C, Poets CF. Early feeding after necrotizing enterocolitis in
Surg. 2005 3;40(3):E31–E34. preterm infants. J Pediatr. 2003 10;143(4):484–487.
23. Stollman TH, de Blaauw I, Wijnen MHWA, van der Staak 39. Albers MJIJ, Steyerberg E, Hazebroek FWJ, et al. Glutamine
FHJM, Rieu PNMA, Draaisma JMT, et al. Decreased supplementation of parenteral nutrition does not improve
mortality but increased morbidity in neonates with jejunoileal intestinal permeability, nitrogen balance, or outcome in
atresia; a study of 114 cases over a 34-year period. J Pediatr newborns and infants undergoing digestive-tract surgery:
Surg. 2009 1;44(1):217–221. results from a double-blind, randomized, controlled trial. Ann
24. Pastor AC, Phillips JD, Fenton SJ, Meyers RL, Lamm AW, Surg. 2005;241(4):599.
Raval MV, et al. Routine use of a SILASTIC spring-loaded 40. Calder P. Immunonutrition in surgical and critically ill
silo for infants with gastroschisis: A multicenter randomized patients. Br J Nutr. 2007;98 (Suppl 1):S133.
controlled trial. J Pediatr Surg. 2008 10;43(10):1807–1812. 41. St. Peter SD, Tsao K, Sharp SW, Holcomb III GW, Ostlie DJ.
25. Phillips JD, Raval MV, Redden C, Weiner TM. Gastroschisis, Predictors of emesis and time to goal intake after pyloromyo-
atresia, dysmotility: Surgical treatment strategies for a distinct tomy: analysis from a prospective trial. J Pediatr Surg. 2008
clinical entity. J Pediatr Surg. 2008 12;43(12):2208–2212. 11;43(11):2038–2041.
26. Walter-Nicolet E, Rousseau V, Kieffer F, Fusaro F, Bourdaud N, 42. van der Kuip M, de Meer K, Westerterp KR, Gemke RJ. Phys-
Oucherif S, et al. Neonatal outcome of gastroschisis is mainly ical activity as a determinant of total energy expenditure in
influenced by nutritional management. J Pediatr Gastroenterol critically ill children. Clin Nutr. 2007 12;26(6):744–751.
Nutr. 2009;48(5):612. 43. Singer P, Berger MM, Van den Berghe G, Biolo G, Calder P,
27. Diamond I, Sterescu A, Pencharz P, Kim J, Wales P. Changing Forbes A, et al. ESPEN guidelines on parenteral nutrition:
the paradigm: Omegaven for the treatment of liver failure in Intensive care. Clin Nutr. 2009 8;28(4):387–400.
pediatric short bowel syndrome. J Pediatr Gastroenterol Nutr. 44. Vervloessem D, van Leersum F, Boer D, Hop WCJ, Escher
2009;48(2):209. JC, Madern GC, et al. Percutaneous endoscopic gastrostomy
28. Muratore CS, Utter S, Jaksic T, Lund DP, Wilson JM. Nutri- (PEG) in children is not a minor procedure: Risk factors for
tional morbidity in survivors of congenital diaphragmatic major complications. Semin Pediatr Surg. 2009 5;18(2):93–97.
hernia. J Pediatr Surg. 2001 8;36(8):1171–1176. 45. Beres A, Bratu I, Laberge J. Attention to small details: Big deal
29. Keshen TH, Miller RG, Jahoor F, Jaksic T. Stable isotopic for gastrostomies. Semin Pediatr Surg. 2009 5;18(2):87–92.
quantitation of protein metabolism and energy expenditure 46. Veenker E. Enteral feeding in neurologically impaired chil-
in neonates on- and post-extracorporeal life support. J Pediatr dren with gastroesophageal reflux: Nissen fundoplication and
Surg. 1997;32(7):958. gastrostomy tube placement versus percutaneous gastroje-
30. Shew SB, Keshen TH, Jahoor F, Jaksic T. The determinants of junostomy. J Pediatr Nurs. 2008 10;23(5):400–404.
protein catabolism in neonates on extracorporeal membrane 47. Kane TD. Laparoscopic Nissen fundoplication. Minerva Chir.
oxygenation. J Pediatr Surg. 1999;34(7):1086. 2009;64(2):147.

PART IV
NUTRITION CARE OF
THE PEDIATRIC PATIENT
33. Assessment of Nutrition Status by Age

and Determining Nutrient Needs. . . . . . . . . . . . . . 409
Jennifer Blair, MA, RD, CSP, LDN
34. Parenteral and Enteral Nutrition Support:
Determining the Best Way to Feed. . . . . . . . . . . . . 433
Andrea Nepa, MS, RD, CSP, LDN
Sherri Shubin Cohen, MD, MPH
Amy Dean, MPH, RD, LDN
Colleen Yanni, MS, RD, LDN
Goldie Markowitz, MSN, CRNP
35. Implementation of the Plan. . . . . . . . . . . . . . . . . . 448
Beth Lyman, RN, MSN
Jennifer M. Colombo, MD
Jodi L. Gamis, OTR
36. Evaluation and Monitoring of Pediatric Patients
Receiving Specialized Nutrition Support . . . . . . . . 460
Elaina Szeszycki, PharmD, BCNSP
Wendy Cruse, MMSc, RD, CNSD
Michelle Strup, PharmD
37. Ethical Issues in the Provision of Nutrition . . . . . . 477
Patrick M. Jones, MD, MA
Brian Carter, MD
33
Assessment of Nutrition Status by Age
and Determining Nutrient Needs
Liesje Nieman Carney, RD, CNSD, LDN and Jennifer Blair, MA, RD, CSP, LDN
Contents Learning Objectives

Background . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 409 1. Identify the important components of a pediatric nutri-
Nutrition Assessment of Premature Infants. . . . . . . . . . 409 tion assessment.
Classification Parameters 2. Describe and differentiate the nutrition needs among
Special Considerations premature infants, full-term infants, children, and
Energy Needs adolescent pediatric populations.
Growth 3. Recognize potential nutrition deficiencies and excesses
Nutrition Assessment of Full-Term Infants and Children.411 commonly found among the pediatric population.
Nutrition Assessment of Adolescents . . . . . . . . . . . . . . 412
Vitamin and Mineral Needs Background
Diet History. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 414 Nutrition assessment of infants, children, and adolescents
Anthropometric Measurements. . . . . . . . . . . . . . . . . . . 414 enables practitioners to identify those at nutrition risk for
Weight weight loss, poor growth, obesity, and nutrient deficits and
Length/Height excesses. Components of a detailed nutrition assessment
Head Circumference include anthropometric measurements with comparison
Body Mass Index-for-Age
Mid-Arm Circumference and Triceps Skinfold
to reference standards, a detailed diet history, biochemical
Growth Charts indices monitoring, and physical examination.
Biochemical Indices
Physical Exam Nutrition Assessment of Premature Infants
Appendix 33-1: Estimating Nutrient Needs . . . . . . . . . . 418 Nutrition assessment of premature infants is a critical
Appendix 33-2: Percentiles of Upper Arm component in the medical management of high-risk
Circumference . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 420 neonates. Routine assessment is vital to ensure adequate
Appendix 33-3: Triceps Skinfold Percentiles. . . . . . . . . 421 nutrition status of the critically ill neonate. Premature
Appendix 33-4: Fetal-Infant Growth Chart. . . . . . . . . . . 422
infants are classified according to their birth weight and
gestational age at birth. The goal for the premature infant is
Appendix 33-5: NCHS/CDC Growth Charts . . . . . . . . . . 423
to mimic intrauterine weight gain.1-3
Classification Parameters
Premature infants are classified by the infant’s gestational
age, growth curve parameters, and maturational exami-
nation. The maturational examination, known as the
Ballard score, is a postnatal, indirect method of assessing a
neonate’s gestational age. It is based upon indicators of fetal
409
neuromuscular and physical maturation.4 Premature infants feeds compared to the premature infant with a healthy gut.
are defined by their weight at birth. Table 33-1 depicts these These conditions often require protein hydrolysate or free
classifications. amino acid formulas while the gastrointestinal tract adapts.
Protein hydrolysates and free amino acid formulas do not
Table 33-1 Classification of Preterm Infants by Birth Weight provide the higher nutrient components provided with
Low birth weight (LBW) < 2500 g premature formulas. This may require additional nutrient
Very low birth weight (VLBW) < 1500 g supplementation, such as calcium and phosphorus, to meet
Extremely low birth weight (ELBW) < 1000 g the needs of the premature infant.
Micronate < 750 g Long-term PN support in the premature infant places
the infant at increased risk for osteopenia of prematurity.
The Lubchenco growth chart is a classification of This is due to the inability to match intrauterine calcium
newborns based on maturity and intrauterine growth. 5 and phosphorus accretion rates, without precipitation of the
Along with intrauterine weight charts, these charts allow parenteral solution.
the identification of infants with unusual growth patterns. The premature infant’s respiratory status may alter his
The Lubchenco growth curve classifies infants as: large or her energy requirements and the ability to feed orally.
for gestational age (LGA), appropriate for gestational age For instance, chronically ventilator-dependent infants
(AGA), or small for gestational age (SGA). AGA infants may require decreased energy requirements since they are
fall between the 10th and 90th percentile on the weight not “working to breathe.” Conversely, infants may have
per gestational age curve, whereas LGA infants plot greater increased energy expenditure during times of weaning
than the 90th percentile and SGA infants less than the 10th from respiratory support. Appropriate caloric provisions
percentile. are often difficult to determine, and are best estimated
Reasons infants may present as LGA include genetic by closely monitoring daily weight changes. Infants with
factors, infants of diabetic mothers, and those who have chronic lung disease (CLD) and bronchopulmonary
transposition of the aorta. 5 dysplasia (BPD) often require fluid restrictions, requiring
SGA infants may simply be genetically small or may formula concentration and the use of modular supplements
have suffered from intrauterine growth restriction (IUGR). to meet their increased energy and nutrient requirements
Symmetrical IUGR generally occurs when the unborn baby within the constraints of fluid restrictions.
experiences a problem during early development; on the
other hand, asymmetrical IUGR is often due to a problem Energy Needs
later in pregnancy. Conditions causing IUGR in infants The premature infant’s weight may decrease 10% to 15%
include exposure to intrauterine infection; poor intra- in the first week of life due to decreased water content of
uterine nutrient provision (eg, placental or umbilical cord the extracellular volume. Until the weight is regained, the
defects); intrauterine exposure to tobacco, narcotics, or infant’s birth weight should be used to estimate energy and
alcohol; chronic lack of oxygen (ie, hypoxia); birth defects nutrient needs.
(eg, severe cardiovascular defect), and congenital malfor-
mations such as Down syndrome, Turner’s syndrome, and Growth
trisomy 18. 5 The premature infant should be weighed nude, at the same
time of day, on the same scale, on a daily basis to evaluate
Special Considerations nutrition status. The infant’s average daily weight gain is
Specific medical conditions will alter the neonate’s nutri- compared (in grams per kilogram daily or grams per day)
tion needs and ability to feed enterally and by mouth. For to expected intrauterine weight velocity charts. Please refer
instance, gastrointestinal anomalies such as gastroschisis, to Table 33-2.6 Extreme weight changes may be due to fluid
omphalocele, and necrotizing enterocolitis (NEC) will shifts or medical conditions, and these factors should be
mandate feeding the infant with parenteral nutrition (PN) considered before modifying an infant’s nutrition support
support for longer time periods until after surgical inter- regimen.
vention. Furthermore, infants with NEC may suffer from
short bowel syndrome (SBS) postsurgery and may require
long-term PN support. The transition to enteral feeds is
often tenuous and requires slower advancement to full

ASSESSMENT OF NUTRITION STATUS BY AGE AND DETERMINING NUTRIENT NEEDS 411
Table 33–2 Average Daily Intrauterine Weight Gain7 a reference standard for other children the same age in the
Age Interval Average Daily Mean Weight Average Daily United States and can aid in the determination of conditions
(weeks) Weight Gain (g) Weight Gain such as malnutrition and obesity. Evaluation of growth is
(g/d) (g/kg/d)
best monitored over a period of time.
24–25 11.4 904–961 12.2
Poor weight gain is an indicator of acute malnutrition
25–26 15.7 961–1001 16
(ie, wasting) while inadequate length or height velocity is
26–27 18.6 1001–1065 18
27–28 21.4 1065–1236 18.6
indicative of chronic malnutrition (ie, stunting). Tables 33-4
28–29 22.6 1236–1300 17.8 and 33-5 provide wasting and stunting criteria.11 Waterlow
29–30 23.1 1300–1484 16.6 developed these standards to classify children as either
30–31 24.3 1484–1590 15.8 stunted (ie, low height-for-age) or wasted (ie, low weight-
31–32 25.7 1590–1732 15.5 for-height). Frisancho12 argues that although the Waterlow
32–33 27.1 1732–1957 14.7 criteria have the advantage of being based on easily obtain-
33–34 30 1957–2278 14.2 able information, measurements of height and weight, the
34–35 31.4 2278–2483 13.3 criteria are ineffective for distinguishing the truly malnour-
35–36 34.3 2483–2753 13.1 ished child from those who are simply underweight. For
36–37 35.7 2753–2866 12.7 instance, a child suffering from protein malnutrition will
37–38 31.4 2866–3025 10.7 present with a low weight-for-height, but so will a tall and
Mean 25.2 14.9 normally lean child.12 Additionally, an obese child will
present with a high weight-for-height, as might a muscular,
large-frame child.12
Nutrition Assessment of Full-Term Infants
and Children Table 33-4 Waterlow Criteria for Degree of Wasting11 (wt/ht %std)
The purpose of the nutrition assessment of infants and chil- > 120% Obese
dren is to (1) evaluate growth, body size measurements, and 110–120% Overweight
composition as compared to national standards; (2) deter- 90–110% Normal variation
mine an estimation of nutrient needs; and (3) evaluate the 80–89% Mild wasting
adequacy of the nutrition regimen. Infants experience a more 70–79% Moderate wasting
rapid growth velocity as compared to children. The need < 70% Severe wasting
for medical care may impact the child’s nutrition status by
altering metabolic requirements and nutrient intake, and can Table 33-5 Waterlow Criteria for Degree of Stunting11 (ht/age %std)
result in weight loss and decreased height or length velocity.8 > 95% Normal
Refer to Table 33-3 for reference standards of growth velocity, 90–95% Mild
both weight and length, in healthy children.9 85-89% Moderate
< 85% Severe
Table 33-3 Recommendations for Weight and Length Gain
for Healthy Children8,9
Age Weight (g/d) Length (cm/mo)
< 3 mo 25–35 2.6–3.5
3–6 mo 15–21 1.6–2.5
6–12 mo 10–13 1.2–1.7
1–3 y 4–10 0.7–1.1
4–6 y 5–8 0.5–0.8
7–10 y 5–12 0.4–0.6
Infants and children’s weights, length or height, head

circumference (measured for those less than 3 years of
age), and weight-for-length or body mass index (BMI)-for-
age should be plotted on the National Center for Health
Statistics (NCHS) and Centers for Disease Control and
Prevention (CDC) standard growth charts.10 This provides

Table 33-6 Recommended Dietary Allowances13,15 The DRI for protein, as outlined in Table 33-6, is used to
Age kcal/kg Protein g/kg estimate protein needs15 for both the healthy child as well as
1989 RDAs 2002 DRIs the hospitalized child. However, clinical conditions should
0–6 mo 108 1.52 (AI) be considered when estimating protein requirements. Some
7–12 mo 98 1.2 situations may require protein intakes greater than the DRI
1–3 y 102 1.05 to achieve a positive nitrogen balance. Examples include
4–6 y 90 0.95 (4–8 y)
major surgery, wound healing, infection, and catch-up
7–10 y 70 0.95 (9–13 y)
growth. Conversely, the critically ill patient with acute renal
Males
failure may benefit from a moderate protein restriction (but
11–14 y 55 0.85 (14–18 y)
15–18 y 45
not less than the DRI for age).
Maintaining adequate hydration is crucial in both the
Females
healthy and hospitalized infant and child. Guidelines for
11–14 y 47 0.85 (14–18 y)
15–18 y 40
determining maintenance fluid requirements are outlined
in Table 33-9.16,17
Estimation of energy requirements can be determined
using the 1989 Recommended Dietary Allowance (RDA) Table 33-9 Fluid Requirements16,17
or the 2002 Dietary Reference Intake estimated energy 1–10 kg 100 mL/kg
requirements (EER). Both of these methods represent 10–20 kg 1000 mL + 50 mL each kg
energy needs of the healthy child. Refer to Table 33-6 for over 10 kg
the RDAs for energy.13 The resting energy expenditure > 20 kg 1500 mL + 20 mL for each kg
over 20 kg
(REE) can be estimated using the World Health Organi-
zation (WHO) equation (Table 33-7).14 Using the WHO
equation to determine the REE with an activity factor (see Nutrition Assessment of Adolescents
Table 33-8) may be more helpful in estimating energy needs Nutrition assessment of adolescents should include
of the acutely ill child. Refer to Appendix 33-1 “Estimating measurements of weight, height, and BMI-for-age with
Nutrient Needs” for a comprehensive description of the plotting on CDC growth curves, an estimation of nutrient
various methods to estimate energy needs. needs, diet history, and analysis of biochemical indices.
Refer to Tables 33-6 through 33-9 for the RDAs for kilo-
Table 33-7 WHO Equation14 calories, the DRIs for protein, the WHO equation, activity
Age kcal/d factors, and maintenance fluid guidelines, respectively.
Males Special conditions during adolescence that need to
0–3 60.9W – 54 be considered include the increased energy and nutrient
3–10 22.7W + 495 requirements that occur during puberty, as well as the
10–18 17.5W + 651 behavioral, social, and emotional changes that occur during
18–30 15.3W + 679 adolescence.18,19 Increases in lean body mass result in an
Females increased demand for energy, protein, calcium, and iron
0–3 61W – 51 intakes.18 Dietary habits during adolescence that pose a
3–10 22.5W + 499 risk for nutrient deficiencies or overnutrition include the
10–18 12.2W + 746 following: skipping meals, eating more meals outside the
18–30 14.7W + 496
home (often high in fat with low-nutrient density), binge
eating, following fad diets, and taking dietary supple-
Table 33-8 Activity and Stress Factors14 ments.18,19 Adolescents are at risk for inadequate calcium
Activity/Stress Adjustment Factors and vitamin D intake due to skipping meals, avoidance
REE x 1.3: For a well-nourished child at bedrest with mild to moderate related to dieting behaviors, and replacing milk intake with
stress sodas and sports drinks. Females are at increased risk of
REE x 1.5: For a normally active child with mild to moderate stress; an iron deficiency due to the onset of menses.
inactive child with severe stress (ie, trauma, stress, cancer), or a child
with minimal activity and malnutrition requiring catch-up growth A comprehensive diet history will aid in the identifi-
REE x 1.7: For an active child requiring catch-up growth or an active cation of nutrition concerns such as nutrient deficiencies,
child with severe stress unhealthy dietary practices, the use of dietary supplements,

and potential eating disorders. Please refer to the Diet History percentage of the Daily Value (DV) in each serving. The DV
section of this chapter for a more detailed explanation.18,19 is currently set at 1000 mg daily. Calcium supplementation
should be considered for children who are unable to achieve
Vitamin and Mineral Needs adequate dietary sources of calcium. Calcium supplements
vary in their bioavailability, and may be comparable to or
Calcium greater than that of dairy sources.20
According to the American Academy of Pediatrics (AAP),
the primary need for dietary calcium in otherwise healthy Iron
infants, children, and adolescents is to enhance bone Iron deficiency is the most common nutrition deficiency in
mineral absorption.20 Maintaining adequate calcium intake the world.22 The incidence of iron deficiency anemia peaks
during childhood is necessary for maximizing peak bone in children between the ages of 6 and 20 months, or earlier
mass and decreasing the risk of osteoporosis later in adult- with premature infants, with a second peak around puberty.
hood.20 Exercise, in addition to calcium intake, is important Iron deficiency may adversely affect the child’s psycho-
for achieving peak bone mass. Wyshak and Frisch21 motor development and cognitive function.22 Those at risk
reported a positive relationship between cola consumption for developing iron deficiency include premature and low
and bone fractures. However, it is uncertain if this may be birth-weight infants, overweight children, children with
attributed to the potential excess phosphorus content found caregivers of low socioeconomic status, adolescent females,
in colas, or due to the diminished calcium intake related and athletes.22 Additionally, toddlers are often at a risk for
to decreased consumption of dairy products (specifically iron-deficiency anemia due to transitioning from iron-forti-
milk). Currently, dual-energy radiograph absorptiometry fied formula to cow’s milk.
(ie, DEXA scan) is the method used in many studies to More than 80% of the iron stores of the term infant are
measure bone mineral content and bone mineral density of accreted during the third trimester of pregnancy. Therefore,
specific areas or the entire skeleton, with notably negligible infants born premature require more iron postnatally during
levels of radiation exposure.20 the first year of life to catch up to infants born at term. 23
According to the AAP, “the optimal primary nutritional Iron intake requirements for premature infants range from
source during the first year of life is human milk. No avail- 2 mg/kg/d for infants with birth weights between 1500 and
able evidence shows that exceeding the amount of calcium 2500 g to 4 mg/kg/d for infants weighing less than 1500 g
retained by the exclusively breastfed term infant during the at birth.24,25 Adequate iron stores are needed for optimal
first 6 months of life or the amount retained by the human growth and development. According to the AAP “Infants
milk-fed infant supplemented with solid foods during the who are not breastfed or who are partially breastfed should
second 6 months of life is beneficial to achieving long-term receive an iron-fortified formula (containing between 4 to
increases in bone mineralization.” 20 The exception to this is 12 mg of iron per liter) from birth to 12 months.”23
premature infants, who benefit from fortified human milk The recommended treatment dose for iron deficiency
and premature infant formulas that have additional mineral anemia is 3 to 6 mg/kg/d in 3 divided doses, ideally with
supplementation. Data demonstrate that the bioavailability concomitant vitamin C intake to enhance iron absorption.
of calcium in human milk is greater than that found in Prophylactic iron supplementation is recommended for those
infant formulas and cow’s milk. Therefore, infant formulas identified at an increased risk of iron deficiency anemia.22
contain increased concentrations of calcium content to be
more comparable to that found in human milk. Vitamin D
According to the AAP, calcium retention is relatively Cases of rickets continue to be reported in the United States
low in toddlers and increases as puberty approaches. 20 Most and other Western countries. One of the causes of rickets is
available data conclude that calcium intakes of 800 mg daily vitamin D deficiency. Vitamin D deficiency is attributed to
are adequate for bone mineral accretion in pre-pubescent exclusively breastfed infants due to breast milk’s low vitamin
children. The majority of bone formation and the efficiency D content and those with decreased sun exposure due to an
of calcium absorption are highest during puberty. Data from inadequate conversion within the body to the active form
balance studies suggest that maximal net calcium balance of vitamin D. As a result, the AAP recently issued updated
is achieved with intakes of 1200 to 1500 mg daily in most guidelines for vitamin D intake for infants, children, and
healthy adolescents.20 adolescents to prevent vitamin D deficiency which in turn
Calcium intakes on food labels are indicated as a will reduce the incidence of rickets. These new guidelines

replaced the 2003 AAP recommendations for a daily intake composition. This will enable the practitioner to gain
of 200 International Units of vitamin D for infants in the insight into energy, protein, micronutrient deficiencies, and
first 2 months of life, children, and adolescents. The 2008 excesses. When interviewing the caregiver, the practitioner
guidelines recommend a daily intake of 400 International must be diligent in obtaining information regarding food
Units of vitamin D for all infants, children, and adolescents and formula preparation, food availability, and behavioral
starting from the first few days of life.26,27 eating patterns. This will aid in providing insight to poten-
tial barriers such as improper formula preparation, potential
Fluoride food insecurities related to poor socioeconomic status, and
According to the CDC, dental caries may be the most prev- behavioral conditions affecting the child’s diet.
alent of infectious diseases in our nation’s children. Primary
tooth decay can affect children’s growth, lead to malocclu- Anthropometric Measurements
sion, and result in pain and potentially life-threatening Anthropometric measurements are a crucial component of
swelling.28,29 Recommendations to aid in the prevention of the nutrition assessment. A series of measurements obtained
dental caries include the establishment and maintenance over a period of time provides a more accurate and compre-
of good oral hygiene, optimizing systemic and topical fluo- hensive indication of a child’s growth.
ride exposure, and the elimination of prolonged exposure
to simple sugars in the diet.28 The American Academy of Weight
Pediatric Dentistry (AAPD) reports that the adjustment of Weights of children under the age of 2 should be measured
fluoride levels in community water to the optimal concen- on a leveled scale that is frequently calibrated. The scale
tration is the most beneficial and inexpensive method of should be calibrated regularly with appropriate standards.
reducing the incidence of dental caries. However, when The nude infant is placed on the scale, making sure the
drinking water fluoridation is not possible, the AAPD weight is evenly distributed on either side of the center of
supports the intake of daily fluoride supplements and the the scale. Weight is recorded to the nearest 10 g.12,32
use of fluoride-containing preparations (eg, toothpastes, For children older than 2 years of age, the weight should
gels, and mouth rinses). Topical fluoride use in children is be measured using a standing scale. The calibration of the
cautioned, due to the risk of excessive exposure to fluoride. 30 scale should also be done regularly with appropriate stan-
Table 33-10 details recommendations for fluoride supple- dards. Subjects are to stand still in the middle of the scale,
mentation based on levels found in community drinking with their body weight evenly distributed between both
water. 31 feet. Light indoor clothing should be worn. Weights should
be recorded to the nearest 100 g.12,32
Table 33-10 Level of Fluoride in Community Drinking Water (ppm)* and
Recommended Fluoride Supplementation Length/Height
Measured Levels < 0.3 < 0.3–0.6 > 0.6 With children under 3 years of age, length should be
Age obtained in the recumbent position using a length board.
0–6 mo None None None This is a device consisting of a flat board and a moveable
6 mo–3 y 0.25 mg/d None None footboard, which are perpendicular to the table surface. A
3–6 y 0.5 mg/d 0.25 mg/d None fixed measuring tape is present with the 0 end at the edge
6–16 y 1 mg/d 0.5 mg/d None of the headboard. The infant’s length should be recorded
*1 ppm = 1 mg/L31 as the distance between the headboard and the footboard.
An assistant should hold the infant/toddler’s head with the
child looking upward and the crown of the child’s head
Diet History against the headboard. The examiner holds the infant’s
A detailed diet history is an important component of the legs straight with the feet against the board and the toes
nutrition assessment. Methods of obtaining diet histories facing up. The footboard is placed flat against the infant/
include usual intake patterns, 24-hour recall, written diet toddler’s feet. The measurement is recorded to the nearest
records provided by the caregiver, and calorie counts for 0.1 cm.12,32
the hospitalized pediatric patient. Of these, the most accu- Children older than 3 years of age are to be measured,
rate method of diet intake assessment is to obtain a 3- to without shoes, using a standiometer. A standiometer is a
5-day diet record, which can then be analyzed for nutrient metric tape affixed to a vertical surface and a moveable

block that is attached to the vertical surface at a right angle, child’s biological parents, called the mid-parental height,
that can be brought down to the crown of the head. Stature which is calculated as follows:
can also be measured on a platform scale, but it is a less
accurate measure than that obtained with a standiometer. Mother’s height + father’s height ÷ 2 = mid-parental
The subject should stand with heels together and his or her height
back as straight as possible. The heels, buttocks, shoulders,
and head should touch the wall or vertical surface of the The impact of mid-parental height on a child’s growth can
measuring device. The subject’s weight should be evenly be evaluated by using one of two methods:
distributed between both feet with the head positioned • Garn and Rohmann defined percentile ranges for
horizontally. The arms should hang freely at the sides, with corrected height of children35; and
palms facing the thighs. The moveable block is brought down • Himes et al36 formulated adjustment factors that are
until it puts sufficient pressure on the head to compress the added to the child’s measured stature.
hair. Measurements are recorded to the nearest 0.1 cm.12,32
When a subject’s stature cannot be obtained standing, Head Circumference
either due to the inability to stand or excessive spinal Occipital-frontal circumference (OFC) should be obtained
curvature, stature can be extrapolated from measuring in infants and children until 3 years of age. Head circumfer-
knee height or tibial length. Knee height is obtained with a ence is measured with a narrow, non-stretchable measuring
sliding broad-blade caliper. While lying in a supine position, tape. The tape should cross the forehead, just above the
the subject’s knee and ankle are bent to form a 90-degree supraorbital ridges, passing around the head at the same
angle. The fixed blade of the caliper is placed under the heel level on both sides to the occiput. The tape should be moved
of the foot, and the other blade is placed over the anterior up and down until maximum circumference is obtained.
surface of the thigh, over the condyle of the femur. The shaft Sufficient tension should be placed on the tape to press the
of the caliber is held parallel to the tibia shaft, with pressure hair against the skull. 37
applied to compress the tissue. Measurements are recorded
to the nearest 0.1 cm and then converted to stature12,32 by Body Mass Index-for-Age
using the following equations: Body mass index-for-age (BMI-for-age) is an indicator of
potential nutrition-related health concerns. The BMI can
Males: 64.19 – (0.04 × age) + (0.02 × knee height) be used to define patients as obese, overweight, adequately
nourished, at risk for underweight, and underweight. The
Females: 84.88 – (0.24 × age) + (1.83 × knee height) BMI (kg/m 2) is derived by taking the subject’s weight in
kilograms and dividing by height in meters squared. BMI is
Tibial length is unique from knee height—it is a valid most useful when measurements are taken periodically and
measurement in children with lower extremity contrac- compared over time for trends. Table 33-11 outlines BMI
tions. Unfortunately, knee height is unable to be obtained criteria.10,12
when the feet are contracted because it is not possible for
the fixed blade of the caliper to be placed under the heel of Table 33-11: Interpretation of BMI for Ages 2–18 Years34
the foot. To obtain a tibial length, one measures from the Percentile Interpretation
superomedial edge of the tibia to the inferior edge of the < 5th %ile Underweight
medial malleolus using a flexible steel tape. The following is 5–15th %ile At risk for underweight
a formula33,34 for the estimation of stature in children with 15–85th %ile Adequate
cerebral palsy using tibial length: 85–94th %ile Overweight
≥ 95th %ile Obese
(3.26 × tibial length in cm) + 30.8 = estimated stature (cm)

Genetic influences should be considered when evaluating Mid-Arm Circumference and Triceps Skinfold
any linear growth abnormality. Obtaining parental stature Mid-arm circumference (MAC) and triceps skinfold
is essential to help differentiate when a growth pattern is measurements (TSF) are utilized to assess fat and muscle
normal for the child’s genetic potential or not. Adjustments mass. These measurements should be monitored over a
for parental stature are based on the average height of the period of time to evaluate for changes. These measurements

are useful for further evaluating fat and muscle mass of (NICU). Limitations of this curve included the small sample
children whose weight-for-height or BMI-for-age fall less size, the 26-week gestational age start, and the 500-g graph
than the 5th percentile or above the 95th percentile, and for increments. In 2003, Tanis R. Fenton6 created an updated
those suffering from malnutrition. Skinfold measurements growth chart, which allows for a comparison of infant’s
may also be obtained on other sites of the body, such as growth from 22 weeks gestation through 10 weeks post-
subscapular and suprailiac.12,32,37 Refer to Table 33-12 for term. Data compilation was also based on a larger sample
methods to calculate MAC and TSF. size. Comparisons were made between the new chart and
the Babson and Benda chart. Growth results from the
Table 33-12 Anthropometric Equations12 National Institute of Child Health and Human Develop-
Arm Muscle Area (AMA) = ment Research Network (NICHD) were then superimposed
[(MAC in cm × 10) - (3.14 × TSF)] on the new chart to validate growth results. Additionally, a
12.56 large-scale grid was used for accuracy of plotting. The incre-
Upper Arm Area = ments are 100 g of weight, as opposed to Babson and Benda’s
[(MAC in cm × 10)] 0.785 500 g, 1 cm for both head circumference and length, and
[3.14]
1-week intervals for time. Refer to Appendix 33-4 for this
Arm Fat Area (AFA) = Upper Arm Area – AMA
growth chart. It can also be downloaded from http://www.
To measure mid-upper arm circumference, the subject’s biomedcentral.com/1471-2431/3/13.
right arm is bent to a 90-degree angle at the elbow, with the While in the NICU, infants’ weights should be plotted
upper arm held parallel to the body. The distance between daily. Head circumference and length should be measured
the acromion, the bony protrusion on the posterior of the and plotted weekly. The optimal body composition of
upper shoulder, and the olecranon (ie, the tip) of the elbow growing premature infants is unknown. However, the most
is measured. Mark the midpoint between these two land- comprehensive growth assessment uses the calculation of
marks with ink. The subject’s arm should be relaxed and growth velocity and size in relation to correlating gesta-
hanging loosely by the side of the body. The metric tape tional ages on the growth chart.6
should be positioned around the upper arm at the marked
midpoint. The tape should be snug, but not pinching the CDC Curves (Birth to 36 Months and 2 to 20 Years)
skin. Record the measure to the nearest 0.1 cm.12,32 Refer to The National Center for Health Statistics (NCHS) growth
Appendix 33-2 for the MAC measurement tables to inter- curves are references of height and weight used to evaluate
pret measurements obtained. 38 growth and nutrition status of infants, children, and adoles-
Triceps skinfold thickness is measured with a skinfold cents. The NCHS curves were compiled from a combined
caliper. Skinfold thickness is measured at the midpoint upper sample of data derived from the NCHS’s Health Examina-
arm circumference (refer to mid-upper arm circumference tion Survey, conducted during 1963-1965 and 1970-1974,
measure above). The subject’s arm should hang loosely at and data from the Fel’s Research Institute.12 The 2000 CDC
the side and the examiner should grasp a vertical pinch of growth charts represent the revised version of the 1977
skin and subcutaneous fat between the thumb and fore- NCHS growth charts.10 Please refer to Appendix 33-5 for
finger, about 1 cm above the previously marked midpoint. the CDC Growth Curves for Males (birth to 36 months),
The skinfold is pulled away from the muscle and the caliper Females (birth to 36 months), Males (2 to 20 years), and
is placed on the marked midsection. Three readings should Females (2 to 20 years).
be taken, and the average of the 3 is recorded in millime-
ters. The reading is measured as soon as the calipers come in Biochemical Indices
contact with the skin and the dial reading stabilizes.12,32 See Biochemical parameters are also an essential component of
Appendix 33-3 for triceps skinfold percentiles. a comprehensive nutrition assessment. Routine laboratory
monitoring with the pediatric population includes complete
Growth Charts blood counts and blood lead levels to rule out lead expo-
sure. Abnormal hemoglobin (Hgb) and hematocrit (Hct)
Fenton for Premature Infants levels can aid in the detection of iron, vitamin B12, and folate
The Babson and Benda 1976 “fetal-infant growth graph” deficiencies.
for premature infants was commonly used to assess growth A complete blood count can identify the degree and
of premature infants in the neonatal intensive care unit features of anemia. Red cells are microcytic and hypochromic

in iron deficiency anemia. In early phases of iron deficiency, Serum albumin, transferrin, and prealbumin are indi-
decreased levels of mean corpuscular volume (MCV) and cators of visceral protein status. Depleted levels can be an
mean hemoglobin content (MCH) are seen. As the iron defi- indication of visceral protein depletion and malnutrition.
ciency progresses, decreased levels of Hgb and Hct develop.22 However, other clinical conditions (eg, altered fluid status,
If iron deficiency is suspected, a complete iron profile should inflammation, acute infection) may falsely decrease levels.
be ordered. A low serum iron concentration with an elevated
total iron-binding capacity (TIBC) and decreased levels of Physical Exam
ferritin are a diagnostic indicator of iron deficiency.22 Physical examination of the pediatric patient is also a vital
However, if Hgb and Hct are low with an elevated component of the nutrition assessment. Physical examina-
MCH, vitamin B12 and folate deficiencies should be consid- tion can provide insight into conditions such as malnutrition,
ered. Serum vitamin B12 and folate levels should be drawn. obesity, edema, dehydration, and vitamin deficiencies and
Those consuming a vegetarian diet or having undergone excesses. Table 33-13 outlines some nutrition concerns
ileocecal valve resection (from gastrointestinal surgery) are based on physical examination.2,33,39
at a greater risk of developing vitamin B12 deficiency.
Table 33-13 Nutrition Concerns Based on Physical Examination1,27,33

Site Physical Examination Potential Nutritional/Metabolic Status
Skin Integrity Pallor Iron, folate, or vitamin B12 deficiency
Dry, scaly skin Vitamin A or essential fatty acid deficiency
Dermatitis Essential fatty acid deficiency; zinc, niacin, riboflavin, or tryptophan deficiency
Nails Spoon shape Iron deficiency
Lackluster, dull Protein deficiency
Mottled, pale, poor blanching Vitamin A or C deficiency
Face Moon face Protein-calorie malnutrition
Bilateral temporal wasting Protein-calorie malnutrition
Neck Enlarged thyroid Iodine deficiency
Mouth Dry, cracked, red lips Riboflavin, niacin, or vitamin B6 deficiency
Bleeding gums Vitamin C deficiency
Inflammed mucosa Vitamin B complex, iron or vitamin C deficiency
Tongue Magenta color Riboflavin deficiency
Beefy red color and diminished taste Niacin, folate, riboflavin, iron, or vitamin B12 deficiency
Eyes Night blindness; dull, dry appearance Vitamin A deficiency
to sclerae or inner lids; dull, milky
appearance of the cornea
Cracked, red corners Riboflavin or niacin deficiency
Hair Dull, lackluster, thin, sparse Protein, iron, zinc, or essential fatty acid deficiency
Easily pluckable Protein deficiency
Dentition Excessive dental caries Excessive simple carbohydrate intake
Abdomen Rounded, distended Gas, edema, ascites, obesity
Temperature Increased temperature Increased energy and fluid requirements
Respiration Increased respiratory rate Altered calorie and protein requirements
Energy needs may be increased if weaning from ventilator support or decreased if
chronically ventilator dependent

Appendix 33-1 Estimating Nutrient Needs
Name of Equation Applicable to Which

Description Calculations for the Equation or Formula Source
or Formula Patient Populations?
ENERGY
1989 Based on the median energy intakes of Infants: Most often used for Committee on Dietary Allowances,
Recommended children followed in longitudinal growth 0–0.5 y: healthy infants and Food and Nutrition Board, National
Daily Allowance studies 108 x Wt (kg) children Research Council. Recommended
(RDA) It can overestimate needs in non-active 0.5–1 y: 98 x Wt Dietary Allowances. 10th ed.
populations (eg, bedridden) and does Children: Washington, DC: National Academy
not provide a range of energy needs. 1–3 y: 102 x Wt Press; 1989.
4–6 y: 90 x Wt
Though an outdated reference, still 7–10 y: 70 x Wt
widely used.
Males:
11-14 y: 55 x Wt
15-18 y:
45 x Wt
Females:
11-14 y: 47 x Wt
15-18 y: 40 x Wt
Estimated Energy Replaces the 1989 Recommended EER = TEE + energy deposition Children with National Academy of Sciences,
Requirements Dietary Allowances (RDA). Ages 0-36 mo: normal growth, body Institute of Medicine, Food and
(EER) (new DRI/ Energy needs were determined from 0-3 mo: (89 x wt [kg] - 100) + 175 composition, and Nutrition Board. Dietary Reference
IOM equation) & children with normal growth, body 4-6 mo: (89 x wt [kg] - 100) + 56 activity, and who are also Intakes for Energy, Carbohydrate,
Physical Activity (PA) composition, and activity, and who are 7-12 mo: (89 x wt [kg] - 100) + 22 metabolically normal. Fiber, Fat, Fatty Acids, Cholesterol,
Co-Efficients also metabolically normal. 13-36 mo: (89 x wt [kg] -100) + 20 Protein, and Amino Acids
(Macronutrients) (2005).
Ages 3-8 y — Boys:
EER = 88.5 - (61.9 x age [y]) + PA x (26.7 x wt [kg] + 903 x ht[m]) + 20 kcal
PA = 1 if PAL is estimated to be > 1 < 1.4 (sedentary)
PA = 1.13 if PAL is estimated to be > 1.4 < 1.6 (low active)
PA = 1.26 if PAL is estimated to be > 1.6 < 1.9 (active)
PA = 1.42 if PAL is estimated to be > 1.9 < 2.5 (very active)
Ages 3-8 y — Girls:
EER = 135.3 - (30.8 x age [y]) + PA x (10 x wt [kg] + 934 x ht [m]) + 20 kcal
Ages 9-18 y — Boys:
EER = 88.5 - (61.9 x age [y]) + PA x ( 26.7 x wt [kg] + 903 x ht [m]) + 25 kcal
Ages 9-18 y — Girls:
EER = 135.3 - (30.8 x age [y]) + PA x (10 x wt [kg] + 934 x ht [m]) + 25 kcal
EER (new DRI/IOM Weight Maintenance TEE in Overweight Boys Ages 3-18 y: Overweight children who National Academy of Sciences,
equation) & obesity TEE = 114 - (50.9 x age [y]) + PA x (19.5 x weight [kg] + 1161.4 x height [m]) are metabolically normal Institute of Medicine, Food and
co-efficients/factors PA = 1 if PAL is estimated to be > 1 < 1.4 (sedentary) Nutrition Board. Dietary Reference
PA = 1.12 if PAL is estimated to be > 1.4 < 1.6 (low active) Intakes for Energy, Carbohydrate,
PA = 1.24 if PAL is estimated to be > 1.6 < 1.9 (active) Fiber, Fat, Fatty Acids, Cholesterol,
PA = 1.45 if PAL is estimated to be > 1.9 < 2.5 (very active) Protein, and Amino Acids
Weight Maintenance TEE in Overweight Girls Ages 3-18 y: (Macronutrients) (2005).
TEE = 389 - (41.2 x age [y]) + PA x (15 x weight [kg] + 701.6 x height [m])
Schofield A predictive equation for calculating Males: Healthy children, acutely Schofield WN. Predicting basal
basal metabolic rate (BMR) in healthy 0-3 y: (0.167 x wt [kg]) + (15.174 x ht [cm]) - 617.6 ill patients in the hospital metabolism rate, new standards and
children that was developed by analysis 3-10 y: (19.59 x wt [kg]) + (1.303 x ht[cm]) + 414.9 setting review of previous work. Hum Nutr:
of Fritz Talbot tables. 10–18 y: (16.25 x wt [kg]) + (1.372 x ht[cm]) + 515.5 Clin Nutr. 1985;39C:5–91.
> 18 y: (15.057 x wt [kg]) + (1.0004 x ht[cm]) + 705.8
Females:
0-3 y: (16.252 x wt[kg]) + (10.232 x ht [cm]) - 413.5
3-10 y: (16.969 x wt [kg]) + (1.618 x ht [cm]) + 371.2
10–18 y: (8.365 x wt [kg]) + (4.65 x ht [cm]) + 200
>18 y: (13.623 x wt [kg]) + (23.8 x ht [cm]) + 98.2)
FAO/WHO The “WHO equation” was developed Males: Healthy children who are World Health Organization. Energy
for use in healthy children; however, it 0–3 y: (60.9 x wt [kg]) - 54 acutely ill patients in the and Protein Requirements. Report
is commonly used to predict resting 3–10 y: (22.7 x wt [kg]) + 495 hospital setting of a Joint FAO/WHO/UNU Expert
energy expenditure (REE) of acutely ill 10–18 y: (17.5 xwt [kg]) + 651 Consultation. Technical Report Series
patients in the hospital setting. Females: 724. World Health Organization,
0–3 y: (61 x wt [kg]) - 51 Geneva, 1985.
3–10 y: (22.5 x wt [kg]) + 499
10–18 y: (12.2 x wt [kg]) + 746
Source: Ludlow V, Randall R, Burritt E, Rago D. Estimating Nutrient Needs, Pediatric Module. A.S.P.E.N. Enteral Nutrition Practitioner Tutorial Project, pending publication.

