Bil

CORRELATION OF CORD BLOOD BILIRUBIN AND
NEONATAL HYPERBILIRUBINEMIA IN NEWBORNS

WITH A SETTING OF ABO INCOMPATIBILITY
By
Dr. SAJJAD SANEEQ C.H
Dissertation Submitted to the
Rajiv Gandhi University of Health Sciences, Karnataka, Bangalore
In partial fulfillment
Of the requirements for the degree of
DOCTOR OF MEDICINE
In
PEDIATRICS
Under the guidance of
Dr. SANJEEV SHRINIVAS MANAGOLI
PROFESSOR
DEPARTMENT OF PEDIATRICS
M.V.J. MEDICAL COLLEGE AND RESEARCH HOSPITAL
DANDUPALAYA, BANGALORE
2012
i
ACKNOWLEDGMENT
It is with great privilege, I express my most humble and profound gratitude to
my Teacher and Guide Dr. SANJEEV SHRINIVAS MANAGOLI Professor
Department of Pediatrics. M.V.J. Medical College and Research Hospital for his
guidance, able supervision, valuable suggestions, cyber help and constant
encouragement throughout the study which facilitated the completion of this
dissertation. He has made me realize that there is no substitution for hard work and
revision for perfection.
I am thankful to Dr. B. RAVI CHANDER Professor, Head of the Department,
Department of Pediatrics, M.V.J. Medical College and Research Hospital for his
valuable suggestions and constant encouragement throughout the study which has
helped me greatly to expedite this dissertation and for his guidance, encouragement
and moral support during my career as a postgraduate, who taught me to take care of
simple things initially so that bigger issues gets solved by its own.
I express my deepest sense of gratitude to my eminent and esteemed teacher
Dr.T.S RAGHU RAMAN, Principal M.V.J. Medical College and Research Hospital
for permitting me to carry out this study, his unabated inspiration, constant support and
encouragement.
I am extremely grateful to Dr. M. J. Mohan and Mrs. Dharani Mohan, for
their kind co-operation, encouragement, moral support in conducting my study and for
providing a home away from home during my career as a postgraduate.
I am extremely grateful to all my distinguished Professors, Dr. Jaishree R.
Kamat, who helped me to take lot of responsibilities and showed importance of
discipline during major part of final year posting under her, Dr. Gopal for his vast
experience filled advices, Associate Professors, Dr. Poornima S and Dr. Santhosh
vi
for helping in literature search and timely advices. Assistant Professors, Senior
Residents and Junior Residents, staff nurses, of the Department of Pediatrics for
their kind co-operation and encouragement in conducting my study and for their
guidance, inspiration and moral support during my career as a postgraduate.
I am thankful to Dr. Gurumurthy, Professor, Head of the Department,
Department of Biochemistry, M.V.J. Medical College and Research Hospital, the
Faculty and the Technicians of Biochemistry for their constant support to complete
my study.
I thank my fellow Post graduates Dr. Amitoj, Dr. Kiran and post-graduate
colleagues in Pediatrics, both past and present, for their support and co-operation.
Most important of all I shall be failing in my duties if I do not thank all the
MOTHERS AND BABIES included in the study, without whom this study would
not have been possible.
I owe my gratitude to my Parents and my lovely Wife and Son whose love
and support constantly beholds me.
I certainly owe my thanks to all the people especially Paediatric Department
Assistant, Office Stenographer, Statistician, who have helped me directly or
indirectly in accomplishing this work.
Finally I thank god, for making all these wonderful people happen to me and
pray for continued blessing and success.
Date: Signature of candidate
Place: Dr. Sajjad Saneeq C.
vii
LIST OF ABBREVIATIONS
(In alphabetical order)
AAP : American Academy of Pediatrics
AGA : Appropriate for Gestational Age
CBB : Cord Blood Bilirubin
DAT : Direct Anti-globin Test
ETCOC : Corrected ambient carbon monoxide
gm : Gram
HDN : Haemolytic disease of newborn
LBW : Low Birth Weight
NH : Neonatal Hyperbilirubinemia
NICU : Neonatal Intensive Care Unit
NPV : Negative predictive value
PPV : Positive predictive value
PT : Phototherapy
Rh : Rhesus
SGA : Small for Gestational Age
TCB : Transcutaneous Bilirubin
TSB : Total serum bilirubin.
viii
ABSTRACT
Background and Objectives
The incidence of Rh D allo-immunization has decreased after the introduction
of anti-D prophylaxis, and so ABO incompatibility is now the major cause of immune
haemolytic disease of newborn (HDN). Various studies has shown ABO
incompatibility occurs in 15-20% of all pregnancies, and have double the risk to
develop jaundice requiring treatment, 5-10 times risk of exchange transfusion, and it
was in 1/10th of newborn that this incompatibility become manifested as HDN
requiring treatment. There is a recent trend of early discharge of the newborn after
birth. At the same time, it has been observed that Neonatal hyperbilirubinemia (NH) is
a significant cause (6.5%) for readmission to the hospital. Hence the present study was
conducted to correlate the Cord Blood Bilirubin (CBB) levels with subsequent NH in
newborns with setting of ABO incompatibility.
Methods
Study was performed at the Department of Pediatrics in a Rural Medical
College Hospital. Healthy term newborns (n=200) with A or B blood group born to
healthy mothers with blood group O positive, were prospectively enrolled in the study.
CBB was estimated. Postnatal Serum Bilirubin estimation was done at 72 hours.
Results
Significant NH in our study is 11%. Mean total bilirubin at postnatal 72 hours
was 11.1 mg/dl. Using CBB level of ≥ 3.5 mg/dl as a cut-off, NH can be correlated
ix
with sensitivity of 94.7%, specificity of 97.7 %, positive predictive value of 81.8 %
and negative predictive value of 99.4%
Interpretation & Conclusion
In the present study a Negative Predictive Value of 99.4% suggests that in
Healthy Term babies with ABO incompatibility having a CBB <3.5 mg/dl, are
unlikely to require further evaluation and intervention. These newborns can be
discharged with assurance to Parents. Whereas the babies who are discharged with a
CBB level ≥ 3.5 mg/dl should have unfailing frequent follow ups in the postnatal 1st
week.
Keywords
Newborn; Neonate; ABO incompatibility; Hyperbilirubinemia; Jaundice prediction;
Cord bilirubin
x
TABLE OF CONTENTS
SL. NO TOPICS PAGE NO
1 INTRODUCTION 1
2 OBJECTIVES 5
3 REVIEW OF LITERATURE 6
4 METHODOLOGY 41
5 RESULTS 43
6 DISCUSSION 55
7 CONCLUSION 60
8 SUMMARY 62
9 BIBLIOGRAPHY 64
10 ANNEXURE I – PHOTOGRAPHS 72
11 ANNEXURE II – PROFORMA 73
12 ANNEXURE III – MASTER CHART 74
xi
LIST OF TABLES
Sl.No Tables Pages