Name of Equation Applicable to Which

Description Calculations for the Equation or Formula Source
or Formula Patient Populations?
Estimating Children with developmental disabilities Cerebral palsy (age 5-11 y*): Children with Rokusek C, Heindicles E. Nutrition
calorie needs for (DD) may have a slower basal energy Mild-moderate activity: 13.9 kcal/cm height developmental and Feeding of the Developmentally
developmental need due to a decreased muscle tone, Severe physical restrictions: 11.1 kcal/cm height disabilities Disabled. Brookings, SD: South
disabilities growth rate, and motor activity. Severe restricted activity: 10 kcal/cm height Dakota University Affiliated
The recommendation to calculate Athetoid Cerebral Palsy: Up to 6,000 kcal/day (adolescence) *This reference applies Program, Interdisciplinary Center for
energy needs in children with DD per Down Syndrome (5-12 y*): to the specific ages Disabilities;1985.
cm of height is based on the fact that Boys 16.1 kcal/cm height listed. Please refer to
they tend to have a shorter height when Girls 14.3 kcal/cm height another equation for
compared to children with normal ages outside of the
Prader-Willi Syndrome (for all children and adolescents): referenced ages, and
growth. 10-11 kcal/cm height for maintenance apply an appropriate
8.5 kcal/cm height for weight loss activity/stress factor.
Myelomeningocele (Spina bifida) (Over 8 years of age and minimally active):
9-11 kcal/cm height for maintenance
7 kcal/cm height for weight loss
Approximately 50% RDA for age after infancy
Peterson’s Failure to This calculates nutrients in excess of the [RDA for weight age (kcal/kg) x Ideal body weight for height] ÷Actual weight Infants and children who Peterson K, et al. Team Management
Thrive (FTT) requirements of the RDA. present underweight and of Failure-to-thrive. J Am Diet Assoc.
Concerns with using this equation need to achieve catch-up 1984;84:810.
include refeeding syndrome. growth
FAO/WHO/UNU Food and Agriculture Organization, World Boys 10–18 y BMR = 16.6 weight (kg) + 77 height (m) + 572 Overweight/obese Dietz WH, Brandini LG, Schoeller DA.
(aka “Dietz Health Organization, United Nations adolescents in an Estimates of metabolic rate in obese
equation”) University Girls 10–18 y BMR = 7.4 weight (kg) + 482 height (m) + 217 outpatient setting and non-obese adolecents. J Pediatr.
1991;118:146–149.
White equation Developed for use in the pediatric EE (kJ/day) = (17 × age [mo]) + (48 × weight [kg]) + (292 × body temperature Pediatric critical care White MS, Shepherd RW, McEniery JA.
critical care population by including [C]) - 9677 population Energy expenditure in 100 ventilated,
temperature as a gauge of the body’s critically ill children: improving the
inflammatory response. accuracy of predictive equations.Crit
It is not commonly used in clinical Care Med. 2000;28(7):2307–2312.
practice, and recent studies have
shown decreased accuracy especially in
smaller, younger patients.
This equation should not be used in
patients less than 2 months of age.
STRESS FACTORS FOR ENERGY
Stress Factors The use of stress factors along with Starvation 0.70–0.85 Pediatric hospitalized Leonberg B. ADA Pocket Guide to
predictive energy equations should Surgery 1.05–1.5 population Pediatric Nutrition Assessment.
be considered for use in hospitalized Sepsis 1.2–1.6 Chicago, IL: American Dietetic
children whose energy requirements Closed head injury 1.3 Association; 2007.
may be altered due to metabolic stress. Trauma 1.1–1.8
Growth failure 1.5–2 TABLE 8.10
Burn 1.5–2.5
PROTEIN
A.S.P.E.N. Clinical Metabolic stress increases catabolism 0–2 y: 2–3 g/kg/d Pediatric critical care Mehta NM, Compher C, A.S.P.E.N.
Guidelines: Nutrition and breakdown of lean body mass. population Board of Directors. A.S.P.E.N. Clinical
Support of the To meet the increased demands of 2–13 y: 1.5–2 g/kg/d Guidelines: Nutrition Support of the
Critically Ill Child metabolic stress and spare the use of Critically Ill Child. J Parenter Enteral
endogenous protein stores, a greater 13–18 y:1.5 g/kg/d Nutr. 2009;33(3):260–276.
amount of protein is needed in this
population until the underlying stress
has been overcome.
Recommendations are based on limited
data.
For the injured child Metabolic stress increases catabolism 0-2 y: 2-3 g/kg/d Pediatric critical/surgical Jaksic T. Effective and efficient
and breakdown of lean body mass. 2-13 y: 1.5-2 g/kg/d care population nutritional support for the injured
To meet the increased demands of Adolescents: 1.5 g/kg/d child. Surg Clin North Am.
metabolic stress and spare the use of 2002;82(2):379–391, vii.
endogenous protein stores, a greater
amount of protein is needed in this
population until the underlying stress
has been overcome.
Dietary Reference Replaces the 1989 Recommended 0–6 mo: 1.52 g/kg/d Children with National Academy of Sciences,
Intake (DRI) Dietary Allowances (RDA). *This is an Adequate Intake recommendation, not enough research has been normal growth, body Institute of Medicine, Food and
Protein needs were determined from conducted to establish an RDA for this age group. composition, and Nutrition Board. Dietary Reference
children with normal growth, body activity, and who are also Intakes for Energy, Carbohydrate,
composition, and activity, and who are 6–12 mo: 1.2 g/kg/d metabolically normal. Fiber, Fat, Fatty Acids, Cholesterol,
also metabolically normal. 12–36 mo: 1.05 g/kg/d Protein, and Amino Acids
4–13 y: 0.95 g/kg/d (Macronutrients) (2005).
14–18 y: 0.85 g/kg/d
>18 y: 0.8 g/kg/d
1989 Based on the median nutrient intakes 0–6 mo: 2.2 g/kg/d Children with Committee on Dietary Allowances,
Recommended of children followed in longitudinal 6–12 mo: 1.6 g/kg/d normal growth, body Food and Nutrition Board, National
Dietary Allowance growth studies 1–3 y: 1.2 g/kg/d composition, and Research Council. Recommended
(RDA) It can overestimate needs in non-active 4–6 y: 1.1 g/kg/d activity, and who are also Dietary Allowances.10th ed.
populations (eg, bedridden) and does 7–14 y: 1 g/kg/d metabolically normal. Washington, DC: National Academy
not provide a range of energy needs. 15–18 y (males): 0.9 g/kg/d Press; 1989.
15–18 y (females): 0.8 g/kg/d
Though an outdated reference, still
widely used.
Peterson’s Failure to This calculates nutrients in excess of the [Protein Required for Weight Age (g/kg/d) x Ideal Weight for Age (kg)] ÷ Actual Infants and children who Peterson K, et al. Team Management
Thrive (FTT) requirements of the RDA. Weight (kg) present underweight and of Failure-to-thrive. J Am Diet Assoc.
Concerns with using this equation need to achieve catch 1984;84:810.
include refeeding syndrome. up growth
It can be calculated using a method
similar to the one for calories above.

Appendix 33-2 Percentiles of Upper Arm Circumference
Reprinted with permission from Frisancho AR. New norms of upper limb fat and muscle areas for assessment of nutritional status.
Am J Clin Nutr. 1981;34:2540–2545.

Appendix 33-3 Triceps Skinfold Percentiles
Reprinted with permission from Frisancho AR. New norms of upper limb fat and muscle areas for assessment of nutritional status.
Am J Clin Nutr. 1981;34:2540–2545.

Appendix 33-4 Fetal-Infant Growth Chart

A new fetal-infant growth chart for preterm infants developed through a meta-analysis of published reference studies.
Fenton TR. Fetal-infant growth chart for preterm infants. BMC Pediatrics. 2003 Dec 16;3(1):13. Reproduced with permission from BioMed Central.

Appendix 33-5








9. Fomon SJ, Haschke F, Ziegler EE, Nelson SE. Body composi-

Test Your Knowledge Questions tion of reference children from birth to age 10 years. Am J Clin
1. Important components of the nutrition assessment of Nutr. 1982;35:1169.
the pediatric population include(s): 10. National Health and Nutrition Examination Survey. CDC
A. Dietary history Growth Charts: United States. http://www.cdc.gov/nchs/
B. Anthropometric measurements about/major/nhanes/growthcharts/background.htm.
Accessed October 18, 2008.
C. Physical examination
11. Waterlow JC, Buzina R, Keller W, Lane JM, Nichamon MZ. The
D. All of the above presentation and use of height and weight data for comparing
2. The American Academy of Pediatrics recommends the the nutritional status of children under the age of 10 years. Bull
following for vitamin D intake: World Health Organization. 1977;55(4):489–498.
A. 200 International Units daily for all age groups 12. Frisancho AR. Anthropometric Standards for the Assessment of
B. 400 International Units daily, starting at 2 months Growth and Nutritional Status. Ann Arbor, MI: The University
of Michigan Press; 2004.
of age 13. Food and Nutrition Board, Committee on Dietary Allow-
C. 400 International Units for all infants, children, and ances. Recommended Dietary Allowances. 10th ed. Washington
adolescents, starting at birth DC: The National Academies Press; 1989.
D. 200 to 400 International Units per day, based on 14. World Health Organization. Energy and Protein Require-
deficiency symptoms and risk of rickets ments. Report of a Joint FAO/WHO/UNU Expert
Consultation. Technical Report Series 724. World Health
3. Spoon-shaped nails and depleted Hgb and Hct levels
Organization, Geneva; 1985.
may be an indication of: 15. Otten JJ, Pitzi Hellwig J, Meyers LD, eds. Dietary Reference
A. Folate deficiency Intakes: The Essential Guide to Nutrient Requirements.
B. Vitamin B12 deficiency 16. Holliday MA, Segar WE. The maintenance for water in paren-
C. Vitamin C deficiency teral fluid therapy. Pediatrics. 1957;19:823–832.
D. Iron deficiency 17. Oh TH. Formulas for calculating fluid maintenance require-
ments. Anesthesiology. 1980; 53:351–353.
18. American Academy of Pediatrics, Committee on Nutrition.
See p. 487 for answers. Adolescent nutrition. In: Kleinman RA, ed. Pediatric Nutri-
tion Handbook. 5th ed. Elk Grove, IL: American Academy of
References Pediatrics; 2004:149–154.
1. American Academy of Pediatrics, Committee on Nutrition. 19. Faulhaber D. Nutrition assessment of adolescents. In:
Kleinman RA, ed. Pediatric Nutrition Handbook. 5th ed. Elk Nevin-Folino N, ed. Pediatric Manual of Clinical Dietetics.
Grove, IL: American Academy of Pediatrics; 2004:149–154. 2nd ed. Chicago, IL: Pediatric Nutrition Practice Group;
2. Faulhaber D. Nutrition assessment of premature infants. In: 2003:163–172.
Nevin-Folino N, ed. Pediatric Manual of Clinical Dietetics. 20. American Academy of Pediatrics, Committee on Nutrition.
2nd ed. Chicago, IL: Pediatric Nutrition Practice Group; Calcium requirements of infants, children, and adolescents.
2003:127–144. Pediatrics. 1999;104:1152–1157. http://aappublications.org/
3. Ziegler EE, Thureen PJ, Carlson SJ. Aggressive nutri- cgi/content/full/pediatrics;104/5/1152. Accessed October
tion of the very low birthweight infant. Clin Perinatol. 11, 2008.
2002;29:225–244. 21. Wyshak G, Frisch RE. Carbonated beverages, dietary calcium,
4. Ballard JL, Khoury JC, Wedig K, et al. New Ballard Score, the dietary calcium/phosphorus ratio, and bone fractures in
expanded to include extremely premature infants. J Pediatr. girls and boys. J Adolesc Health. 1994;15:210–215.
1991;119:417–423. http://www. Ballardscore.com. Accessed 22. Borgna-Pignatti C, Marsella M. Iron deficiency in infancy and
September 17, 2008. childhood. Pediatric Annals. 2008;37(5):329–337.
5. Lubchenco LO, Hansman C, Boyd E. Classification of 23. American Academy of Pediatrics, Committee on Nutri-
newborns – based on maturity and intrauterine growth. Pedi- tion. Iron fortification of infant formulas. Pediatrics.
atrics. 1966;37:403. 1999;104:119–123. http://aappublications.org/cgi/content/
6. Fenton TR. A new growth chart for premature babies: Babson full/pediatrics;104/1/119. Accessed October 12, 2008.
and Benda’s chart updated with recent data and a new format. 24. American Academy of Pediatrics, Committee on Nutri-
BMC Pediatrics. 2003;(3)13. http://biomedcentral.com/1471- tion. Iron supplementation for infants. Pediatrics.
2431/3/13. Accessed September 17, 2008. 1976;58:765–768.
7. Katrine KF. Anthropometric assessment. In: Groh-Wargo S, 25. Siimes MA, Jarvenpa AL. Prevention of anemia and iron
Thompson M, Hovasi-Cox J, eds. Nutritional Care for High- deficiency in very-low-birth-weight infants. J Pediatr.
Risk Newborns. 3rd ed. Chicago, IL: Precept Press; 1994:13. 1982;101:277–280.
8. Faulhaber D. Nutrition assessment of infants and children. 26. Pupillo J. Bone up on new vitamin D recommendations: all
In: Nevin-Folino N, ed. Pediatric Manual of Clinical Dietetics. infants, children, adolescents should get at least 400 IU a day.
2nd ed. Chicago, IL: Pediatric Nutrition Practice Group; AAP News. 2008;29:1.
2003:145–162.

27. Wagner CL, Greer FR, and the Section on Breastfeeding and 32. Lohman TG, Roche AF, Martorell R, eds. Anthropometric
Committee on Nutrition. Prevention of rickets and vitamin Standardization Reference Manual. Champaign, IL: Human
D deficiency in infants, children, and adolescents. Pediat- Kinetics Books; 1998.
rics. 2008;122:1142–1152. http://aappublications.org/cgi/ 33. Splender Q , Cronk C, Charney E, et al. Assessment of
content/full/pediatric;122/5/1142. Accessed November 13, linear growth of children with cerebral palsy: use of alter-
2008. native measures of height or length. Dev Med Child Neurol.
28. American Academy of Pediatrics, Section on Pediatric 1989;31:206–214.
Dentistry. Policy statement: Oral health risk assessment 34. Stevenson RD. Use of segmental measures to estimate stature
timing and establishment of the dental home. Pediatrics. in children with cerebral palsy. Arch Pediatr Adolesc Med.
2003;111:1113–1116. 1995;149:658–662.
29. US Department of Health and Human Services; National 35. Garn S, Rohmann C. Interaction of nutrition and genetics
Institute of Dental and Craniofacial Research. Oral health in the timing of growth and development. Pediatr Clin North
in America: A report of the surgeon general. Rockville, MD: Am. 1966;13:353–379.
National Institutes of Health; 2000. 36. Himes J, Roche A, Thissen D, et al. Parent-specific adjustments
30. American Academy of Pediatric Dentistry, Council on Clin- for evaluation of recumbent length and stature of children.
ical Affairs. Policy statement on the use of fluoride. Adopted Pediatrics. 1985;75:304–313.
5/2000; revised: 5/2001. http://www.aapd.org/members/ 37. Leonberg BL. ADA Pocket Guide to Pediatric Nutrition Assess-
referencemanual/pdfs/Fluoride.pdf. Accessed October 11, ment. Chicago, IL: American Dietetic Association; 2008.
2008. 38. Frisancho AR. New norms of upper limb fat and muscle
31. US Department of Health and Human Services. Recommen- areas for assessment of nutritional status. Am J Clin Nutr.
dations for using fluoride to prevent and control dental caries 1981;34:2540–2545.
in the United States. MMWR Recomm Rep. 2001;50(-14). 39. Hammond K. The nutritional dimension of physical assess-
http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5014a1. ment. Nutrition. 1999;15:412–417.
htm. Accessed November 13, 2008.

34
Parenteral and Enteral Nutrition Support:
Determining the Best Way to Feed
Liesje Nieman Carney, RD, CNSD, LDN, Andrea Nepa, MS, RD, CSP, LDN, Sherri Shubin Cohen, MD, MPH, Amy Dean, MPH, RD, LDN,
Colleen Yanni, MS, RD, LDN, and Goldie Markowitz, MSN, CRNP

When to Use Enteral versus 1. Discuss indications for nutrition support in infants and
Parenteral Nutrition Support. . . . . . . . . . . . . . . . . . . . . . . 431 children.
Determining the Best Enteral Approach. . . . . . . . . . . . . . 432 2. Identify when it is appropriate to utilize parenteral
Functional Barriers to Oral Enteral Nutrition nutrition versus enteral nutrition.
Structural Barriers to Enteral Nutrition 3. Name examples of structural or functional barriers to
Candidates for Enteral Nutrition safe oral intake in medically compromised children.
Inadequate Oral Intake and Prematurity
Inadequate Oral Intake and Bronchopulmonary Dysplasia
4. Explore the types of enteral nutrition formulas, access
Inadequate Oral Intake and Cystic Fibrosis options, and administration modalities.
Inadequate Oral Intake and Congenital Heart Disease 5. Distinguish between a feeding disorder and an eating
Inadequate Oral Intake and Renal Disease disorder.
Inadequate Oral Intake in Burns, Sepsis/Critical Illness, and HIV 6. Explore why an interdisciplinary approach is necessary
Enteral Nutrition: Routes of Administration
to treat feeding disorders.
Parenteral Nutrition. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 434
Gastrointestinal Conditions
Prematurity
When to Use Enteral versus
Congenital Heart Disease Parenteral Nutrition Support
Anorexia Nervosa The decision to utilize enteral versus parenteral nutrition
Relative Indications for PN primarily depends upon whether the gastrointestinal (GI)
Access for Administering PN tract can be used safely or not. Peripheral parenteral nutri-
Macronutrients tion (PPN) is generally reserved for patients for a short
Electrolytes
Vitamins, Minerals, and Trace Elements
period of time who cannot use their GI tracts, whereas
PN Additives: Heparin, Carnitine, and Cysteine central parenteral nutrition (CPN) is appropriate for long-
Complications of PN term needs.1 Whenever possible, oral feeding or enteral
Monitoring nutrition (EN) is preferred over parenteral nutrition (PN)
Aluminum in PN to maintain GI mucosal integrity, absorptive ability, and
Feeding Teams . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 440 immune function.2
Etiologies of Feeding Disorders Medical conditions that usually require PN support
Evaluation and Treatment of Feeding Disorders
include the following: necrotizing enterocolitis (NEC),
Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 443 diaphragmatic hernia, omphalocele, meconium ileus,
intestinal atresia, gastroschisis, and short bowel syndrome
(SBS). 3,4 There are some clinical situations in which enteral
feeding may be contraindicated, but this must be evalu-
ated on a case-by-case basis. Examples of clinical situations
433
where PN may be warranted due to an increased risk for Patients with congenital anomalies such as tracheoesopha-
poor bowel perfusion include hemodynamic instability or geal fistula (TEF), esophageal atresia, cleft palate, and
use of high-dose vasopressors. Severe pulmonary disease, Pierre Robin syndrome require a source of nutrition that
cystic fibrosis, congenital heart disease, chylothorax, renal bypasses the oral route, at least until the condition is surgi-
disease on peritoneal dialysis, severe sepsis, and anorexia cally repaired.4 EN support would also be indicated in cases
nervosa are additional conditions in which PN support has of obstruction of the oral cavity and surrounding areas such
been utilized in special circumstances. 3,4 as cancer of the head/neck, or mechanical ventilation. Inju-
ries such as caustic ingestion, trauma, or burns to the head/
Determining the Best Enteral Approach neck area may impede ability to consume oral intake as
Infants and children with a variety of disorders may be well.4 Other types of severe oral injury that may warrant EN
unable to meet their nutrient needs via exclusive oral intake. support include mucositis and Stevens-Johnson syndrome
Some medical conditions make it difficult or impossible to cases that involve oral lesions.
safely consume food and hydration by mouth, or to digest
and/or absorb food effectively. Other diagnoses are associ- Candidates for Enteral Nutrition
ated with high energy needs, making it is difficult for the Candidates for EN vary in the degree to which they depend
infant or child to consume adequate amounts orally. In upon the tube. Children with the ability to eat yet are stunted
general, children who require EN support are those who are in growth or malnourished may only need tube feedings as
unable to obtain more than 80% of caloric needs by mouth, a supplement to oral intake, which may be administered
or who require an extended period of time to eat (ie, more nocturnally or as bolus feedings between meals. Tube feed-
than 4 hours per day). Children who are malnourished or ings can also be administered on an as-needed basis, such
exhibit poor growth also benefit from EN support. Children as only when intake of a meal is poor or when the child
under the age of 2 who have poor growth or weight gain for goes through a period of feeling poorly (eg, during chemo-
more than 1 month or children over the age of 2 with weight therapy). Likewise, children with significant oral aversions
loss or lack of weight gain for 3 months also require nutri- who consume a limited variety and/or volume of food may
tion support. A child who has decreased 2 or more weight or need supplemental tube feedings to provide the remainder
height growth channels, or persistently has a triceps skinfold of their daily nutrient needs.
(TSF) of less than the 5th percentile, is likely malnourished On the other hand, children who are not capable of
enough to warrant nutrition support as well. 3 consuming food orally receive tube feedings as their sole
source of nutrition. Children with neuromuscular disorders
Functional Barriers to Oral Enteral Nutrition often fall into this category. Children who require highly
Functional barriers to safe oral intake may include neuro- specialized diets, such as the ketogenic diet or formulas
logical or neuromuscular diseases, genetic/metabolic indicated for metabolic disorders, may require EN. This
syndromes, and prematurity.4 For example, bulbar dysfunc- is usually due to the unpalatable formulas or the absolute
tion is common in patients with severe spinal muscular need for the child to receive 100% of the daily formula
atrophy, which can lead to problems with eating and swal- prescription.
lowing, as well as aspiration pneumonia. Reflux related to Children who have experienced delayed introduction
delayed gastric emptying can also occur. 5 Chewing and of oral feeding (eg, when tube feedings are required for a
swallowing difficulties are common in children affected long period of time in infancy) or unpleasant oral-tactile
by neuromuscular disorders, and can lead to aspiration.6 experiences (eg, frequent or prolonged oral intubation and
In fact, most children with cerebral palsy benefit from tube suctioning) are especially at risk. 3,7 It appears that there is
feedings.6 Children with neurological impairments, such a “window of opportunity” in which the infant learns how
as severe seizure disorders or anoxic brain injury, usually to eat by mouth. 3 When infants are unable to take anything
require enteral feeding long-term. 3 Infants or children with orally for a prolonged time (eg, prolonged oral intubation)
neurological impairments may also develop oral aversions they are at risk for long-term oral aversion due to tactile
due to sensory integration disorders. defensiveness.
Structural Barriers to Enteral Nutrition Inadequate Oral Intake and Prematurity

Structural barriers to oral intake include congenital anoma- In premature infants, the inability to coordinate the suck-
lies, obstructions, injuries, and some types of surgery. swallow-breathe pattern may prevent safe oral feedings. 8

PARENTERAL AND ENTERAL NUTRITION SUPPORT: DETERMINING THE BEST WAY TO FEED 435
Although historically it was thought that the ability to Inadequate Oral Intake and Congenital Heart Disease
coordinate sucking and swallowing with breathing did not Children with congenital heart disease often show growth
develop until 32 to 34 weeks gestation, studies are presently failure for a variety of reasons. Anorexia, hypermetabo-
investigating the theory that there is a positive association lism, frequent respiratory infections, decreased circulation,
between attainment of successful oral feedings at less than malabsorption, and pulmonary hypertension are all factors
32 weeks gestation and the implementation of oral stimu- that contribute to poor nutrition status. 8 Increasing respi-
lation protocols. Multiple medical issues in the premature ratory effort as a result of accumulation of pulmonary fluid
infant, such as long-term dependency on mechanical can cause feeding difficulties as well. In this case EN may
ventilation, make it difficult to achieve normal oral intake. be required to prevent excessive energy expenditure from
One study demonstrated a significant correlation between occurring during oral feedings. Infants and children may
prematurity and feeding disorders.9 Children with feeding have delayed feeding skills as a result of chronic illness and
disorders had significantly lower birth weights for gesta- prolonged hospitalization. Chronic malnutrition is espe-
tional age, and infants born before 34 weeks gestation had cially common in children with cyanotic heart disease.15
more GI and oral sensory problems.9 It has been observed Depending on the degree of malnutrition and the ability
that a very small percentage of premature infants require to tolerate oral feedings, infants and children with congen-
long-term EN because they are unable to meet all their ital heart disease may need supplemental EN to maintain
nutrient needs orally.10 adequate nutrient intake. Energy needs may be increased
20% to 33% due to congenital heart disease.7
Inadequate Oral Intake and
Bronchopulmonary Dysplasia Inadequate Oral Intake and Renal Disease
Bronchopulmonary dysplasia (BPD) occurs relatively Infants and children with renal disease often exhibit poor
frequently in infants who are born prematurely.11 Infants and appetite. In addition, the need for a restrictive diet (eg, low
young children with BPD are at increased risk for growth sodium, low potassium, and low phosphorus) may decrease
failure and nutrient deficits. This is thought to be a result the child’s intake since preferred foods must be limited. The
of the excessive energy expenditure required for breathing decision to provide nutrition support needs to be consid-
and/or poor nutrition intake. Poor oral intake is common ered on an individual basis, depending upon many factors
due to oral aversion, fatigue secondary to increased work some of which include nutrition status and willingness to
of breathing, and anorexia secondary to chronic illness.12 eat.7 It is generally accepted that most infants and young
Therefore, patients with BPD often require EN support to children on peritoneal dialysis need supplemental tube
promote normal growth and maintain good weight gain. feedings to maximize their growth potential.16 At this time,
there are limited data regarding the use of nutrition support
Inadequate Oral Intake and Cystic Fibrosis in infants and children on hemodialysis. Therefore, general
Due to increased work of breathing and pancreatic insuffi- nutrition support recommendations for this population are
ciency, infants and children with CF have increased caloric not available.
needs, as much as 200% above that of the general popula-
tion. 3,13 Pancreatic insufficiency occurs in most (85%–90%) Inadequate Oral Intake in Burns,
individuals with CF, which causes malabsorption of nutri- Sepsis/Critical Illness, and HIV
ents.14 The CF Foundation recommends that children with Children with severe burns, sepsis, or advanced HIV may
CF who have growth deficits receive oral and enteral supple- have extremely high metabolic rates that demand full or
ments to achieve better weight gain, and recommend a BMI supplemental tube feedings. 3 Calorie, protein, and micronu-
of at least the 50th percentile.13 The initiation of enteral trient needs are increased in burn patients to allow wound
feedings is suggested when oral supplementation does not healing. Individuals with burns affecting over 20% surface
achieve adequate weight gain.14 This is especially impor- area are more likely to require supplemental tube feedings to
tant because studies have demonstrated that better weight meet their needs.17 Small bowel feedings are often preferred
status is associated with better lung function and improved due to the risk of gastric ileus in this population.17
survival rates.13
Enteral Nutrition: Routes of Administration
The route chosen for the administration of EN depends
upon the anticipated length of time that tube feeding will

Table 34-1 Indications for Enteral Nutrition1

Inadequate Oral Increased Increased Primary Oral Motor Structural or Injury/Critical
Intake Nutrient Needs GI Losses Therapy Dysfunction Functional Abnormality Illness
of GI Tract
Anorexia nervosa Cystic fibrosis Pancreatic Metabolic Prematurity Congenital malformation Burn
insufficiency diseases
Anorexia related BPD SBS Intolerance to Neuromuscular Intestinal pseudo- Trauma
to medical FTT (requires fasting disorders obstruction
condition catch-up growth)
Anorexia due Congenital heart Cholestatic liver Unpalatable diet Neurological TEF Surgery
to treatment/ disease disease (eg, elemental impairment (eg, Proximal fistula with
medications (eg, Renal disease Biliary atresia or metabolic cerebral palsy) high output
chemotherapy) formula)
Food aversion Infection Malabsorption IBD Proximal intestinal Oral intubation
Mucositis obstruction
be required, the anatomy of the patient, and the disease PN. However, in some pediatric intestinal failure cases a
state. 3 Short-term EN can be administered via nasoenteric semi-elemental or elemental diet may be tolerated. 23,24 The
route (eg, nasogastric, nasoduodenal, or nasojejunal tube) removal or absence of a part of the GI tract will impact the
or placed orally (eg, orogastric). Examples of long-term ability to tolerate enteral feeding; for some this intolerance
enteral access include percutaneous endoscopic gastros- is transient and for others it is long term.23
tomy (PEG), percutaneous endoscopic jejunostomy (PEJ), Obstruction of the GI tract and major surgery that
surgical jejunostomy, or surgical gastrostomy.18 When impairs the GI tract also require PN. Other GI conditions
choosing enteral access one should consider the following: such as severe inflammatory bowel disease, severe reflux,
(1) indication for EN, (2) duration of EN, (3) anatomical motility disorders of the GI tract, severe/acute pancreatitis,
integrity of the GI tract, (4) functional integrity of the GI intractable diarrhea, intussusception, volvulus, high output
tract, and (5) risk of aspiration.1 fistulas, severe Hirschsprung’s disease, and severe GI side
effects of chemotherapy including radiation enteritis (as
Parenteral Nutrition well as cancer cachexia) can in extreme cases require PN
support. 3,4,23
Gastrointestinal Conditions
Infants born with congenital anomalies of the GI tract Prematurity
generally require PN. Children who develop GI disorders Premature and low birth weight infants need a source
that prohibit the use of enteral feedings rely on PN for their of nutrition immediately after birth due to low nutrient
nutrition, either temporarily or permanently. For instance, reserves, increased energy expenditure, immaturity of the
SBS may result from major surgical resection of the GI GI tract, as well as their increased propensity for acute and
tract, or may develop in infants born with gastric anoma- chronic illness.8,21 Infants should receive PN if it is antici-
lies.19 Intestinal atresia that requires extensive resection or pated that they will be unable to receive enteral feedings
gastroschisis that causes necrotic bowel can lead to SBS. for more than 2 to 3 days. Infants have very limited fat and
Necrotizing enterocolitis (NEC), trauma, and volvulus are glycogen stores, and when these have been depleted infants
other examples of conditions in which SBS can occur. PN begin to catabolize protein stores for energy. However,
is always indicated for SBS in the immediate postoperative EN is commonly withheld if the following conditions are
period.19,20 Eventually, many individuals with SBS can adapt present: severe respiratory failure associated with hypoxia
to enteral feeds with the successful weaning of PN.19 NEC and acidosis; hypotension treated with vasopressors; peri
in infants requires PN, as enteral feedings are withheld for a natal asphyxia with signs of organ involvement; clinical
period of time to support bowel healing and recovery. 3,21,22 signs of NEC or intestinal obstruction; congenital heart
Those with intestinal failure, as defined by inability of disease with decreased left-sided outflow; patent ductus
the gut to digest or absorb an adequate amount, or exten- arteriosus with left to right shunt or requiring Indomethacin
sive lesions and/or motor dysfunction, usually require or surgical ligation; or sepsis-associated paralytic ileus.

PN is typically provided, as premature infants may tubes.27 There were no documented cases of NEC or intes-
be unable to digest nutrients enterally due to immature tinal perforation. Although the parenteral group achieved
intestinal development and low digestive enzyme produc- goal calories first (3.07 days ± 2.1 days for PN; 4.25 days
tion. These infants are also prone to reflux, generalized ± 2.6 days for enteral), the benefits of EN far outweigh the
GI dysmotility and delayed gastric emptying.8,21 These GI risks of PN. Pettignano et al concluded that vasoactive drug
issues are particularly prevalent in infants who weigh less infusions should not be considered a contraindication to
than 1500 g.4,21 “Organized” gut motility does not begin enteral feeding.27
until 32 to 34 weeks gestation.25 PN is weaned slowly as
EN and/or oral intake increases, so that overall the nutrient Access for Administering PN
intake remains optimal during this transition. Venous access is not defined by the initial point of entry,
but by the position of the catheter tip. With central venous
Congenital Heart Disease lines (CVL) the catheter tip terminates in the superior
In infants and children with congenital heart disease, PN vena cava (SVC) or the right atrium of the heart. PN can be
may be used until tolerance to EN is established, especially administered through a peripheral vein; however, the final
postoperatively due to increased nutrient needs to support osmolality is limited to 900 mOsm/kg to minimize risk of
recovery.7 In addition to supporting postoperative recovery, phlebitis and infiltration.29 To do this the dextrose concen-
the infant or child needs to be anabolic to promote growth; tration is limited to 10% to 12.5%; this means that the PPN
therefore nutrient requirements are especially high in requires a relatively large volume to supply adequate admin-
the chronically ill infant and child with congenital heart istration of nutrients. In the critically ill infant or child,
disease.26 In patients who are receiving vasopressor medica- nutrient requirements often cannot be met with PPN due
tions (eg, dopamine, dobutamine, epinephrine), EN may be to the fluid restriction. Adequate PN requires a CVL and
contraindicated, but this remains an area of controversy. 27 allows for administration of a solution with a high osmola-
PN is occasionally needed to treat individuals with chyle lity (ie, > 900 mOsm/kg).
leaks (ie, chylothorax, chylous effusion, chylous ascites, or
chylopericardium) who do not respond to diets restricted in Macronutrients
long-chain triglycerides (LCTs) and high in medium-chain Parenterally, carbohydrates are administered in the form
triglycerides (MCTs).28 Because the lipids in PN go directly of dextrose, which provides 3.4 kcal/g. Protein is adminis-
into the bloodstream and bypass the lymph system, they do tered as a crystalline amino acid solution, which provides
not increase the volume of chyle produced. 4 kcal/g. Specialized amino acid solutions are available for
infants and children; these include TrophAmine 6% and
Anorexia Nervosa 10% (B.Braun), Premasol 6% and 10% (Baxter Healthcare),
Severely malnourished patients with anorexia nervosa who and Aminosyn-PF 7% and 10% (Hospira). These special-
require urgent nutrition rehabilitation may more readily ized solutions contain high concentrations of essential
accept PN than EN support. However, this is a last resort amino acids, including histadine and tyrosine; low concen-
because PN is more expensive and carries increased risk for trations of phenylalanine, methionine, and glycine; as well
complications.7 as glutamic acid, aspartic acid, taurine, and N-acetyl-L-
tyrosine. The amino acid solutions for infants are designed
Relative Indications for PN to replicate plasma amino acids in breastfed infants. They
Treatment with extracorporeal membrane oxygenation also have a lower pH, which allows higher levels of calcium
(ECMO) and use of vasopressor support may not be abso- and phosphate to be added to the solution.
lute contraindications to enteral feedings; however, many Using a more concentrated amino acid solution allows
clinicians are hesitant to enterally feed infants and chil- for a smaller volume to be administered, which then allows
dren with hemodynamic instability due to risk of bowel for a greater volume to be allotted for other solutions (ie,
ischemia. Concerns about NEC and the possible effect of dextrose), as well as electrolytes, minerals, trace elements,
hypoxia on the gut during ECMO have led to the use of vitamins, and intravenous fat emulsion (IVFE). Using a
PN as the main source of nutrition support in pediatrics. less concentrated amino acid solution may sometimes be
However, a study was done in which infant subjects on necessary because of the difficulty in measuring extremely
ECMO received full-strength, continuous enteral feedings small volumes of the more concentrated solutions. When an
administered via either nasogastric or post-pyloric feeding infant or child is severely fluid restricted, it may be difficult

Table 34-2. Chart Comparing Various Pediatric Amino Acid Solutions
Comparison of Various Pediatric AA Solutions

Ten percent pediatric amino acid formulations
Company B. Braun (McGaw), Hospira (Abbott), Baxter,

Bethlehem, PA Abbott Park, IL Deerfield, IL
Product TrophAmine Aminosyn PF PremaSol
Introduction date (FDA approval date) July 20, 1984 Sept. 6, 1985 June 23, 2003
Amino acid content (gm/100mL)
Essential amino acids
Isoleucine 0.820 0.760 0.820
Leucine 1.400 1.200 1.400
Lysine 0.820 0.677 0.820
(added as lysine acetate) 1.200 -- --
Methionine 0.340 0.180 0.340
Phenylalanine 0.480 0.427 0.480
Threonine 0.420 0.512 0.420
Tryptophan 0.200 0.180 0.200
Valine 0.780 0.673 0.780
Cysteine <0.016 -- <0.016
(as cysteine HCI H2O) <0.024 -- --
Histidine 0.480 0.312 0.480
Tyrosine 0.240 0.044 0.240
(added as tyrosine 0.044 -- --
and N-acetyl-L-tyrosine) 0.240 -- --
Nonessential amino acids
Alanine 0.540 0.698 0.540
Arginine 1.200 1.227 1.200
Proline 0.680 0.812 0.680
Serine 0.380 0.495 0.380
Glycine 0.360 0.385 0.360
L-Aspartic acid 0.320 0.527 0.320
L-Glutamic acid 0.500 0.820 0.500
Taurine 0.025 0.070 0.025
Sodium metabisulfite NF (as an antioxidant) <0.050 0 0
pH adjusted with glacial acetic acid USP
pH: Average and (range) 5.5 (5.0-6.0) 5.5 (5.0-6.5) 5.5 (5.0-6.0)
Calc. osmolarity (mOsmol/L) 875 788 865
Total amino acids (gm/L) 100 100 100
Total nitrogen (gm/L) 15.5 15.2 15.5
Protein equivalent (gm/L) 97 100 --
Electrolytes (mEq/L)
Sodium 5 None --
Acetate 97 46 94
Chloride <3 None <3
Source: FDA, US Food and Drug Administration
Reprinted with permission from: Nieman Carney L. Neonatal Nutrition Support (CEU Self-Study Course),
Nutrition Dimension, Ashland, OR. 2009.

TABLE 34-3: Comparison of Selected Intravenous Fat Emulsions
Comparing ofofSelected
Comparison SelectedIntravenous
IntravenousFat
Fat Emulsions
Emulsions
Intralipid Liposyn II Liposyn III
Product and 10% and 20% 10% and 20 % 10% and 20%
distributor (Clintec) (Abbott) (Abbott)
Oil base Soybean 50% Soybean and Soybean
50% safflower
Fatty acid content (%)
Linoleic 50 65.8 54.5
Oleic 26 17.7 22.4
Palmitic 10 8.8 10.5
Linolenic 9 4.2 8.3
Stearic 3.5 3.4 4.2
Calories/ml
10% 1.1 1.1 1.1
20% 2.0 2.0 2.0
Egg yolk phospholipids (%) 1.2 1.2 1.2
Glycerin (%) 2.25 2.5 2.5
Osmolarity mOsm/L
10% 260 276 284
20% 260 258 292
Source:Drug
Source: Drugfacts
facts and
and comparisons.1998
Comparisons®. 1998ed.
ed.St.St.Louis:
Louis: Wolters
Wolters Kluwer
Kluwer Co.
Health.
Reprinted with permission from: Nieman Carney L. Neonatal Nutrition Support (CEU Self-Study Course),
Nutrition Dimension, Ashland, OR. 2009.
to meet the estimated nutrient needs via PN due to the lack the primary enzyme for lipid clearance, resulting in higher
of a concentrated infant amino acid solution (ie, 15%). triglycerides and other plasma lipids in infants.22 In recent
Research has shown a potential decrease in PN-associ- years some institutions have been utilizing 30% lipid solu-
ated cholestasis with the use of TrophAmine, as compared tions without adverse effects, but this is not a common
to Aminosyn- PF. 30 Another benefit of TrophAmine is that practice.
when L-cysteine is added, there is an increased solubility IVFE not only supplies a concentrated source of calo-
of calcium and phosphorus. TrophAmine is the only infant ries but also provides essential fatty acids (EFAs) for cell
amino acid product available in the United States that has membrane integrity and brain development. IVFE also
been utilized when conducting stability studies for the addi- helps to prolong the integrity of peripheral lines because of
tion of cysteine to PN solutions. their lower osmolality. It is crucial to provide infants and
IVFE consists of either soybean oil or a combination children a minimum amount of lipids (0.5–1 g/kg/d) to
of safflower and soybean oil. These products provide 10 prevent essential fatty acid deficiency (EFAD). However,
kcal/g, regardless of the product concentration, and are premature infants require at least 0.6 to 0.8 g/kg/d.1 EFAD
available in 10% (1.1 kcal/mL), 20% (2 kcal/mL), and 30% was historically defined as a triene:tetraene ratio equal to
concentrations. The 20% concentration is preferred over or greater than 0.431; however, Mayo Clinical Laboratories
the 10% product because it allows adequate lipid intake in recently developed a new set of standards for assessing the
less volume. The 10% solution has a higher phospholipid/ triene:tetraene ratio for various age groups, but this is only
triglyceride weight ratio than the 20% solution, and this applicable if the test is run by its laboratory.
higher ratio may affect the activity of lipoprotein lipase,

Table 34-4 Recommendations for Initiation and Advancement of Parenteral Nutrition

Initiation Advance By Goals
Infants (< 1 y) Preterm Term Preterm Term Preterm Term
Protein (g/kg/d) 1.5–3 1.5–3 1 1 3–4 2–3
CHO (mg/kg/min) 5–7 6–9 1–2.5% dextrose 1–2 or 2.5–5% 8–12 (Max 14–18) 12 (Max 14–18)
per day dextrose per day
Fat (g/kg/d) 1–2 1–2 0.5–1 0.5–1 3–3.5 (Max 3 (Max 0.15g/
0.17g/kg/hr) kg/hr)
Children (1–10 y)
Protein (g/kg/d) 1–2 1 1.5–3
CHO (mg/kg/min) 10% dextrose 5% dextrose per day 8–10
Fat (g/kg/d) 1–2 0.5–1 2–3
Adolescents
Protein (g/kg/d) 0.8–1.5 1 0.8–2.5
CHO (mg/kg/min) 3.5 or 10% dextrose 1–2 or 5% dextrose per day 5–6
Fat (g/kg/d) 1 1 1–2.5
Electrolytes conditions, such as renal or hepatic disease, some may use

Close monitoring of electrolyte status is essential. In “custom” trace elements.
newborns, the addition of electrolytes to PN may be
deferred until the second day of life in some cases. Potas- Table 34-6 Comparison of MTE Products (quantity per 1 mL of solution)
sium is generally added once normal kidney status and good Mineral Multitrace®-4 Multitrace®-4 Multitrace®-5
urine output are established, and sodium is often added once Neonatal Pediatric Concentrate
(Adolescent/
diuresis begins.22 Daily adjustments to electrolyte intake Adult)
are often necessary. Electrolyte requirements of preterm Zinc (as Sulfate) 1.5 mg 1 mg 5 mg
and full-term infants are generally similar, with the excep- Chromium 0.85 mcg 1 mcg 10 mcg
tion of calcium and phosphorus. Electrolytes are typically (as Chloride)
prescribed per kilogram in infants and younger children, Selenium none none 60 mcg
and as units per day in larger children and adolescents. (as Selenious Acid)
Copper (as Sulfate) 0.1 mg 0.1 mg 1 mg
Manganese 25 mcg 25 mcg 0.5 mg
Table 34-5 PN Electrolyte Dosing Guidelines*
(as Sulfate)
Electrolyte Preterm Infants/ Adolescents &
Neonates Children Children > 50kg Source: American Regent Product Catalog
http://www.americanregent.com/multiple_trace.html
Sodium 2-5 mEq/k 2-5 mEq/k 1-2 mEq/kg
Potassium 2-4 mEq/kg 2-4 mEq/kg 1-2 mEq/kg Zinc is important for the maintenance of cell growth
Calcium 2-4 mEq/kg 0.5-4 mEq/k 10-20 mEq/d and development. When PN is supplemental to EN or of
Phosphorus 1-2 mmol/kg 0.5-2 mmol/kg 10-40 mmol/d
short duration, zinc is the only trace element that requires
Magnesium 0.3-0.5 mEq/kg 0.3-0.5 mEq/kg 10-30 mEq/d
supplementation. Some conditions that require additional
Acetate As needed to maintain acid base-balance
zinc intake include elevated urinary zinc excretion (eg,
Chloride As needed to maintain acid base-balance
high-output renal failure) and increased GI excretion (eg,
*Assumes normal organ function and losses
high-volume stool loss and fistula/stoma losses).
Reprinted with permission from Mirtallo J, Canada T, Johnson D, et
al. Safe practices for parenteral nutrition. J Parenter Enteral Nutr.
Copper is an essential constituent of many enzymes.
2004;28(6):S-39–S70. Current daily recommendations are adequate to prevent
deficiency. Clinical manifestations of copper deficiency
include hypochromic anemia that is unresponsive to
Vitamins, Minerals, and Trace Elements iron therapy, neutropenia, and osteoporosis. Conditions
Standard infant and pediatric trace element commercial requiring higher copper intake include increased biliary
products are available. However, in cases of specific medical losses due to jejunostomy and losses via external biliary

Table 34-7 Trace Element Requirements*

Trace Element Preterm Neonates Term Neonates 3-10 kg Children 10-40 kg Adolescents > 40 kg
< 3 kg (mcg/kg/d) (mcg/kg/d) (mcg/kg/d) (per day)
Zinc 400 50-250 50-125 2-5 mg
Copper 20 20 5.0-20 200-500 mg
Manganese 1 1 1 40-100 mcg
Chromium 0.05-0.2 0.2 0.14-0.2 5-15 mcg
Selenium 1.5-2 2 1.0-2 40-60 mcg
*assumes normal organ function and losses
In order to meet these trace element needs, one would need to use individual trace element products. Commercially available multi-trace element products
would not meet these needs.
Reprinted with permission from Mirtallo J, Canada T, Johnson D, et al. Safe practices for parenteral nutrition. J Parenter Enteral Nutr. 2004;28(6):S-39–S70.
drainage. Historically, copper was withheld in PN for Iron supplementation should be considered only among
patients with cholestasis; however, cases of copper defi- long-term PN-dependent patients who are not receiving
ciency have recently been reported when copper was frequent blood transfusions. Monitoring iron status is
withheld in PN. 32 In patients with cholestasis, it is recom- imperative with iron supplementation as there is a risk of
mended to reduce supplementation by 50% of the amount iron overload. 36
typically provided for age, monitor serum copper levels and Parenteral vitamin products for infants and children
ceruloplasmin, and adjust supplementation accordingly. 33 (< 11 years of age) have not been reformulated since their
Manganese is an important component of several inception in the 1970s and 1980s.1 Currently available
enzymes. 34 Manganese deficiency has not been docu- commercial products do not meet the vitamin needs of
mented in humans. However, manganese toxicity has been malnourished patients, those affected by renal or liver
reported. Manganese supplementation in PN should be disease, premature infants, and children with SBS.1 Greene
withheld in patients with cholestasis or other liver function at al explored this issue in depth in 1998; however, new
impairment. 34,35 Fok et al. provided evidence suggesting parenteral vitamin products intended for infants and
that high manganese intake contributes to the development younger children have yet to be released. 37
of cholestasis. 35 Manganese should therefore be used with
caution in PN provided to infants because they are more Table 34-8 Dosing Recommendations for Pediatric Parenteral Multiple
susceptible to cholestasis. 35 It is recommended to monitor Vitamins (MVI-Pediatric®)*
serum manganese levels and adjust supplementation as Manufacturer Recommendations NAG-AMA Recommendations◊
needed. Weight (kg) Dose (mL) Weight (kg) Dose (mL)
Selenium is a component of the enzyme glutathione <1 1.5 < 2.5 2 mL/kg
peroxidase, which is involved in protecting cell membranes 3-Jan 3.25 > 2.5 5 mL
>3 5
from peroxidase damage through detoxification of perox-
ides and free radicals. 34 Supplementation with selenium is *Assumes normal organ function
recommended when a patient is on long-term PN (ie, longer ◊ Nutrition Advisory Group-American Medical Association
than 1 month). It is recommended to decrease selenium
intake when renal dysfunction is present. 33
Chromium potentiates the action of insulin and plays PN Additives: Heparin, Carnitine, and Cysteine
a role in glucose, protein, and lipid metabolism; therefore, Heparin is added to PN solutions to reduce the formation of
chromium is essential for growth. 34 It is also recommended a fibrin sheath around the catheter and may reduce phlebitis
to decrease chromium intake with renal dysfunction. and increases the duration of catheter patency. 22 Heparin
Molybdenum supplementation is recommended in cases also stimulates the release of lipoprotein lipase, which may
when exclusive PN exceeds 4 weeks. Deficiency of molyb- improve lipid clearance. It is recommended to add heparin
denum has not been reported in pediatrics; however, one in units of 0.25 to 1/mL PN solution. 22 There is an increased
adult case of deficiency has been documented. 34 Iodine is risk of anti-coagulation with the higher doses of heparin.
often omitted from PN since iodine-containing disinfec- Carnitine is responsible for the transport of fatty acids
tants and detergents are used on the skin and absorbed. into the mitochondria for oxidation. Carnitine deficiency

results in impaired fatty acid oxidation and can present Monitoring

as hypertriglyceridemia. Carnitine synthesis and storage Prior to initiation of PN support, it is recommended to
are not optimal at birth, when compared to older children check the following biochemical indices: basic metabolic
and adults. Premature infants less than 34 weeks gesta- panel (BMP), calcium, magnesium, phosphorus, liver func-
tion receiving PN without carnitine can develop carnitine tion tests (ie, Alk Phos, ALT, AST, GGT), total bilirubin,
deficiency 6 to 10 days after birth. 38 Carnitor™ (Sigma-Tau conjugated or direct bilirubin, prealbumin, albumin, and
Pharmaceuticals) is available for PN supplementation. triglyceride. Following the initiation of PN the patients
An initial, safe dose to consider for infants on exclusive require close biochemical monitoring. The monitoring
PN for more than 4 weeks is 8 to 10 mg/kg/d.22 A recent is then slowly decreased in frequency depending on the
study revealed that parenteral supplementation of 20 mg/ patient’s demonstration of stable parameters. Patients on
kg/d carnitine resulted in plasma total carnitine concen- long-term PN, such as those with SBS, need regular moni-
trations that exceeded the reference range, which supports toring of vitamin and mineral status.
the use of smaller doses of carnitine supplementation. 39
It is recommended to monitor carnitine levels and titrate Aluminum in PN
supplementation from 8 to 10 mg/kg/d, up to a maximum It has come to light that various products utilized during
of 20 mg/kg/d. PN compounding contain high levels of aluminum, which
Cysteine, a conditionally essential amino acid, is not a can be especially dangerous for infants and children.
component of crystalline amino acid solutions because it is Preterm infants are extremely vulnerable to aluminum
unstable and will form an insoluble precipitate. 22 In adults, toxicity due to immature renal function and the likelihood
cysteine can be synthesized from methionine; however, for long-term PN. 36 As of July 2004, the Food and Drug
preterm infants lack adequate hepatic cystathionase to Administration (FDA) mandated that products used in
facilitate this conversion. Commonly recommended dosing compounding PN should state the aluminum content on
for L-cysteine hydrochloride is 40 mg per gram of amino the label. The FDA identified 5 mcg/kg/d as the maximum
acids. Current practice suggests supplementation with amount of aluminum that can be safely tolerated and
L-cysteine hydrochloride for the first year of life, although amounts exceeding this limit may be associated with central
practice varies widely. 36 One benefit of the addition of nervous system or bone toxicity. 36 It is essential for phar-
L-cysteine hydrochloride to PN is the decrease in the pH of macists, dietitians, physicians, and nurses to collaborate
the solution, which increases the solubility of calcium and to minimize the use of higher aluminum content prod-
phosphorus. It should be noted though that the addition ucts. However, it is difficult to achieve the recommended
of cysteine to PN warrants close monitoring of acid-base aluminum intake level set by the FDA when patients are
status as it may increase risk for acidosis, and acetate may receiving multiple medications and PN.
need to be added to the solution. Providing PN is wrought with unique potential risks
and complications and calls for a diligent interdisciplinary
Complications of PN team approach. Initiating EN as soon as medically appro-
Short-term potential adverse effects of PN include the priate is the key to minimizing the potential adverse effects
following: infection, hyperglycemia, electrolyte abnormali- of PN support.
ties, disturbance of acid-base balance, hypertriglyceridemia,
phlebitis, bacterial translocation, and compromised gut Feeding Teams
integrity. With long-term PN support adverse effects Pediatric feeding disorders are common, affecting 25% of
may include infection, PN-associated cholestasis, meta- typically developing children and up to 80% of developmen-
bolic complications, disturbance of acid-base balance, tally delayed children.40 Prolonged feeding disorders have
osteopenia, risk of vitamin/mineral deficiency or toxicity, significant short- and long-term medical consequences,
and continued risk of bacterial translocation. Nosocomial including poor growth and development, severe malnutri-
infections appear to result either from improper care of the tion, increased susceptibility to illness, and even death.40
catheter and/or frequent use of the catheter for purposes Feeding disorders are often confused with eating
other than delivery of nutrients (eg, blood draws, medica- disorders. The American Psychiatric Association has
tion administration).1 established criteria for the diagnosis of eating disorders,
anorexia nervosa and bulimia, based on DSM-IV criteria
that “focuses on weight loss, attitudes and behaviors, and

amenorrhea displayed by patients with eating disorders.”41 at any period in an infant or child’s lifetime; if this occurs
Eating disorders are more commonly seen in older children early in life there is an increased risk for long-lasting effects.
with a dysmorphic body image; they do not eat because Examples of inadequate parent-child interaction during
their focus is the intent to be thin. A feeding disorder has feeding may include: a parent not looking at an infant or
been defined as the inability or refusal to consume certain reading hunger cues during a bottle feeding, and feeding
foods in sufficient quantity or variety to maintain normal a meal to a toddler separate from the family.44 The family’s
growth.42,43 Generally, feeding disorders involve younger cultural and religious beliefs surrounding food change
children whose intent is not centered on body image— how eating and weight is perceived. In addition, the ability
they refuse to eat due to lack of desire or lack of oral-motor to buy food, the quality of food available, and the feeding
skills. equipment within the home can impact the success of the
feeding experience.
Etiologies of Feeding Disorders Behavioral issues can stem from a combination of any
Feeding disorders have numerous causes, which are often of the aforementioned concerns. Internationally adopted
inter-related. Organic, environmental, and behavioral children frequently have feeding issues likely related to the
issues can all adversely impact feeding. Organic factors feeding conditions they experienced before adoption. A
can be categorized as those affecting the ability to eat, child with GI pathology may develop a learned avoidance
the desire to eat, and the developmental readiness to eat. and/or feeding-related anxiety, resulting in limited intake of
The ability to eat is a complex process and there are many volume and inconsistent acceptance. An infant who required
potential impediments to functional chewing and swal- prolonged intubation may have an oral aversion and food
lowing. The following are examples of organic causes of refusal. Patients with significant food allergies may refuse
feeding disorders: anatomical defects, genetic disorders/ to eat foods to which they are not allergic. Parents who have
syndromes, and GI issues. Anatomic abnormalities within difficulty setting limits can lose control of the meal and be
the oral cavity and airway include aspiration syndromes, unable to establish a consistent mealtime structure.
micrognathia, cleft lip and palate, vocal cord paralysis
(frequently as a complication of cardiac surgery), laryn- Table 34-9 Commonly Utilized Behavioral Strategies for Treating Feeding
gomalacia, asthma, and Treacher-Collins Syndrome. Many Disorders
syndromes and chromosomal abnormalities have a high ■ Offer liquids primarily between meals, and limit drinking during meals
risk for feeding difficulties. Examples include Trisomy ■ Encourage a structured and consistent schedule for 3 meals
21, Williams syndrome, CHARGE syndrome, WAGR and 2 to 3 snacks daily
Syndrome, 22 q deletions, Trisomy 13, and Trisomy 18. ■ Limit meals to 20–30 minutes
■ Eliminate “grazing” behavior on liquids and foods between meals
Some gastroesophageal pathologies that impact feeding
■ Use a timer to have a child sit at the table for a finite period of time
include tracheoesophageal fistula, esophageal strictures,
■ Offer foods on a divided plate
malrotation, gastroesophageal reflux, esophagitis (including ■ Offer 1 new or non-preferred food with 1 to 2 preferred foods
eosinophilic esophagitis), dysmotility, constipation, cystic ■ Continue to offer non-preferred foods in a positive way (as with all
fibrosis, and irritable bowel syndrome. Some conditions children, repeated exposure to new foods increases acceptance)
warrant interventions whose iatrogenic effects adversely ■ Encourage exploration of a non-preferred food (touching to lips,
impact the desire to eat. These may include side effects from touching with fingers)
some chemotherapeutic agents and medications for atten- ■ Establish a non-food reward system (for children older than
12–15 months) where positive behavior is praised and negative
tion deficit hyperactivity disorder, or oral aversion after the behavior is ignored
prolonged intubation of premature infants. Supplemental ■ Be as consistent as possible
tube feedings can also affect the desire to eat orally. Impaired ■ Encourage training and cooperation of all caregivers to support
“developmental readiness” to eat arises from developmental a cohesive treatment approach
delays and sensory and oral-motor issues. These impact the ■ Encourage family mealtimes
ability to accept foods, advance textures, and eat in an age- ■ Provide age-appropriate portions and developmentally
appropriate textures
appropriate manner, which is frequently seen in children on
the autistic spectrum.
Environmental factors impact feeding. The parent-child Evaluation and Treatment of Feeding Disorders
interaction around food creates the environment in which Feeding disorders are best evaluated and treated by interdis-
the child eats. Poor interactions during feeding may present ciplinary teams with expertise in the complexities inherent

Figure 34-1
to feeding disorders. Feeding teams usually include medical They range from an initial evaluation with referrals to
and behavioral health specialists, registered dietitians, and outside therapists to intensive inpatient feeding therapy. At
a variety of therapists and social support personnel. The the initial evaluation, various members of the team inter-
medical team may consist of a physician (often with special- view the child and primary caregivers. The child undergoes
ized training in gastroenterology, neurology, neonatology, a physical examination, and team members observe the
otolaryngology, or child development), nurse practitioner, child being fed and eating. The team then collaborates at the
and/or registered nurse. The behavioral health practitioner end of the evaluation to discuss their findings and synthe-
is commonly a psychologist or family counselor, who may size family-centered goals and recommendations.
be aided by feeding therapists with training in psychology. Teams frequently refer patients to other sub-specialists
The therapists may include occupational therapists, speech and clinics for evaluation and/or treatment of feeding-
pathologists, physical therapists, and respiratory thera- related medical issues if they cannot be addressed within
pists. Social support personnel include social workers, case the team setting. Some hospital-based teams offer addi-
managers, and child life or recreational therapy specialists. tional services such as inpatient consults or diagnostic
The composition of the team varies by facility and by the testing (eg, modified barium swallow study, gastrointes-
needs of the patient (Figure 34-1). tinal endoscopy).
Services offered by feeding teams also vary by facility. Most teams either provide or refer patients to outpatient

or home-based therapies including occupational, speech, well as intensive programs, caregivers are typically present
nutrition, and individual or group psychological therapy. for follow-up appointments to monitor the child’s prog-
These services focus specifically on behavioral feeding ress, support the child’s advancement towards long-term
issues, sensory processing difficulties, development of self- treatment goals, and engage with the team to address any
feeding skills, and oral-motor swallowing function. Therapy questions or concerns. The frequency of follow-up is deter-
goals may include increasing a child’s acceptance of a variety mined on an individualized basis.
of foods, managing food refusal behaviors, texture progres-
sion (ie, smooth puree to lumpy puree to soft solids), and Conclusion
establishing developmentally appropriate manipulation Every child should be evaluated individually when deter-
of liquid and food. Therapists are also able to recommend mining the best way to provide optimal nutrition to promote
adaptive equipment, if appropriate. growth and development. What works for one child and
caregiver may not work for another. One must consider
Table 34-10 Common Feeding Problems many factors when initiating nutrition support including,
■ Excessive liquid intake, impeding acceptance of solid foods but not limited to, the patient’s baseline nutrition status, the
■ Grazing, unstructured meals/snacks functionality of the GI tract, access options, administration
■ Prolonged feeding time (> 30 minutes) schedule, and modality. In pediatrics, one must consider the
■ Inadequate or immature oral-motor skills (unable to handle complex effect that the nutrition support regimen will have on the
textures)
infant/child and the caregivers. It is essential to be flexible
■ Sensory integration issues (will only consume foods/liquids of one
color and/or texture) and supportive when working with caregivers to develop a
nutrition plan of care that is best for their child and their
lives.
Table 34-11 Nutrition Interventions for Children with Feeding Disorders
■ Initiate a multivitamin with mineral (or age-appropriate vitamin Test Your Knowledge Questions
supplement) 1. Which of the following are common behavioral strate-
■ Offer nutrient-dense snacks and increase the caloric concentration gies to address picky eating?
in foods (add butter/oils, modulars)
A. Offer foods on a divided plate
■ Limit juice to 4-oz per day
■ Recommend using pureed table food in place of jarred baby food
B. Offer 1 new or non-preferred food with 1 or 2
to increase caloric density preferred foods
■ Gradual increase of the thickness of the pureed food may help C. Be consistent
advance children with difficulty to advance to more complex textures D. Encourage family mealtimes
■ Initiate nutrition supplementation, either orally or via enteral nutrition, E. All of the above
if the patient is unable to sustain age-appropriate weight gain
2. All of the following findings may justify nutrition
■ Initiate enteral nutrition immediately if the child is < 80% ideal
body weight support in a toddler except:
■ Adjust tube feeding regimen in conjunction with behavioral A. Height at the 25th percentile on the growth curve
strategies to increase oral acceptance since infancy
B. No weight gain for 4 months
Eating is an integral part of our social interactions, and C. Decrease in 2 weight percentiles channels over the
families can experience significant difficulty coping with past 6 months
the stress of caring for a child with a feeding disorder. Fami- D. Eats very slowly
lies are therefore commonly referred to support groups, 3. A child with CF who has a very good appetite, yet is
where they may discuss building social supports, strategies moderately underweight, should receive:
for establishing mealtime structure at home, coping mecha- A. PN in addition to oral feedings
nisms for handling stress, and strategies for implementing B. Tube feedings only
behavior management. 43 C. No nutrition intervention
For patients who require more intensive intervention, D. Oral nutrition supplements in between meals
some teams offer outpatient day hospital treatment or inpa-
tient treatment, which allow therapists to work with children See p. 487 for answers.
at every meal and to monitor their nutrition and medical
status closely. For outpatient evaluations and therapies, as

19. Abad-Sinden A, Sutphen J. Nutrition management of pediatric

References short bowel syndrome. Pract Gastroenterol. 2003; Nutrition
1. Baker S, Baker R, Davis A. Pediatric Nutrition Support. Boston,
Issues in Gastroenterology, series #12:28–48.
MA: Jones & Bartlett; 2007.
20. Serrano M, Schmidt-Sommerfeld E. Nutrition support
2. Mahesh C, Sriram K, Lakshmiprabha V. Extended indications
of infants with short bowel syndrome. Nutrition.
for enteral nutritional support. Nutrition. 2000;16:129–130.
2002;18:966–970.
3. Axelrod D, Kazmerski K, Iyer K. Pediatric enteral nutrition. J
21. Puntis JWL. Nutritional support in the premature newborn.
Parenter Enteral Nutr. 2006;30(1):S21–S26.
Postgraduate Med Journal. 2006;82:192–198.
4. Samour PQ , King K. Handbook of Pediatric Nutrition. 3rd ed.
22. Groh-Wargo S, Thompson M, Cox J, ed. Nutritional Care for
Lake Dallas, TX: Helm Publishing; 2005.
High-Risk Newborns, Revised. 3rd ed. Chicago, IL: Precept
5. Wang C, Finkel R, Bertini E, et al. Consensus statement for
Press, Inc; 2000.
standard of care in spinal muscular atrophy. J Child Neuro.
23. Okada A. Clinical indications of parenteral and enteral
2007;22:1027–1049.
nutrition support in pediatric patients. Nutrition.
6. Ramelli G, Aloysius A, Davis T, Muntoni F. Gastrostomy
1998;14(1):116–118.
placement in paediatric patients with neuromuscular disor-
24. Vanderhoof J. New and emerging therapies for short bowel
ders: indications and outcome. Dev Med & Child Neuro.
syndrome in children. J Ped Gastr Nutr. 2004;39:S769–S771.
2007;49:367–371.
25. Thureen PJ, Hay WW. Early aggressive nutrition in preterm
7. Ekvall S, Ekvall V. Pediatric Nutrition in Chronic Diseases and
infants. Semin Neonatol. 2001;6:403–415.
Developmental Disorders. 2nd ed. New York, NY: Oxford
26. Dudrick S. Early developments and clinical applica-
University Press; 2005.
tions of total parenteral nutrition. J Parenter Enteral Nutr.
8. Watkins JB, WalkerW , Duggan C. Nutrition in Pediatrics: Basic
2003;27(4):291–299.
Science and Clinical Applications. 3rd ed. Hamilton, Ontario:
27. Pettignano R, Heard M, Hart M, Davis R. Total enteral
BC Decker Inc; 2003.
nutrition versus total parenteral nutrition during pediatric
9. Rommel N, De Meyer AM, Feenstra L, Veereman-Wauters G.
extracorporeal membrane oxygenation. Crit Care Med.
The complexity of feeding problems in 700 infants and young
1998;26(2):358–363.
children presenting to a tertiary care institution. J Pediatr
28. Parrish C, McCray S. When chyle leaks: Nutrition manage-
Gastroenterol Nutr. 2003 Jul;37(1):75–84.
ment options. Pract Gastroenterol. 2004; Nutrition Issues in
10. Geggie JH, Dressler-Mund DL, Creighton D, Cormack-
Gastroenterology, series # 17: 60–76.
Wong ER. An interdisciplinary feeding team approach for
29. American Academy of Pediatrics, Committee on Nutri-
preterm, high-risk infants and children. Can J Diet Pract Res.
tion. Commentary on parenteral nutrition. Pediatrics.
1999;60(2):72–77.
1983;71(4):547.
11. Bott L, Beghin L, Hankard R, Pierrat V, Gondon E, Gottrand
30. Wrught K, Ernst KD, Gaylord MS, et al. Increased incidence of
F. Resting energy expenditure in children with neonatal
parenteral nutrition-associated cholestasis with Aminosyn PF
chronic lung disease and obstruction of the airways. British J
compared to Trophamine. J Perinatol. 2003;23(6):444–450.
Nutr. 2007;98:796–801.
31. Kerner JA. Parenteral nutrition. In: Walker WA, Durie PR,
12. Guimber D, Michaud L, Storme L, Deschildre A, Turck D,
Hamilton JR, Walker-Smith JA, Watkins JB, eds. Pediatric
Gottrand F. Gastrostomy in infants with neonatal pulmonary
Gastrointestinal Disease: Pathophysiology, Diagnosis, Manage-
disease. J Pediatr Gastroenterol Nutr. 2003;36:459–463.
ment. Vol 2. St. Louis, MO: Mosby; 1996:1904–1951.
13. Stallings V, Stark L, Robinson L, Feranchak A, Quinton H.
32. Hurwitz M, Garcia MG, Poole RL, Kerner J. Copper defi-
Evidence-based practice recommendations for nutrition-
ciency during parenteral nutrition: a report of four pediatric
related management of children and adults with cystic fibrosis
cases. Nutr Clin Pract. 2004;19:305–308.
and pancreatic insufficiency: results of a systemic review. J Am
33. McFarland C. Evaluating trace element status in long-term
Diet Assoc. 2008;108:832–839.
parenteral nutrition-dependent pediatric patients. Building
14. Borowitz D, Baker R, Stallings V. Consensus report on
Block for Life. 2009; 32(2):3–5.
nutrition for pediatric patients with cystic fibrosis. J Pediatr
34. Reifen RM. Microminerals. In: Tsang RC, ed. Nutritional
Gastroenterol Nutr. 2002;35(3):246–259.
Needs of the Preterm Infant: Scientific Basis and Practical Guide-
15. Da Silva V, de Oliveira Lopes M, de Araujo T. Growth and
lines. 2nd ed. Digital Educational Publishing, Inc.; 2005.
nutritional status of children with congenital heart disease. J
35. Fok TF, Chui KKM, Cheung R, Ng PC, Cheung KL, Hjelm
Cardiovasc Nurs. 2007;22(5):390–396.
M. Manganese intake and cholestatis jaundice in neonates
16. Ledermann S, Spitz L, Moloney J, Rees L, Trompeter R.
receiving parenteral nutrition: a randomized controlled study.
Gastrostomy feeding in infants and children on peritoneal
Acta Paediatr. 2001;90(9):1009–1015.
dialysis. Pediatr Nephrol. 2002;17:246–250.
36. Mirtallo J, Canada T, Johnson D, et al. Safe practices for paren-
17. Merritt R, ed. The A.S.P.E.N. Nutrition Support Practice
teral nutrition. J Parenter Enteral Nutr. 2004;28(6):S39–S70.
Manual. 2nd ed. Silver Spring, MD: The American Society for
Parenteral and Enteral Nutrition; 2005.
18. Pearce CB, Duncan HD. Enteral feeding. Nasogastric, nasoje-
junal, percutaneous endoscopic gastrostomy, or jejunostomy:
its indications and limitations. Postgraduate Medical Journal.
2002;78:198–204.

37. Greene HL, Hambidge KM, Schanler R, Tsang RC. Guidelines 43. Tobin S, Cheng V, Schumacher C, et al. The role of an inter-
for the use of vitamins, trace elements, calcium, magnesium, disciplinary feeding team in the assessment and treatment of
and phosphorus in infants and children receiving total paren- feeding problems. Building Block for Life. 2005;28(3):1–11.
teral nutrition: report of the Subcommittee on Pediatric 44. Satter E. Child of Mine; Feeding with Love and Good Sense. Bull
Parenteral Nutrition Requirements from the Committee on Publishing; 2000.
Clinical Practice Issues of the American Society for Clinical
Nutrition. Am J Clin Nutr. 1998;48(5);1324–1342. Additional Readings
38. Schmidt-Sommerfield E, Penn D, Wolf H. Carnitine blood Cloud HH. Recent trends in care of children with special needs:
concentrations and fat utilization in parenterally alimented nutrition services for children with developmental disabili-
premature newborn infants. J Pediatr. 1982;100:260. ties and special health care needs. Topics in Clinical Nutrition.
39. Crill CM, et al. Relative bioavailability of carnitine supple- 2001;16(4).
mentation in premature neonates. J Parenter Enteral Nutr. Puntis JWL. Specialist feeding clinics. Arch Dis Childhood.
2006; 30(5):421–425. 2008;93:164–167.
40. Manikam R. Pediatric Feeding Disorders. J Clin Gastroenter. Rudolph C, Link T. Feeding disorders in infants and children.
2000;30(1):34–46. Pediatr Clin North Am. 2002;49(1):97–112, vi.
41. American Academy of Pediatrics. Identifying and treating
eating disorders. Pediatr. 2003;111(1):204–211.
42. Piazza C, Carrol-Hernendez T. Assessment and Treatment
of Pediatric Feeding Disorders. Encyclopedia of Early Child-
hood Development; 2004. http://www.enfant-encyclopedie.
com/Pages/PDF/Piazza-Carroll-HernandezANGxp.pdf.
Accessed July 20, 2008.

35
Implementation of the Plan
Beth Lyman, RN, MSN, Jennifer M. Colombo, MD, and Jodi L. Gamis, OTR

Background . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 446 1. Evaluate the patient for specific issues that can impact
Parenteral Nutrition. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 447 the plan of care.
Type of Intravenous Catheter Needed 2. Implement an evidence-based nutrition plan of care
Site Care that blends parenteral, enteral, and oral intake as appro-
Safety Issues priate for that patient.
Nursing Care
3. Discern the key safety measures that are age appropriate
Enteral Nutrition. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 449
and patient specific when implementing the nutrition
Enteral Route Selection
Types of Tubes plan of care.
Tube Insertion
Verification of Placement Background
Bolus vs. Continuous Feeds. . . . . . . . . . . . . . . . . . . . . . . . 452 Implementation of a nutrition plan of care may involve a
Bolus Feedings combination of parenteral nutrition (PN), enteral nutrition
Continuous Feedings (EN), or oral nutrition therapies in pediatric patients.
Combination Feedings
In order to stimulate intestinal growth and adaptation, pediatric
Initiation and Advancement of Feedings . . . . . . . . . . . . . 452 patients who require PN need some amount of EN, oral intake,
Bolus Feedings
Continuous Feedings
or both. Depending on the patient-specific characteristics that
Combination Feedings have been discussed elsewhere, a balancing of PN nutrients with
Safety Issues . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 453 EN and/or oral intake is the accepted mode of intervention for
Preparation most pediatric patients. Goals for each of these interventions
Hang Time for Formula are constantly redefined based on patient assessment
Feeding Pumps by all involved health care providers and the parents (or
Nursing Care. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 454 caregivers). Clear communication of the plan and goals is
Securing the Tube essential for successful implementation of any nutrition
Site Care
support plan. These patients are medically complex and
Checking Residual Volumes
Flushing the Tube require close observation to accurately assess how they
Use of Sterile vs. Non-Sterile Water tolerate the interventions.
Reflux For pediatric patients who receive nutrition support
Aspiration Precautions the goal of therapy is to first wean off of PN and on to full
Intake and Output enteral feedings. Oral feeding is introduced as developmen-
Weights
Assessment of Feeding Tolerance
tally and physiologically appropriate. This careful balance
Medication Administration of all 3 modalities requires skilled observation and evalua-
Oral Nutrition. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 456 tion by everyone involved with the patient.
448
IMPLEMENTATION OF THE PLAN 449
Parenteral Nutrition PICCs should be secured to the skin. The use of sutures
Malnourished children need PN if they cannot tolerate or to secure a PICC has been documented to result in less
safely receive EN for > 3 days.1 Implementation of a nutri- migration, occlusion, and leakage when compared to the use
tion care plan that involves PN begins with the goals of of tape.9 However, sutures can become inflamed requiring
therapy and considers fluid status, appropriate intravenous removal. The use of an adhesive securement device has
(IV) access and nutrition needs, and anticipated length been shown to be easier to place and associated with fewer
of therapy. Fluid status and PN solution composition is complications than sutures in pediatric patients.10
discussed previously (see Chapter 34). The anticipated Critically ill children who require PN will typically
length of therapy often dictates the IV access choice. Gener- have a temporary VAD placed via the subclavian or internal
ally, the longer the need for PN, the more likely a patient jugular veins. Reduction of bloodstream infections (BSIs)
will need a more permanent central vascular access device related to CVCs continues to be an ongoing focus in all health
(VAD). In pediatrics, the use of peripheral parenteral nutri- care settings, including critical care units. One approach has
tion (PPN) may be the initial nutrition intervention. been to coat CVCs with antibiotics. This is controversial in
pediatrics due to concerns of sensitization and development
Type of Intravenous Catheter Needed of drug resistance. One study using antibiotic-coated CVCs
Neonatal and pediatric patients may receive a short course of shows comparable infection rates but the antibiotic-coated
PPN prior to the initiation of PN. Peripheral intravenous vein CVCs were in place an average of 18 days compared to 5
(PIV) selection is important in these patients. Avoidance of days for the non-coated CVCs before infection occurred.11
the antecubital fossa is recommended if peripherally inserted Many critical care units advocate removal of a temporary
central catheter (PICC) placement is anticipated. PPN use is CVC after 7 days. The use of antibiotic-coated CVCs in
the most common cause of infiltration-related tissue necrosis pediatric patients remains controversial.
in pre-term infants so diligent site assessment is crucial.2 When it is clear long-term PN is needed for a patient,
Ideally, PIVs should not be placed in the scalp or feet of infants plans for the most appropriate VAD need to be made. A
who receive PPN.2 One study documented an average of 2.2 patient who will go home for up to 6 weeks of PN can often
attempts per PIV for PPN placement with an average duration use the same PICC already in place. A surgically placed
of 2.19 days in neonates receiving PPN.3 Investigators recom- tunneled catheter is most often used for infants and children
mended PICC placement as soon as possible.3 who require home PN for an extended period of time. Occa-
When PICC placement is needed for PPN, placement sionally an implanted VAD is placed when intermittent PN
of the tip in the superior vena cava, right atrium, or inferior or a few nights per week infusions are prescribed. This VAD
vena cava above the level of the diaphragm is recommended has definite benefits for adolescents who are already strug-
to prevent complications such as occlusion and leakage.4 Also, gling with body image issues.
a PICC that has been in place for an extended period of time Once a CVC is in place for PN, it is also used to obtain
before being used for PN should have tip placement verified lab specimens to avoid venipuncture. Vigorous cleaning
before use as this type of VAD is associated with a higher rate of the injection cap prior to accessing the CVC is essential
of malposition than other central venous catheters (CVCs). 5 to prevent intraluminal contamination. The approaches to
Case reports in the literature document intracranial malpo- obtaining lab specimens are compared in Table 35-1. Two
sitioning resulting in seizures and stroke in pediatric patients studies in the literature document the safe and reliable
who had a PICC for PN.6,7 method of blood sampling involving repeated pushing and
As PICCs are the preferred VAD for neonates receiving pulling of blood into an empty syringe before obtaining a
PN, it is important to discern the best placement; ie, upper specimen in a new syringe.12,13 Nursing should have options
extremity (UE) versus lower extremity (LE). One retrospective for specimen collection based on what is best for that patient.
study documented a preferred site placement of UE by nearly It is important for nursing staff to stop all infusions when
3 to 1 with UE placement at an average of day of life (DOL) 6 using a multi-lumen catheter to assure accurate lab sample
compared to LE placement around DOL 8. This study found a results. When the waste approach is used, one study does
significantly longer duration of usefulness for PICCs placed in validate the safety of 3 mL versus 5 mL of waste when blood
the LE. There was also a lower incidence of coagulase-negative samples are obtained from a tunneled or implanted VAD.14
Staphylococcus (CoNS) in the LE group.8 Care should be taken Regardless of the method used to obtain a blood specimen
in site selection for PICCs in neonates. The antecubital fossa or through a CVC, it is recommended to change the injection
above is the preferred site for PICC placement in children. cap after every blood sample or within 24 hours.

Table 35-1 Comparison of Techniques Used to Obtain Blood Samples from a VAD
Type of Technique Description Pros Cons
Traditional 1. Stop infusion “Gold standard” procedure at Increases blood loss when doing
2. Flush VAD with NS this time frequent blood sampling
3. Obtain a waste specimen of 3–5 mL Increases exposure of staff to
When done properly, low risk blood
4. Obtain blood needed for labs ordered
of infection associated with Potential for confusing the waste
5. Flush VAD with NS obtaining labs. syringe with the sample syringe
6. Restart infusion
Return the Waste 1. Fill a syringe with heparin and remove it Decreases the blood loss for the Potential for reinfusion of blood
2. Stop infusion patient clots
3. Flush VAD with NS Potential for contamination of
blood being reinfused
4. Obtain a waste specimen of 3–5 mL
5. Have a nurse rotate the waste specimen
6. Obtain blood needed for labs ordered
7. Return the waste specimen to the patient
8. Flush VAD with NS
9. Restart infusion
Push-Pull Method 1. Stop infusion Limits patient blood loss from Potential for hemolysis due
2. Aspirate 3–5 mL of blood into a syringe blood sampling to turbulence created by the
pushing and pulling
3. Reinfuse that blood and repeat the aspiration/
reinfuse procedure a total of 3 times May not be feasible for some
VADs that are difficult to
4. Place a new syringe on the VAD and obtain blood draw from
needed for ordered labs
Site Care summarizes these recommendations. Aside from institu-

Once the CVC is in place, routine skin disinfection and tion processes to safeguard the patient, individual patients
dressing changes are necessary. In 2002, the Guidelines for will require infection prevention measures as well. Attempts
the Prevention of Intravascular Catheter Infections recom- must be made to prevent contamination of the catheter hub
mended the use of chlorhexidine gluconate (ChloraprepTM ) by draining gastrostomy tubes, a leaking ostomy bag, or
for skin antisepsis for all patients over the age of 7 days or 26 other body fluids. Babies who are teething need to have a
weeks gestation.15 Since that time, this product has become pacifier to prevent them from sucking on their IV tubing.
the standard antiseptic used for routine VAD dressing Children who are suspected or known to be self-destructive
change skin antisepsis in this country. It is generally well should be carefully monitored. Siblings need to be super-
tolerated. Transparent dressings that are replaced every 7 vised when visiting their brother or sister.
days or when loose or soiled are the dressing of choice over For children who have a parent in the room at all times
gauze and tape as the insertion site can easily be inspected. monitoring of the parent and any activity with the CVC is
A trial of chlorhexidine gluconate-impregnated dressings warranted. Parents should not be allowed to access or care
(BiopatchTM) in neonates resulted in contact dermatitis for a CVC unless specifically trained to do so and only with
making it not recommended for use in this population.16 the permission of the nurse.
Another key aspect of the dressing is to place a “stress” One of many reports in the literature described the use
loop in the VAD if it is tunneled or in the extension tubing of a CVC by parents with Munchausen Syndrome by Proxy.18
and tape to provide another method to prevent accidental This condition is now referred to as Pediatric Condition Falsi-
dislodgement of the CVC. fication which is a form of child abuse where the caregiver is
the perpetrator. Because this condition can be life threat-
Safety Issues ening for the child, any suspicion of this condition needs to
BSIs related to the CVC are known to be associated with an be addressed prior to placement of a CVC for PN. While this
increase in cholestasis in infants on PN.17 Therefore, many condition is difficult to prove, certain typical behaviors seen
measures must be in place to assure adequate infection in the caregivers include “doctor shopping” to different health
control processes to prevent CVC-related BSIs. Table 35-2 care facilities, discrepancy between reported symptoms and

Table 35-2 Prevention of CVC-Related Bloodstream Infections

Aspect of Care Action
Hand Hygiene • Use an antiseptic skin soap to wash hands before placing or accessing a VAD or
• use an alcohol-based hand sanitizer.
Catheter Insertion • Staff involved in CVC placement must be competent to do this procedure.
• Use maximal sterile barriers including masks, gowns, drapes, sterile gloves, and a kit with all
needed supplies.
• Allow nursing to call a “time out” for an observed break in sterile technique.
• Avoid placement of a CVC in a febrile patient.
• Avoid guidewire replacement of a CVC.
Catheter Accessing • Vigorously clean the hub of the catheter with 70% alcohol or chlorhexidine wipes before entering the line.
• Have a policy on routine injection cap changes.
• Avoid stopcocks on CVCs.
• Use sterile, prefilled syringes for CVC flushing.
• Limit accessing for labs to 1 time per day if possible.
Catheter Dressing Changes • Use a kit with all supplies needed.
• Use ChloraprepTM as preferred skin disinfectant.
• Use a mask and gown for PICC dressings.
• Use a transparent dressing preferentially over a gauze and tape dressing to allow for the site
to be assessed.
• Restrain the patient as needed to prevent accidental dislodgement.
• Place a stress loop in the VAD tubing or extension tubing.
Diagnosis of BSI • Obtain a peripheral and central blood culture.
• Staff obtaining blood cultures should be specially trained and competent to avoid contamination.
• Draw a minimum of 1mL for the blood culture.
• Use clinical and other labs to validate diagnosis.
• Do not necessarily remove the CVC.
IV Tubing Changes • Lipids—every 24 h
• PN—every 72 h unless a 3-1 solution, then every 24 h or if cycled off a few hours/day
Other • Evaluate all supplies used on CVCs for defects that could lead to infections.
• When using outside pharmacies, surveillance of possible IV fluid related infections is needed.
• Have a surveillance plan within the institution to trend infections and look for a root cause.
what is observed, caregiver reluctance to leave the child and Enteral Nutrition
to allow others to provide care, and overzealous attachment
to certain healthcare providers.19 Enteral Route Selection
Enteral nutrition should be considered in all children with
Nursing Care an intact and functional gastrointestinal (GI) tract who can
In addition to prevention of VAD-related infections, the not take in enough calories orally to meet their needs for
nursing care of a child requiring PN is extensive. Table 35-3 growth and development. Ideally a multidisciplinary team
summarizes the nursing activities required when taking care including a pediatric physician, a nurse, a dietitian, a speech
of a child who requires PN. Most hospitals and other care therapist, and/or an occupational therapist should assess
settings require competencies in the areas of CVC dressing each patient and develop a feeding plan. Balancing caloric
changes, obtaining lab specimens, and appropriate flushing, needs with the child’s ability to digest and absorb nutrients
etc. Meticulous nursing care for any patient receiving PN is is a dynamic process that may necessitate low rates of EN
absolutely essential in the pediatric care setting. via feeding tube.
Once a clearly identified indication for enteral tube
feeding has been established, several ways to administer EN
exist. Enteral access can be obtained through a nasogastric

Table 35-3 Nursing Care of the Patient Requiring PN

Action Frequency
Weigh patient using the same scale Daily at approximately the same time.
Weigh babies nude
Assure the competency of staff who weigh patients As needed
Repeat any weight that is clearly aberrant As needed
Vital signs As needed but usually at least every 12 h
Notify physician for temp > 38.5°C
Monitor intake and output Every shift and as needed
Note stool/ostomy output and notify physician for excessive losses
Assess CVC site At least every 4 h and more often if warranted
Assure the CVC is secure At least every 4 h and more often if warranted
Flush the CVC with the appropriate amount of NS and Heparin if TPN After every interruption in TPN
cycled off a few hours/day
Only use the appropriate concentration of heparin if needed for pt As needed
Change injection cap Within 24 h of drawing blood and per hospital policy
Shower or bathe patient with consideration for the safety of the CVC Daily
Assure the safety of the CVC as age appropriate At all times
Infuse the PN as ordered—match the order with the bag Daily
Double check the pump settings to assure the PN is infusing as ordered Hourly
If the CVC comes out or becomes dysfunctional, contact the physician for As needed
orders for dextrose-containing solution
Monitor lab results and redraw when results look contaminated by PN As needed
Monitor blood glucose Per hospital policy
Promote normal growth and development of the patient Ongoing
tube, orogastric tube, gastrostomy tube, nasoduodenal emptying or severe gastroesophageal reflux will impair
tube, nasojenunal tube, gastro-jejunostomy, and jejunos- tolerance. Bypassing the stomach by way of nasoduodenal,
tomy. The choice of access is dependent on several factors nasojejunal, gastrojejunal, or direct jejunal feedings may be
(described below) and should be made with the guidance of necessary at times.
the multidisciplinary team.20 The family and the older child The last factor that should be considered is aspiration
should be involved in the decision-making process to ease risk. Any patient with a potential risk of aspiration should
potential fears and concerns related to providing EN and to be evaluated. Preventive measures, such as bypassing the
improve compliance. stomach by using nasoduodenal, nasojejunal, gastrojejunal,
The expected duration of therapy for EN is key in or jejunal tubes, or by operative fundoplication should be
selecting the most appropriate feeding tube. A child considered by the healthcare team.
expected to require EN for less than 3 months should have
a temporary means of providing formula, such as a nasogas- Types of Tubes
tric tube, nasoduodenal tube, or an orogastric tube. More
permanent access should be considered in a child requiring Nasogastric Tube
enteral formula for greater than 3 months. Nasogastric (NG) tubes are indicated for children who have
Anatomic abnormalities of the GI tract may dictate the an intact and functional GI tract and will only require enteral
most appropriate feeding tube for the patient, especially if formula for a short period of time. These patients should have
there are known strictures. The GI tract should be free of an minimal gastroesophageal reflux, normal gastric emptying,
obstruction that would impede normal movement of enteral and low risk of aspiration.20 NG tubes are soft flexible tubes
nutrients. There should be appropriate length to allow for made of Silastic or polyurethane ranging in size from 5 Fr.
digestion and absorption of nutrients. to 12 Fr. The tube size is chosen based on the patient’s age,
Proper functioning of the GI tract is necessary for size, and type of formula needed. Small-diameter tubes are
successful administration of EN. Feeding directly into the more comfortable for the patient, but can become clogged,
stomach is preferred as it provides a more normal physio- particularly if the patient receives fiber-containing formula
logical process, digestively and hormonally. Delayed gastric or additives to the formula.

Nasogastic tubes can be easily placed by the family. stomach because of delayed gastric emptying, gastroe-
However, they can be dislodged as well, especially by an sophageal reflux, or risk of aspiration.20 These must be
active or agitated child. NG tubes should be replaced or administered as continuous drip feedings.
changed every 30 days. Children with NG tubes can be
encouraged to eat orally while receiving NG tube feedings. Jejunostomy Tube
Jejunostomy (J) tubes are surgically placed jejunal tubes.
Orogastric Tube These tubes can be inserted directly into the jejunum endo-
Orogastric (OG) tubes are not used as frequently because scopically or surgically. Typically, they are used in patients
they restrict oral feedings. Orogastric tubes are most useful who will require enteral nutrition access for the small bowel
in infants to avoid nasal obstruction or in children where an for more than 6 months.20 The negative side to jejunostomy
NG tube cannot be passed (ie, choanal atresia). tube use includes mandatory continuous feedings as well as
surgical emergencies (volvulus) around the tube.
Nasojejunal Tube
Nasojejunal (NJ) tubes are similar to NG tubes, but longer Tube Insertion
for passage through the pylorus, duodenum, and into the Most NG tubes are placed at the bedside. An attempt is made
jejunum. Nasojejunal tubes are necessary when there is to make the child as comfortable as possible. An infant or
delayed gastric emptying, severe gastroesophageal reflux, or young child should be swaddled for comfort and to prevent
risk of aspiration.20 These tubes are challenging to place and their arms from flailing about during tube insertion. The
require either a skilled nurse, gastroenterologist, or inter- cervical spine of the child should be slightly flexed and not
ventional radiologist to place. They can migrate back into hyperextended.21 A small amount of lubricant is applied to
the stomach or duodenum or clog with thickened formulas the tip of the tube or water may be used. The tip is inserted
or medication administered in the tube. Feeding tubes in into a nostril and then slid carefully down the nasopharynx,
the small bowel must be given as continuous drips since the oropharynx, esophagus, and into the stomach. It is then
reservoir function of the stomach is bypassed. secured into place at the nares. Parents are taught the tech-
nique of inserting NG tubes so the tubes can be replaced at
Gastrostomy Tube home when necessary.
Gastrostomy (G) tubes or buttons are a more permanent Nasojejunal tubes are inserted in a similar manner;
way of administering EN, and are recommended for any however, they usually require the assistance of radiology or
child who requires long term (greater than 3 months) EN.20 fluoroscopy for accurate placement or confirmation. These
Formula is directly administered into the stomach similar tubes cannot be replaced at home. If the tube migrates back
to an NG tube. These tubes can be placed either endoscopi- into the stomach, it must be replaced.
cally or surgically. The gastrostomy tube size is usually 14 Fr. Gastrostomy tubes, gastrojejunostomy tubes, and
to 24 Fr.; however, smaller and larger tubes are available. jejunostomy tubes must be placed endoscopically by a
Gastrostomies are soft pliable devices made of silicone pediatric gastroenterologist, radiologist, or by a pediatric
or polyurethane. They are less noticeable to the general surgeon. If a tube is dislodged, families should be instructed
public, which is important to some patients and families. to insert a replacement tube or temporary tube in the tract
The primary gastrostomy may be a G-tube or primary place- immediately to avoid premature closure of the tract until a
ment G-button. Once the gastrostomy tract has matured more permanent tube can be replaced.
(in 2 to 3 months), the gastrotomy may be replaced with a
low-profile, skin-level device (Mickey button) that the care- Verification of Placement
givers can change themselves. Verifying correct placement of an enteral tube is imperative
prior to administering enteral formula. A tube accidentally
Gastrojejunostomy Tube inserted into the respiratory tract will certainly have disas-
Gastrojejunostomy (GJ) tubes are also permanent tubes trous or even deadly consequences.
that are inserted into the wall of the stomach similar to a
G-tube; however, there are two ports: one into the stomach Radiology
for fluids, medication, and venting and the other into the A chest and abdominal x-ray which identifies the length of
jejunum. They are recommended for patients who require the tube is the gold standard for confirming placement. The
long-term EN and who cannot tolerate feedings into their tip of the feeding tube can be seen within the stomach or

jejunum. There is concern regarding increasing exposure to Bolus vs. Continuous Feeds
X-rays, and alternative methods have been used to confirm Enteral formulas can be given through bolus feedings, con-
placement of feeding tubes.22 tinuous feedings, or a combination of both depending on a
number of factors. These factors include the child’s condition
Air Insufflation and nutrition status, anatomy, type of tube selected, indica-
Air is pushed through an NG tube using a syringe, with tion for tube feedings, and family schedule. It is important to
auscultation over the patient’s left upper quadrant. If the air consider family lifestyle when implementing a feeding plan.
bolus is heard in the left upper quadrant, then placement is The goal is to maximize the benefit of enteral feeding while
thought to be in the stomach. This method is inexpensive, minimizing the complexity of nutrition support.
but is also the least sensitive. Air pushed into a feeding
tube that is mistakenly placed in the thoracic cavity can be Bolus Feedings
heard in the abdomen. 23 Many case reports describe the Bolus feedings imitate regular mealtimes and, therefore,
inability of clinicians to determine gastric versus respira- are more physiologic compared to continuous feedings. A
tory placement.22 feeding schedule is determined by a dietitian and pediatric
physician depending on the child’s caloric and fluid require-
Gastric Aspirate/pH Testing ments. Bolus feedings can only be administered into the
Aspirating gastric contents and confirming pH is an stomach and should never be administered past the pylorus.
alternative to the gold standard radiograph and is the recom- Formula can be administered by gravity or over a pre-deter-
mended bedside method to confirm NG placement. 22,23 The mined period of time by a feeding pump. Bolus feedings are
Children’s Hospital in Boston recommends use of gastric often more convenient for the patient and family because
pH performed at the bedside. Correct placement may be the schedule is more flexible and the child is not tethered to
confirmed if the gastric pH measures less than 5. The use an infusion pump.
of medications for acid suppression is widely used in pedi-
atrics and would invalidate the confirmation of placement. Continuous Feedings
Delivery of feeds, time of last feed, and medications also Continuous feedings are infusions of enteral formula over
impact gastric pH. If the gastric pH is greater than 5, gastric time. Patients, who cannot tolerate large volumes because
aspirate cannot be obtained, the patient clinically deterio- of delayed gastric emptying, GERD, or dumping syndrome,
rates during placement, or develops low oxygen saturation, are given slow continuous feeds. The continuous feedings
an x-ray would be necessary to confirm placement.24 are generally smaller volumes infused slowly. A feeding
pump is required for these infusions which may limit the
Colorimetric CO2 Detector child’s ability to move. For ambulatory patients, there are
The colorimetric CO2 detector was initially used to deter- smaller feeding pumps that can be carried in a backpack
mine placement of an endotracheal tube within the trachea. allowing for more flexibility and mobility.
It has been used in adults to assess appropriate feeding tube
placement. Unfortunately, there are no published studies in Combination Feedings
children regarding the reliability and validity of colorimetric Combination feedings are ideal for patients who need a
CO2 detectors verifying placement of enteral feeding tubes.25 significant amount of calories but cannot tolerate large
volumes. Smaller bolus feedings can be given during the
Electromagnetic Tube Placement day and the remainder can be administered continuously
The Cortrak SystemTM assists with feeding tube placement overnight. This method also allows the child and parents to
by displaying the approximate location of the feeding tube sleep at night.21
during real-time placement. This system uses feeding tubes
with a specialized stylet that has an electromagnetic trans- Initiation and Advancement of Feedings
mitter. A receiver unit is placed on the patient’s xiphoid Enteral feedings are often started in a hospital to observe
process and acquires the signal from the stylet. It tracks the feeding tolerance and monitor for complications. A feeding
course of the stylet as the feeding tube is inserted and displays schedule is designed by the health care team which may
it on a monitor. Pediatric patients who can tolerate an 8 Fr. or include a dietitian, attending physician, and an occupational
larger feeding tubes are candidates for this device.25 therapist, and a GI nurse. The family receives support and
reassurance during the hospitalization from all members

of the team. The family learns about the formula, feeding Daytime feedings are compressed by 1 to 2 hours each day
schedule, enteral device, and safety concerns regarding until the desired number of boluses is given (3 to 4 hours
feedings. apart). Boluses may be given over 30 to 60 minutes if intol-
Choice of formula is discussed in other chapters. Full- erance presents.
strength formula should be used. There is no need to dilute the
formula for initiation or advancement of feedings.21 For neuro- Safety Issues
logically intact children, it is important to encourage the child
to eat orally to maintain oral motor skills. If oral feeding cannot Preparation
be done, a referral for occupational therapy is warranted for oral Formula should be prepared by personnel and family
stimulation while receiving enteral feeding. members who are trained to prepare formula in a clean
environment.21 Good hand washing is imperative prior
Bolus Feedings to preparation.21 The warm and nutrient-rich environ-
The total calculated volume of formula is based on the child’s ment of enteral formulas promote the growth of bacteria.
caloric needs and requirements. This volume is divided into Using appropriate handling, hygiene, and adherence to
6 to 8 boluses. It is recommended to give 25% of the child’s guidelines for hang time will prevent most episodes of
caloric needs on day 1 and advance by 25% each day until contamination.26
the final caloric goal is achieved.21 The child is monitored Ready-to-feed and formulas from liquid concentrate
closely for tolerance to the increased volume. Signs of intol- are and should remain sterile; however, bacteria and other
erance include vomiting, abdominal distention, or pain. micro-organisms can populate rapidly if the right conditions
Bolus feedings are given over 15 to 20 minutes, however, are met. Powdered, reconstituted formulas or those with
longer times may be required. additives tend to grow more bacteria and therefore require
Once the child is doing well with the initial feeding meticulous attention to principles of aseptic technique in
schedule and is meeting the caloric goal, boluses can be the preparation and administration of the formula. 21
compressed to 4 to 6 feedings. This allows for ease and
flexibility of administration by the family at home. Again, Hang Time for Formula
the child is monitored for tolerance during this transition. Contamination of enteral formula can occur at any time,
Boluses may need to be given more frequently in infants or even after it is prepared and placed in a container or bag and
children who have metabolic disorders or increased caloric ready to be given to the child. Hang time refers to the length
needs (ie, burns, catch-up growth). of the time that the formula flows through an administration
set. During this time, it is possible for bacteria to populate
Continuous Feedings and contaminate the formula. Because bolus feedings are
It is recommended to start continuous feedings at 1 to 2 usually administered within 1 hour and have a lower risk of
mL/kg/h for 24 hours and increase by 0.5 to 1 mL/kg/h contamination, hang time usually refers to a continuous or
every 8 to 12 hours until the final caloric goal is met. 22 overnight feeding.
When the final goal is achieved, compressing the feeding Liquids in an open system, human breast milk, and
into a shorter time interval should be considered so the powdered formula that is reconstituted should not hang for
child can have a few hours each day free from the feeding more than 4 hours. Sterile, ready-to-feed formula may hang
tube. Generally 16 to 18 hours each day should enable a full for up to 8 hours. Liquid formula in a closed system can be
daily caloric requirement. The child is monitored closely for safely hung for 24 hours.21,27
tolerance to each increase in volume and during compres-
sion of feedings. Feeding Pumps
Feeding pumps are useful for delivering continuous feed-
Combination Feedings ings or slower infusions for bolus feedings. Some feeding
When a child cannot tolerate large volumes of bolus feed- pumps are small enough to be worn in a small backpack
ings, combination feedings should be considered. The total for ease of mobility and flexibility of schedules. The ideal
daily caloric requirement is divided between 3 to 4 smaller pediatric pump is not position sensitive, can be increased
bolus feedings during the day followed by a continuous in increments of 0.1 mL up to 5 mL/h, and is relatively
infusion overnight. This can be accomplished starting with light weight. Providers and caregivers need to be aware
continuous feedings and working up to the caloric goal. that enteral feeding pumps are not free of malfunctions.

Most manufacturers of feeding equipment and pumps have Checking Residual Volumes
safeguards in place to prevent flow errors. Pumps should It is not recommended to check residual volumes as there is
accurately administer formula within 5% of the ordered much debate over their significance. Intolerance to feedings
amount. Periodic calibration of the pump is important to is demonstrated by mood (ie, fussy or irritable), vomiting,
ensure the accuracy of the delivery system.21 retching, or abdominal distention. Residuals are influenced
by enteral formulation, gastric emptying, gastroesophageal
Nursing Care reflux, respiratory embarrassment, timing of measurement
in relation to feed, and delivery method. Residuals that are
Securing the Tube collected should be re-fed to the patient as this can be a
Nasoenteric tubes can easily be pulled out of the nose by an significant source of calorie loss.
infant or a child tugging on the tube, sneezing, or vomiting.
To prevent dislodgement, the tube is secured in place on the Flushing the Tube
child’s face. It is recommended to fix the excess tubing to In general, routine flushing of enteral tubes after each bolus
the back of the infant’s or child’s shirt (ie, with a tape tab feeding or interrupting continuous feeding for water flushes
and safety pin). This helps to keep the tube out of sight and is not recommended in children.21 If a tube becomes clogged,
prevents the child from grabbing it. water is readily available and is the preferred flushing solu-
Transparent dressing is usually applied to the cheek on tion. Sterile or purified water is preferred over tap water
the same side of the face as the nasoenteric tube. The enteral when flushing the tube.21
tube is inserted as described previously. The portion of the It is important to take the child’s age into account when
tube that remains outside the body is laid across the Duo- flushing an enteral feeding tube with water. Immature
dermTM and then a transparent dressing is applied over the kidneys cannot remove excess water and too much free
tube and Duo-dermTM securing the tube to the face. This water can dilute normal sodium levels causing hypona-
method protects the child’s skin from harsh adhesive tape tremia. Hyponatremia may promote complications (eg,
that may tear the skin.28 seizures). Typically, 3 to 5 mL is enough to flush an NG tube
J tubes, G tubes, and low-profile skin-level G buttons in children. Smaller volumes may be used in premature and
can also be pulled out by the child, although it is less likely. smaller infants.
Most types of permanent feeding devices have an internal
retaining device which may be a collapsible rubber stopper Use of Sterile vs. Non-Sterile Water
or a water-filled balloon. Many permanent feeding devices It is generally recommended to use sterile or purified water
also have an external retaining device. when preparing formulas for infants or immunocompro-
A similar technique can be used to secure a G or J tube mised children.26
to the child’s stomach. There are commercially available
products to help keep some tubes in place. Reflux
Severe gastroesophageal reflux may be an indication for
Site Care enteral tube feeding when frequent emesis results in food
Keeping the site clean and dry is the most important aspect refusal and failure to thrive. Gastroesophageal reflux can
of caring for an enteral feeding tube. Washing the nose and be frustrating and anxiety provoking for both the child
face with mild soap and water daily is enough to keep the and caregivers. Frequent episodes of emesis are a source of
nasoenteric tubes clean. calorie loss in young children.
Ostomy sites should be monitored for cleanliness Reflux can worsen with enteral tube feedings. Children
daily. Mild soap and water is enough to keep these sites are unable to self-limit their intake. Their stomach may not
clean, gently scrubbing off any crusted areas. A 2×2 gauze be able to accommodate their goal volumes. Also, in older
dressing that is cut half way through can be placed between children, the diet is changed from relatively thickened or
the device and the skin to keep the ostomy site dry if there is solid feeds to liquid formula, which can predispose them to
some leakage. For the most part, a dressing is not required. more reflux.20
Antibiotic ointment may be needed if the site becomes Worsening reflux may be a sign of intolerance to a
erythematous or tender. Caregivers are taught to apply the feeding schedule or formula. Sepsis, respiratory embarrass-
ointment for up to 3 days and if the symptoms persist, a ment, or metabolic abnormalities have an impact on the
physician should be contacted. number of reflux episodes.

The cause and extent of GERD affects nutrition patterns of the child and be able to discuss them with the
management. Common tests in the evaluation include an multidisciplinary team at follow-up visits. For patients with
esophagram, upper GI study, pH/impedance probe study, ostomies, ostomy output should be recorded and a contact
or esophagogastroduodenoscopy with biopsies. Changing given if that amount is exceeded.
the enteral formula, slowing the rate of the bolus feed-
ings, or changing to continuous feedings may need to be Weights
considered. Weights should be monitored daily during the initiation and
Medications to treat reflux such as H2 blockers or advancement phases of a feeding plan. The infant or child
proton pump inhibitors may be prescribed. If delayed should be weighed without clothing and on the same scale
gastric emptying is the cause for increased reflux, prokinetic every day at the same time. Ostomy bags should be emptied
medications, changing formula, or post-pyloric feeding may just prior to the weight measurement. Individual weights
be considered.20 If all other methods have failed, a surgical are less important than an overall weight trend.
consultation for fundoplication procedure or JT may be Monitoring a child’s weight at every follow-up visit
necessary. ensures that the child is receiving appropriate calories for
growth. If the child fails to gain weight or loses weight,
Aspiration Precautions healthcare providers should investigate any potential
Infants and children lying flat are at increased of refluxing sources of calorie loss.
and aspirating. It is important to position the infant or child
in a manner to prevent aspiration episodes with the head of Assessment of Feeding Tolerance
the child elevated at least 30° while receiving a feed.20,21 It Successful enteral nutrition will allow a child to grow in
may also be necessary to feed the child at risk for aspiration both weight and length without significant distress. Toler-
transpylorically. ance to a feeding plan should be assessed during initiation,
advancement, and maintenance of feedings. Any issues with
Intake and Output feeding intolerance should be addressed early to minimize
During the initiation and advancement of enteral feeding, interruption of nutrition support.
intake and output should be measured frequently, accurately, Monitoring parameters that should be assessed routinely
and recorded for each 24-hour period. This information include vital signs, intake and output, daily weights, enteral
helps monitor the child’s caloric adequacy and fluid balance, access, and physical exam with close attention to abdominal
and assists the multidisciplinary team’s decision making assessment. Laboratory assessment including electrolytes,
regarding needed changes to the nutrition plan. glucose, calcium, magnesium, and phosphorus should be
Intake should be documented as both oral and enteral obtained prior to initiating enteral nutrition. They may need
feeding. Caregivers should record the name and the amount to be monitored frequently until they are stable, especially
that was given. They also should include if the feeding was in the severely malnourished child at risk for refeeding
held or for medications or intolerance, or decreased. syndrome.21
Output can be in the form of vomiting, voiding, and Parents and caregivers should be made aware of the
elimination. A normal voiding pattern ensures that the child signs and symptoms of feeding intolerance so that they
is receiving enough fluid and that the child’s kidneys are may seek medical attention in a timely manner. Signs and
functioning properly. A normal stooling pattern indicates symptoms of feeding intolerance include changes in mood
that the child is tolerating the feedings and likely absorbing or behavior (ie, fussiness during feeds), coughing, choking,
the appropriate macro- and micronutrients. Patients with retching, abdominal distention, vomiting, or diarrhea.
an ostomy should have written parameters for when to call Modifications to the feeding plan can be made to decrease
the physician. Diarrhea is a cause for concern as it is source these problems.
of significant fluid and calorie loss.
Maintaining a strict intake and output diary can be chal- Medication Administration
lenging especially for the family at home. When the child is Enteral feeding tubes can be utilized for medication admin-
tolerating maintenance or caloric goal feeds, monitoring of istration. Some medications can be given via enteral tube
intake and output can be more flexible. The parents or care- easily (eg, liquid suspension or solution, crushed solid
givers should note modifications to the feeding schedule, tablets, and capsules). More complex formulations including
episodes of vomiting, or changes in the voiding or stooling extended or sustained released products are problematic.

Liquid forms of medications are preferred. Some solu- Table 35-4 Weaning Off Tube Feedings
tions and suspensions may be too viscous or thick to safely Using spoon foods, baby foods, or blenderized table food aim for 1–2
put through an enteral tube. These medications must be bites swallowed with no vomiting.
diluted with sterile water. Suspensions must be shaken thor- Increase bite amount if reaching goal 75% of the time, about every 3–4
days
oughly prior to administration.21 Improper administration
Once 10 bites achieved per meal, go to amounts/quantity.
can lead to inaccurate medication provision. Taking 1–4 oz per meal consumed, start tube reduction
Medications in the solid form such as tablets or capsules Reduce the tube feeding early in the day to benefit meals. Reduce the
must be crushed or opened and mixed with purified water bedtime/evening tube feedings last.
prior to administering through an enteral feeding tube. It Continue to advance oral motor and oral sensory but not at mealtimes.
is important to mix the medication well to prevent under- Begin activating chewing skills while continuing to spoon feed
dosing or overdosing of the prescribed medication. Introduce cup and straw.
After administering medications through an enteral When swallowing of chewables is established, offer finger foods at each
meal before the spoon feeding.
feeding tube, the tube must be flushed with purified water to
Offer liquid by cup or straw throughout the meal but do not leave on
prevent the feeding tube from being clogged and to ensure the tray.
that the entire dose of medication is given to the child. Naked weights will be needed monthly. This will help determine tube
Caregivers should be aware of what medication is being reduction. Reduce 4–8 oz depending on weight gain/loss.
administered and where the medication is being adminis- Increase finger foods as skill allows.
tered. Certain medications including vitamins and minerals Add water to tube feedings as needed during reduction.
require activation in the stomach or are predominantly Need 2–3 months of normal growth without tube use before removing
the tube.
absorbed in the upper small intestine. Medications that alter
gastric pH may also affect the activity of concomitant medi-
cations. A consultation with a pharmacist is warranted when Test Your Knowledge Questions
deciding to give medications through an NJ tube or a GJ tube 1. A patient who has a documented weight loss of 5%,
as these tubes bypass the stomach and upper small intes- whose body mass index is < 3rd percentile, and is not
tine altogether. A pharmacist will also provide information expected to have normal gut function for at least 7 more
regarding medication compatibility if the decision is made to days should receive PN via:
add the medication directly to an enteral formula.21 A. Peripheral IV
B. PICC
Oral Nutrition C. Surgically placed CVC
A patient is ready to have the tube feedings reduced when D. No PN
he or she can tolerate the amount of calories needed for 2. A baby with short bowel syndrome is anemic and needs
growth. In transition off tube feeds, it is typical for the child daily lab specimens. The most appropriate technique to
to receive more bolus feedings and to get those feedings in obtain the lab specimens for this patient is:
30 minutes or less. An established meal schedule offered A. Return the waste
before bolus feedings provides the opportunity to eat B. Push Pull method
orally before tube feeds. Table 35-4 is an example of a tube C. Traditional method using the least amount of waste
weaning program. possible
The goal of tube reduction should not be to just get off 3. A toddler with failure to thrive who plots at < 3rd
the tube but to be able to eat a variety of age-appropriate percentile for body mass index needs nasogastric tube
foods with age-appropriate skills and growth. Progress is feeds due to presumed postviral food aversion. The
determined by many factors (eg, ongoing medical compli- most appropriate approach to feeding this child is:
cations, cooperation and consistency of caregivers, and A. Continuous drip feedings
realistic expectations). Communication, consistency, and B. Bolus feedings during the day only
commitment are needed by all providers and the family to C. Daytime bolus, nighttime drip
achieve the goal of oral eating. D. None of the above. Do an occupational therapy
consult for food aversion.

16. Garland JS, Harris MC, Naples M, et al. A randomized trial

References comparing povidone-iodine to chlorhexidine gluconate-
1. Duggan C, Rizzo C, Cooper A, et al. Effectiveness of a clinical
impregnated dressing for prevention of central venous catheter
practice guideline for parenteral nutrition: a 5-year follow-up
infections in neonates. Pediatrics. 2001;1431–1437.
study in a pediatric teaching hospital. J Parenter Enteral Nutr.
17. Sondheimer JM, Asturias E, Cadnapaphornchai M. Infec-
2002;26:377–381.
tion and cholestasis in neonates with intestinal resection and
2. Wilkins CE, Emmerson AJB. Extravasation injuries on
long-term parenteral nutrition. J Pediatr Gastroenterol Nutr.
regional neonatal units. Arch Dis Child Fetal Neonatal Ed.
1998;27:131–137.
2004;89:F274–275.
18. Feldman KW, Hickman RO. The central venous catheter as a
3. Franck LS, Hummel D, Connell K, et al. The safety and efficacy
source of medical chaos in Munchausen syndrome by proxy. J
of peripherally inserted intravenous catheters in ill neonates.
Pediatr Surg. 1998;33(4):623–627.
Neonatal Network. 2001;20(5):33–38.
19. Ayoub CC, Alexander R. Definitional issues in Munchausen
4. Racadio JM, Doellman DA, Johnson NA, et al. Pediatric
by proxy. APSAC Advisor. 1998;11(1):7–10.
peripherally inserted central catheters: complication rates
20. Baker SS, Bakers RD, Davis AM. Pediatric Nutrition Support.
related to catheter tip location. Pediatrics. 2001;107(2):1–4.
Sudbury, MA: Jones and Bartlett Publishers; 2007.
5. DiChicco R, Seidner DL, Brun C, et al. Tip position of
21. Bankhead R, Boullata J, Brantley S, et al. Enteral nutri-
long-term central venous access devices used for parenteral
tion practice recommendations. J Parenter Enteral Nutr.
nutrition. J Parenter Enteral Nutr. 2007;31(5):382–387.
2009;33(2):122–167.
6. Anderson C, Graupman PC, Hall WA. Pediatric intracranial
22. Wilkes-Holmes C. Safe placement of nasogastric tubes in chil-
complications of central venous catheter placement. Pediatr
dren. Paediatr Nurs. 2006;18(9):14–17.
Neurosurg. 2004;40:28–31.
23. Westhus N. Methods to test feeding tube placement in chil-
7. Parikh S, Narayanan V. Misplaced peripherally inserted
dren. Am J Matern Child Nurs. 2004;29(5):282–287.
central catheter: an unusual cause of stroke. Pediatr Neurol.
24. Richardson DS, Branowicki PA, Zeidman-Rogers L, Mahoney
2004;30(3):210–212.
J, MacPhee M. An evidence-based approach to nasogastric
8. Hoang V, Sills J, Chandler M, et al. Percutaneously inserted
tube management: special considerations. J Pediatr Nurs.
central venous catheters for total parenteral nutrition in
2006;21(5):388–393.
neonates: complication rates related to upper versus lower
25. Ellett ML. What is known about methods of correctly placing
extremity insertion. Pediatrics. 2008;121(5):1152–1159.
gastric tubes in adults and children. Gastroenterol Nurs. 2004
9. Graf JM, Newman CD, McPherson ML. Sutured secure-
Nov-Dec;27(6):253–259.
ment of peripherally inserted central catheters yields fewer
26. Smith SL. Guidelines for safety and quality assurance
complications in pediatric patients. J Parenter Enteral Nutr.
when preparing infant feedings. Newborn Infant Nurs Rev.
2006;30(6):532–535.
2008;8(2):101–107.
10. Frey AM, Shears GJ. Why are we stuck on tape and suture? J
27. Hustler D. Delivery and bedside management of infant
Infusion Nurs. 2006;29(1)34–38.
feedings. In: Robbins ST, Beker LT, eds. Infant Feedings:
11. Chelliah A, Heydon KH, Zaoutis TE, et al. Observational trial
Guidelines for Preparation of Formula and Breastmilk in Health
of antibiotic-coated central venous catheters in critically ill
Care Facilities. Chicago, IL: American Dietetic Association;
pediatric patients. Pediatr Infect Dis J. 2007;26(9):816–820.
2003:88–95.
12. Barton SJ, Chase T, Latham B, et al. Comparing two methods
28. Guenter P, Silkroski M. Tube Feeding: Practical Guidelines and
to obtain blood specimens from pediatric central venous cath-
Nursing Protocols. Sudbury, MA: Jones and Bartlett Publishers;
eters. J Pediatr Oncol Nurs. 2004;21(6):320–326.
2001.
13. Adlard K. Examining the push-pull method of blood sampling
from central venous access devices. J Pediatr Oncol Nurs.
2008;25(4):200–207.
14. Cole M, Price L, Parry A, et al. A study to determine the
minimum volume of blood necessary to be discarded from a
central venous catheter before a valid sample is obtained in chil-
dren with cancer. Pediatr Blood Cancer. 2007;48:687–695.
15. Centers for Disease Control and Prevention. Guidelines for
the prevention of intravascular catheter-related infections.
MMWR Morb Mortal Wkly Rep. 2002;51(RR10):1–26.

36
Evaluation and Monitoring of Pediatric Patients
Receiving Specialized Nutrition Support
Elaina Szeszycki, PharmD, BCNSP, Wendy Cruse, MMSc, RD, CNSD and Michelle Strup, PharmD

Management of Pediatric Patients Receiving 1. State objective and subjective data necessary for a
Nutrition Support Therapy. . . . . . . . . . . . . . . . . . . . . . . . . 460 thorough evaluation of currently stated nutrition
Nutrition Monitoring and Evaluation. . . . . . . . . . . . . . . . . 461 support goals.
Enteral Nutrition. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 461 2. Identify parameters utilized to evaluate gastrointestinal
Monitoring tolerance of enteral nutrition.
Evaluation of Growth and Nutrition Adequacy 3. Identify parameters utilized to evaluate tolerance to
Evaluation of Formula Tolerance parenteral nutrition.
Monitoring Laboratory Values 4. List factors affecting calcium and phosphorus
Oral Feeding
Revision of Enteral Plan
solubility.
5. Discuss the laboratory monitoring required for patients
Parenteral Nutrition. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 463
Evaluate for Infusion-Related Incidents receiving specialized nutrition support.
Evaluate Tolerance of Volume
Evaluate Tolerance of Macronutrients Management of Pediatric Patients Receiving
Monitoring the Integrity of PN Formulations Nutrition Support Therapy
Comparison of 3-n-1 and 2-n-1 Formulations Management of pediatric patients receiving nutrition support
Combination Enteral and Parenteral Nutrition
therapy is based on continuously assessing the tolerance and
Reassessment of the Plan. . . . . . . . . . . . . . . . . . . . . . . . . 466
efficacy of the nutrition intervention based on the initial
Evaluate Drug and Nutrient Interactions. . . . . . . . . . . . 466 nutrition care plan. The nutrition care plan must consist of
Compatibility of Medications
nutrition goals that are both short term and long term. The
Guidelines for Monitoring Nutrition Laboratory Values in Children
Receiving Enteral and Parenteral Nutrition patient-specific set of goals must be continually monitored to
Physical Data assess the efficacy of therapy and adequacy of growth.
Chemistry Profile Monitoring When initiating any form of nutrition support in a
Nutrition-Related Laboratory Tests severely malnourished child, careful monitoring must take
Liver Function Tests and Bilirubin place to avoid refeeding syndrome.1 Hypophosphatemia
Trace Elements
Iron Studies and Anemia
has been reported to be associated with malnutrition in
Vitamins children and in the first 10 days of intensive care hospital-
Metabolic Bone Disease ization.2 Although hypophosphatemia is most commonly
Infectious Complications. . . . . . . . . . . . . . . . . . . . . . . . . . 470 associated with refeeding syndrome, careful monitoring of
Appendix 36-1: PN Limits . . . . . . . . . . . . . . . . . . . . . . . . . 471 phosphorus as well as potassium and magnesium is critical
Appendix 36-2: Neonatal and Pediatric when initiating nutrition support in severely malnourished
PN Monitoring Form. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 472 patients. 3 Baseline electrolyte levels should be obtained
Appendix 36-3: Long-Term PN Lab Tracking Sheet . . . . . 473 and depleted mineral and electrolytes should be replaced
460
EVALUATION AND MONITORING OF PEDIATRIC PATIENTS RECEIVING SPECIALIZED NUTRITION SUPPORT 461
before initiation of nutrition therapy.1 It has been suggested malnourished children at risk for refeeding syndrome or
that electrolyte levels should be monitored thereafter every during the transition periods between PN, EN, and oral diet
6 hours, 12 hours, then daily for the first 3 days or until may require more frequent monitoring.
levels are stable.4,5 Daily monitoring of serum electrolytes,
minerals, and vital signs during advancement of nutrition Enteral Nutrition
support would be a minimum expectation in malnourished
patients. Oral supplements can be administered by mouth Monitoring
or feeding tube as tolerated when patients are being fed There are many parameters that can be used to monitor
enterally. Intravenous (IV) electrolytes can be provided patients receiving EN. During the initiation and advance-
when patients are receiving primarily parenteral nutrition ment of EN, monitoring will be more frequent and become
(PN). Should the child experience diarrhea when receiving less frequent as the child becomes more stable. A proposed
oral therapy or serum levels are moderately to severely monitoring protocol for infants and children receiving EN
depleted, electrolyte replacement may need to be switched initially and then stable, both while in hospital and at home,
to IV infusion. is provided in Table 36-1.9,10
It is also critical to avoid providing excess or inadequate
calories during controlled feeding situations when the child Evaluation of Growth and Nutrition Adequacy
is not utilizing hunger and satiety cues. Children receiving Baseline anthropometric data must be assessed initially,
tube feeding do not have the ability to choose more or followed by periodic monitoring of growth velocity. Calorie,
less calories as their growth and nutrition needs change; protein, vitamin, mineral, and fluid intake must be assessed
therefore, it is critical to monitor growth frequently. It is initially, then monitored daily then weekly and later monthly
important to utilize growth charts with serial measurements as needed. Fluid status can be assessed by balancing fluid
and growth velocity.6,7 Excessive calories from PN may intake with fluid output including urine, stool, or ostomy
contribute to cholestatic liver disease, which is discussed output, emesis, wound losses, and tube drainage.
later in this chapter.
The route of nutrition support needs to be reevaluated Evaluation of Formula Tolerance
frequently. Enteral nutrition (EN) is the preferred route Monitoring tolerance to EN includes monitoring changes
when possible. PN should be used when the gastrointestinal in GI function. Stool frequency and consistency as well as
(GI) tract is not functional or if inadequate absorption is presence of blood should be recorded daily. If a patient has
apparent and thus adequate nutrition support is not possible an ostomy, consistency and volume of ostomy output should
via the enteral route.8 Adequacy and appropriateness of the also be recorded daily. Volume goal may be < 40 mL/kg/d
route for nutrition support must be reassessed frequently or < 30% of formula volume.11 A large amount of stool or
and adjusted as needed. ostomy output may indicate the need to reduce formula
volume or avoid advancement of feeding volume. Large
Nutrition Monitoring and Evaluation stool volume or ostomy output may require the initiation
Complications associated with the delivery of EN and of IV fluids to avoid dehydration. If small bowel bacterial
PN can be prevented with monitoring and timely formula overgrowth is present based on the presence of D-lactate or
adjustments based on the patient’s tolerance. Development a positive breath hydrogen test, a low-carbohydrate formula
of enteral and parenteral monitoring guidelines is critical may be beneficial. Measuring stool for reducing substances
to assure all parameters are being assessed. Monitoring also identifies when a patient is experiencing small bowel
parameters are based on nutrition goals set in the nutri- bacterial overgrowth. Antibiotics administered enter-
tion care plan as well as patient tolerance. Initially, baseline ally in a cyclical fashion, probiotics, and avoidance of acid
weight, height or length, and head circumference should be suppression may also be beneficial in patients with bacterial
plotted on age-appropriate growth curves. Monitoring will overgrowth. 5 The presence of blood in the stool may require
include the patient’s growth, fluid status, clinical status, an elemental formula with lower allergenicity or in extreme
tolerance to EN and PN, medication changes, and labora- cases an amino acid-based formula. Other symptoms of GI
tory values. Frequency of monitoring depends on the age, intolerance may include nausea, vomiting, gastric residuals,
severity of illness, tolerance of specialized nutrition support abdominal distention, and increase in abdominal girth.
(SNS), comorbid diseases, and degree of malnutrition.
Preterm neonates, infants, critically ill patients, and severely

Monitoring Laboratory Values Oral Feeding

Routine laboratory monitoring may include serum electrolytes, Introduction to oral feeding is critical in all infants receiving
glucose, blood urea nitrogen (BUN), creatinine, calcium, phos- EN. Allowing the infant to take a minimal volume of
phorus, magnesium, albumin, prealbumin, complete blood formula orally may reduce the amount of oral aversion so
count with differential, and iron indices as well as assessment of commonly seen in these children. It is also critical in older
acid-base status. Routine monitoring of laboratory values is not children receiving tube feeding to be allowed to eat and
indicated for medically stable pediatric patients receiving EN drink once safety has been established either via observa-
at advised levels and achieving adequate growth.9 Serum zinc tion or oximetry-swallow study.
may need to be monitored when fat malabsorption is present.
Physical assessment including clinical signs of nutrient excess
or deficiency must be assessed periodically.
Table 36–1 Suggested Parameters to Monitor for Infants and Children Receiving Enteral Nutrition9,10
Outpatient EN-Only Outpatient PN and/
Initial Week During Hospitalization
Patient or EN Patient
Growth Parameters
Weight
NICU Daily Daily Weekly–Monthly Weekly
Infants Daily Daily Weekly–Monthly Weekly
Children Daily Daily–Twice Weekly Weekly to Every Clinic Weekly
Length
NICU Baseline Weekly Monthly or at Clinic Monthly or at Clinic
Infants Baseline Monthly
Children Baseline Monthly
Height Baseline Monthly
(> 36 mo)
Head circumference Baseline Weekly–Monthly Monthly or at clinic Monthly or at clinic
(< 36 mo)
Weight gain Daily–Weekly Daily–Weekly Weekly–Monthly Weekly
Linear growth Monthly Monthly Monthly Monthly
Intake Parameters
Intake Daily Weekly Monthly Weekly
Calories
Protein
Vitamins
Minerals
Fluid balance
GI Tolerance
Abdominal girth As indicated As indicated As indicated As indicated
Gastric residuals As ordered or reported As ordered or reported As ordered or reported As ordered or reported
Emesis As reported As reported As reported As reported
Stool Daily as reported Daily as reported Report changes in stool Report changes in stool
(volume, frequency, pattern pattern
consistency, color)
Ostomy
(volume, consistency)
Physical
Temperature Per nursing policy Per nursing policy Report when > 101ºF Report when > 101ºF
(38.5ºC) (38.5ºC)
Tube placement Prior to each feeding Prior to each feeding Prior to each feeding Prior to each feeding
Tube site care Daily Daily Daily Daily

Revision of Enteral Plan site needs to be monitored closely (every 3 to 4 hours) for
Revision of the EN care plan will be based on patient’s toler- early signs of infiltration. It is difficult to provide 100% of
ance of the EN regimen and achievement of goals. If goals nutrition goals with a peripheral solution but may be effec-
are not being met, the nutrition care plan must be adjusted tive for a short period of time. If EN cannot be initiated and
according to patient’s tolerance. When the child has grown advanced to goal within 5 to 7 days, serious consideration
and is older the formula type and volume will need to be should be given to placement of a catheter for central venous
adjusted based on the child’s needs, recommended daily access.10
allowance (RDA), and dietary reference intake (DRI). If the Once central access is obtained it is helpful to note the
EN plan is not supporting appropriate growth and making date of insertion, location, type of catheter, and number of
adjustments to the EN plan does not support the nutrition lumens. These initial data will be useful when monitoring for
goals, then supplementation with PN or a transition to all catheter-related complications. Heparin is routinely added
PN may be required. It is important to assess if the patient to neonatal and pediatric PN solutions to maintain patency
has achieved the nutrition goals. EN can be transitioned to of the central venous catheter.16 Lower flow volumes, smaller
oral diet should the child be able to tolerate an oral diet. catheters, and frequent interruptions of PN solutions may
play a roll in increased incidence of catheter clotting than
Parenteral Nutrition in adults.17 Preliminary data suggest that a heparin concen-
If nutrition goals are unattainable by EN then PN will need tration of 0.5 units/mL in neonatal PN solutions may be as
to be considered. As with EN, patient allergy information effective for maintaining catheter patency as 1 unit/mL.18
or any history of infusion-related incidents should be evalu- Prospective data are currently being collected to further
ated prior to the initiation of PN. validate these preliminary results (Elaina Szeszycki,
personal communication).
Evaluate for Infusion-Related Incidents
Patients with an egg allergy may require a test dose of lipid Evaluate Tolerance of Volume
emulsion to better evaluate for any reaction.12 The emulsifier Generally PN volume is based on a patient’s maintenance
in currently marketed long-chain triglyceride lipid emul- volume requirement (refer to Chapter 9). Fluid volume may
sions contains egg phospholipid. Even though reactions to be restricted or increased depending on disease processes
PN components are rare, there are case reports suggesting and clinical condition. There are a number of subjective and
that multivitamins, lipid emulsions, iron dextran, or objective data that can be evaluated to aid in determining if
preservatives may be the causative agent.13,14 If a reaction the volume of PN or total fluid intake is appropriate. Weight,
does occur and PN is suspected, eliminating 1 agent at a intake from all sources, output from all sources, laboratory
time helps to determine the causative ingredient. If PN is results (refer to Table 36-7), vitals, and physical assessment
required for more than a week with no EN then alternate should be evaluated on a daily basis initially when PN is
routes may need to be identified to provide the particular started (Table 36-2). Routine weights and laboratory results
causative agent. Vitamins may be administered orally or can be decreased as the patient stabilizes. If a patient is going
via a feeding tube or topical safflower oil in the case of lipid home on PN or has limited access, total fluid requirement
intolerance. may be incorporated into the PN solution as possible.
Once the patient allergy profile has been reviewed, IV
access needs to be identified. Peripheral parenteral nutrition Evaluate Tolerance of Macronutrients
(PPN) is limited based on osmolarity due to the vesicant Amino acid tolerance can be evaluated by monitoring
properties of PN ingredients. Institutions generally set the BUN level.19 If an elevated BUN cannot be explained
osmolarity limits for neonatal PPN at 900 to 1200 mOsm/L by changes in renal function, medications (eg, high-
and pediatric PPN at 600 to 900 mOsm/L.10 Maximum dose steroids, amphotericin, aminoglycosides, and
dextrose concentration for pediatric and neonatal PPN is diuretics), bleeding, or dehydration then the non-protein
12.5% but ultimately the osmolarity of the solution dictates calorie:nitrogen (NPC:N) ratio needs to be evaluated. The
the amount of nutrients, electrolytes, and minerals that ideal NPC:N ratio in stable patients is 150–250:1.20 The ratio
can be ordered.15 Lower concentrations of dextrose may be may be less in critically ill patients or higher in renal failure
necessary in children with poor peripheral access. Amino patients. Ammonia levels and mental status are monitored
acids, dextrose, calcium, sodium, and potassium are the in liver disease patients. Please refer to Chapter 26.
main determinants of osmolarity. If PPN is utilized, the IV

Table 36-2 Parameters to Evaluate Adequacy of PN Volume cycled 12 to 22 hours per day in an effort to ease daily activi-
Parameter DehYDRATION FLUID OVERLOAD ties and decrease hepatic complications related to PN. 23
Weight Change: Real Rapid ↓ weight Rapid ↑ weight
Initially, blood glucose levels should be obtained during the
versus fluid high rate of cyclic PN infusion and 1 to 2 hours after cycle
completion to evaluate for hyper- and hypoglycemia. Levels
Intake: Intravenous Total intake < total Total intake > total
fluids, PN, output output > 150 mg/dL will require a decrease in dextrose amount or
blood products, lengthening of cyclic infusion to decrease the GIR. Levels
medications, EN < 60 mg/dL or any symptoms of hypoglycemia will require
Output: Urine, Decreased urine Increased urine a longer taper period off of the cyclic PN or adjustment of
gastric, stool, bile, output, dark urine output in patients
chest tube, wound, with normal renal insulin if present in PN solution.24
skin and liver function Triglyceride levels are monitored daily as lipid intake is
Laboratory ↑ Blood urea ↓ sodium, ↓ serum increased and then decreased to weekly once dose is stable
nitrogen, ↑ sodium, osmolality, ↓ urine and levels are adequate. Maximal lipid infusion for adults
↑ serum osmolality, specific gravity
↑ urine specific ↓ albumin or Hgb is 0.125 g/kg/h.25 There is limited information regarding
gravity, ↑ albumin maximal infusion rate for pediatrics but it is well-docu-
or Hgb mented that longer infusion rates, 12 to 24 hours, improve
Vitals ↑ Heart rate, ↑ Respiratory rate tolerance to lipid infusions.26 Decreasing the lipid dose or
↑ losses with fever
infusing lipids every other day or 3 to 5 times a week instead
Medications Addition of diuretic Fluid retention with of daily in long-term PN patients will allow for further clear-
or change in steroids or excessive ance of the lipid and possibly avoid triglyceride levels > 200
frequency sodium intake
Physical Exam Thirst, dry lips, dry Peripheral, facial,
mg/dL. Limiting the dose and therefore decreasing phytos-
mucous membranes, and orbital edema, terol intake may also reduce the cholestasis commonly
dry skin, headache, ↑ abdominal girth, noted in pediatric patients receiving long-term PN. 27 Calcu-
dizziness shortness of breath lating the lipid infusion rate in g/kg/h would be helpful if
hypertriglyceridemia is an issue.
Dextrose is best monitored by venous blood glucose and
capillary glucose. The frequency of venous or capillary Monitoring the Integrity of PN Formulations
glucose monitoring depends on history of glucose intoler- Changes in any of the PN ingredients may affect the stability
ance, presence of diabetes, or concurrent medications or solubility of the formulation and thus warrants constant
affecting blood glucose control. Capillary glucose moni- surveillance during compounding and administration.
toring is useful for frequent monitoring so that the central There are a number of factors that influence solubility
line does not have to be accessed an inordinate amount of of minerals such as calcium and phosphorus, the compat-
times during the day or when verifying an abnormal glucose ibility of PN solutions, and the integrity of total nutrient
level from a venous sample. The frequency of monitoring admixtures (TNA). Factors that influence calcium and
can be modified once the patient has established good blood phosphorus solubility are listed in Table 36-3. The pH of the
glucose control on the goal PN formula. Ordering dextrose amino acid solution drives the pH of the PN solution. The
in PN as final dextrose concentration has been the standard ideal pH for calcium and phosphorus solubility is ~ 5–6.28
for years but there is a push to order dextrose in mg/kg/min Solubility will decrease as the pH becomes more acidic or
or g/kg/d as a glucose infusion rate (GIR). alkaline. Higher concentrations of amino acid allow for
Maximal dextrose infusion varies according to age higher calcium and phosphorus doses to be admixed in
and there is growing information about the maximal GIR a 2-n-1 or 3-n-1 solution. There is a myth that the amount
range for differing age groups.21 This should allow for more of lipid emulsion influences how much calcium and phos-
appropriate dextrose ordering and potentially decrease phorus that can be admixed together in PN solutions but
complications associated with excess carbohydrate intake the concentration of lipid emulsion is not a variable evalu-
(eg, hyperglycemia, elevated liver enzymes, cholestasis, and ated in calcium/phosphorus solubility graphs. Solubility
ultimately fatty liver).22 Unexplained hyperglycemia should graphs in Trissel’s and King®’s reference texts have been a
prompt the calculation of the GIR from the PN solution primary source for determining adequacy of calcium and
and other dextrose-containing solutions. Pediatric patients phosphorus amounts ordered in various PN solutions. 29,30
receiving PN for > 2 weeks on a stable regimen may be Today, some of the order-entry software utilized with the

automated compounding hardware has incorporated the integrity of TNA. 35 Refer to Appendix 36-1 for an example
calcium/phosphorus solubility graphs into alerts. The of institutional-derived dosing and stability limits.
order entry pharmacist is alerted when the solubility graphs
are exceeded. This feature eliminates manual plotting of Table 36-4 Factors Affecting Total Nutrient Admixture Stability
concentration points but still requires critical evaluation of Final pH (5–6) Optimal pH for stability
all graphs to determine if each individual solution is appro- Divalent cation concentration Maximum concentration limits
priate for compounding. (calcium, magnesium, zinc) required
Trivalent cations (iron dextran) Not stable in TNA
Type of amino acid & Higher concentrations improve
Table 36-3 Factors Affecting Calcium and Phosphorus Solubility
concentration stability
Temperature Dextrose concentration Lower concentrations will limit
Concentrations of calcium and phosphorus stability
Type of amino acid product and concentration Anionic emulsifier Protects emulsion integrity
Dextrose concentration Multivitamin products Protects emulsion integrity
pH of final solution Temperature Avoid administration in warm areas
Cysteine Order of mixing Critical to avoid precipitation &
Lighting instability
Order of mixing Product packaging Lipids in plastic – ? affect on
stability
Calcium and phosphorus amounts are limited in PPN
solutions when low amino acid concentrations are ordered
(initial PN solutions, renal insufficiency or disease, and Comparison of 3-n-1 and 2-n-1 Formulations
dilute solutions). Once amino acid concentrations can PN is a general term referring to IV PN whereas 2-n-1 refers
be safely advanced, calcium and phosphorus solubility to PN compounded with amino acids and dextrose. TNA or
should improve and these mineral doses can be increased. 3-n-1 refers to PN solutions compounded with amino acids,
Increasing concentrations of dextrose affects the solubility dextrose, and lipids. The opaque nature of a TNA or 3-n-1 is
curve positively as well.29 Some institutions set maximum considered a disadvantage due to the inability to see obvious
concentrations allowed for calcium and phosphorus in addi- precipitates. Calcium and phosphorus intakes are felt to be
tion to evaluating the solubility curves to avoid excessive less with TNA but again lipid is not a limiting factor in the
dosing and avoid infiltrations with PPN (Appendix 36-1). solubility of these two minerals. Divalent cations such as
Practitioners were reminded in a tragic fashion how calcium, magnesium, and zinc may be somewhat limited
important order of mixing is when compounding PN in TNA due to the anionic nature of the lipid emulsions. 33
solutions. At least 2 deaths have been associated with calcium- It may be difficult to provide higher doses of these divalent
phosphorus precipitation in PN solutions. 31 Temperature cations in low-volume solutions or for patients receiving
and lighting also play a role and need to be investigated when magnesium-wasting medications.
precipitation occurs, PN solutions look abnormal or become As with calcium and phosphorus solubility, higher
discolored, PN filters occlude, and when the solution other- concentrations of amino acid and dextrose provide a
wise meets all solubility and stability limits. Neonatal PN protective effect on the emulsion. The amino acids form a
solutions are particularly at risk for stability issues due to bili- protective layer around the lipid globules while the hyper-
rubin lights, heat from the extensive amount of equipment tonicity of the dextrose prohibits excessive movement and
utilized in these units, and frequent co-infusion of medica- possible coalescence of globules. 36 The most problematic
tions with limited intravenous access. TNAs are the initial neonatal formulations for extremely
TNAs are complex solutions that require additional low birth weight (ELBW) infants with low dextrose and
scrutiny and compounding limits due to their opaque nature. lipid concentrations. Centers that compound TNAs or
Factors involved for ensuring the integrity of the emulsion 3-n-1 formulations must invest in automated compounding
are listed in Table 36-4. Minimum concentrations of the systems that interface with advanced order-entry software
macronutrients should be determined, especially for TNA, containing multiple manufacturer and institutional limits.
to maintain the integrity of the emulsion. 32,33 A minimum These dosing and stability limits will aid in identifying solu-
amount of IV lipid is required to provide adequate emul- tions potentially unsafe for patient administration.
sifier for a TNA. 34 It is yet to be determined how product Although TNAs require rigorous review, they do
packaging of current lipid formulations will affect the allow for all nutrients to be in one bag and therefore only

one infusion pump. Nursing time is less compared to lipids surgical history, feeding tolerance, or any sign/symptoms of
administered separately in syringes every 12 hours and nutrient deficiencies. Transitioning from EN via a feeding
co-infused with a 2-n-1 solution. Some institutions infuse tube to oral nutrition requires periodic monitoring of weight,
lipids in syringes over 24 hours but the latest Centers for length or height, and skinfold thickness to determine how
Disease Control and Prevention (CDC) recommendation quickly the transition can occur and its success. A key point
states IV lipids should not be infused longer than 12 hours for monitoring is follow-up once a plan is in place.
to avoid microbial growth. 37 There is a concern for increase
in lipid peroxidation once lipids are transferred from their Reassessment of the Plan
original container. 38 Clinical consequence is not known at Patients receiving SNS require periodic reassessment of their
this time and it is not clear whether peroxidation occurs at progress and goals. Pediatric patients differ from adults in
a quicker rate in TNA or lipids administered via syringe. that growth and development is a dynamic process and these
Another advantage of TNA is 24-hour infusion of lipid 2 elements should be taken into account when assessing the
and decreased risk of microbial growth compared to lipid patient. Weight, fluid, calorie, protein, vitamin, and mineral
alone. 37 Table 36-5 outlines the advantages and disadvan- goals all need to be adjusted as the patient grows, with
tages of 3-n-1 or TNA over 2-n-1 solutions. Each institution subsequent adjustment in his or her SNS regimen. Ideally
needs to determine which mode of PN ordering works best these restated goals and therapy recommendations should
for its patient populations. be communicated to all physicians involved in the patient’s
care so that evaluation of changes can be monitored. If the
Table 36-5 Advantages and Disadvantages of Total Nutrient Admixtures current nutrition regimen is not successful, an alterna-
Advantages Disadvantages tive plan needs to be developed, initiated, and monitored.
Allows for 24-hour lipid infusion Prohibits visual inspection Assessment, recommendation of a plan, activation of the
Decrease labor costs Limited compatibility information plan, and evaluation of the plan is a continuous cycle that
Decreased equipment and Minimum macronutrient amount needs to be followed by practitioners involved with patients
supply cost required for stability requiring SNS.
Decreases microbial growth
opportunity
Figure 36-1
Combination Enteral and Parenteral Nutrition

Once EN is initiated along with current PN, the amount of
monitoring and evaluation of specialized nutrition support
(SNS) increases during this transition phase. The plan is to
advance EN to goal as soon as possible while scaling back on
PN but still maintaining adequate nutrition intake. Moni-
toring of weight, enteral tolerance, linear growth, skinfold
thickness, protein stores, electrolytes, minerals, and other
laboratory values will aid in determining if the EN regimen
is appropriate. This can occur through once or twice weekly
lab draws and communication with parents or caregivers.
This is in addition to monthly clinic visits. Frequent commu-
nication regarding the patient’s progress with the medical
team will allow for quicker advancement of enteral feedings
per patient tolerance. When adequate nutrient intake can
be achieved enterally and/or orally and appropriate growth
demonstrated, then PN can be discontinued and vascular
access removed. EN can be gradually decreased as oral
intake improves. When the patient is stable on a goal EN Evaluate Drug and Nutrient Interactions
regimen and PN is discontinued, the frequency of moni- The process of evaluating for drug-nutrient interactions
toring can be decreased. Laboratory monitoring is required begins with the patient medication profile and nutri-
periodically depending on other pertinent medical history, tion regimen. There are a number of excellent published

resources and pharmacy computer databases that can be and compatible medications that can be safely added to
utilized to identify drug-drug and drug-nutrient interac- PN solutions. Certain medications may be co-infused
tions. 39,40 Pharmacy order entry systems can provide alerts with PN or TNA if no other access is available. There are
for particular medications (eg, fluoroquinolones and a number of published compatibility charts but it is still a
phenytoin) when patients are receiving enteral feedings. good practice to compare your own institution’s PN solu-
Once an interaction is identified, the severity along with tions against published charts and studies.43,44 A range of
the source of the interaction needs to be evaluated closely PN solutions and TNA have been tested but there is no
to determine a course of action. A number of interactions way to test each individual solution for stability that may
may be avoided by administering the drug and the partic- be prescribed in clinical practice.
ular nutrient, vitamin, or mineral at separate times during
the day. If enteral formula ingredients interfere with drug Guidelines for Monitoring Nutrition Laboratory Values
absorption, consultation with a pharmacist and dietitian in Children Receiving Enteral and Parenteral Nutrition
can aid in developing a revised enteral regimen for the The goals for monitoring patients receiving SNS are to
patient that will allow for improved drug absorption. ensure the efficacy of the regimen and to identify and
Particular medications may induce certain electro- prevent potential complications. It is important that the
lyte and mineral wasting or retention. Oral, enteral, or nutrition support team (physician, nurse, pharmacist, and
parenteral electrolyte and mineral supplementation may dietitian) establish goals for the patient prior to initiating
be required while a patient is receiving these offending SNS. The monitoring of patients requiring EN and/or PN
agents. PN is not meant to be a vehicle for acute electrolyte must include both clinical data and laboratory testing.
and mineral replacement but can aid in supplementing Sample patient data sheets are included (Appendices 36-2
patients with chronic electrolyte and mineral abnormali- and 36-3). Appendix 36-2 may be utilized for patients
ties. Electrolyte and mineral supplementation should not started on PN or a combination of PN/EN. Appendix
be added directly to enteral formulas due to the potential 36-3 can be utilized in addition to Appendix 36-2 for those
for instability but should be diluted and given orally or patients receiving PN for greater than 3 months. Every
flushed via a feeding tube. Table 36-6 lists some common patient must have documented baseline data in order for
drug-induced metabolic disorders.41,42 Patients on these appropriate evaluation and monitoring to take place.
particular medications require at least weekly laboratory It is important to note that it is impossible to create a
monitoring. Frequency of monitoring is dependent on “one size fits all” set of monitoring guidelines. Each patient’s
renal and hepatic function as well. monitoring regimen must be created based on the specific
disease state and individualized long-term goals. New
Table 36-6 Drug-Induced Metabolic Disorders patients will require the most frequent monitoring, while
Loop Diuretics hyponatremia, hypokalemia, hypocalcemia, stable long-term SNS patients may require less intense
metabolic alkalosis monitoring. EN-only patients will require less laboratory
H2 antagonists hyponatremia monitoring while those on PN will require regular labora-
Corticosteroids hypokalemia, hypocalcemia, tory testing. The following information should be used as
hypophosphatemia, metabolic alkalosis
Amphotericin B hypokalemia, hypomagnesemia, metabolic
a general guideline and can be customized to the specific
acidosis patient needs. Please refer to disease-specific chapters in
Cyclosporine, Tacrolimus hypomagnesemia, hyperkalemia, this book for additional monitoring that may be required.
hypertriglyceridemia Tables 36-7 and 36-8, which appear at the end of this
Aminoglycosides metabolic acidosis chapter, are examples of suggested monitoring for short-
Citrate hypocalcemia and long-term laboratory testing.
Compatibility of Medications Physical Data

In addition to calcium and phosphorus solubility, stability There are a number of objective physical pieces of data
of the PN solution needs to be evaluated at order entry. that can be collected to aid in evaluating adequacy and
Critical review of available PN stability literature, paren- tolerance to SNS. Developing standards of practice, order
teral product manufacturer studies, and in-house stability sets, policies, and procedures in all institutions caring for
studies are what nutrition support practitioners rely on to patients requiring SNS can assist those individuals respon-
determine maximum concentrations for micronutrients sible for monitoring these complex patients. Table 36-1

delineates some general guidelines but individual patient patient receiving PN for > 7 days. 56 Although most EN
needs and clinical situation should dictate specific moni- formulas contain adequate dietary carnitine, supplementa-
toring parameters and the frequency. tion can be considered in EN patients with malabsorption
or bowel resection if deficiency is suspected or confirmed
Chemistry Profile Monitoring45–50 by laboratory testing. A carnitine profile, including ester/
The monitoring of electrolytes, minerals, renal function, free ratio, should be monitored every 3 to 6 months if the
glucose, and acid-base balance is essential in PN. When patient is being supplemented. A yearly carnitine profile is
initiating a patient on PN, a baseline basic metabolic panel sufficient for patients not receiving supplementation.
(BMP), magnesium, phosphorous, and triglyceride level There are 2 fatty acids in humans that must be sup-
should be ordered and monitored daily until the patient plied via the diet primarily from plants. They are linoleic
has reached the calorie goal established at initial assess- and α-linolenic acid and are known as essential fatty acids
ment. The frequency may be decreased to twice weekly (EFAs). Patients receiving EN and PN must be adequately
in which one day includes the comprehensive metabolic supplemented with both EFAs because their oral intake
panel (CMP), which encompasses the hepatic function may be minimal. If inadequate amounts are provided, an es-
along with the BMP. As the patient stabilizes, labs may be sential fatty acid deficiency (EFAD) may eventually occur.
decreased to weekly. Finally, these labs may be reduced to If lipid-free PN is provided for a significant amount of time
every 2 to 4 weeks when the PN formula is stable and if or there is clinical manifestation of an EFAD, it is possi-
appropriate goals are being met for the current condition ble to order an EFA profile. The resulting triene:tetraene
and growth needs. ratio can determine if an EFAD exists. 26,60–62
Nutrition-Related Laboratory Tests Liver Function Tests and Bilirubin

(see also Chapters 4 and 5) Liver complications are a well-documented adverse
Prealbumin is commonly used to monitor protein status effect of PN in children. 63–66 It is necessary to monitor
due to its shorter half-life of 2 to 3 days in comparison liver function enzymes, which generally include alkaline
to albumin. 51 However; there are other factors that can phosphatase, aspartate aminotransferase, and alanine
influence prealbumin levels such as inflammatory states, aminotransferase, on a weekly basis when initiating PN.
end-stage liver disease, untreated thyroid disease, renal A total bilirubin should also be followed. If prolonged PN
disease, and zinc deficiency. These limitations should is anticipated or the patient becomes jaundiced, a direct
be considered when interpreting a patient’s prealbumin or conjugated bilirubin level is helpful to monitor for
level. 52–54 Monitoring of prealbumin levels can be helpful cholestasis. 24 A direct bilirubin > 2 mg/dL may prompt
especially for long-term stable patients. Prealbumin can earlier monitoring of the trace elements, copper, and
be monitored on a weekly basis initially and then monthly manganese. 67 The liver function enzymes and total bili-
in stable patients. rubin are included when ordering the CMP as previously
Changes in triglyceride levels can be influenced by a discussed. Once stabilized these laboratory tests can be
variety of factors including disease state, organ function, monitored every 2 to 4 weeks.
medications, nutrition status, and current nutrient intake. Gamma glutamyl transpeptidase (GGTP) is another
They should be monitored daily when SNS is initially liver enzyme that is more specific for liver and biliary tract
started, followed by a weekly level, and then increased to problems. 24 GGTP is the most sensitive liver enzyme for
monthly.19,26,45,55 detecting biliary obstruction, cholangitis, or cholecys-
Carnitine is often supplemented in the formula of PN titis. 51 It can be ordered for further diagnosis when the
patients, particularly neonates and infants due to their traditional liver enzymes are elevated or as a regularly
inability to synthesize an adequate amount. In addition, monitored monthly test if the patient is at risk for biliary
premature neonates will also have limited carnitine stores problems.
that are needed for long-chain fatty acid transport. 56 A The prothrombin time (PT) and international normal-
deficient patient may present with increased triglyceride ized ratio (INR) can be utilized in long-term monitoring
levels, hyperbilirubinemia, or decreased weight gain along of PN. The PT can be elevated in a patient who is devel-
with a multitude of other clinical symptoms. 57–59 Currently oping hepatocellular disease or obstructive biliary disease
a carnitine dose of 10 to 20 mg/kg/d is recommended for or more rarely a vitamin K deficiency. 24,68,69 A baseline and
IV or oral supplementation and should be initiated in any then monthly check of the PT/INR is adequate.

Trace Elements Iodine is an element not supplied by standard multi-

(see also Chapter 6) trace products in PN. Therefore it is possible, although
When a patient is receiving PN for several months, it is unlikely, for a SNS patient to become deficient.77,78 This
important to assess the status of trace elements due to can routinely be assessed with a yearly thyroid stimulating
the standardized way in which they are initially ordered hormone (TSH), triiodothyronine (T3) test, or urine
in PN patients and the known contamination of commer- iodine concentration.
cial products used to compound PN.70 After 3 consecutive
months on PN (unless clinically indicated earlier),71 a Iron Studies and Anemia
patient should be assessed for zinc, selenium, manga- (see also Chapters 6–8)
nese, copper, and chromium.45 Long-term use of standard When patients are dependent on EN and/or PN, there is
multi-trace products can result in both excessive and always the potential for the patient to become anemic.
deficient concentrations, especially in patients who have The 4 nutrients that are most likely to be the reason for
abnormalities in the GI tract. Although measuring blood an anemia are iron, copper, vitamin B12 , and folic acid.
concentrations of these trace elements is not necessarily Standard PN contains 3 of the previous nutrients with
the most accurate due to the body’s ability to store these the exception being iron. Enterally fed patients typically
elements, it is generally the easiest and least costly way to are provided with all 4 nutrients. However, the standard
monitor.72 It is also important to note that these elements quantities provided may not always be adequate for the
should not be checked during times of acute inflammatory specific disease process that is being treated. For example,
type conditions due to the body’s sequestration of some a patient who has shortened bowel will generally have less
elements during this time. Levels may be falsely decreased absorption of the nutrients from EN and may become defi-
in these types of situations.73 cient over time.
Assessment of these elements should occur every 3 Iron deficiency can be recognized by abnormalities
to 12 months while receiving PN.45,72 If a patient is found in the complete blood count (CBC). In general there is
to have an elevated level of any standard element, the a decrease in hemoglobin and mean corpuscular volume
multi-trace element of the PN can be omitted and sepa- (MCV).45 It may take some time for the deficiency to
rate elements may be added. Additionally, if any element occur so a routine CBC (at least monthly) is recom-
is found to be deficient, it can be added in addition to the mended to monitor for these changes.46,47,50 When these
standard multi-trace. There are limits to concentrations of abnormalities are present an iron panel can be ordered if
trace elements in PN so this must be considered, and in that indicated to confirm the deficiency. An iron panel should
situation, oral supplementation may be an option. After include serum iron, ferritin, transferrin saturation, and
altering the dosage of any element it should be rechecked iron-binding capacity. In a deficient patient, the iron and
in approximately 1 to 3 months. If a patient’s condition ferritin may be reduced and the binding capacity elevated.
has completely stabilized, it is reasonable to monitor only After confirming the deficiency, the iron may be supple-
once per year. mented orally. If the patient does not respond to oral iron,
Aluminum, considered an ultratrace element, is a parenteral iron may be used as a separate infusion or added
known contaminant of PN products. It is important to to the PN. The only parenteral iron that may be used in
monitor due to the patient’s continued exposure and risk PN is iron dextran, and it can only be used in the absence
for toxicity. It is reasonable to check an aluminum level of lipids in the formulation for stability reasons.44 Moni-
each year during PN therapy. If the aluminum is elevated, toring of iron status should occur every 3 to 6 months in a
the PN pharmacist can look at the current PN compo- deficient patient or a patient receiving supplementation.
nents and make adjustments if possible since aluminum Copper deficiency can also present with anemia and
contamination varies even between different PN product neutropenia.79,80 This can result from decreased absorp-
manufacturers.74 tion or increased losses from the intestinal tract. Copper
Molybdenum deficiency is rare but can occur in a PN deficiency can also occur due to high zinc, vitamin C,
patient, especially those with decreased intestinal absorp- or iron supplementation or from the use of gastric acid
tion.75,76 If desired, a molybdenum level may be checked suppressing medications. 81 Iatrogenic copper deficiency
yearly unless otherwise clinically indicated. If a deficiency may occur with inadequate amounts in PN due to concern
is detected, molybdenum may be supplemented via PN in for accumulation in patients with cholestasis. Measuring
the form of ammonium molybdate. serum copper or serum cerulosplasmin levels can assess

the patient’s copper status.72 This can be performed with pain or non-traumatic fracture, the following laboratory
the other multi-trace elements as previously discussed. tests may indicate MBD: low to normal PTH, elevated
Both vitamin B12 and folic acid deficiencies can alkaline phosphatase, altered vitamin D levels, changes in
present as a macrocytic anemia with an elevated MCV. serum calcium levels, and hypercalciuria. 50,84,85 Therefore,
Because these 2 nutrients have an intertwined relation- monitoring a yearly PTH along with vitamin D may be
ship in the body, it is recommended to assess the status indicated in long-term PN patients.
of both whenever either is measured. Patients without an
ileal cecal valve are particularly at risk for development of Infectious Complications
vitamin B12 deficiency since this is a site for absorption. Catheter-related bloodstream infections (CRBSIs) are a
It is possible for the body to maintain serum vitamin B12 well-known complication of vascular access devices. By
levels even though storages have been depleted. Therefore, monitoring for fever and changes in the CBC, potential
it can also be beneficial to check methylmalonic acid and infections can be identified and treated promptly.45 The
homocysteine levels when vitamin B12 deficiency is truly most recent CDC guidelines for catheter maintenance were
suspected. These 2 tests will be elevated in most patients published in 2002.86 The replacement of the infected cath-
even with a minimal vitamin B12 deficiency. 82 However, eter is recommended in most CRBSIs. However, continual
homocysteine levels may also be elevated in the presence replacement of the catheter can lead to the loss of venous
of folic acid and vitamin B6 deficiency, therefore it is not access sites. This can be problematic for many PN patients
a specific indicator of vitamin B12 deficiency. 83 A yearly due to their long-term need for a vascular access device.
measure of these vitamins is normally sufficient unless One strategy used to prevent CRBSIs has been the use of
deficiency is suspected71 or in evaluating after increased agents to sterilize the catheter lumen. The first of these was
supplementation. antibiotic lock therapy (ALT), which has been studied since
the late 1980s.87 This method involves using concentrated
Vitamins antibiotic solutions and dwelling the solution in the cath-
(see also Chapters 7 and 8) eter lumen for a period of time. Problems associated with
Fat-soluble vitamins A, D, E, and K are standard compo- ALT are the development of antibiotic resistance with
nents of most parenteral multivitamin products and EN long-term use, lack of documented stability, and expense. 88
products. It is possible for a patient to accumulate exces- A newer agent that has been shown to reduce CRBSI is
sive amounts due to the body’s storage of these vitamins, ethanol. Opilla MT et al specifically studied the use of
but it is also possible for deficiency to occur with certain ethanol for the home PN patient and showed a statistically
disease states. Monitoring the levels of vitamins A, D, and significant reduction in CRBSIs and catheter exchanges. 89
E once yearly is recommended unless otherwise clinically The use of an ethanol lock has been shown to be safe for
indicated.45 Vitamin K status is more commonly assessed the pediatric patient.90–92 Currently, there is not a standard-
by the PT as previously discussed. ized dose, concentration, frequency, or dwell time for the
The water-soluble vitamins including B1, B2 , B6, B12 , use of ethanol lock. Factors that must be considered when
niacin, folic acid, pantothenic acid, biotin, and vitamin choosing to utilize an ethanol lock include catheter mate-
C are also components of parenteral multivitamins and rial, catheter age, and compliance.93
EN. Routine monitoring of these vitamins is not indicated Bacterial overgrowth can be a complication of patients
(except for B12 and folic acid as previously discussed) with intestinal failure receiving PN and requires treatment
unless there is a clinical reason to believe that there is a when identified. Abdominal discomfort, bloating, cramps,
deficiency or toxicity.71 gas, changes in stool color, consistency, and odor are
common signs and symptoms. When the preceding signs
Metabolic Bone Disease and symptoms are identified, the patient should be treated.
Metabolic bone disease (MBD) is a complication that may If a fever is also present, the patient should be evaluated for
result from long-term PN. It may present as osteomal- bacteremia due to possible translocation from the GI.45 (See
acia, osteopenia, or osteoporosis. Several factors may Chapter 27.)
increase the incidence of MBD. Those include medica-
tions, calcium, and vitamin D malabsorption, metabolic
acidosis, high aluminum concentrations in PN, and other
nutrient deficiencies. In addition to the presence of bone

Table 36-7 Table 36-8

Parameter Initial Follow–up Parameter Initial Follow–up
BMP Daily Included in CMP Iron Studies 3 mo Every 3–6 mo
CMP Weekly Every 1 to 4 weeks Zinc 3 mo Every 3–6 mo
Magnesium Daily to Weekly Every 1 to 4 weeks Selenium 3 mo Every 3–6 mo
Phosphorous Daily to Weekly Every 1 to 4 weeks Manganese 3 mo Every 3–6 mo
Prealbumin Weekly Monthly Copper 3 mo Every 3–6 mo
Triglycerides Daily to Weekly Monthly Chromium 3 mo Every 3–6 mo
PT/INR Weekly Monthly Vitamins A, D, and E 6 mo Every 12 mo
CBC differential/ Weekly Every 1 to 4 weeks Vitamin B12 and Folate 6 mo Every 12 mo
platelets Carnitine 3 mo Every 3–12 mo
GGT Baseline if indicated Monthly TSH Baseline if indicated Every 12 mo
Appendix 36-1 PN Limits

Adult Pediatric NICU Stability Usual Dose Comments
180 180 180 mEq/L
Na Osmolarity
0–6 0–6 mEq/kg X
150 150 150 mEq/L X
K
0–6 0–5 mEq/kg X
30 30 30 mEq/L X
Ca
0–2 0–4.5 mEq/kg X
35 30 30 mmol/L X
PO4
0–2 0–2 mmol/kg X
24 24 13 mEq/L X
Mg
0–0.5 0–1 mEq/kg X
300 250 250 mEq/L
Cl
0–8 0–10 mEq/kg X
300 250 250 mEq/L
Ac
0–8 0–10 mEq/kg X
10 5 5 mg/L X Total zinc
Zn
300 400 Mcg/kg X or DC fat
Cysteine 120 mg/kg X
Vitamin K 10 10 n/a ***mg*** X mg/day
n/a 100 100 mg/L X
Ranitidine
0–6 2 mg/kg X
40 n/a n/a mg/L X
Famotidine
mg/kg
2.5 2.5 ***mg*** Not mg/L
Folic Acid
10 10 mg/d X
Heparin 1000 1000 1000 units/L X
Vitamin C 500 700 700 mg/d X Total dose
Carnitine 50 50 50 mg/kg/d X X
Need 20 g/L if
Min 10 g/L or Min 10 g/L or Dextrose
Amino Acid Min 20 g/L X
DC Lipids DC Lipids < 10% or DC
Lipids
DC Lipids if
Dextrose Min 50 g/L Min 50 g/L Min 50 g/L X
< 50 g/L
DC Lipids if
Lipid Min 5 g/L Min 5 g/L Min 5 g/L X
< 5 g/L

Appendix 36-2 Neonatal and Pediatric PN Monitoring Form

Name: MRN: Admit Date: MD:
DOB: Age:___y____m____d DX: Date:
wt_____ :____%ile WA_______
Goals: Calories (kcal/d):_ ___________________ kcal/kg: ________________________________
ht/lt_ __ :____%ile HA________
Protein (g/d):_______________________ g/kg: __________________________________
wt/ht________%ile BMI_______
Fluid (mL/d):_ ______________________ mL/kg:_ ________________________________
dry wt__________ IBW_______
LABS
Date
Weight (kg)
Sodium / Potassium / / / / / / / /
Chloride / Carbon Dioxide / / / / / / / /
BUN / Creatine / / / / / / / /
Glucose / Calcium / / / / / / / /
Phosphorous / Magnesium / / / / / / / /
Total/conj. Bilirubin / / / / / / / /
Cholesterol / Triglyceride / / / / / / / /
AST / ALT / / / / / / / /
AlkPhos / GGT / / / / / / / /
Hgb / Hct / / / / / / / /
WBC / platelets / / / / / / / /
INR
Zinc
Albumin / Prealbumin / / / / / / / /
TPN SCRIPT
AA/Dex/lipid / / / / / / / / / / / / / / / /
Na (mEq/kg)
K (mEq/kg)
Cl (mEq/kg)
Anions (A,C)
Ca (mEq/kg)
P (mmol/kg)
Mg (mEq/kg)
Heparin
MVI:Peds/Adult
TMS:Peds/Adult
Zinc (mcg/kg)
Copper (mcg/kg)
Manganese (mcg/kg)
Chromium (mcg/kg)
Selenium (mcg/kg)
Carnitine (mg/kg)
Rate/Cycle
Total Volume/day
Total Calories/day
kcal/kg
GIR
NPC:N
Wt used for script
kcal/mL
ENTERAL
Formula
Rate/Cycle / / / / / / / /
Route
TOTALS
mL PN/EN / / / / / / / /
kcal / kcal/kg
% PN/EN
Protein (g)
Protein (g/kg)
OUTPUT
UOP mL/kg/h / / / / / / / /
Emesis
Stool
Ostomy mL/d / mL/kg / / / / / / / /
Total mL
Appendix 36-3 Long-Term PN Lab Tracking Sheet

Patient: D.O.B. Physician: Diagnosis:
Medical Record Number: Fax: Phone: Home Health Care:
TPN start date: Pager: Lab Location / Phone:
Enteral Formula: Other Contact: Family Contact:
Lab Location:
Date:
Every Month
Pre-Albumin
Triglyceride
GGT
MCV
Every 3 Months
Selenium
Manganese
Copper
Chromium
Zinc
Ferritin
Iron Serum
TIBC
Transferrin Saturation
Carnitine Total
Carnitine Free
Carnitine Ratio
Every 12 Months
Vitamin A
Vitamin D
Vitamin E
Vitamin B12
RBC Folate
TSH
Free T4
Aluminum
Recorded By:
Reviewed By:
Date Faxed to Physician:

Test Your Knowledge Questions 11. Wessel JJ, Kocoshis SA. Nutritional management of
infants with short bowel syndrome. Semin Perinatol.
1. Meeting a weight goal is the primary goal for SNS patients. 2007;31:104–111.
A. True 12. Intralipid® 20% A 20% I.V. Fat Emulsion [package insert].
B. False Clayton, NC: Kabi Pharmcia; 1991.
2. Bloating, fullness, and abdominal cramping may be 13. Bullock L, Etchason E, Fitzgerald JF, et al. Case report of an
related to the rate of enteral nutrition infusion. allergic reaction to parenteral nutrition in a pediatric patient. J
Parenter Enteral Nutr. 1990;14:98–100.
A. True
14. Market AD, Lew DB, Schropp KP, et al. Parenteral nutri-
B. False tion-associated anaphylaxis in a 4-year-old child. J Pediatr
3. Examining the GIR from PN may provide insight to Gastroenterol Nutr. 1998; 26(2):229–231.
hyperglycemia of unknown etiology. 15. Seashore JH, Hoffman M. Use and abuse of peripheral
A. True parenteral nutrition in children. Nutr Support Serv. 1983;
B. False 3(10):8–13.
16. Imperial J, Bistrain BR, Bothe A Jr, et al. Limitation of central
4. Final amino acid and dextrose concentrations do not vein thrombosis in total parenteral nutrition by continuous
affect calcium and phosphorus solubility. infusion of low–dose heparin. J Am Coll Nutr. 1983;2:63–73.
A. True 17. Kakzanov V, Monagle P, Chan A. Thromboembolism in infants
B. False and children with gastrointestinal failure receiving long-term
5. Only selenium and zinc levels should be monitored parenteral nutrition. J Parenter Enteral Nutr. 2008;32:88–93.
18. Szeszycki E, Kastner A, Mobley L, Gervasio J. A comparison
periodically in patients receiving PN with cholestasis
of the efficacy of 0.5 units/mL versus 1 unit/mL of heparin
or specifically a direct bilirubin > 2 mg/dL. in neonatal parenteral nutrition. A.S.P.E.N. 2009, Nutrition
A. True Practice Poster Presentation.
B. False 19. Shulman RJ, Phillips S. Parenteral nutrition in infants and
children. J Pediatr Gastroenterol Nutr. 2003;36(5):588–607.
See p. 487 for answers. 20. Wesley JR, Coran AG. Intravenous nutrition for the pediatric
patient. Semin Pediatr Surg. 1992;1:212.
21. Koletzko B, Goulet O, Hunt J, et al. 1. Guidelines on paediatric
References parenteral nutrition of the European Society of Paediatric
1. A.S.P.E.N. Enteral Nutrition Practice Recommendations Gastroenterology, Hepatology and Nutrition (ESPGHAN)
Task Force. Enteral nutrition practice recommendations. J and the European Society for Clinical Nutrition and Metab-
Parenter Enteral Nutr. 2009;33(2):122–167. olism (ESPEN), supported by the European Society of
2. Santanan e Meneses JF, Leite HP, de Carvalho WB, et Paediatric Research (ESPR). J Pediatr Gastroenterol Nutr.
al. Hypophosphatemia in critically ill children: preva- 2005;41:S28–S32.
lence and associated risk factors. Pediatr Crit Care Med. 22. Burke JF, Wolfe RR, Mullany CJ, et al. Glucose requirements
2009;10:234–238. following burn injury. Ann Surg. 1979;190(3):274–285.
3. Dickerson R. Refeeding syndrome in the intensive care unit. 23. Jensen AR, Goldin AB, Koopmeiners JS, et al. The associa-
Hosp Pharm. 2002;37(7):770–775. tion of cyclic parenteral nutrition and decreased incidence of
4. Parrish CR. The refeeding syndrome in 2009: prevention is cholestatic liver disease in patients with gastroschisis. J Pediatr
the key to treatment. J Support Oncol. 2009;7:20–21. Surg. 2009;44(1):183–189.
5. McCray S, Walker S, Parrish CR. Much ado about refeeding. 24. Btaiche IF, Khalidi N. Parenteral nutrition-associated
Practical Gastroenterol. 2005;30(1):26–44. liver complications in children. Pharmacotherapy.
6. Danner E, Joeckel R, Michalak S, et al. Weight velocity in 2002;22:188–211.
infants and children. Nutr Clin Pract. 2009;24:76–79. 25. Mirtallo J, Canada T, Johnson D, et al. Task Force for the
7. Guo S, Roche AF, Fomon SJ, et al. Reference data on gains in Revision of Safe Practices for Parenteral Nutrition. Safe
weight and length during the first two years of life. J Pediatr. practices for parenteral nutrition. J Parenter Enteral Nutr.
1991;119:355–362. 2004;28(6):S39–S70. Erratum 2006; 30:177.
8. A.S.P.E.N. Board of Directors and Task Force on Standards 26. Kerner JA, Poole RL. The use of IV fats in neonates. Nutr Clin
for Specialized Nutrition Support for Hospitalized Pediatric Pract. 2006;21:374–380.
Patients. Standards for specialized nutrition support: hospi- 27. Pianese P, Salvia G, Campanozzi A, et al. Sterol profiling in
talized pediatric patients. Nutr Clin Pract. 2005;20:103–116. red blood cell membranes and plasma of newborns receiving
9. Moyer-Mileur L. Anthropometric and laboratory assessment total parenteral nutrition. J Pediatr Gastroenterol Nutr.
of very low birth weight infants: the most helpful measure- 2008;47(5):645–651.
ments and why. Semin Perinatol. 2007;31:96–103. 28. Clintec Nutrition Company in cooperation with Wagner DR
10. A.S.P.E.N. Board of Directors and the Clinical Guidelines and Atkins J. Total Nutrient Admixtures: Clinical and Practical
Task Force. Guidelines for the use of parenteral and enteral Guidelines. USA: Clintec Nutrition Co; 1992.
nutrition in adult and pediatric patients. J Parenter Enteral
Nutr. 2002;1SA.

29. Trissel LA, ed. Handbook on Injectable Drugs. 11th ed. 47. Vanderhoof J, Young R. Overview of considerations for the
Bethesda, MD: American Society of Health-System Pharma- pediatric patient receiving home parenteral and enteral nutri-
cists®; 2001:195–205. tion. Nutr Clin Pract. 2003;18:221–226.
30. IV Compatibility. King® Guide to Parenteral Admixtures®. 48. Sacks G, Mayhew S, Johnson D. Parenteral nutrition imple-
Lexi-Comp Online. Lexi-Comp, Inc. Hudson, OH. Available mentation and management. In: Merritt R, ed, et al. The
at: http://online.lexi.com/crlonline. Accessed January 2009. A.S.P.E.N. Nutrition Support Practice Manual. 2nd ed. USA:
31. Food and Drug Administration. Safety Alert: Hazards of American Society for Parenteral and Enteral Nutrition;
precipitation associated with parenteral nutrition. Am J Hosp 2005:108–117.
Pharm. 1994;51:1427–1428. 49. American Society for Parenteral and Enteral Nutrition Board
32. Bullock L, Fitzgerald JF, Walter WV. Emulsion stability in of Directors and the Standards for Specialized Nutrition
total nutrient admixtures containing a pediatric amino acid Support Task Force, Kovacevich DS, Frederick A, Kelly D,
formulation. J Parenter Enteral Nutr. 1992;16:64–68. Reid N, Young L. Standards for specialized nutrition support:
33. Driscoll DF, Bhargava HN, Zaim RH, et al. Physicochemical home care patients. Nutr Clin Pract. 2005;20:579–590.
stability of total nutrient admixtures. Am J Health Syst Pharm. 50. Ireton-Jones C, DeLegge MH, Epperson LA, et al. Manage-
1995;52:623–634. ment of the home parenteral nutrition patient. Nutr Clin Pract.
34. Driscoll DF, Giampietro K, Wichelhaus DP, et al. Physico- 2003;18:310–317.
chemical stability assessments of lipid emulsions of varying 51. Pagana KD, Pagana TJ, eds. Mosby’s Diagnostic and Laboratory
oil composition. Clin Nutr. 2001;20:151–157. Test Reference. 8th ed. St Louis, MO: Mosby; 2007:755–756.
35. Driscoll DF, Ling PR, Bistrain BR. Physical stability of 20% 52. Fuhrman MP, Charney P, Mueller CM. Hepatic proteins and
lipid injectable emulsions via simulated syringe infusion: nutrition assessment. J Am Diet Assoc. 2004;104:1258–1264.
effects of glass vs. plastic product packaging. J Parenter Enteral 53. Marshall WJ. Nutritional assessment: its role in the provision
Nutr. 2007;31:148–153. of nutrition support. J Clin Pathol. 2008;61:1083–1088.
36. Warshawsky KY. Intravenous fat emulsions in clinical prac- 54. Johnson AM, Merlini G, Sheldon J, et al. Clinical indica-
tice. Nutr Clin Pract. 1992;7(4):187–196. tions for plasma protein assays: transthyretin (prealbumin)
37. O’Grady NP, Alexander M, Dellinger EP, et al. Guidelines for in inflammation and malnutrition. Clin Chem Lab Med.
the prevention of intravascular catheter-related infections. 2007;45:419–426.
Infect Control Hosp Epidemiol. 2002;23:759–769. 55. Crook MA. Lipid clearance and total parenteral nutrition:
38. Neuzil J, Darlow BA, Inder TE, et al. Oxidation of paren- the importance of monitoring plasma lipids. Nutrition.
teral lipid emulsion by ambient and phototherapy lights: 2000;16:774–775.
potential toxicity of routine parenteral feeding. J Pediatr. 56. Crill CM, Helms RA. The use of carnitine in pediatric nutri-
1995;126:785–790. tion. Nutr Clin Pract. 2007;22:204–213.
39. Nyffeler MS, Frankel E, Hayes E, et al. Drug-nutrient interac- 57. Borum PR. Carnitine in neonatal nutrition. J Child Neurol.
tions. In: Merritt R, DeLegge MH, Holcombe B, et al., eds. 1995;10(suppl):2S25–2S31.
The A.S.P.E.N. Nutrition Support Practice Manual. 2nd ed. 58. Winter SC, Szabo-Aczel S, Curry CJ, et al. Plasma carnitine
USA: American Society for Parenteral and Enteral Nutrition; deficiency: clinical observations in 51 pediatric patients. Am J
2005:118–136. Dis Child. 1987;141:660–665.
40. Drug Interactions. Thomson Micromedex. Greenwood 59. Tao RC, Yoshimura NN. Carnitine metabolism and its
Village, CO. http://thomsonhc.com. Accessed January 2009. application in parenteral nutrition. J Parenter Enteral Nutr.
41. Navaneethan SD, Sankarasubbaiyan SG, Jeevanantham VM. 1980;4:469–486.
Tacrolimus-associated hypomagnesemia in renal transplant 60. Hamilton C, Austin T, Seidner DL. Essential fatty acid defi-
receipients. Transplantation Proc. 2006;38(5):1320–1322. ciency in human adults during parenteral nutrition. Nutr Clin
42. Brown RO. Drug-nutrient interactions. In: Cresci G., ed. Pract. 2006;21:387–394.
Nutrition Support for the Critically Ill Patient: A Guide to Prac- 61. Postuma R, Pease PW, Watts R, et al. Essential fatty acid defi-
tice. Boca Raton, FL: CRC Press; 2005:341–355. ciency in infants receiving parenteral nutrition. J Pediatr Surg.
43. Robinson CA, Lee JE. Y-site compatibility of medications 1978;13:393–398.
with parenteral nutrition. In: Phelps SJ, Hak EB, Crill CM, 62. Panel on Macronutrients, Panel on the Definition of Dietary
eds. Teddy Bear Book: Pediatric Injectable Drugs. 8th ed. Fiber, Subcommittee on Upper Reference Levels of Nutrients,
Bethesda, MD: American Society of Health–System Pharma- Subcommittee on Interpretation and Uses of Dietary Refer-
cists; 2007:459–463. ence Intakes, and the Standing Committee on the Scientific
44. Trissel LA. Compatibility of medications with 3-in-1 parenteral Evaluation of Dietary Reference Intakes. Dietary Reference
nutrient admixtures. J Parenter Enteral Nutr. 1999;23:67–74. Intakes for Energy, Carbohydrate, Fat, Fatty Acids, Cholesterol,
45. Siepler J. Principles and strategies for monitoring home paren- Protein, and Amino Acids. Washington DC: The National
teral nutrition. Nutr Clin Pract. 2007;22:340–350. Academies Press; 2005:422–541.
46. Kovacevish D, Canada T, Lown D. Monitoring home and 63. Postuma R, Trevenen CL. Liver disease in infants receiving
other alternate site nutrition support. In: Gottschlich M, parenteral nutrition. Pediatrics. 1979;63:110–115.
ed., Fuhrman M, ed, et al. The Science and Practice of Nutri- 64. Kelly DA. Liver complications of pediatric parenteral nutri-
tion Support. Dubuque, IA: Kendell/Hunt Publishing Co; tion-epidemilogy. Nutrition. 1998;14:153–157.
2000:731–756.

65. Quigley EM, Marsh MN, Shaffer JL, Markin RS. Hepa- 80. Fuhrman MP, Herrmann V, Masidonski P, et al. Pancytopenia
tobiliary complications of total parenteral nutrition. after removal of copper from total parenteral nutrition. J
Gastroenterology. 1993;104:286–301. Parenter Enteral Nutr. 2000;24:361–366.
66. Payne-James JJ, Silk DB. Hepatobiliary dysfunction associ- 81. Beshgetoor D, Hambidge M. Clinical conditions
ated with total parenteral nutrition. Dig Dis. 1991;9:106–124. altering copper metabolism in humans. Am J Clin Nutr.
67. McMillan NB, Mulroy C, MacKay MW, et al. Correlation of 1998;67:1017–1021S.
cholestasis with serum copper and whole-blood manganese 82. Hoffbrand AV. Chapter 100 Megaloblastic anemias. In: Harri-
levels in pediatric patients. Nutr Clin Pract. 2008;23:161–165. son’s Online. http://www.accessmedicine.com/content.
68. Duerksen DR, Papineau N. The prevalence of coagulation aspx?aID=2893392. Accessed October 21, 2009.
abnormalities in hospitalized patients receiving lipid-based 83. Clark SF. Vitamins and trace elements. In: Gottschlich MM,
parenteral nutrition. J Parenter Enteral Nutr. 2004;28:30–33. DeLegge, MH, Mattox T, Mueller C, Worthington P, eds. The
69. Deitcher SR. Interpretation of the international normalized A.S.P.E.N. Nutrition Support Core Curriculum: A Case–Based
ratio in patients with liver disease. Lancet. 2002;359:47–48. Approach – The Adult Patient. Silver Spring, MD: American
70. Pluhator-Murton MM, Fedorak RN, Audette RJ, et al. Trace Society for Parenteral and Enteral Nutrition; 2007:129–159.
element contamination of total parenteral nutrition. 1. 84. Ferrone M, Geraci M. A review of the relationship between
Contribution of component solutions. J Parenter Enteral Nutr. parenteral nutrition and metabolic bone disease. Nutr Clin
1999;23:222–227. Pract. 2007;22:329–339.
71. Jensen GL, Binkley J. Clinical manifestations of nutrient defi- 85. Klein GL. Metabolic bone disease of total parenteral nutri-
ciency. J Parenter Enteral Nutr. 2002;26:S29–S33. tion. Nutrition. 1998;14:149–152.
72. Fuhrman MP. Micronutrient assessment in long-term 86. Centers for Disease Control and Prevention. Guidelines for
home parenteral nutrition patients. Nutr Clin Pract. the Prevention of Intravascular Catheter-Related Infections.
2006;21:566–575. MMWR Recomm Rep. 2002;51(RR–10):1–29.
73. Prelack K, Sheridan RL. Micronutrient supplementation 87. Messing B, Peitra-Cohen S, Debure A, Bernier J. Antibiotic-
in the critically ill patient: strategies for clinical practice. J lock technique: a new approach to optimal therapy for
Trauma. 2001;51:601–620. catheter-related sepsis in home-parenteral nutrition patients.
74. Poole RL, Hintz SR, Mackenzie NI, et al. Aluminum exposure J Parenter Enteral Nutr. 1988;12:185–189.
from pediatric parenteral nutrition: meeting the new FDA 88. Bestul MB, VandenBussche HL. Antibiotic lock technique:
regulation. J Parenter Enteral Nutr. 2008;32(3):242–246. review of the literature. Pharmacotherapy. 2005;25:211–227.
75. Heimburger DC, McLaren DS, Shils M. Clinical manifesta- 89. Opilla MT, Kirby DF, Edmond MB. Use of ethanol lock
tions of nutrient deficiencies and toxicities: a resume. In: Shils therapy to reduce the incidence of catheter-related blood-
ME, Shike M, Ross AC, Caballero B, Cousins RJ, eds. Modern stream infections in home parenteral nutrition patients. J
Nutrition in Health and Disease. 10th ed. Philadelphia, PA: Parenter Enteral Nutr. 2007;31(4):302–305.
Lippincott Williams & Wilkins; 2006:595–612. 90. Mouw E, Chessman K, Lesher A, Tagge E. Use of an ethanol
76. Nielsen FH. Boron, manganese, molybdenum, and other lock to prevent catheter-related infections in children with
trace elements. In: Bowman BA, Russel RM, eds. Present short bowel syndrome. J Pediatr Surg. 2008;43(6):1025–1029.
Knowledge in Nutrition. 8th ed. Washington, DC: ILSI Press; 91. Onland W, Shin CE, Fustar S, Rushing T, Wong WY.
2001:384–400. Ethanol-lock technique for persistent bacteremia of long–
77. Ibrahim M, Morreale de Escobar GM, Visser TJ, et al. term intravascular devices in pediatric patients. Arch Pediatr
Iodine deficiency associated with parenteral nutrition in Adolesc Med. 2006 Oct;160(10):1049–1053.
extreme preterm infants. Arch Dis Child Fetal Neonatal Ed. 92. Dannenberg C, Bierbach U, Rothe A, Beer J, Korholz D.
2003;88:F56–57. Ethanol-lock technique in the treatment of bloodstream infec-
78. Moukarzel AA, Buchman AL, Salas JS, et al. Iodine supple- tions in pediatric oncology patients with broviac catheter. J
mentation in children receiving long-term parenteral nutrition. Pediatr Hematol Oncol. 2003;Aug;25(8):616–621.
J Pediatr. 1992;121:252–254. 93. Crnich CJ, Halfmann JA, Crone WC, Maki DG. The effects
79. Nagano T, Toyoda T, Tanabe H, et al. Clinical features of of prolonged ethanol exposure on the mechanical properties
hematological disorders caused by copper deficiency during of polyurethane and silicone catheters used for intravascular
long-term enteral nutrition. Intern Med. 2005;44:554–559. access. Infect Control Hosp Epidemiol. 2005;26:708–714.

37
Ethical Issues in the Provision
of Nutrition
Patrick M. Jones, MD, MA and Brian Carter, MD

Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 485 1. Explain 3 models of sharing information with a pedi-
Clinical Care as a Team Approach . . . . . . . . . . . . . . . . . . 486 atric patient.
2. Define “natural” versus “medical” provision of nutrition.
Approaching the Pediatric Patient: What Should
We Let Them Know?. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 486 3. Review the importance of determining goals of treatment.
The Good Shepherds 4. Examine the unique values associated with providing
The Liberators nutrition to children.
The Educators
“Natural” versus “Medical” Provision of Nutrition . . . . . 487 Introduction
Determining the Goals of Nutrition. . . . . . . . . . . . . . . . . . 487 There are ever-expanding clinical applications to ethics in the
Values Ascribed to Feeding. . . . . . . . . . . . . . . . . . . . . . . . 488 practice of the healing arts. The uniqueness of the pediatric
Do we tend to see medical feeding in a patient, who is dynamic in her growth, development, and
different light from other interventions? communication and cognitive capacities, requires special
Why is unique value assigned to feeding? sensitivity on the part of all healthcare professionals. Simi-
Ethical Dimensions of Clinical Nutrition Issues. . . . . . . . 489 larly, decisional processes that early on rely solely on parents/
The Intensive Care Environment: Neonatal and Beyond guardians gradually must change to incorporate the child
Palliative Care and, ultimately, yield to the child as a maturing and autono-
The Special Needs Infant and Toddler
Vegetarian Diets, Fad Diets, and Feeding Disorders
mous young adult. As interdisciplinary team members work
Childhood Obesity together to bring about cure, prolong function, and provide
The Adolescent comfort to children living with acute and chronic health
Summary care conditions, a common approach, language, and under-
Case Studies. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 491 standing of values that are important to patients, families,
A Decision Not to Start Medical Nutrition Support? and health care professionals will serve everybody.
The Withdrawal of Nutrition Support Like other specialty areas, pediatric nutrition comes
with its own set of ethical challenges. Approaching these
challenges requires that the clinician be able to communi-
cate effectively with patients, families, and other caregivers.
This chapter is not intended to make a person competent to
handle any or all situations, but instead it intends to help the
reader become more comfortable when engaging in conver-
sations regarding ethics so that the important voice of the
nutritionist is heard by families and caregivers discussing
these issues.
477
Clinical Care as a Team Approach Approaching the Pediatric Patient:

The practice of medicine, even when dealing with deci- What Should We Let Them Know?
sions that raised fundamental ethical and social questions, Pediatric medicine has at its core a unique figure: the
was historically the domain of an individual physician. ever-changing and developing child. Most of the time, the
Physicians would decide if a critically ill baby had enough medical community’s interaction with children is brief—
potential to continue on the ventilator, whether an organ they get sick, they recover, they blissfully run off to their
should be given to a patient in heart failure, or if the elderly old routines. Occasionally, however, the encounters last
woman’s pneumonia should be treated with antibiotics. much longer and involve illnesses that do not allow a quick
However, events such as abuses in human experimenta- recovery or even a return home. A foundational concern
tion and the formation of a national commission to explore for the caregivers of these patients is that of knowing what
medical ethics in the late 1960s and early 1970s began to information, if any, to give the child regarding an illness.
change the number of persons gathering around the bedside. There are certain children for which this question is rather
During the 1970s and 1980s, institutional review boards straightforward; an example being a child who is unable to
(IRBs) examined research protocols to ensure subject comprehend the world around her (eg, a newborn or a child
protection; orders to limit life-saving interventions began with severe traumatic brain injury). However, an 8-year-
to be documented and justified in the medical chart; and old with leukemia is able to understand some aspects of
ethics committees discussed situations that spurred moral her illness, and may need to participate in conversations
disagreement in the medical staff and/or the family. The regarding her disease and its treatment.
result has been a dramatic shift in how health care interacts To help summarize the best approach to involving the
with the medical patient.1 pediatric patient, it is useful to turn to the work of Robert
Today, health care is not only affected by this history Cassidy in his chapter on truth-telling.2 Cassidy describes
but also the increasing role of the medical specialist. Any or 3 broad communication strategies for communicating with
all of the following caregivers may be found participating in a sick child. His first 2 models are described as the “good
the care of a sick child and her family: bedside nurse, charge shepherd” and the “liberator” models. After discussing the
nurse, respiratory therapist, physician (including various history of these approaches and providing critiques, he
physician subspecialists and trainees), dietitian, physical offers up a compromise, the “educator” model of pediatric
therapist, occupational therapist, speech pathologist, social engagement, which best describes the approach used by
worker, case manager, psychologist, nurse practitioner, most pediatricians today.
physician assistant, chaplain, child life specialist, and music
therapist. The potential for benefit is high, as many profes- The Good Shepherds
sionals focus on specific aspects of that patient’s care, but This model is rooted in the historical model of patient-physi-
an obvious, and frequent, drawback is a lack of true team- cian interaction in which the physician, because of his or her
work. Most of the time, this problem originates from a lack special knowledge concerning health and the human body,
of defined roles mixed with poor communication; the result primarily made all decisions regarding a patient’s treatment,
may be conflicting messages presented to the family. sometimes even choosing not to inform the patient of an
It is important to acknowledge that within the team lies underlying medical condition. With the emphases of patient
people with individual experiences and personal circum- autonomy in the late 1960s and early 1970s, this paternalistic
stances. Cultivating an environment where the team can practice began to disappear, and patients became intimately
openly discuss concerns about patient care is a formidable, involved in choices regarding their medical care.
but extremely valuable undertaking. As a participating However, the autonomy movement was not quick
member of a health care team, it is each person’s responsi- to “trickle down” to the pediatric population, as medical
bility to form this team environment by communicating providers and parents continued to treat children in a
effectively, understanding the underlying issues at hand, similar manner. These adults viewed it as their duty to take
and maintaining a complete picture of the goals and objec- responsibility for all decisions, due to their more advanced
tives of the clinical care of a patient. level of knowledge and maturity. Caregivers feared that
telling the truth to a sick child about her condition would
be harmful, and therefore selfish and irresponsible, so they
adamantly guarded the child from any discussions about
their medical care.

ETHICAL ISSUES IN THE PROVISION OF NUTRITION 479
The Liberators 4. Soliciting an expression of the patient’s willingness to

Cassidy describes the liberators are those who fought to accept the proposed care. 8
counter the arguments of the Good Shepherds, especially A frequent objection to obtaining assent is the fear that the
as researchers in the medical and social sciences made the child may refuse to assent to a needed procedure. However,
following important discoveries: as noted by Cassidy, this potential roadblock for the care
• Withholding illness-related information from children team may be extremely beneficial for the patient. As chil-
tends to increase their anxiety and fear. 3 dren are typically eager to please the important figures in
• Some sick children feel pressure to continue the façade their lives, a refusal to give assent could be an important
of not knowing about their illness in order to protect signal that a misunderstanding or fear needs to be addressed
their parents.4 by the parent or care team prior to the procedure being
• Children are exceptionally observant and adept at performed. The result is improved communication and
discovering the truth, regardless of the intent of parents trust (and potentially an improved outcome).2
or health care providers to shield them from it. 5,6
• Although a mature concept of death was thought to “Natural” versus “Medical” Provision
be unattainable by a child, a majority of children reach of Nutrition
such an understanding by the age of 7 years.7 When discussing ethical issues it is helpful to begin the
While this information argued for children to be given conversation by making sure that the terms and phrases
information about their illness, the liberators erred in being used are understood in the same manner. Therefore,
assuming that the solution was to apply adult standards to prior to looking at individual clinical examples, it is impor-
the pediatric population. The result was a standoff between tant to discuss what is meant by the “natural” provision of
2 approaches that stood at opposing ends of the spectrum: nutrition as opposed to the “medical” provision of nutrition.
either tell children nothing in order to “protect” them from These terms can be used in various manners, but for the
a harsh reality, or tell children everything and potentially purposes of this chapter, the definitions put forth by Nicolas
bombard them with age-inappropriate information. Porta and Joel Frader are helpful as they describe their
typical usage in the clinical and bioethical literature.9 The
The Educators natural provision of nutrition refers to all feedings that do
A compromise is forged by approaching the patient in a not require medical intervention, specifically breast, bottle,
manner that makes use of a skill already rooted within the cup, and other oral feedings. Medical provision of nutrition
practice of pediatrics: the assessment of a child’s develop- refers to nutrition that requires a special physician order (eg,
ment. In this approach, caregivers interact with the pediatric the usage of a nasogastric tube, central intravenous cath-
patient in a manner that is appropriate to her level of devel- eter, or the placement of a gastrostomy feeding tube). As
opment; autonomy is not given fully and freely to the child, they are quick to point out, these classifications into natural
but caregivers act in a manner that will inform and foster and medical do not connote that one is ethically optional
the development of her increasing autonomy. This gradual while the other is not.9 For example, medical nutrition is
approach, especially in children with chronic, yet survivable frequently used in premature infants until they develop the
medical conditions (eg, diabetes) makes the transition to ability to suck and swallow safely; discontinuation of such
adulthood more realistic than the sudden placement of full feedings to a child without another complication (such as a
responsibility upon a patient when she becomes an adult. fatal underlying condition) would be unacceptable.
Used within this model is the concept of obtaining
“assent” from the pediatric patient. The American Academy Determining the Goals of Nutrition
of Pediatrics (AAP) describes assent as having 4 elements: Another useful practice prior to discussing an ethical ques-
1. Helping the patient achieve a developmentally appro- tion, particularly one that focuses on the use or disuse of
priate awareness of the nature of his or her condition a particular medical intervention, is to define the goals of
2. Telling the patient what he or she can expect with tests the act in question. For instance, when a child is placed on a
and treatment(s) ventilator, certain goals are set for the usage of that interven-
3. Making a clinical assessment of the patient’s under- tion (although this process is rarely formalized). Often the
standing of the situation and the factors influencing goal is the provision of oxygen and the removal of carbon
how he or she is responding (including whether there is dioxide until appropriate lung healing, or maturation, can
appropriate pressure to accept testing or therapy) take place. Once that goal is no longer served because the

lungs have developed enough to sustain life, the ventilator Values Ascribed to Feeding
is discontinued. On a similar, yet more tragic vein, if the
infant is found to have a genetic condition that will prevent Do we tend to see medical feeding in a different light
the lungs from ever healing or maturing to the point that from other interventions?
the ventilator is unnecessary, it can be said that the inter- Although identifying the goals of medically provided nutri-
vention (assisted ventilation) is not serving the initial goal. tion is critical, to limit the discussion to this process alone
The physiological purpose of the ventilator, to provide fails to address the complete picture. Outside of the intended
oxygen and remove carbon dioxide, is still being met, but goals, the provision of nutrition to a pediatric patient often
the overarching goal of using the ventilator to support the has values assigned to it that make this intervention unique
infant until lung healing or maturation is achieved is no from other life-sustaining interventions. An example of this
longer applicable. While the ventilator may be continued, assignment of value can be seen in the description of with-
it is now with a completely different set of goals in mind. holding nutrition as “starving the patient to death.” This is a
This may be to sustain life at all costs; however this long- phase rather unique to discussions on nutrition; rarely is the
term management goal is often fraught with complications. removal of a ventilator described as “suffocating the patient
The new goal might be to briefly continue physiological to death” or the decision to forgo dialysis as “drowning the
support until the family has adjusted to the terminal nature patient to death.” The tendency to use this language shows
of the child’s condition. This could include waiting for other that a certain value is being placed upon the provision of
family members to come together, perhaps from a distance, medical feeding.10
to provide emotional support and assist with funeral plans. Another example of this perspective of value assigned
Regardless of the decision made, it should be recognized to feeding and nutrition is seen in a pair of surveys done
that the underlying goal has changed, and it is no longer to with pediatric health care providers. The Pediatric Section
support until a cure. of the Society for Critical Care Medicine found that 98% of
Thus, when discussing nutrition in light of ethical physicians were apt to withhold cardiopulmonary resuscita-
dilemmas posed by individual cases, it is important to tion (CPR), 86% withdrew ventilators, but only 42% would
consider the underlying goal of providing nutrition. In its withdrawal tube feedings.11 Likewise, a survey of pediatric
very basic form, the goal of providing pediatric patients with residents in their third year of training demonstrated that
nutrition (natural or medical) is to provide them with the 100% would withhold CPR and vasoactive medicines, 97%
substrate, vitamins, and minerals needed to meet basic meta- would withdraw ventilator support, but only 45% would
bolic demands for appropriate growth and development. Of withdrawal fluids and nutrition.12 Again, it appears that
course, there are many other goals for nutrition in addition there are underlying values assigned to providing a child
to this rather basic purpose. For example, in the patient with with nutrition that reach beyond the set medical goals.
cystic fibrosis, adequate nutrition to meet increased needs Because of this, ethical issues involving the provision or
becomes a key factor in decreasing morbidity and mortality. withholding of nutrition often take place in a unique and
Also, in a patient with liver failure, the goals of providing complex social dynamic, charged with emotion.
nutrition include optimizing his chance for a successful
transplant. However, just as in the aforementioned example Why is unique value assigned to feeding?
with the ventilator, should the clinical situation change, it is What is it about feeding that makes it more likely to have
important to reevaluate the goals of nutrition therapy as they additional value ascribed to it as opposed to dialysis? A
may no longer apply and the team may find itself pursuing possibility is that providing nutrition to a child is a funda-
a nutritional strategy based on an outdated set of goals. As mental responsibility of the caregiver. A child is born unable
an example of this, if a child with liver failure suffers a new to provide himself with nutrition, and several years of devel-
complication that makes transplant impossible, the goal opment must take place before he is able to independently
of nutrition would no longer be to optimize the patient for obtain and consume nutrition. Perhaps this responsibility is
surgery. The realization of new goals, such as improving so ingrained in the caregiver’s being, that limiting its provi-
quality of life, may allow the team to be less aggressive (no sion, no matter how beneficent the motives, causes feelings of
central lines, less emphasis on caloric intake) and begin to guilt or neglect in attending to care-giving duties. Contrast
“de-medicalize” the family and the child during the final this to the act of breathing: should assistance be needed
months of life. with this life-sustaining function, its provision is beyond the
usual parental duty. Therefore, while the discontinuation of

a ventilator is difficult for all who care for the child, perhaps be important in making certain choices about the appropri-
the feeling that all “natural” caregiving responsibilities have ateness of medically delivered nutrition in the hospital or
been fulfilled allows this to be more palatable limitation of at home. At the very least, open and transparent decisional
treatment than the withholding of nutrition.10 processes and communication with parents that allow for
Another potential reason for the uniqueness of feeding their understanding of why, and how, and for how long a
is the typical time course and physical appearance of a certain method may be used, is required.
person who dies from starvation or dehydration. This is not When surgically placed devices (eg, central venous
to imply that starvation is not a natural part of the dying catheters, gastrostomy, or jejunostomy feeding tubes) are
process, in fact the body’s reaction to a deprivation of nutri- considered, the risks and benefits require special attention
tion may actually serve to ease a person’s death. However, as the potential for pain, wound healing, aspiration, infec-
for families who are caring for a child who is not being tion, thrombosis, or other complications must be weighed
adequately fed, the visual appearance and the prolonged against the patient and family goals. For most patients the
time course prior to death may be too difficult to endure benefits are clear and the health care team makes reason-
regardless of any medical considerations. Additionally, able decisions with the family to proceed with placement of
the supportive care programs that could provide palliative such devices. But on occasion, the initial placement, or their
care throughout the dying process for these children are replacement, become burdensome and cause all involved
unavailable in many geographic locales.13,14 Therefore, it is to pause and reconsider their appropriateness. This may be
understandable why the medical provision of nutrition may especially true in the terminal stages of many chronic and
be seen as such an essential element of care. debilitating conditions. In these cases, adequate time needs
to be devoted to discerning the best interests of the pedi-
Ethical Dimensions of Clinical Nutrition Issues atric patient—often addressed differently by the patient,
parents, and clinicians. Clinicians’ sensitivity to parental or
The Intensive Care Environment: Neonatal and Beyond patient goals and values that differ from their own, whether
Common practice in the neonatal intensive care unit in matters of culture and custom, faith and religious tradi-
(NICU) includes a nutrition plan that facilitates growth, tion, or social and family norms and expectations must be
development, healing, and immune function. All newborns present and allow for considerations beyond what may be
are born dependent upon caregivers for nutrition support. simply metabolically or physiologically apparent as a best
Those with special considerations such as prematurity, course of action. With long-term care and chronic debili-
congenital anomalies requiring surgery, and numerous tation, one may need to ask “Does more always equate
disease states all may require medically delivered nutrition to better?”17
and hydration. In a similar light, pediatric intensive care Perhaps the most heated ethical debates in nutrition
unit (PICU) patients may also be in need of nutritional management of patients dependent upon medically delivered
support as infants, surgical patients, trauma victims, or nutrition and hydration are in the context of the withholding
because of chronic and debilitating conditions that may be or withdrawal (WH/WD) of such nutrition. For children,
associated with increased energy and nutrient demands or especially those in whom a cognitive capacity is not appro-
special needs for nutritional delivery. priate for them to participate in decisions, parents normally
In the ICU, medically administered nutrition may well serve as surrogate decision makers as they are entrusted by
be the norm. As such, its goals and decided benefits must society with discerning and acting upon their child’s best
be reexamined as the patient’s condition changes. Risks (or interests. These interests, though not always knowable,
burdens), as well as benefits of nutritional delivery systems certainly include not being treated as mere passive objects,
must be acknowledged and clarified for the pediatric patient and the same ethical and legal posture toward WH/WD
and his/her parents.15,16 The mere capability to “do some- medical nutrition is due them that is due adult patients.10
thing” does not equate with the absolute medical indication, Decisions that are made concerning medical nutrition
or prerogative, to do so. should be made like all other decisions about WH/WD
Ethical challenges in nutrition management for neonatal life-sustaining treatments, although as previously noted
and pediatric ICU patients, then, can be evaluated in the these decisions may be fraught with greater psychological
context of goals and values, and warrant open communica- and emotional duress among all parties—especially when
tion and a collaborative approach among the medical team the patient is not imminently dying.18, 19 As noted by Porta
involved. In a family-centered context, parental input may and Frader, clinicians should neither demand nor reject

medical nutrition without examining and considering each On occasion an ethical dilemma may arise in deter-
situation’s context (eg, goals, values, burdens, and benefits), mining that the placement of a medical nutrition device
through which the provision of medical nutrition may be (feeding gastrostomy tube), is in the best interests of the
found morally optional.9 patient. The dietician as a key interdisciplinary health care
team member, or consultant, may bring clarity to decisions
Palliative Care to go forward with such a plan, or to reconsider it. Goals
The subject of palliative, and end-of-life, care has been of clarification may be the greatest contribution to be made.
increasing interest in pediatric medicine over the past decade. The dietician may also be called to advocate for correct
Among resources that address what pediatric palliative care ethical action in beginning, sustaining, or advancing nutri-
should entail, the 2003 Institute of Medicine Report When tion support for special needs children. She may find herself
Children Die is among the most often cited.20 Among issues in tension with primary or specialty clinicians who have
noted therein, the attention to medically administered [arti- not prioritized nutrition for the NICU graduate, missed
ficial] nutrition and hydration (ANH) is noted as one that faltering growth, or are uncertain about what to do next
warrants acknowledgement by clinicians of some residual for a child in whom a medical feeding device is not being
controversy and continued need for inquiry. The recent AAP used and oral nutrition is inadequate to secure the goals of
Clinical Report, Forgoing Medically Provided Nutrition and health. Ethical action here requires professional compe-
Hydration in Children, helps by providing further guidance tence, self-confidence, and a stance of advocacy for the child.
in this sensitive area.21 Both of these resources, and numerous Effectively communicating with involved clinicians, and
articles that have been published in the peer-reviewed parents, may include the provision of past and present goals
medical literature, address aspects of ANH in the context of nutrition, observed and documented failures (growth
of life-limiting or threatening conditions, and specifically at curves, illness, and other outcomes), and recommendations
the end of life.22,23 Matters of values, open communication, with evidence-based expectations for measurable outcomes
assigned meanings to feeding, and the overall goals of care in an appropriate timetable.
require attention in addressing this matter as much as any Additionally, some NICU graduates have chronic
other life-sustaining interventions. gastrointestinal illnesses such as cholestatic jaundice, liver
The dietician may need to be a resource for parents, disease, or short bowel syndrome (SBS) following neonatal
families, other care team members, and for physicians in surgery. The care of the child with SBS requires attentive-
particular as the issue of ANH is examined in the acute care ness to detail and elements of psychosocial support for the
setting (hospital or clinic), home health, or home palliative and child and family that complement the necessary medical,
hospice care. Attention to the “normalcy” of assisted feeding nutrition, and pharmacy (home parenteral nutrition)
devices, such as gastrostomy feeding tubes, is another sensitive management of this condition. Those who await eventual
area that may require education as well as a values clarifica- liver-bowel transplantation have lengthy waiting periods
tion. Petersen and colleagues reported a different perspective and high morbidity and mortality.27
on feeding through a gastrostomy tube by a majority of daily Other children with special nutrition needs include
caregivers of children with cerebral palsy.24 those born with an inborn error of metabolism. Perhaps
diagnosed prenatally, or even after discharge home from the
The Special Needs Infant and Toddler hospital, many metabolic conditions result in acute illness
Among the varied special needs children cared for by dieti- and nearly all have significant impact upon child growth
cians, perhaps the most labor-intensive and demanding are and development. The nutritionist must remind himself that
graduates from the NICU. These children may be followed he is part of a team and work collaboratively in addressing
by an interdisciplinary team in NICU Graduate Follow-up parent education, child health, and the provision of special
Clinics that include a dietitian, may be seen only by primary nutrition products. In extreme cases, such as certain urea
care clinicians (pediatricians, family physicians, nurse prac- cycle disorders, liver transplantation may be the ultimate
titioners, physician assistants), in county health department goal and nutrition assessment and daily management brings
clinics, or they may be altogether lost to follow-up. Their the nutritionist in close and frequent contact with the family.
nutrition needs are fundamental to their care as continued Should such contact lead to shared feelings about the child’s
growth, physical development, neurodevelopment, resil- illness, goals, and values, it is the nutritionist’s duty to raise
ience with acute illness, and overall health are all predicated issues that might seem contrary to the goals of the current
on good nutrition.25,26 care plan with the responsible physician or team leader.

Vegetarian Diets, Fad Diets, and Feeding Disorders from parents and siblings but also a claim to independent
The dietician is a key team member in addressing nutrition thinking. For some, this may include the choice of separate
education for children of all ages. While this chapter cannot dietary preferences, vegetarian dieting (while the remainder
address the broad concerns raised and management issues of their family, or even circle of friends continue omnivorous
required for children with feeding disorders such as bulimia dieting), or participation in fad dieting that may actually
and anorexia (Chapter 19), the dietician must attend to the reflect issues of reckoning with bodily changes of adoles-
priority of care being focused on the patient’s well-being cence, or even self-image and psychological well-being.
and best interests as they can best be discerned. In conjunc- In this period of life, clinicians need to attend to the
tion with other clinicians and behavioral health specialists, complexity of intersecting issues—clinical, social, and
the nutritionist may need to address facts, falsehoods, and behavioral—which affect dieting and overall nutritional
fallacies about the goals of nutrition, nutrition essentials, well-being. A balance of respect for the adolescent accom-
and how all concerned parties may help children attain and plishing individual identity and independence must be
maintain good health. met with informing and educating the young person about
When addressing vegetarian diets, it may be important healthy habits and avoidance of negative behaviors. While
to understand the rationale for such dieting can be clinical matters of eating disorders exceed the subject of this chapter
(eg, improved cardiovascular health and longevity), a means and are discussed elsewhere (Chapter 19), ethical precepts
of addressing weight control, upholding religious tenets, or of respect for persons, doing good and avoiding harm, and
ethical life-style choices (addressing concern for the ecosys- attending to the fine line of confidentiality for and with the
tems on the planet, and for animal well-being).28 At the adolescent patient and his or her family must be recognized
same time vegetarianism may be a marker for disordered by all health care team members.
eating practices (or tendencies) and a preoccupation with
weight that may not serve the child’s overall interests. 29 The Summary
dietician must balance appropriate support of choices and The timely, appropriate, and beneficial provision of pedi-
dieting habits with responsibilities of addressing potential atric nutrition requires attention to the pediatric patient and
clinical and behavioral health matters. his or her parents and family. Ethical challenges may best
be met with open dialogue, respectful listening, clarity of
Childhood Obesity communication, and sensitive provision of support directed
The recent increase in childhood obesity may be seen by toward mutually derived nutrition goals. The dietician has
some as a mere medical, or strictly nutrition, condition. an integral role to play in these matters as a valued interdis-
This is far from the reality of complex social, behavioral, ciplinary team member across diverse diagnostic categories,
educational, and even economic contributors to this care environments, and the age continuum of pediatrics.
growing concern. Some have raised the issue of obesity
constituting medical neglect, and thereby warranting inter- Case Studies
ventions that include social and legal actions akin to those
expected in physical or sexual child abuse, or gross parental A Decision Not to Start Medical Nutrition Support?
neglect of meeting a child’s due needs (eg, food, clothing, A term infant is delivered by emergency cesarean section
shelter, education, and health care). Recently, Varness and for fetal bradycardia to a 25-year-old gravida I mother
colleagues have addressed the nature of these concerns and with diabetes mellitus. He required extensive resuscitation
how they are rarely borne out in such a manner that obesity and had Apgar scores of 0, 0, and 3 at 1, 5, and 10 minutes
could legitimately be considered neglect. 30 after birth, respectively. He is admitted to the NICU with
respiratory distress and hypoglycemia. His birth weight is
The Adolescent 4.5 kg. He has poor cardiovascular function, hypotension,
The period of adolescence is accompanied by major devel- and metabolic acidosis. His respiratory depression and
opmental and cognitive goals, not the least of which are apnea require assisted ventilation. At 2 hours of age he has
individuation—the process in which the young person a convulsion and after receiving an anticonvulsant he is
engages in developing his or her own self-identity and placed on a head-cooling protocol for severe birth asphyxia.
strives to become an individual, distinct from parents and An MRI confirms diffuse and devastating ischemic brain
siblings—and independence, whereby the young person injury. On postnatal day 4 he fails a trial of extubation due
takes actions that allow for not only a separate identity to apnea and inability to handle his own secretions. He has

no urine output for 7 days and after receiving initial intrave- Jill’s neurological status. Unlike prior hospitalizations with
nous dextrose the question of providing parenteral nutrition aspiration pneumonia, this time she has never opened her
or a trial of nasogastric tube feedings is raised on morning eyes, is only reflexively responsive to pain, and he fears she
ICU rounds. A discussion follows in which his prognosis may never improve, or even assume her prior level of infan-
for recovery is described as bleak—his future survival is tile function. He also believes that Jill’s overall condition
contingent on the provision of a tracheostomy and placing warrants not only the tracheostomy but that she will need
a feeding gastrostomy—but his potential for future neuro- a fundoplication to protect her airway if she were to receive
logical function (motor, cognitive, and communicative) and gastric feedings—stating for clarification that feeding
development is gone and he will remain infantile. should now only be pursued via a gastrostomy tube. In
This infant presents a number of opportunities for realizing the extent of Jill’s injury and poor prognosis, the
evaluating nutrition support: a large for gestational age parents begin to sob, “We knew this day might come.” After
infant of a diabetic mother (complicated by hypoglycemia), a minute, the physician re-appraises the matter of nutrition
birth asphyxia (with circulatory shock, acidosis, and likely support for Jill, stating, “Just because we can place a feeding
impaired gastrointestinal perfusion, mucosal barrier func- gastrostomy does not necessarily mean we should. And
tion, and poor gut motility), neurological injury, and renal frankly, that is true for the tracheostomy as well.” This gives
failure. At a week of age he evidences multiple organ system the parents initial pause, but then they express a desire to
injury and failure of function. His prognosis for successful speak with extended family members, their church, and be
oral feeding is nil, and in the face of renal failure the provi- given “some time.” The physician leaves them alone to talk
sion of parenteral nutrition must be questioned. with the unit social worker.
1. What is the ethical rationale for placing a central line 1. What are the key considerations for this family to
and providing parenteral nutrition? consider in making their decision for Jill?
2. What is the burden:benefit analysis of pursuing a 2. How does the ethical standard of doing what is in the
feeding gastrostomy and fundoplication? child’s best interest pertain to this case?
3. What are the goals of nutrition support for this baby? 3. What level of burden, pain, or suffering might be accept-
4. Can palliative care be provided without a specific able in doing surgery for Jill?
feeding regimen? 4. If the parents elect not to have a gastrostomy, fundopli-
cation, and tracheostomy done, what nutrition support
The Withdrawal of Nutrition Support goals should exist for this patient?
Jill, a 3-year-old girl with severe cerebral palsy (spastic
quadriplegia), seizures, and mental retardation after infan- Test Your Knowledge Questions
tile meningitis, has recently required management in the 1. When a developmentally appropriate child with cystic
PICU following a fourth episode of aspiration pneumonia. fibrosis asks questions to the medical team regarding his
She is sedated in order to allow adequate assisted venti- or her disease, the method of communication thought
lation, and has been receiving medically administered to be most beneficial is to:
intravenous nutrition and hydration for the past 5 days. Her A. Carefully talk to the child, trying to stay posi-
parents meet with the PICU team to discuss the prognosis tive, while also avoiding any potentially negative
and plan of care. The team states they are hoping for the best information.
for Jill, as nobody knows how long she was hypoxic after she B. Try to give the child the worse case scenarios in
arrested at home. A trial of lifting her sedation, reducing hopes of preparing him or her for the worst.
ventilator support, extubating Jill, and providing enteral C. Tell the child that you are going to focus on today’s
nutrition through a transpyloric nasal feeding tube is agreed plan of care, but that you will schedule an appoint-
to by Jill’s parents—who are anxious to see any signs of Jill ment with the nurse educator.
“getting better.” Two days later, however, Jill’s respiratory D. With the guardian’s permission, try to answer the
condition worsens after failing a trial of extubation and a questions in an honest, but developmentally appro-
tracheostomy must now be considered. priate, manner.
Jill’s mother and father are overwhelmed by her decom- E. All of the above.
pensation following this most recent aspiration event. She is
not responding to their voice or touch. At a follow-up family
meeting her attending physician discusses his concern for

2. How do Porta and Frader distinguish between “natural” 11. Society of Critical Care Medicine, Task Force on
and “medical” nutrition? Ethics. Consensus report on the ethics of forgoing life-
sustaining treatments in the critically ill. Crit Care Med.
A. Natural nutrition is a mandatory act.
1990;18(12):1435–1439.
B. Medical nutrition is a mandatory act. 12. Rubenstein JS, Unti SM, Winter RJ. Pediatric resident atti-
C. Natural nutrition is always optional. tudes about technologic support of vegetative patients and
D. Medical nutrition is always optional. the effect of parental input—a longitudinal study. Pediatrics.
E. None of the above. 1994;94(1):8–12.
3. Which of the following actions is not recommended as 13. Contro N, Larson J, Scofield S, Sourkes B, Cohen H. Family
perspectives on the quality of pediatric palliative care. Arch
a way to help reach an ethical decision regarding the Pediatr Adolesc Med. 2002;156:14–19.
provision of nutrition? 14. Liben S, Papadatou D, Wolfe J. Paediatric palliative care: Chal-
A. Make sure everyone on the team is using the same lenges and emerging ideas. Lancet. 2008;371(9615):852–864.
definition for commonly used medical and ethical 15. Hobbs N. Decisions for a baby in foster care. J Clin Ethics.
terms. 2004;15(3):292–295.
16. Mello M. The experience of a community representative on an
B. Avoid talking to the family or the patient until a
Ethics Consult Team. J Clin Ethics. 2004;15(3):296–301.
decision is made so that the team does not appear 17. Essex C. More is not necessarily better. Arch Dis Child.
uncertain. 2006;91:202.
C. Define the long-term goal of providing nutrition to 18. Mitchell C, Truog RD, Ethics Advisory Committee at Chil-
the patient. dren’s Hospital Boston. Excerpts from the ethics consult
D. Discuss with the family their views and beliefs report: MT. J Clin Ethics. 2004;15(3):302–306.
19. Johnson JA. Withdrawal of medically administered nutrition
regarding feeding and/or the provision of and hydration: the role of benefits and burdens, and of parents
nutrition. and ethics committees. J Clin Ethics. 2004;15(3):307–311.
E. Carefully examine the context (goals, values, 20. Field MJ, Behrman RE, eds. When Children Die: Improving
burdens, and benefits) of the nutrition dilemma. Palliative and End-of-Life Care for Children and Their Families.
Washington, DC: National Academies Press; 2003:39, 143,
298–299.
21. Diekema DS, Botkin JR, American Academy of Pediatrics
Committee on Bioethics. Clinical Report—Forgoing medi-
References cally provided nutrition and hydration in children. Pediatrics.
1. Rothman DJ. Strangers at the Bedside. New York, NY: Walter 2009;124(2):813–822.
de Gruyter, Inc; 2003. 22. Levi BH. Withdrawing nutrition and hydration from chil-
2. Cassidy RC. Tell all the truth? Shepherds, liberators, or educa- dren: legal, ethical and professional issues. Clin Pediatr.
tors. In: Cassidy R, Fleischman A, eds. Pediatric Ethics: From 2003;42:139–145.
Principles to Practice. Amsterdam, The Netherlands: Harwood 23. Truog RD, Cochrane TI. Refusal of hydration and nutrition:
Academic; 1996:67–82. irrelevance of the “artificial” vs “natural” distinction. Arch
3. Slavin LA, O’Malley JE, Koocher GP, Foster DJ. Communica- Intern Med. 2005;165:2574–2576.
tion of the cancer diagnosis to pediatric patients: Impact on 24. Petersen MC, Kedia S, Davis P, Newman L, Temple C. Eating
long-term adjustment. Am J Psychiatry. 1982;139(2):179–183. and feeding are not the same: caregivers’ perceptions of
4. Bluebond-Langner M. The Private Worlds of Dying Children. gastrostomy feeding for children with cerebral palsy. Dev Med
Princeton, NJ: Princeton University Press; 1978. Child Neurol. 2006;48:713–717.
5. Spinetta JJ, Rigler D, Karon M. Anxiety in the dying child. 25. Ehrenkranz RA, Dusick AM, Vohr BR, Wright LL, Wrage
Pediatrics. 1973; 52(6):841–845. LA, Pool WK and the NICHD Neonatal Research Network.
6. Spinetta JJ, Maloney MS. Death and anxiety in the outpatient Growth in the neonatal intensive care unit influences neurode-
leukemic child. Pediatrics. 1975;56(6):1034–1037. velopmental and growth outcomes of extremely low birth
7. Speece MW, Brent SB. Children’s understanding of death: weight infants. Pediatrics. 2006;117(4):1253–1261.
A review of three components of a death concept. Child Dev. 26. Bhatia J. Post-discharge nutrition of preterm infants. J Peri-
1984;55:1671–1686. natol. 2005;25:S15–S16.
8. American Academy of Pediatrics, Committee on Bioethics. 27. Horlsen S. Organ allocation for liver-intestine candidates.
Informed consent, parental permission, and assent in pedi- Liver Tranpl. 2004;10:S86–S89.
atric practice. Pediatrics. 1995;95(2):314–317. 28. Klopp SA, Heiss CJ, Smith HS. Self-reported vegetarianism
9. Porta N, Frader J. Withholding hydration and nutrition in may be a marker for college women at risk for disordered
newborns. Theor Med Bioeth. 2007;28:443–451. eating. J Am Diet Assoc. 2003;103:745–747.
10. Carter BS, Leuthner SR. The ethics of withholding/ 29. Perry CL, McGuire MT, Neumark-Sztainer D, Story M. Char-
withdrawing nutrition in the newborn. Semin Perinatol. acteristics of vegetarian adolescents in a multiethnic urban
2003;27(6):480–487. population. J Adolesc Health. 2001;29:406–416.

30. Varness T, Allen DB, Carrel AL, Fost N. Childhood obesity

and medical neglect. Pediatrics. 2009;123:399–406.
Ethical Issues and Nutrition Therapy:
Pediatric End of Life
Donnelly JP, Huff SM, Lindsey ML, McMahon KA, Schumacher
Additional Readings of Interest JD. The needs of children with life-limiting conditions: a
healthcare-provider-based model. Am J Hosp Palliat Care.
2005;22(4):259–267.
Ethical Issues and Nutrition Therapy in General Fleischman AR, Collogan L. Addressing ethical issues in everyday
Carrese JA. Refusal of care: patients’ well-being and physicians’ practice. Pediatr Ann. 2004;33(11):740–745.
ethical obligations. JAMA. 2006;296(6):691–695. Frader JE. Discontinuing artificial fluids and nutrition: discussions
Ferrie S. A quick guide to ethical theory in healthcare: solving with children’s families. Hastings Cent Rep. 2007;37(1):49.
ethical dilemmas in nutrition support situations. Nutr Clin Glover JJ, Caniano DA, Balint J. Ethical challenges in the care of
Pract. 2006 21:113–117. infants with intestinal failure and lifelong total parenteral
Fine RL. Ethical issues in artificial nutrition and hydration. Nutr nutrition. Semin Pediatr Surg. 2001;10(4):230–236.
Clin Pract. 2006;21:118–125 Heine RG, Bines JE. New approaches to parental nutrition in infants
MacDonald C. Treatment resistance in anorexia nervosa and the and children. J Paediatr Child Health. 2002;38(5):433–437.
pervasiveness of ethics in clinical decision making. Can J National Hospice and Palliative Care Organization. Standards of
Psychiatry. 2002;47:267–270. Practice for Pediatric Palliative Care and Hospice. Alexandria,
O’Sullivan Maillet J, Vyas A, Rodrigues J. Ethical issues in nutri- VA: National Hospice and Palliative Care Organization;
tion and human immunodeficiency virus. Nutr Clin Pract. 2009.
2004;19:365–374. Nelson LJ, Rushton CH, Cranford RE, Nelson RM, Glover JJ, Truog
Sayers GM, Lloyd DA, Gabe SM. Parenteral nutrition: RD. Forgoing medically provided nutrition and hydration in
ethical and legal considerations. Postgrad Med J. 2006 pediatric patients. J Law Med Ethics. 1995;23(1):33–46.
Feb;82(964):79–83. Repenshek M, Slosar JP. Medically assisted nutrition and hydra-
Sharp HM, Bryant KN. Ethical issues in dysphagia: When tion: a contribution to the dialogue. Hastings Cent Rep.
patients refuse assessment or treatment. Semin Speech Lang. 2004;34(6):13–16.
2003;24(4):285–299. Saad L. Americans choose death over vegetative state: most would
Thomson C, Diekman C, Fragakis AS, Meerschaert C, Holler have feeding tube removed for their child, spouse, or them-
H, Devlin C. Guidelines regarding the recommenda- selves. In: Gallup A, Newport F, eds. The Gallup Poll: Public
tion and sale of dietary supplements. J Am Diet Assoc. Opinion March 29, 2005. Lanham, MD: Rowman & Little-
2002;102:1158–1164. field; 2006:116–118.
Unknown. Artificial feeding for a child with a degenerative Velez G Jr. Death of John Paul II and the basic human care for the
disorder: a family’s view. The mother and grandmother of sick and the dying. Ethics Med. 2005;Fall;21(3):167–177.
Frances. Arch Dis Child. 2005 Sep;90(9):979.

0
Test Your Knowledge Answers
Chapter 1: Mechanics of Nutrient Intake Chapter 4: Fats

1. The correct answer is C. 1. The correct answer is B. The problems of overweight and
2. The correct answer is B. obesity are the result of excess calories and not simply
3. The correct answer is A. too much fat. In addition to customizing the caloric
intake to meet the individual patient’s needs, the ideal
Chapter 2: Gross Digestion Principles: Gastric Grinding nutritional support will provide appropriate ratios of
and Gastrointestinal Motility preformed LA, α-LA, ARA, EPA, and DHA that cannot
1. The correct answer is C. Liquids empty from the be made in adequate amounts by the patient.
stomach faster than solids; feeding higher in fiber, fat, 2. The correct answer is D. Medium-chain fatty acids and
and protein will empty more slowly. long-chain fatty acids are oxidized in mitochondria.
2. The correct answer is B. The other three answers each Very long-chain fatty acids are oxidized in peroxisomes
describe characteristics of one of the 3 phases of the and mitochondria. Although it is normally a minor
migrating motor complex seen in the fasting state. pathway, omega-oxidation in the endoplasmic retic-
3. The correct answer is D. It has been demonstrated that ulum of the cytoplasm becomes important if there is
even small amounts of enteral feeding in the premature mitochondrial dysfunction.
infant will encourage maturation of intestinal motility. 3. The correct answer is D. The neonate cannot synthe-
Bolus feeds will actually cause a cessation of contrac- size LA or α-LA. Although the enzymes are present to
tions in the proximal small bowel of the premature convert LA to ARA and α-LA to EPA and DHA, the
infant. Both gastric emptying and intestinal transit are capacity to do so is not adequate to meet the needs of
slower in the premature infant. the neonate.
Chapter 3: Carbohydrates: Changes with Development Chapter 5: Protein Digestion, Absorption, and
1. The correct answer is D. Lactose, sucrose, and maltose Metabolism
are disaccharides. Amylose is a polysaccharide consisting 1. The correct answer is C.
of multiple glucose units and is a component of starch. 2. The correct answer is A.
2. The correct answer is B. 3. The correct answer is A.
3. The correct answer is B. Lactase activity at the start of 4. The correct answer is C.
the third trimester is < 25% of that at term.
4. The correct answer is D. The prevalence of hypolactasia Chapter 6: Minerals
amongst individuals of different ethnic backgrounds is 1. The correct answer is E.
as follows: 90% Asians, 80% African-Americans, 53% 2. The correct answer is E.
Hispanics, and 15% to 25% non-Hispanic whites. 3. The correct answer is E.
4. The correct answer is D.
487
5. The correct answer is B. Chapter 10: Nutrition and Early Development

6. The correct answer is A. 1. The correct answer is D.
2. The correct answer is C.
Chapter 7: Water-Soluble Essential Micronutrients 3. The correct answer is B.
2. The correct answer is E. Chapter 11: Human Milk
3. The correct answer is C. 1. The correct answer is E. Some of these infants have
4. The correct answer is D. been shown to have an insufficient suck and negative
5. The correct answer is A. pressure needed for good milk extraction. They may
fool mothers and as this problem persists, the mother’s
Chapter 8: Fat-Soluble Vitamins milk supply may dwindle. This may cause dehydration
1. The correct answer is A. as well as poor growth and create a cycle that can lead
2. The correct answer is E. to lactation failure. Encouraging mothers to pump to
3. The correct answer is C. stimulate milk supply is helpful; also, the use of teat
4. The correct answer is D. weights to determine whether there is sufficient milk
5. The correct answer is E. transferred can also be helpful. Further information is
included in references 39 and 40.
Chapter 9: Fluids and Electrolytes 2. The correct answer is B. Although calories are impor-
1. The correct answer is C. Fluid gains in the body tant which will be supplied in greater amounts with the
compartments depend on the volume and osmolarity of higher fat content of hind milk, the premature infant
the fluid administered. Administering 100 mL of 0.9% needs fortification for protein, calcium, phosphorus,
sodium chloride (154 mEq/L of sodium) will not alter magnesium, and zinc.
the plasma osmolarity because it is iso-osmotic. The 3. The correct answer is A. Donor banked human milk
sodium will be held in the ECF by the Na+-K+-ATPase may often be from donations of mothers of term
pump, and the water stays with the sodium. Therefore, infants. This milk would have lower protein content
all of the administered volume (100 mL) will stay in the than the milk from a mother of a preterm infant. The
ECF compartment. Because 25% of the ECF compart- pasteurization process alters some of the properties of
ment is intravascular volume, the intravascular volume human milk as well. There will be increased needs for
will increase by 25 mL. supplemental protein, calcium, and phosphorus.
2. The correct answer is A. A low serum sodium concen-
tration is the result of either an increase in TBW or Chapter 12: Infant Formulas and
a decrease in total body sodium with a subsequent Complementary Feeding
decrease in TBW. The weight has not changed signifi- 1. The correct answer is C.
cantly over the past 3 days and the sodium intake 2. The correct answer is B.
(3 mEq/kg/d) may not be sufficient for a 1250-g 3. The correct answer is A.
neonate. Therefore, the renal and GI losses are probably 4. The correct answer is D.
exceeding the sodium intake, resulting in the decreased
serum sodium concentration. The correct treatment Chapter 13: Growth Assessment and Monitoring
would be to increase the sodium concentration in the 1. False. BMI not available for children age < 2 years. BMI
maintenance IV fluids. patterns after age 2 years can be linked to adolescent.
3. The correct answer is C. The low serum phosphorus 2. False. BMI percentile 85th – 95th represents “risk
concentration is cause for concern and needs to be for overweight.” BMI percentile > 95th represents
treated acutely. A supplemental IV infusion of sodium “overweight.”
phosphate would be more appropriate than adding 3. True. The CDC recommends using terminology
sodium phosphate to the maintenance IV solution. A “obesity” for BMI ≥ 95th percentile or calculated BMI
serum potassium concentration of 3.4 mEq/L does not ≥ 30 kg/m2 . This is a change from Expert Committee
necessitate acute treatment; increasing the potassium recommendations in 1998 that discouraged use of
in the maintenance IV fluids would be most appropriate “obesity” terminology in children. The term obesity
to address this issue. denotes excess body fat and the associated serious health

TEST YOUR KNOWLEDGE ANSWERS 489
risks. It also provides continuity with adult definitions where the child sleeps, and no television if the child is <
and avoids the vagueness of previous terminologies of 2 years of age; and ≥ 1 hour of physical activity per day.
“risk for overweight” for BMI 85th to 94th percentile 3. The correct answer is B. The Traffic Light Diet™ was
and “overweight” for BMI > 95th percentile. designed to promote weight loss, provide adequate
4. The correct answer is D. FTT or wasting is an involun- kilocalories and nutrients for growth and develop-
tary decline falling below 2 or more major percentile ment, and be easy to follow. The Food Guide Pyramid
channels. The major percentile channels are 90th, 75th, was designed as a general guide for diet and exercise
50th, 25th, 10th, and 5th. in adults; however it was used as a dietary component
5. The correct answer is C. The 50th percentile is the mean in childhood weight management in one study of
and median value. This corresponds to a z score of 0. adolescents.
6. The correct answer is D. Timeline of progression was 4. The correct answer is D. For children and adolescents,
not given; otherwise, answer B is also potentially life these diets have not been studied due to potential risks
threatening if rapid in onset (ie, < 1 to 2 months). for growing children and adolescents from elimination
7. The correct answer is B. Length refers to linear of key food groups, greater than recommended caloric
measurements taken with the subject in a supine posi- restriction, adverse behavioral patterns of eating and/
tion. Lengths are longer than heights. Linear growth or lack of scientific evidence for the basis of the diet’s
in the birth to age 36-month growth reference charts recommendations. The key requirement for dietary
is based on length measurements. Linear growth in the treatment of overweight children and adolescents is to
2- to 20-year growth reference charts is based on height initiate and maintain lifelong healthy eating habits that
measurements. focus on unhealthy weight in the short term and foster
improved health outcomes in the long term.
Chapter 14: Obesity and Metabolic Disorders
1. The correct answers are A, B (as relates to cut-points), Chapter 17: Sports Nutrition
D, and E. 1. The correct answer is B.
2. The correct answer is B. 2. The correct answer is C.
3. The correct answers are E and F. 3. The correct answer is A.
Chapter 15: Lipid Disorders
1. The correct answer is B. Chapter 18: Developmental Delay
2. The correct answer is D. 1. The correct answer is D.
3. The correct answer is B. 2. The correct answer is C.
3. The correct answer is B.
Chapter 16: Use of Popular and Fad Diets
1. The correct answer is C. The ADA evidence-based Chapter 19: Eating Disorders
analysis of pediatric overweight literature on interven- 1. The correct answer is C. Physical presentation of a
tion programs reported positive effects from 2 specific person with anorexia nervosa includes lanugo-type
kinds of interventions: multi-component, family-based hair, muscle wasting, dry skin, cyanosis of extremities,
programs for children between the ages of 5 and 12 bradycardia less than 60 beats/min, and cachexia. When
and multi-component school-based programs for anorexia develops in childhood, the first clinical sign
adolescents. The components included were behav- may be failure to make weight gains while continuing to
ioral counseling, promotion of physical activity, parent grow in height as opposed to documented weight loss.
training/modeling, dietary counseling, and nutrition Growth charts should be evaluated for typical growth
education. patterns of the individual
2. The correct answer is A. Interventions should be based 2. The correct answer is B. Parenteral nutrition (PN) is
on the family’s readiness to change and include the only indicated in cases of digestive inability as it leads
following recommendations: consumption of ≥ 5 serv- to a continued loss of hunger cues in the eating-disor-
ings of fruits and vegetables per day; minimization or dered individual.
elimination of sugar-sweetened beverages; limits of ≤ 2 3. The correct answer is A. Patients with a weight loss of
hours of screen time per day, no television in the room ≥ 10% within 2 to 3 months or those at or below 70%

ideal body weight are at the greatest risk. Categories milk is the most important therapy. A protein hydro-
of patients who may meet these criteria include those lysate formula would be an effective substitute and if
with anorexia nervosa, alcoholics, cancer patients, post- not tolerated, an elemental formula.
operative patients, the elderly, uncontrolled diabetics,
marasmus, prolonged fasting, morbid obesity with Chapter 21: Diabetes Mellitus and Other
profound weight loss, patients NPO greater than 5 to Endocrine Disorders
7 days, malabsorptive syndrome (such as pancreatitis, 1. The correct answer is D. The concentration of dextrose
cystic fibrosis, short bowel), prolonged antacid use (due used in the PN should be chosen based on the optimal
to binding of phosphorus), and long-term diuretic use formulation of the PN, rather than on the fact that the
(due to electrolyte losses). child has diabetes mellitus.
2. The correct answer is A. The hospitalized child with
Chapter 20: Food Allergies CF-related diabetes mellitus often has increased insulin
1. The correct answer is D. Allergens are usually proteins resistance and therefore requires a larger amount of
or glycoproteins. Allergies do not develop to carbo- insulin to control blood glucose excursions.
hydrates. Allergies to intravenous lipid, amino acid 3. The correct answer is C. Acceptable blood glucose
solution, and the multivitamin solution have all been control in children with diabetes mellitus on EN can
described. usually be obtained by using subcutaneous insulin.
2. The correct answer is B. Children under 2 years of age Insulin is usually not administered enterally.
and avoiding milk and soy protein are at increased 4. The correct answer is D. Acceptable serum sodium
risk of consuming insufficient fat, protein, calcium, concentrations in a child with diabetes insipidus on
vitamin D, zinc, iron, and total energy. Enriched rice nutrition support can usually be obtained by using an
milk provides adequate vitamin D and calcium but intravenous drip of aqueous vasopressin.
does not provide appropriate fat, protein, and energy
intake. Appropriate substitute for liquid intake would Chapter 22: Inborn Errors of Metabolism
be a hydrolysate formula or if that is not tolerated, an 1. The correct answer is D. Disorders selected for newborn
elemental formula. screening programs must be cost-effective and reliably
3. The correct answer is D. In a patient with a history of detected by population-based screening methods.
anaphylaxis to a food, a food challenge at home should Realistic and effective treatment modalities should be
never be recommended. Follow-up with an allergist is available for the disorder to prevent severe sequelae of
the only safe way to assess if a patient has “outgrown” the disease.
or developed tolerance to the food. Annual follow-up 2. The correct answer is C. Specialty total parenteral nutri-
assessment with an allergist is recommended for chil- tion solutions for MMA provide all essential amino
dren with food allergies. The nutrition assessment of a acids except met, val, ile, and thr. As metabolic control
these children should always review growth and nutrient improves, standard total parenteral nutrition may need
intake. By obtaining a 24-hour recall and reviewing to be added in limited quantities to prevent protein
common foods consumed, exposures to food allergens deficiency.
can be identified. If a patient is tolerating exposures 3. The correct answer is B. Individuals with VLCADD
to foods that were allergenic, again the patient must cannot metabolize long-chain fats effectively and
follow up with the allergist to clarify the allergen list. Intralipid® is a long-chain fat source. Answer A is incor-
Liberalizing a patient’s diet will provide more options rect because MCTs provide a source of fat that can be
for improving the overall nutrition intake. metabolized to meet caloric needs. Answer C is incor-
4. The correct answer is A. In IgE-mediated anaphylaxis, rect because carbohydrates provide an energy source
there are usually cutaneous signs such as an urticarial that can be utilized without fatty acid oxidation. Answer
rash. The absence of cow’s milk-specific IgE on RAST D is incorrect because cornstarch is a slowly digested
testing makes an IgE-mediated mechanism unlikely. carbohydrate source that can be effective to prevent low
This clinical scenario is consistent with food protein- glucose concentrations during fasting.
induced enterocolitis syndrome and avoidance of cow’s

Chapter 23: Cardiac Disease 3. The correct answer is C. Cardiovascular disease is the
1. The correct answer is D. Surgical correction has major cause of mortality in patients with CKD. Not
emerged as the most efficient method to improve only do CKD patients typically have traditional risk
the nutrition status of these infants. Surgical correc- factors including hypertension, dyslipidemia, and left
tion eliminates the cardiac factors contributing to ventricular hypertrophy they also have non-traditional
malnutrition. markers or uremic factors that can contribute to CVD
2. The correct answer is D. Considering the diversity in adult patients. These factors include inflammation,
of the population and varying degrees of anomalies, anemia, fluid overload, proteinuria, abnormal calcium
an infant with congenital heart disease may require and phosphorus levels, dyslipidemia, and vascular
energy intakes of 140–200 kcal/kg/d body weight to injury.
induce growth. 4. The correct answer is A. Recent studies indicate nPCR
3. The correct answer is D. The exact etiology for growth is a superior marker of nutrition status in children on
impairment in children with congenital heart disease maintenance hemodialysis. In these studies, serum
remains unclear. Many factors have been identified as albumin was a poor indicator of nutrition status. An
contributing to growth failure in this population. nPCR of < 1 g/kg/d was a strong predictor of weight
4. The correct answer is C. The use of a medium-chain loss in adolescent patients. However, increased risk of
triglyceride enriched diet is based on the understanding mortality has been associated with hypoalbuminemia.
that enterocytes directly absorb MCT into circulation Therefore, serum albumin may be used as a nutrition
allowing adequate calories while reducing lymphatic status marker, but with caution if hypoalbuminemic
flow to allow for healing. At least 3% to 4% of fat calo- factors are present.
ries should come from LCT to prevent essential fatty
acid deficiency. Chapter 25: Gastrointestinal Disease
1. The correct answer is D. This patient has Crohn’s
Chapter 24: Renal Disease disease. Diet therapy is effective in the treatment of
1. The correct answer is C. The use of CRRT provides Crohn’s disease. There is no difference in effectiveness
greater solute clearance and thus electrolytes typically of the polymeric vs elemental diets. A clear liquid diet
do not need to be limited and are often supplemented. is inadequate.
Therefore, use of a regular formula as opposed to a low- 2. The correct answer is A. Patients with inflammatory
electrolyte “renal” formula is appropriate. Additionally, bowel disease often have deficits of several nutrients.
enteral products designed for renal patients often are This patient has disease of the ileum and is therefore at
more concentrated, which can cause GI discomfort. greater risk of B12 malabsorption. The combination of
GI side effects are common in this population and use anemia and low MCV are suggestive of iron deficiency.
of trans-pyloric feeding improves tolerance. Only if Both sulphasalazine and methotrexate interfere with
continued tolerance problems or poor gut perfusion is folate metabolism and therefore routine supplementa-
suspected should PN be considered. tion with folate is recommended. It should be mentioned
2. The correct answer is D. Although dialysis losses may be that patients with inflammatory bowel disease are also
minimal, vitamin B6 intake is often inadequate, likely at risk for bone disease and vitamin D and calcium may
due to restriction of high-protein foods to limit excess also be considered.
intake of phosphorus and potassium. Recent studies 3. The correct answer is C. Currently a strictly gluten-
indicate that 25-hydroxyvitamin D may have a role, free diet is the sole recommended treatment for celiac
in addition to well-known 1,25-(OH)2D, with bone disease and it should be maintained lifelong. (AGA
metabolism and prevention of hyperparathyroidism. Institute Medical Position Statement Diagnosis and
Supplementation to keep serum levels in the appro- Management of Celiac Disease 2006; 131:1977-80).
priate reference range is recommended. Folic acid, There is ongoing research to discover alternative treat-
although controversial in its role with homocysteine ments including enzyme therapy and immune agents
reduction and cardiovascular implications, may have a but as yet none are recommended (Sollid LM, Khosla
role with anemia management. C. Future therapeutic options for celiac disease. Nat
Clin Pract Gastroenterol Hepatol. 2005; 2:140–145). It

should be emphasized that the gluten-free diet should 4. The correct answer is B. Energy requirements are
be continued even after all symptoms have abated. increased and are in the range of 125 to 150 kcal/kg/d.
4. The correct answer is B. Vitamin A supplementation is important and is often
5. The correct answer is D. used in the intensive care unit to prevent BPD. Vitamin
E supplementation is not helpful. These patients also
Chapter 26: Hepatic Disease have large insensible water losses and need extra fluid,
1. The correct answer is B. which results in opening of the patent ductus arteriosus
2. The correct answer is B. and further stress on the lungs. Fluid restriction often
3. The correct answer is D. results in inadequate nutrition intake. Calcium status is
4. The correct answer is E . poor due to decreased intake and increased losses due to
diuretics. Adequate intakes of calcium and phosphorus,
Chapter 27: Intestinal Failure protein (3–3.5 g/kg/d), and antioxidants (copper, zinc,
1. The correct answer is C. The small intestine doubles and manganese) are required, and it is important to
in length during the last trimester. Therefore, the avoid excessive carbohydrate intake because it can
remaining length of small bowel has a greater inherent impact pulmonary function.
capacity to increase in length when the bowel resection
occurred earlier in the third trimester. Chapter 29: Organ Transplantation
2. The correct answer is B. Features associated with enteral 1. The correct answer is C. Immunosuppressive therapy
autonomy include absence of cholestasis, an intact ileal- after transplant can exacerbate or cause problems with
cecal valve, bowel in continuity, shorter duration of PN, hyperglycemia, renal insufficiency, electrolyte and fluid
residual intestinal length > 15 cm, and an intact colon. provision, and hyperlipidemia. Moreover, tacrolimus
Stool number, by itself, is not a predictor. has been shown to cause hyperkalemia and hypomag-
3. The correct answer is D. The cause of PN-related liver nesemia. All of these imbalances may necessitate a
disease is likely multi-factorial and not related to just change in nutrition therapy. Close nutrition monitoring
one issue. is essential.
4. The correct answer is D. Oral feedings not only enable 2. The correct answer is D. The use of corticosteroids after
the infant to maintain oral feeding skills and decrease renal transplant can result in hyperglycemia, hyperlipi-
the likelihood of developing oral aversion, but oral feed- demia, and obesity. Biochemical testing should include
ings will stimulate salivary secretion of hormones such a lipid profile and glucose levels. A healthy diet including
as epidermal growth factor which is important to the unsaturated fats and exercise as tolerated should be
intestinal adaptive process. encouraged in an effort to prevent these complications.
3. The correct answer is B. Children with cystic fibrosis and
Chapter 28: Pulmonary Disorders pancreatic insufficiency will continue to have pancreatic
1. The correct answer is C. Acidity in the GI tract may disease after lung transplantation. Therefore, pancreatic
prevent or retard dissolution of enteric-coated pancre- enzyme supplementation with meals and snacks will
atic enzymes. If activation does not occur in the small need to continue. In general, a semi-elemental enteral
intestine, then it may be difficult for a person with CF formula should be provided if kilocalorie requirements
to absorb macro- and micronutrients. cannot be met with oral intake alone. Parenteral nutri-
2. The correct answer is B. Blood levels of fat-soluble vita- tion may be needed if neither enteral nor oral intake is
mins should be measured to assure adequacy (vitamins sufficient.
A, E, D). Prothrombin time is insensitive to vitamin K
deficiency in CF. PIVKA II provides a better indicator Chapter 30: Oncology, Hematopoietic Transplant,
of vitamin K nutrition. and Survivorship
3. The correct answer is A. All risk factors need to be 1. The correct answer is A. Methotrexate leads to the
evaluated. Treatment includes optimizing nutrition, development of mucositis which severely compromises
increasing physical activity, controlling underlying oral intake.
inflammation, decreased corticosteroid use, and 2. The correct answer is B. Weight gain, ascites, hyperbili-
addressing hormone deficiencies. rubinemia, hepatomegaly, and increased transaminases

are all symptoms of the development of SOS. Nutrition hepatobiliary secretions and lead to resolution of
management includes fluid and sodium restriction of cholestasis. Excessive lipid and carbohydrate calories
the diet, EN, or PN solution. are considered provocateurs of cholestasis. Cycling of
3. The correct answer is D. EN through the use of PN has been touted to reduce cholestasis.
feeding tubes is often discouraged among the pediatric 2. The correct answer is D. Persistent bilious drainage from
hematopoietic transplant population because of the need the stomach implies distal obstruction. The exception to
for frequent tube replacement as a result of vomiting, the this rule is congenital duodenal atresia due to congen-
risk of bleeding in the presence of thrombocytopenia ital dilation and incompetence of the pyloric channel.
and pancytopenia with mucositis, dislodgement of the Despite evacuation of duodenal content in a prograde
feeding tube, the presence of delayed gastric emptying, manner there may be some retrograde flow into the
and malabsorption of nutrients. stomach. Contrast extravasation in esophageal atresia
4. The correct answer is D (increase or decrease the should initially be managed with continued NPO to
absorption of other drugs). allow the leak to seal without exogenous contamination
5. The correct answer is D. All of the above can contribute of the mediastinum. Passage of a transpyloric feeding
to osteoporosis in the cancer survivor. tube would require excessive manipulation. Abdom-
inal distention with lack of stoma output is indicative of
Chapter 31: Trauma and Burns ileus or intestinal obstruction.
1. The correct answer is C. Solid organ injuries are 3. The correct answer is A. Advancement of enteral feed-
common in the child due to the exposure of the liver ings is safe when there is no evidence of diarrhea or
and spleen in the upper abdomen. Unless there is malabsorption. Reducing substances < 1/2% and fecal
hemodynamic instability, these rarely require opera- pH > 7 are indicative of appropriate absorption. Mucoid
tive intervention and can be managed with physical stools are a nonspecific finding that only becomes
limitations. Nutrition support generally consists of concerning if they contain gross blood. Increased
resumption of an age-appropriate diet with caloric frequency of bowel movements is a generic indicator for
supplementation, when caloric intake is inadequate. feeding intolerance; however, consideration must also
2. The correct answer is D. While the extent of pancre- be given to the quantity and nature of the stool. Small
atic trauma is quite variable, it is often accompanied smears should not be considered as bowel movements
by chemical pancreatitis and ileus. When resection whereas large-volume watery output is of concern.
occurs, it is usually over the neck of the pancreas and 4. The correct answer is A. The hallmark of gastroschisis
leaves sufficient endocrine tissue for normal glucose is that in the majority of patients there is intestinal
control, but may impact exocrine function as evidenced wall edema and serositis resulting in the inability to
by steatorrhea. determine whether there is continuity or an atresia
3. The correct answer is B. While the concept of immu- present. This is further compounded by the fact that
nonutrition is appealing in this population of patients, this intestine returns to normal morphology over a
randomized clinical studies have failed to show variable period of time that ranges from 4 to 10 weeks.
benefit. The intestine in omphalocele is normal other than its
4. The correct answer is A. TBSA remains a predictor covered extra-abdominal location. In the absence of
of mortality. In children, age under 4 years, inhala- other disorders, these infants tolerate enteral feed-
tion injury combined with a TBSA injury of > 30% ings promptly. Hirschsprung’s disease patients have
defines the highest mortality risk group. It is not clearly impaired motility but once diagnosed either undergo
proportional to the extent of the stress response, which primary reconstruction or diverting colostomy and
is mediated by multiple additional factors. Estimates of therefore should have no extended dependence on total
energy needs based on TBSA are consistently inaccu- parenteral nutrition. The intestine in congenital malro-
rate in their targets. tation is functionally normal although there may be
some delayed gastric emptying associated with Ladd’s
Chapter 32: Surgery bands. If midgut volvulus occurs the patient is at risk
1. The correct answer is D. The initiation of enteral feed- for loss of the entire midgut intestine.
ings is the most effective intervention to stimulate

Chapter 33: Assessment of Nutrition Status by Age Chapter 35: Implementation of the Plan
and Determining Nutrient Needs 1. The correct answer is B as the expected need for the
1. The correct answer is D. Components of a detailed CVC is short term.
nutrition assessment include anthropometric measure- 2. The correct answer is B as there is no waste and minimal
ments with comparison to reference standards, a risk of contamination during the procedure.
detailed diet history, laboratory monitoring, and phys- 3. The correct answer is B—bolus feed during the day—
ical examination. after being offered food and nighttime drip feedings.
2. The correct answer is C. Rickets and vitamin D defi-
ciency continue to be a concern in the United States and Chapter 36: Evaluation and Monitoring of Pediatric
other Western countries due to exclusively breastfed Patients Receiving Specialized Nutrition Support
infants and decreased sun exposure. As a result, on 1. False. There are many goals in addition to weight that
October 13, 2008, the American Academy of Pedia may be identified for a patient such as wound healing,
trics issued updated guidelines for vitamin D intake for increased energy, improved protein stores, etc.
infants, children, and adolescents to prevent vitamin 2. True. Decreasing the rate and extending the time of
D deficiency and the incidence of rickets. These new infusion may improve the symptoms.
recommendations report a daily intake of 400 Interna- 3. True, evaluating the GIR in addition to calorie content will
tional Units of vitamin D for all infants, children, and help determine if PN is contributing to hyperglycemia.
adolescents starting from the first few days of life. 4. False. Higher concentrations of amino acids and dextrose
3. The correct answer is D. Depleted levels of Hgb and can improve calcium and phosphorus solubility.
Hct, along with spoon-shaped nails, may be an indica- 5. False. Copper and manganese are excreted via the
tion of iron deficiency anemia. biliary system and these levels should be monitored
periodically in patients with cholestasis receiving PN.
Chapter 34: Parenteral and Enteral Nutrition Support:
Determining the Best Way to Feed Chapter 37: Ethical Issues in the Provision of Nutrition
1. The correct answer is E. All of the above are common 1. The correct answer is D.
behavioral strategies to address picky eating. A divided 2. The correct answer is E.
plate helps children to feel more in control, because 3. The correct answer is B.
they don’t want the “non-preferred” foods touching
the preferred foods. Offering a new food with preferred
foods encourages a child to try the new food, but keeps
the situation from being overwhelming. Family meal-
times are an opportunity for caregivers and siblings to
model healthy, positive mealtime behaviors.
2. The correct answer is A. A height at the 25th percentile
is within normal growth parameters. It is not normal for
a toddler to have no weight gain for an extended period
of time. A decrease of 2 weight channels and taking
longer than 4 hours to eat in a day are both considered
criteria for supplemental nutrition support in children.
3. The correct answer is D. Children with CF have
increased calorie needs. If they are unable to maintain
a good weight with oral intake alone, then the next step
is to provide nutrition supplements. Parenteral Nutri-
tion is not indicated if the child is able to digest/absorb
food. Tube feedings may be needed in the future to
supplement oral intake, if the initiation of oral nutrition
supplements does not produce the desired results.

Index
Page numbers followed by f or t indicate figures or tables, respectively.
A Allergy testing, 216 metabolism

Abdominal injuries, 381–382 Aluminum role of kidney, 39
Absorption in antacids, 49 role of liver, 38–39
of carbohydrates, 20 infant formula content, 273 and nitrogen balance, 35
of fats, 26 toxicity, 268, 273 non-essential, 35t
of minerals, 46–47 American Academy of Pediatric placental concentrations, 106
of proteins, 33–34 Dentistry (AAPD), 414 urea cycle, 37–38
of vitamins, 57 American Academy of Pediatrics Amylase
Academy of Breastfeeding Medicine, (AAP) in pancreatic trauma, 381
121 breastfeeding policy, 120 Anaphylaxis, 214t, 215–216
Acanthosis nigricans, 154 dietary calcium needs, 413 Anemia, 413
Acute kidney injury (AKI) hydration guidance, 181t in transplant recipients, 343
classification American College of Sports Animal models
postrenal, 257 Medicine fetal origins of disease, 110
prerenal, 257 hydration guidance, 181t glucocorticoid exposure, 114
renal, 257 American Dietetic Association iron-deficient diets, 113
defined, 269 (ADA) nutrient-restricted diets, 112–113
electrolyte and fluid restrictions, breast milk guidelines, 124 of dietary manipulation, 112–113
270 pediatric obesity, 170 uterine artery ligation, 114
neonatal issues, 271–272 American Institute for Cancer Anorexia nervosa, 205
nutrition assessment, 270 Research Recommendations for diagnostic criteria, 205f
Adolescents Cancer Prevention, 364 diet-induced thermogenesis, 206
acne treatment, 78 American Psychiatric Association, energy requirements, 206
calcium requirements, 413 205 in childhood, 205
dietary habits, 412 Amino acid(s) liver disease and, 303
nutrition assessment, 412–414 classification, 38t physical presentation, 205
protein requirements, 40 conditionally essential, 35t, 36–37 zinc deficiency, 207
Adrenal glands, injury to, 381 essential, 35t
Alagille syndrome, 304, 305 in fetal development, 106
495
496 INDEX
Anthropometric measurements deficiency state, 70 Burn patient

body mass index-for-age, 146, 415, dietary reference intake, 58t energy requirements, 383–384
415t excretion, 69–70 hyperalbuminemia, 384
head circumference, 144t, 145, 415 metabolism, 69–70 hyperglycemia in, 384
length/height, 144–145, 414–415 physiology, 69 nutrition support, 384
parental stature, 415 source, 69 pediatric, 383
using knee height, 415 supplementation, 70 postpyloric feeding, 384
using length board, 414 Bloodstream infections, 317, 449, protein requirements, 384
using standiometer, 414–415 470 resting energy expenditure, 384
using tibial length, 415 Body mass index (BMI)
mid-arm circumference, 415–416 developmental delay and, 195 C
triceps skinfold, 415–416 in growth assessment, 146 Calcium
percentiles, 421t Body mass index-for-age, 415, 415t absorption, 48–49
upper arm circumference Breast milk body content, 45, 48
percentiles, 420t adding infant formula to, 138 deficiency, 47, 49
weight, 414 in chronic kidney disease, 273 deposits in kidney, 276
method for obtaining, 144, 414 cytomegalovirus in, 125 dietary reference intake, 46t
Appetite fortification, 122–123, 122t excess intake, adverse effects, 50
control, 4 hang time, 124 excretion, 49
cultural aspect, 3 hind milk, 122–123 homeostasis, 49
development during infancy, 4 intestinal adaptation and, 313–314 in chronic kidney disease, 267
hypothalamus role, 4 labeling, 124 medication interactions, 50
nutrient intake and, 3–4 maternal medications and, 125 physiological functions, 48
phases preterm, 122, 122t requirements, 413
cephalic, 4 pumping, 122 sources, 47t, 48
gastric, 4 safety, 124–125 Campylobacter, 346t
intestinal, 4 storage, 124, 124t Canadian Pediatric Society, 120
programming of, 113 in tube feedings, 124 Cancer
Arachidonic acid (ARA) Breastfeeding Children’s Oncology Group
in infant formulas, 135–136 advocacy of, 120 Long‑Term Follow-Up
Arginine appetite development Guidelines for Survivors, 362
hyperammonemia and, 37 exposure to taste, 4 complementary and alternative
in fetal development, 106 benefits of, 120–121, 121t medicine, 354
Asthma, 333 dyad management, 121 disease outcome, 353
effect on later obesity, 111 gastrointestinal supportive care
B infant growth and, 123–124 medications
Baby Friendly Hospital Initiative steps for successful, 121t acid-blockers, 368–369
(BFHI), 121 Bronchopulmonary dysplasia (BPD), antiemetics, 369
Ballard score, 409–410, 410t 332–333 antihistamines, 371
Bartter’s syndrome, 277 Bulimia nervosa appetite stimulants, 371–372
Bifidobacteria lactus, 137 diagnostic criteria, 205f atypical antipsychotics, 371
Bifidobacterium bifidum, 120 energy requirements, 206 cannabinoids, 371
Bile acid malabsorption, 316 physical presentation, 205–206 glucocorticoids, 370
Binge-eating disorder Russell’s sign, 205 motility agents, 368
diagnostic criteria, 206f zinc deficiency, 207 pheothiazines, 370
energy requirements, 206 Burn(s) malnutrition in, 349–350
Biotin inhalation injury, 383 mucositis medications, 372–373
absorption, 69–70 pediatric vs adult, 383 nutrition aspects
biochemistry, 69 total body surface area, 383 metabolic, 351
INDEX 497
physiological, 351 Centers for Disease Control and Congenital posterior urethral valves,
psychological, 351 Prevention (CDC) 256
nutrition assessment, 352–353, breast milk guidelines, 124 Constipation, 296
352t Epi-Info nutrition calculator, 146 Continuous feedings, 454
nutrition intervention, 365f, food allergies statistics, 214 Continuous renal replacement
366t–367t growth charts, 143, 411, 416, therapy (CRRT)
overview, 349 423f–430f caloric needs, 270
survivors Central diabetes insipidus, 229 defined, 270
gastrointestinal problems, Cerebral palsy enteral nutrition and, 270
362–363 abnormal energy expenditure, 193 Copper, in Wilson’s disease, 306
heart health, 363–364 inappropriate dietary intake and, Cornstarch, 306
osteoporosis, 363 192 Cow’s milk
treatment oral motor dysfunction, 192 phosphorus content, 51
complications, 354 Child abuse, 381 protein allergy, 222
tolerance, 353 Cholestasis, 439 Creatinine clearance, 257
chemotherapy, 350–351 Cholesterol, 162, 253t Critically ill patient
radiation therapy, 350, 350t Cholestyramine, 315 hyperglycemia in, 227–228
surgery, 350 Choline nutrition needs, 378–379
Cancer cachexia, 351, 351t absorption, 70–71 Cyclic vomiting syndrome, 296
Candida esophagitis, 315 biochemistry, 70 Cysteine
Carbohydrate(s) deficiency state, 71 as parenteral nutrition additive,
absorption, 20 dietary reference intake, 58t 442
as energy source, 17 metabolism, 70–71 intake requirements, 36
classification, 17 physiology, 70 Cystic fibrosis
complex, 17 sources, 70 clinical features, 324t
digestion supplementation, 71 diagnosis, 324t
lactose, 17–19 Chyle loss, 294 eating behaviors in, 330–331
starch, 19 Chylothorax, 252 fat-soluble vitamin requirements,
malabsorption, 20 Chylous ascites, 341 326, 327t
disorders, 20t Chyme, 12 gastroesophageal reflux, 332
metabolism, 20 Colon injury, 382 gastrointestinal complications, 332
in sports nutrition, 179–180, 180t Complementary and alternative lung transplantation, 332
starches medicine (CAM) nutrition-related complications
oligosaccharides, 17 in cancer treatment, 354 cystic fibrosis related diabetes,
polysaccharides, 17 drug interactions, 194 331–332
storage, 17 Congenital heart disease osteoporosis, 331
sugars acyanotic, 247, 247t pancreatic insufficiency in, 324
disaccharides, 17 cyanotic, 247, 247t pathophysiology, 323–324
monosaccharides, 17 Fontan procedure, 251 sodium chloride supplementation,
Cardiovascular disease (CVD) growth impairment, 248–249, 328
in chronic kidney disease, 268, 269 248t transplant complications
lipid management and, 268 malnutrition, 248 distal intestinal obstruction
in pediatric patients, 252–254 nutrition management, 250 syndrome, 345
risk factors, 162, 268 bolus tube feeds, 250 zinc loss in, 328
Celiac disease, 287–289 postsurgical complications Cystic fibrosis-related diabetes
at-risk groups, 288t chylothorax, 252 (CFRD), 227, 229, 324, 331–332
symptoms, 288t feeding difficulties, 251 Cystine stones, 274
nutrition management, 251–252 Cystinuria, 276
protein-losing enteropathy, 251
498 INDEX
D future health implications, 115 commercial meal/snack

D-lactic acidosis, premature infant, early replacements, 173–174
in intestinal failure, 316 programming, 112 food group guides/exchange
Dental caries, 414 research needs, 116 systems, 173
Dentition, 4–5 “thrifty phenotype” hypothesis, food timing/meals and snacks
by age of eruption, 5t 112 combinations, 173
Depression, 205 Diabetes mellitus food-focused weight loss plans,
Developmental delay cystic fibrosis related, 227 172
abnormal energy expenditure, 193 glucose control reduced macronutrient content
clinical features, 193 in healthy children, 228 plans, 172–173
determining dietary energy needs, on enteral nutrition, 229 WeightWatchers, 173–174
197t on parenteral nutrition, Digestion
inappropriate dietary intake, 192 228–229 carbohydrates, 17
micronutrient deficiencies, type 1, 226–227 fats, 25
193–194 type 2, 227 motor activity factors
nutrient loss, 193 Diarrhea, 291–292, 291t caloric density, 13
nutrition assessment Diet-induced thermogenesis (DIT), consistency, 13
diagnostic studies, 196 206 nutrient content,13
growth and anthropometric Dietary manipulation osmolarity, 13
measurements, 195 animal models physiology of, 12
growth history, 194 low-protein, 113 proteins, 32–33
meal observation, 196 programmed hypertension, 113 small bowel motility, 12-13
medical history, 194 severe food restriction, 113 Distal intestinal obstruction
medications, 194 Dietary reference intakes (DRIs) syndrome, 324, 345
physical examination, 195 during pregnancy, 108t Docosahexaenoic acid (DHA),
review of systems, 194 for minerals, 46t 135–136
social history, 194–195 in neurologically impaired Drug-nutrient interactions, 466–467
nutrition problems children, 197t Duodenal hematoma, 381–382
growth failure, 192 for vitamins, 58t, 75t Duodenal injuries, 381–382
osteopenia, 194 Diets, 169–176 Duodenal perforation, 381–382
overweight, 192 Atkins Diet, 172 Dutch famine, 114–115
pathophysiology of, 192 Dean Ornish Diet, 173 Dyslipidemia, 268
prevalence of, 192 Eat Right for Your Type, 174 Dysphagia, 8
undernutrition, 192 for children
nutrition support balanced macronutrient E
behavioral modification, 197 low‑kilocalorie, 174 Eating disorder(s)
enteral tube feeding, 197–198 Food Guide Pyramid, 175 anthropometric monitoring,
feeding intolerance, 199 multidisciplinary programs 208–209
formula administration, 198 Kidshape, 175 classification of, 205
nutrition requirements, SHAPEDOWN, 175 etiology, 206
196–197 Traffic Light Diet, 174–175 laboratory tests for, 207t
positioning and oral feeding, French Women Don’t Get Fat Diet, meal-planning guidelines, 208
197 171–172 oral nutrition, 208
oral motor dysfunction, 192–193 Pritikin Diet, 173 prevalence, 204
z scores, 192, 193 South Beach Diet, 172 Eating disorder not otherwise
Developmental origins of health and Suzanne Somers Diet, 173 specified, 206f
disease (DOHaD), 112, 115 types Egg allergy, 233, 463
animal models, 112–114 behavioral weight-loss plans, Electrolyte(s)
“fetal salvage” hypothesis, 112 171–172 assessment, 90, 90t
INDEX 499
dosing guidelines, 440t feeding tolerance assessment, 457 Epi-Info nutrition calculator, 146
in parenteral nutrition, 440 in food allergies, 223 Escherichia coli, 346t
in renal disease, 267 for eating-disordered patients Essential fatty acid deficiency
Energy bolus feedings, 208 (EFDA)
requirements formula type, 208 in cystic fibrosis, 326
in acute kidney injury, 271 manipulative behaviors, 208 in developmental delay, 193
in anorexia nervosa, 206 route of feeding, 208 infant formulas and, 135
in binge-eating disorder, 206 formula in liver disease, 304
in burn patient, 383–384 hang time, 455 in parenteral nutrition, 439
in cancer patient, 367t preparation, 455 Ethics
in chronic kidney disease, 263, in hematopoietic stem cell case studies, 483–484
277t transplant recipients, 358 childhood obesity, 483
in congenital heart disease, 249 indications for, 436t clinical care as team approach, 485
in cystic fibrosis, 325-326 intake and output, 457 in feeding disorders, 483
in eating-disordered patient, in intestinal failure/short bowel in intensive care environment, 481
206 syndrome, 313–314 models
in hematopoietic stem cell in liver disease, 308 educators, 479
transplant patient, 356, 356t in renal disease, 435 good shepherds, 478–479
in liver disease, 307 medication administration, liberators, 479
in premature infant, 410 457–458 “natural” vs. “medical” nutrition
Enteral nutrition nursing care, 456 provision, 479
aspiration precautions, 457 reflux, 456–457 nutrition goals determination,
bolus feedings, 454, 455 residuals, 456 479–480
in bronchopulmonary dysplasia, route of administration, 435–436 overview, 477
436 route selection, 451–452 palliative care, 482
in cancer patients, 353–354 safety issues, 455–456 special needs, infants and toddlers,
in chronic kidney disease, 272 site care, 456 482
in congenital heart disease, 250, transplant recipients truth-telling, 478
436 intestine, 340–341 values ascribed to feeding,
combination feedings, 454, 455 kidney, 342–343 480–481
continuous feedings, 454, 455 liver, 341 Extrauterine growth retardation, 116
in continuous renal replacement lung, 344
therapy, 270 tube flushing, 456 F
in critically ill patients, 435 tube placement, 453 Failure to thrive, 145, 286
in cystic fibrosis, 436 verification methods, 453–454 Familial hypercholesterolemia (FH),
in developmental delay, 197–198 tube securement, 456 163
in diabetes mellitus tube weaning, 458, 458t Fat(s)
choice of formula, 229 types of tubes absorption, 26
insulin administration, 229 gastrojejunostomy, 453 adipose tissue, 24
evaluation and monitoring gastrostomy, 453 classification, 23f
anthropometric measurements, jejunostomy, 453 digestion, 25
462t nasogastric tube, 452–453 in eating disorders, 207
formula tolerance, 461 orogastric, 453 fuel for preterm infant, 27
laboratory values, 462, 462t when to use, 433–434 functions, 24f
oral feeding, 462 Enterobacter sakazakaii, 123, 124, in sports nutrition, 181
parameters, 462t 137 trans, 23
revision of plan, 463 Eosinophilic esophagitis, 222–223 triglycerides, 22
feeding advancement, 454–455 Eosinophilic gastroenteritis, Fatty acid(s)
feeding pumps, 455–456 296-297, 297t essential, 23–24
500 INDEX
long chain, 23 macronutrients, 107–108 mandatory food labeling, 221

medium chain, 23 vitamin B12, 108 Food allergies, 213–224
monounsaturated, 22–23 vitamin E, 108–109 algorithm for evaluation of, 217f
oxidation, 26–27 metabolic mediators anaphylaxis, 214t, 215–216
polyunsaturated, 23 cortisol, 106 and other allergic conditions, 215
Vitamin E intake, 23 insulin, 106 Centers for Disease Control and
saturated, 22, 23f insulin-like growth factors, 106 Prevention statistics, 214
short chain, 23 prenatal stress, impact of, 109–110 clinical assessment, 218
synthesis, 26 substrate metabolism, 106 clinical presentation, 215–216
Feeding difficulties Fetal origins of adult disease, common definitions, 214t
aspiration, 193 110–111 cow’s milk protein allergy, 222
nutrient losses, 193 Fluid(s) definitions, 213–214, 214t
solid foods, 4 body distribution, 87–88, 88t eosinophilic esophagitis, 222–223
Feeding disorders deficit calculation, 89 epidemiology, 214–215
ethical considerations, 483 imbalance, 90 food protein-induced enterocolitis
etiology of, 443 maintenance, 412, 412t syndrome, 216
evaluation and treatment, regulation, 88–89 immunoglobulin E mechanisms,
443–444 requirements 213–214
nutrition intervention, 445t in chronic kidney disease, 265 laboratory assessment, 218
posttransplant in hematopoietic stem cell major allergens, 215
liver, 342 transplantation patient, 357 management, 216–217
treating, 443t Holliday-Segar Formula, 89t micronutrient supplementation,
Feeding teams, 8–9, 442–443, 444, in intestinal failure/short bowel 221–222
444f syndrome, 314 milk substitutes, 221
Female Athlete Triad, 185t in kidney transplant, 269, National Health and Nutrition
Fenton fetal-infant growth chart, in liver disease, 308 Examination Survey results,
422f pediatric, 89–90 215
Fetal development Fluoride nutrition assessment, 217–218
epigenetic changes, 107 drinking water levels, 414t nutrition intervention, 220
glucose supply, 106 requirements, in adolescents, 414 nutrition risk, 218t
growth, supplementation, 414, 414t oral allergy syndrome, 214t, 215
effect of calcium, 108 topical, 414 pathophysiology, 215
effect of iron, 108 Folate, 65–66 pediatric formulas, 220t
effect of protein, 107–108 absorption, 65–66 radioallergosorbent test, 216
effect of vitamin E, 108–109 biochemistry, 65 resources, 220t
folic acid and, 108 deficiency state, 66 skin prick testing, 216
vitamin B12, 108 dietary reference intake, 58t toddler diets, case scenarios, 219t
hypothalamic-pituitary-adrenal excretion, 65–66 tolerance, 213
(HPA) axis, 107, 109–110 metabolism, 65–66 Food and Drug Administration
insulin-responsive tissues, 106 physiology, 65 (FDA)
intrauterine insults, 107 source, 65 aluminum content labeling, 442
liver, 106 supplementation, 66 breast milk safety, 124
macronutrients in Folic acid, 108, 264 regulation of dietary supplements,
amino acids, 106 Food Allergen and Consumer 46
glucose, 106 Protection Act (FALCPA), 221 Food protein-induced enterocolitis
maternal nutrition and Food allergens syndrome (FPIES), 216
calcium, 108 alternative substitutes, 219t Food safety, 345
folic acid, 108 cross-contamination, 221 Foodborne pathogens, 346t
iron, 108 hidden, 221, 222t
INDEX 501
G height (length/stature), 144–145, recipient

Galactosemia 144t anthropometric assessment,
etiology, 241–242 ideal body weight, 146 356
management percentiles caloric requirements, 356, 356t
acute, 242 z score comparisons, 146t fluid requirements, 357
chronic, 242 time intervals, 144t mineral requirements, 357
diet, 242t weight, 144, 144t nutrition evaluation, 355–356
Gastroesophageal reflux (GER), 286, weight-for-length percentiles, 145 protein requirements, 356, 356t
332, 390 Growth charts vitamin requirements, 357
Gastrointestinal disease Fenton fetal-infant, 422f Hemodialysis (HD)
disordered ingestion, 283-284 interpreting, 146–147 in chronic kidney disease,
failure of absorption, 284 limitations, 147 258–259
failure of digestion, 284 Lubchenco, 410 in hypercalcemia, 97
functional disorders, 295-296 National Center for Health for hypermagnesemia, 96
increased needs, 284 Statistics, Centers for Disease phosphorus clearance, 267
nutrition assessment, 284-285, Control and Prevention, 143, Holliday-Segar Formula, 49t
285t 411, 416, 423f–430f Honey, 139
Gastrojejunostomy tube(s), 198, 404, World Health Organization, Human milk, 120–124
453 143–144 banked, 123
Gastroparesis, 295-296, 295t Growth hormone (GH) therapy, calcium content, 48
Gastrostomy (G) tube 260f fortification, 122–123, 122t
“button” device, 198t Growth velocity, 411t hind milk, 122–123
in esophageal atresia, 393 iron content, 123
insertion, 404, 453 H phosphorus content, 51
PERT supplements, 330 Healthy People 2010, 120 vitamin D content, 123
safety issues, 450 Heart transplantation Human Milk Banking Association of
Glucocorticoids biochemical tests, 339t North America, 124
effect on fetus, 109–110 recipient Hydration
as preterm delivery treatment, 109 dietary modificiation, 344 guidance, 181t
Glucose nutrition requirements, 344 in sports nutrition, 181–182
as fetal energy source, 106 Hematopoietic stem cell Hydrochloric acid, 32
in trauma response, 378–379 transplantation (HSCT), 354–362 Hyperalbuminemia
Glycogen storage diseases (GSDs), complications in burn patients, 384
306 bacterial overgrowth, 361 Hyperammonemia
Graft versus host disease, 360–361, graft versus host disease, treatment of, 37
361t 360–361, 361t Hypercalcemia, 50
Growth hemorrhagic cystitis, 362 Hypercalciuria
average daily intrauterine weight infections, 361 kidney stones and, 275
gain, 411t mucositis, 360, 372–373 Hypergastinemia, 316
breastfed infants, 123–124 pancreatic insufficiency, 361 Hyperglycemia
chronic kidney disease and, sinusoidal obstruction in burn patient, 384
259–260 syndrome, 362 in critically ill patient, 227–228
overview, 143–144 diet restrictions, 357–358 in refeeding syndrome, 209
of premature infant, 410 medication side effects, 359t in organ transplant recipient, 269,
Growth assessment nutrition support, 358-360 341, 343, 344, 345
body mass index, 146 enteral nutrition, 358 in trauma patient, 380
failure to thrive (FTT), 145 oral, 357 Hyperhomocysteinemia, 264
head circumference, 144t, 145 procedure, 355 Hyperkalemia, 341
502 INDEX
Hyperlipidemia, 341, 343 Immunosuppressive medications, extensively hydrolyzed protein,

Hypermagnesemia 344, 345 134, 135t
manifestations, 53 kidney damage from, 269 reduced fat/modified fat, 135,
neonatal, 53 side effects, 269 137t
Hypermetabolism Immunosuppressive therapy reduced mineral, 135, 137t
in cirrhotic patients, 304–305 noncompliance with, 346 types
in liver disease, 304–305 Inborn errors of metabolism (IEM), for symptoms of intolerance,
Hypernatremia 232-242 130, 132t
in nephrogenic diabetes insipidus, defined, 232 added rice starch, 132–133,
277 newborn screening, 233 132t
Hyperphosphatemia, 52 nutrition management, 233f lactose-free, 132, 132t, 220,
Hypertension symptoms, 233t 220t
in transplant recipients, 341, 343, Indirect calorimetry, 197t partially hydrolyzed
344 Infant formula protein,130-131, 132t,
Hypervolemia, 89 as breast milk additive, 138 220, 220t
Hypocalcemia, 49 calcium salts, 48 premature discharge, 134, 135t
Hypoglycemia concentrating, 250t premature or low birth weight,
in liver disease, 302 contamination, 124, 137 133, 134t
in young children, 228 design of, 129–130 soy-based,133, 133t, 220, 220t
Hypokalemia forms standard milk-based, 130, 131t
in chronic kidney disease, 266 liquid concentrate, 137 whey-based, for chronic kidney
in refeeding syndrome, 209, 210 powder, 137–138 disease, 273
Hypomagnesemia ready-to-feed, 137 Infant(s)
definition, 53 functional ingredients appetite development, 4
etiology, 53 arachidonic acid (ARA), complementary foods, 139
in refeeding syndrome, 209, 210 135–136 feeding problems, 6–7
in transplant recipients, 341 docosahexaenoic acid (DHA), feeding skills, 5–6
manifestations 135–136 hypomagnesemia, 53
adults, 53 nucleotides, 136 iron deficiency, 123
infants, 53 prebiotics, 136 neonatal cholestasis, 305
Hypophosphatemia probiotics, 136–137 neophobia, 4
etiology, 51 lactose in, 17 premature
in chronic kidney disease, 266 magnesium requirements, 52 birth weight classification, 410t
in refeeding syndrome, 209 manufacturers’ Web sites, 130t calcium requirements, 413
manifestations, 51 medium-chain triglyceride, 252t delayed gastric emptying, 13
Hypothalamic-pituitary-adrenal mixing magnesium overdose, 53
(HPA) axis, 107 increasing caloric necrotizing enterocolitis, 18
prenatal programming, 109-110, concentration, 138, 138t nutrition assessment, 409–411
110f modular macronutrients, 138 Inflammatory bowel disease,
in trauma response, 378 standard dilution, 138 289–291
Hypothalamus, 4 water, 138 Inhalation injury, 383
Hypovolemia, 89 phosphorus content, 51 Insensible water loss, 90, 332
Portagen®, 124 Insulin
I regulation, 130 in enteral nutrition, 229
Immunoglobulin E (IgE) specialized in parenteral nutrition, 229
in food allergies, 214 amino acid based, 134–135, Intestinal adaptation
mediated allergic diseases, 136t, 220, 220t role of ileal-cecal valve, 313
215–216 carbohydrate free, 135, 136t surgical procedures
reaction, 214 Bianchi procedure, 313
INDEX 503
longitudinal intestinal K Lipid disorders, 162–167

lengthening and tailoring Kidney(s) fasting lipid profile interpretation,
(LILT), 315 amino acid metabolism, 39 164t
Serial Transverse Enteroplasty functions, 257 genetic
(STEP), 313, 315 injury, 381 familial hypercholesterolemia,
Intestinal failure (IF) nephrogenesis, 257 163
causes, 312t phosphorus homeostatis and, 51 lipoprotein lipase deficiency,
complications transplantation 163
bacterial overgrowth, 316 biochemical tests nutrition management
bile acid malabsorption, 316 339t antioxidants, 166
D-lactic acidosis, 316 calcium intake, 269 dietary cholesterol, 164, 166t
hypergastinemia, 316 cardiovascular disease and, 269 fiber, 165
nephrolithiasis, 316 complications, 343–344 garlic, 166
rapid intestinal transit, 316 fluid intake, 269 monounsaturated fats, 165
definition, 312 recipient omega-3 fatty acids, 166, 166t
etiology of, 313 nutrition requirements, plant sterols/stanols, 165–166
management 342–343, 343t polyunsaturated fats, 165
enteral nutrition, 313–314 trauma to, 381 saturated fats, 164–165, 166t
fluids, 314 Kidney disease. See also Acute simple carbohydrates, 165, 166t
general principles, 315–316 kidney injury soy protein, 166
medications, 314–315 chronic trans fats, 165, 166t
parenteral nutrition, 314 effect on growth, 259–260 pharmacologic intervention, 167
nutrition deficiencies, 316 incidence, 256 physical activity, 166, 166t
prevalence of, 312 nutrition assessment, 261–268 polygenic
Intestine transplantation, 318, 339t, primary diagnosis, 258t hypercholesterolemia
340, 341 stages of, 257t, 258 (nonfamilial), 163
Intrauterine growth restriction nephrotic syndrome, 274 screening for, 163t
(IUGR), 106, 410 stages, 257t, 258 Lipoprotein lipase (LPL) deficiency,
maternal dietary deficiencies, 107 Kidney stones. See Renal stones 163
placental transport insufficiency Listeria monocytogenes, 346t
and, 106 L Liver
placental weight, 106 Lactase, 17, 18, 18f amino acid metabolism, 38–39
Intravenous fat emulsion (IVFE), Lacto engineering, 122 functions, 302
437, 439, 439t Lactobacillus, 120 injuries to, 380–381
Irritable bowel syndrome, 296 Lactobacillus GG, 137 transplantation
Iron Lactoferrin, 123 biochemical tests, 339t
human milk fortifier, 123 Lactose, 17–19 recipient
deficiency, 113, 413 Lanthanum carbonate, 267 feeding disorders, 342
fetal growth and, 108 Length board, 414 growth and development,
lactoferrin and, 123 Leptin 342
requirements appetite control, 4 nutrition requirements, 341
adolescents, 413 food intake and adiposity, 113 parenteral nutrition, 341,
premature infants, 413 liver disease and, 303 342t
Iron deficiency anemia, 413 Leucine, 35 Liver disease, 302–309
in fetal development, 106 anorexia in, 303
J Lipase energy requirements, 307
Jejunostomy tube, 453 gastric, 25, 32 fat-soluble vitamin
in pancreatic trauma, 381 supplementation, 307–308,
308t
504 INDEX
fluid requirements, 308 Malnutrition, inflammation, and deficiency states, 47–48

glycogen storage diseases, 306 atherosclerosis syndrome (MIA), dietary requirements, 46
malnutrition in 268 metabolism, 47
hypermetabolism, 304–305 Mastication, 4–5 serum concentrations, 45
iatrogenic factors, 303–304 Meconium ileus, 324 sources, 46
inadequate dietary intake, 303 Medium-chain triglyceride(s) in sports nutrition, 182
malabsorption, 304 (MCTs) supplements, 46
non-cholestatic, 305–306 in chylothorax management, 252 Minimal change disease, 274
nonalcoholic fatty liver disease in enteral nutrition, for liver Motility
(NAFLD), 306 disease, 308 delayed gastric emptying, 13–14
parenteral nutrition and, 308, 317 formulas, 252t dumping, 14
protein requirements, 307 Metabolic bone disease, 263, 470 gastric, 12
salt depletion syndrome, 303 Metabolic disorders, 149–158, 467t intake and motor activity
Wilson’s disease, 306 Metabolic syndrome caloric density, 13
Lung disease Acanthosis nigricans, 154 consistency, 13
asthma, 333 cluster nutrient content, 13
bone health and, 334 pediatric population and, 153 osmolarity, 13
bronchopulmonary dysplasia, in adults, 150–151 rapid intestinal transit, 14
332–333 controversies slow intestinal transit, 14
nutrition assessment, 333 cut-points, 151 small bowel, 12–13
nutrition recommendations, 334 etiology, 151 in trauma patients, 379
pathophysiology, 332 risk and treatment, 151 Mucositis, 360, 372–373
technology dependent, 333 diagnostic criteria, 150t Munchausen Syndrome by Proxy,
Lung transplantation etiology, 150t 450
biochemical tests, 339t in children, 151–153 Myelomeningocele, 192, 193, 333
complications, 344–345 controversies
in cystic fibrosis, 332, 344 cut-points, 152 N
non-traditional Nasogastric tube, 329, 452–453
M cardiovascular risk Nasojejunal tube, 453
Magnesium factors, 152–153 National Cholesterol Education
absorption, 52 puberty, 152 Program, Adult Treatment Panel
body content, 45, 52 Northern Manhattan Family III (NCEP-ATP III)
deficiency, 53 Study, 154 metabolic syndrome, 150t
dietary reference intake, 46t overview, 149–150 recommendations, 155–156,
excess intake, adverse effects, 53 risk factor profile, 153–155 157
excretion, 52 Methylmalonic acidemia risk factor profile, 153–155
in infant formulas, 52 etiology, 237, 238f National Health and Nutrition
metabolism, 52–53 management Examination Survey
in chronic kidney disease, 268 acute, 238 food allergies, 215
physiological function of, 52 chronic, 238–239 National Kidney Foundation, 258
renal transport, 52 Migrating motor complex (MMC), National Kidney Foundation Kidney
sources, 52 12 Disease Outcomes Quality
tissue distribution, 52 Milk substitutes, 221 Initiative (NKF KDOQI), 257,
Malnutrition nutrition comparison with whole 266
in chronic kidney disease, 258 milk, 221t Necrotizing enterocolitis (NEC)
in liver disease, 303–305 Mineral(s), 45–55 breast milk and, 121
Waterlow criteria, 411, 411t absorption in premature infants, 18
World Health Organization intestinal, 46 Neonatal hypermagnesemia, 53
classification, 145t renal, 46 Neonatal cholestasis, 305
INDEX 505
Neonatal iron storage disease, 305 of premature infants nutrition assessment, 339–340
Nephrocalcinosis, 276, 278 Ballard score, 409–410, 410t nutrition requirements,
Nephrogenesis, 257 classification parameters, 340–341, 342–343, 344
Nephrogenic diabetes insipidus 409–410 survival rates, 346
(NDI), 277–278 Lubchenco growth chart, 410 Ornithine transcarbamylase
Nephrolithiasis, 276, 316 physical examination, 417, 417t deficiency
defined, 274 pretransplant, 339–340 etiology, 239
risk factors, 274 Waterlow criteria management
Nephrotic syndrome, 274 stunting, 411, 411t acute, 239
Neural tube defects, 108 wasting, 411, 411t chronic, 240
Niacin, 63–64 Nutrition intervention urea cycle, 239f
absorption, 63–64 in cancer patients, 352, 353t Orogastric tube, 453
biochemistry, 63 feeding disorders, 445t Osteopenia, 46, 194, 442
deficiency state, 64 Nutrition support Osteoporosis
dietary reference intake, 58t in burn patients, 384 and cystic fibrosis, 331
excretion, 63–64 closed head injuries, 380 in pediatric cancer patients, 363
metabolism, 63–64 for cystic fibrosis, 329–330 in transplant recipients, 344, 345
physiology, 63 developmental delay, 196–199
source, 63 during trauma, 379 P
supplementation, 64 for eating disorders, 208 Pancreas
Non-cholestatic liver disease, pancreatic trauma, 381 fetal, 106
305–306 traumatic brain injury, 380 injury to, 381, 385
Non-insulin-dependent diabetes Pancreatic enzyme replacement
mellitus, 110–111 O therapy (PERT), 330
Nonalcoholic fatty liver disease Obesity posttransplant, 344
(NAFLD), 306 breastfeeding, 111 Pancreatic insufficiency, 292–293,
Normalized protein catabolic rate cardiovascular disease, 252–254, 292t
(nCPR), 258–259 268 Pancreatic pseudocyst, 381
Norovirus, 346t childhood, 169–170 Pancreatitis, 293–294
North American Pediatric Renal clinical approach, 170 Panhypopituitarism, 230
Trials and Collaborative Studies ethical considerations, 483 Pantothenic acid
(NAPRTCS), 257 postnatal weight gain and, 111 absorption, 69
Northern Manhattan Family Study, in trauma patients, 379, 384–385 biochemistry, 69
154 Oral allergy syndrome, 214t, 215 deficiency state, 69
Nutrition assessment Oral motor dysfunction, 192–193 dietary reference intake, 58t
of adolescents, 412–414 Organ transplantation excretion, 69
biochemical indices, 416–417 biochemical tests pretransplant, metabolism, 69
of children, 411t , 411–412 339t physiology, 69
in cancer patients, 352–353, 352t complications, 343, 346 source, 69
in cystic fibrosis, 325, 325t foodborne illnesses, 345 supplementation, 69
in chronic lung disease, 333 immunosuppressive therapy, 344, Parenteral nutrition
in congenital heart disease, 346 access, 437
249–250, 249t indications for, 338–339, 338t additives
in developmental delay, 194–196 physical examination, 339 carnitine, 441–442
in food allergies, 217–218 quality of life, posttransplant, 346 cysteine, 442
of full-term infants, 411t, 411–412 recipient cysteine hydrochloride salt, 36
in gastrointestinal disease, anthropometric assessment, heparin, 441
284–285, 285t 338 aluminum in, 442
in liver disease, 307, 413–414 dietary modification, 344 amino acid solutions, 37
506 INDEX
in anorexia nervosa, 437 limits, 471t Peripheral parenteral nutrition

in burn patients, 384 in liver disease, 308, 317 (PPN), 433, 437, 449
in cancer, 354 macronutrients Peripherally inserted central catheter
central parenteral nutrition, 433 amino acids, 437–439, 438t (PICC), 449
central venous lines, 437 carbohydrates, 437 Peristalsis, 12
cholestasis, 389–390, 439 magnesium overdose, 53 Peritoneal dialysis (PD), 259
in chronic kidney disease, 274 medications Phenylalanine, 35
complications, 442 compatability of, 467 Phenylketonuria (PKU)
metabolic bone disease, 470 drug-nutrient interactions, etiology, 234, 234f
in congenital heart disease, 466–467, 467t low-phe formula calculation, 235f
250–251, 437 nursing care, 451, 452t management
in diabetes mellitus, 228 peripheral, 433, 449 acute, 234–235
choice of dextrose solution, 228 in premature infants, 410, chronic, 235
insulin infusion, 228–229 436–437 maternal, 234
in eating-disorders, 208 safety issues meal plan for, 236t
egg allergy, 233 bloodstream infections, 317, recommended nutrient intakes,
electrolyte dosing guidelines, 440t 450, 470 235t
evaluation and monitoring prevention of, 451t supplementation
blood urea nitrogen level, 463 Munchausen Syndrome by Proxy, cofactors, 237
calcium solubility, 465t 450 large neutral amino acids, 237
calcium-phosphorus site care, 450 tyrosine requirement in, 37
precipitation, 465, 465t chlorhexidine gluconate, 450 Phosphorus
form, 472f Guidelines for the Prevention absorption, 51
formulation integrity, 464–465 of Intravascular binding medications, 51
infusion-related incidents, 463 Cather Infections biochemistry, 50
macronutrient tolerance, recommendations, 450 body content, 45, 50
463–464 total nutrient admixtures deficiency, 51
parameters, 464t advantages and disadvantages, dietary reference intake, 46t
phosphorus solubility, 465t 466t effect on calcium, 49
total nutrient admixtures, factors affecting stability, 465t excess intake, adverse effects,
464–465, 465t, 466t in trauma, 379 51–52
volume tolerance, 463 trace elements excretion, 51
for food allergic patient, 223–224 chromium, 441, 441t glomerular filtration rate and, 51
gastrointestinal conditions, 436 copper, 440, 441t human milk content, 51
in hematopoietic stem cell manganese, 441, 441t intake from soft drinks, 50
transplant, 358 selenium, 441, 441t kidney as regulator as, 51
indicators for, 437 zinc, 440, 441t management, in chronic kidney
initiation and advancement of, in transplantation disease, 266–267
440t intestine, 340–341 physiological function of, 50
in intestinal failure/short bowel liver, 341, 342t serum concentration, 50
syndrome, 314 vitamins, 441t sources, 50–51
intradialytic, 274 when to use, 433–434 tissue distribution, 50
intravenous catheters Pelvic injury, 382 Phosphorus binders, 267
central venous catheter, 449 Pepsinogen, 32–33 Placental transport insufficiency, 106
peripherally inserted central Peptide, 32, 32t Prebiotics 136
catheter, 449 Peripheral blood stem cell Pregnancy
intravenous fat emulsion, 437, 439, transplantation (PBSCT). dietary reference intakes, 108t
439t See Hematopoietic stem cell epigenetic changes, 107
laboratory tracking sheet, 473f transplantation (HSCT) intergenerational effects, 114–115
INDEX 507
intrauterine growth restriction, Renal failure Short bowel syndrome (SBS), 312
106 creatinine clearance, 257 Shwachman-Diamond syndrome,
intrauterine insults, 107 nutrition management, 277t 304
maternal nutrition effect on fetus, oxalosis, 278 Sinusoidal obstruction syndrome
107–109 Renal stones (SOS), 359
nutrition physiology, 105–107 2,8-dihydroxyadenine calculi, 276 Sirolimus, 269, 343
recommended daily nutrient calcium-based, 275–276 Skeleton
intakes, 108t cystine stones, 274 as mineral reservoir, 45–46
Primary hyperoxaluria, 278 cystinuria, 276 growth, 46
Probiotics, 136–137 “infection stones,” 276 injuries to, 382
Protein catabolic rate (PCR), 258 nutrition management, 275t Skin prick testing, 216
Protein(s) in pediatric patients, 275 Small intestine
absorption, 33–34 struvite calculi, 274, 276 injuries, 382
dietary reference intake, 412t uric acid, 274, 276 motility, 12–13
digestion, 32–33 xanthine stones, 276 Sodium
effect on fetal growth, 107–108 Renal tubular acidosis, 276–277 absorption, 91
ontogeny and gastrointestinal Renal tubular disorders balance, 91
tract, 31–32 Bartter’s syndrome, 277 deficiency, in cholestatic liver
requirements nephrogenic diabetes insipidus, disease, 303
in acute kidney injury, 271 277–278 losses, 91, 182
in burn patient, 384 renal tubular acidosis, 276–277 management, in chronic kidney
in chronic kidney disease, 263, Resting energy expenditure (REE) disease, 265
277t in burn patient, 384 physiological effects, 91
in continuous renal replacement in developmentally delayed child, serum level
therapy, 270 193 normal, 91
in cystic fibrosis, 326 in liver disease, 304 Spastic hemiplegia, 192
in eating disorders, 207 in trauma patients, 379 Spastic quadriplegia, 192
in hematopoietic stem cell World Health Organization Specialized nutrition support (SNS)
transplant patient, 356, 356t equation, 412, 412t chemistry profiles, 468
in liver disease, 307 Rett syndrome, 192, 193 evaluation and monitoring of,
in sports nutrition, 180–181, Riboflavin, 62–63 460–473
180t absorption, 62–63 laboratory values, 467, 471t, 473f
in transplant recipients, 340, biochemistry, 62 liver function tests, 468
344 deficiency state, 63 nutrition-related laboratory tests,
Protein-losing enteropathy (PLE), dietary reference intake, 58t 468
251 excretion, 62–63 physical data, 462t, 467–468
Pulmonary disorders, 323–334 metabolism, 62–63 reassessment of plan, 466, 466f
Purine, in uric acid stones, 276 physiology, 62 Spinal cord trauma, 380
source, 62 Spleen injury, 380
R supplementation, 63 Sports nutrition
Refeeding syndrome Rickets, 46, 413 at bedtime, 183
definition, 209 carbohydrates, 179–180
hyperglycemia, 209 S practical application, 180, 180t
hypokalemia, 209, 210 Salmonella, 346t challenges, 183, 185t
hypomagnesemia, 209, 210 Seatbelt injury, 381, 382 fat, 180t, 181
hypophosphatemia, 209 Serial transverse enteroplasty practical application, 180t, 181
incidence of, 209 (STEP), 313, 315 Female Athlete Triad, 185t
preventing, 210–211, 210t Serum albumin, 262 fueling for competition, 184t
treatment, 210–211, 210t Sevelamer carbonate, 267 hydration, 181–182, 181t
508 INDEX
practical application, 182 Swallowing metabolic response, 378–379

hyponatremia, 182 esophageal phase, 5 obesity and, 384–385
minerals, 182 oral phase, 5 pancreatic, 381
overview, 178–179 pharyngeal phase, 5 pelvic injury, 382
protein, 180–181 Syndrome of inappropriate physiological response, 378–379
practical application, 180t, 181 antidiuretic hormone (SIADH), renal, 381
recovery nutrition, 183 89, 380 small intestine and colon injuries,
resources, 183, 186t 382
timing to sport, 182–183, 184t T spinal cord injury, 380
vitamins, 182 Tacrolimus, 53, 269, 341, 345 syndrome of inappropriate
Standiometer, 414–415 magnesium deficiency and, 53 antidiuretic hormone (SIADH)
Starvation pathophysiology, 209 Thiamin, 61–62 in, 380
Stomach absorption, 61 thoracic injuries, 382
and food intake, 12 biochemistry, 61 traumatic brain injury, 380
injury to, 381 deficiency state, 61–62 Traumatic brain injury, 380
motility, 12 dietary reference intake, 58t Triglyceride(s)
Stool, monitoring, 461, 462t excretion, 61 defined, 22
Stunting, 411, 411t metabolism, 61 Tube feeding. See Enteral nutrition
Surgery physiology, 61 Tumor necrosis factor (TNF)
airway disorders, 400–401 source, 61 in trauma response, 378
anorectal malformations, 397 supplementation, 62 Type IIa Na/phosphate
biliary atresia, 399–400 toxicity, 78 cotransporter (Npt2a) protein, 51
choledochal cyst, 400 Thoracic injuries, 382 Tyrosine
colon atresia, 396 Toddler(s) intake requirements, 37
congenital diaphragmatic hernia, feeding problems, 7–8 N-acetyl-tyrosine (NAT), 37
399 feeding skills, 7 phenylketonuria and, 37
congenital heart disease, 251–252 formula, 139, 140t
distal intestinal obstruction, Total body water (TBW), 87, 88t U
395–396 Total nutrient admixtures (TNAs), U.S. Department of Agriculture,
duodenal atresia, 394–395 464–465, 465t, 466t Food Safety and Inspection
esophageal atresia, 393–394 Trans-fatty acids, 23 Service, 345
gastroschisis, 397–399 Transsulfuration pathway, 36 Umbilical cord blood transplantation
Hirschsprung’s disease, 396–397 Trauma (UCBT). See Hematopoietic stem
intestinal malrotation, 402 adrenal hemorrhage, 381 cell transplantation (HSCT)
intestinal perforation, 402 age-related injuries, 379 United Nations International
meconium ileus, 396 anatomical classification, 379 Children’s Fund (UNICEF), 121
midgut volvulus, 402 blunt abdominal, 380–381 Baby Friendly Hospital Initiative,
necrotizing enterocolitis, 401–402 hollow visceral injuries, 121
neonatal, 388–389 381–382 Urea cycle, 38f, 239f
neurosurgical disorders, 400 solid visceral injuries, 380–381 Uric acid stones, 274, 276
nutrient considerations, 387–388 brain injury, 380 Urinary extravasation, 381
omphalocele, 397 child abuse, 381
orthopedic disorders, 400 childhood, 379 V
proximal intestinal obstruction, clinical examples, 384–385 Vascular access device (VAD), 449
393 closed head injuries, 380 blood sample techniques, 450t
pyloric stenosis, 402–403 duodenal injuries, 381–382 Very long chain acyl-CoA
thoracic disorders, 400 extremity injury, 382 dehydrogenase deficiency
urologic disorders, 400 facial, 382 (VLCADD)
hyperglycemia and, 380 etiology, 240
INDEX 509
fatty acid oxidation and, 240f in chronic kidney disease, 264 Winkler, Marion, 3
management deficiency state, 68 World Health Organization
acute, 240 dietary reference intake, 58t breastfeeding, 120, 129
chronic, 241 excretion, 68 growth charts, 143–144
Video feeding study, 340 metabolism, 68 malnutrition classification, 145t
Vitamin(s) physiology, 67–68 metabolic syndrome, 150t
allergen-free, 222, 222t source, 68 resting energy expenditure
fat-soluble, 74–86 supplementation, 69 equation, 412, 412t
in sports nutrition, 182 Vitamin D
water soluble, 56–71 absorption, 79–80 X
Vitamin A biochemistry, 78–79 Xanthine stones, 276
absorption, 76–77 in chronic kidney disease,
biochemistry, 76 263–264, 266 Z
deficiency, 77–78 in cystic fibrosis-specific z scores
dietary reference intake, 75t multivitamins, 328, 327t in developmental delay, 192, 193
metabolism, 76–77 deficiency, 80, 413-414 percentile comparisons, 146t
physiology, 76 dietary reference intake, 75t Zinc
sources, 76 metabolism, 79–80 in chronic kidney disease, 265
toxicity, 78 physiology, 78–79 in cystic fibrosis-specific
Vitamin B1. See Thiamin sources, 79 multivitamins, 327t, 328
Vitamin B2 . See Riboflavin toxicity, 80 in eating disorders, 207
Vitamin B3. See Niacin Vitamin E in liver disease, 303, 308
Vitamin B5. See Pantothenic acid absorption, 81–82
Vitamin B6 biochemistry, 81
absorption, 64–65 in chronic kidney disease, 264
biochemistry, 64 in cystic fibrosis-specific
deficiency state, 65 multivitamins, 328, 327t
dietary reference intake, 58t deficiency, 82
excretion, 64–65 dietary reference intake, 75t
metabolism, 64–65 metabolism, 81–82
physiology, 64 physiology, 81
source, 64 sources, 81
supplementation, 65 toxicity, 82–83
Vitamin B7. See Biotin Vitamin K
Vitamin B9. See Folate absorption, 83
Vitamin B12 biochemistry, 83
absorption, 66–67 in chronic kidney disease, 264
biochemistry, 66 in cystic fibrosis-specific
in cystic fibrosis, 328 multivitamins, 328, 327t
deficiency state, 67 deficiency, 83–84
dietary reference intake, 58t dietary reference intake, 75t
excretion, 66–67 metabolism, 83
metabolism, 66–67 physiology, 81
physiology, 66 sources, 83
source, 66 toxicity, 84
supplementation, 67
Vitamin C W
absorption, 68 Wasting, 411, 411t
biochemistry, 67–68 Wilson’s disease, 306

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The A.S.P.E.N.

Pediatric Nutrition Support

Elizabeth Bobo, MS, RD, LDN, CNSD

Steve Plogsted, PharmD, BCNSP

Jane Anne Yaworski, MSN, RN

AMERICAN SOCIETY FOR PARENTERAL AND ENTERAL NUTRITION

Copyright © 2010. American Society for Parenteral and Enteral Nutrition.

Printed in the United States of America.

Contributors. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . v 7. Water-Soluble Essential Micronutrients. . . . . . . . . . . . . . 56

Janice Antino, RD, MS, CNSD, CSP Brian S. Carter, MD

Jane P. Balint, MD Anupama Chawla, MD, CNSP, DCH (UK)

Neelam Katyal, MS, RD, LDN Allison Mallowe, RD, LDN

John A. Kerner, MD Goldie Markowitz, MSN, CRNP

Samuel A. Kocoshis, MD Barbara Marriage, PhD, RD

Kathleen J. Motil, MD, PhD Susan R. Rheingold, MD

Robert Murray, MD Judith C. Rodriguez, PhD, RD

Robert H. Squires, Jr., MD Letitia Warren, RD, CSP

Michelle Strup, PharmD Jacqueline J. Wessel, RD, CNSD

Craig Lawrence Kien, MD, PhD Carrie McFarland, RD, CNSD

Jill Rockwell, RD, LD, CNSD Eric Sibley, MD, PhD

The A.S.P.E.N. Pediatric Nutrition Support Core Curriculum

I have to thank Michelle Spangenburg and Nina Seebeck

1. Mechanics of Nutrient Intake. . . . . . . . . . . . . . . . . . . . 3

CONTENTS Learning Objectives

© 2010 A.S.P.E.N. www.nutritioncare.org

© 2010 A.S.P.E.N. www.nutritioncare.org

© 2010 A.S.P.E.N. www.nutritioncare.org

© 2010 A.S.P.E.N. www.nutritioncare.org

© 2010 A.S.P.E.N. www.nutritioncare.org

• a child psychologist; Test Your Knowledge Questions

© 2010 A.S.P.E.N. www.nutritioncare.org

© 2010 A.S.P.E.N. www.nutritioncare.org

CONTENTS Learning Objectives

© 2010 A.S.P.E.N. www.nutritioncare.org

an abrupt cessation of intestinal contractions after a bolus Caloric Density

© 2010 A.S.P.E.N. www.nutritioncare.org

© 2010 A.S.P.E.N. www.nutritioncare.org

17. Berseth CL Effect of early feeding on maturation of the

© 2010 A.S.P.E.N. www.nutritioncare.org

© 2010 A.S.P.E.N. www.nutritioncare.org

Contents Learning Objectives

Reprinted from Shulman RJ. Intraluminal digestion and absorption in

In many individuals, lactase activity begins to decline

© 2010 A.S.P.E.N. www.nutritioncare.org

© 2010 A.S.P.E.N. www.nutritioncare.org

Absorption breath test. Stool pH of < 5.5 is indicative of short-chain

© 2010 A.S.P.E.N. www.nutritioncare.org

© 2010 A.S.P.E.N. www.nutritioncare.org

CONTENTS Learning Objectives

Different Types of Fat

Figure 4-1 Structural Representation of a Saturated Fatty Acid

Membrane fluidity is important in the function of many

© 2010 A.S.P.E.N. www.nutritioncare.org

© 2010 A.S.P.E.N. www.nutritioncare.org

© 2010 A.S.P.E.N. www.nutritioncare.org

Absorption EPA, and DHA.22,23 The optimal ratio of preformed EPA

© 2010 A.S.P.E.N. www.nutritioncare.org

Steps of Beta-Oxidation Metabolism During Pathophysiologies

© 2010 A.S.P.E.N. www.nutritioncare.org

To Esterify or To Oxidize: That Is the Cell’s Question

© 2010 A.S.P.E.N. www.nutritioncare.org

© 2010 A.S.P.E.N. www.nutritioncare.org

© 2010 A.S.P.E.N. www.nutritioncare.org

CONTENTS Learning Objectives