Clinical Features of Bilirubin Encephalopathy
1 20
Study population and Significant Jaundice

2 43
Parity of Mothers
3 44
Distribution of Neonates according to Sex.

4 45
Distribution of Neonates according to Birth weight

5 46
Distribution of Neonate according to Blood group

6 47
Significant Jaundice in relation to Blood group A&B

7 48
8 Sex distribution in Significant Hyperbilirubinemia. 49
Bilirubin, Haemoglobin and PCV profile of the Study

9 Population 50
Comparative evaluation of Cord and Postnatal 72hours,

10 Haemoglobin & PCV 51
Diagnostic predictability of Cord Blood Bilirubin for

11 Significant Hyperbilirubinemia. 52
Predictability of Cord Blood Bilirubin for

12 Hyperbilirubinemia 53
Comparison of Cord Serum Bilirubin and Significant

13 Jaundice in ABO incompatibility 57
xii
LIST OF GRAPHS
Sl.No Graphs Pages
I Study population and Significant Jaundice 43
II Maternal Parity 44
III Distribution of Neonates according to Sex 45
IV Distribution of Neonates according to Birth Weight 46
V Distribution of Neonates according to Blood Group 47
VI Blood Group and Significant Jaundice 48
VII Sex distribution in Significant Hyperbilirubinemia 49
Cord Blood Bilirubin and Significant

IX 52
Hyperbilirubinemia
xiii
LIST OF FIGURES
Sl. No Figure Pages
I Bilirubin Metabolism and Elimination 13
II Algorithm for the management of Jaundice in newborn 18
III Important factors in the efficacy of Phototherapy 23
Risk designation of Term and Near-term well Newborns

IV 39
based on their Hour Specific Serum Bilirubin Values.
xiv
LIST OF PHOTOGRAPHS
Sl.No Photograph Pages
Visual assessment of Neonatal

I
Hyperbilirubinemia
72
xv
Introduction
INTRODUCTION
Neonatal hyperbilirubinemia (NH) is a cause of concern for the parents as well
as for the pediatricians.1 It affects nearly 60% of term and 80% of preterm neonates
during first week of life 2
Neonatal hyperbilirubinemia is the most common reason for readmission after
early hospital discharge. Concerns regarding Jaundice have increased after reports of
bilirubin induced brain damage occurring in healthy term infants even without
hemolysis.3, 4
As the incidence of Rh D alloimmunization has decreased after the
introduction of anti-D prophylaxis, ABO incompatibility is now the major cause of
immune hemolytic disease of new born (HDN) in developed countries.5,6
Approximately 20% of all pregnancies are associated with ABO
incompatibility between mother and the fetus and only less than 10% of all these
cases manifest ABO HDN.7 Clinically and almost exclusively ABO incompatibility
occurs in ‘A’ and ‘B’ blood group babies of ‘O’ positive mothers. These babies are
reported to be at high risk of severe hyperbilirubinemia (serum bilirubin level more
than 16mg/dl).8
Hemolysis associated with ABO incompatibility is due to the fact that
maternal anti A or anti B antibodies enter the fetal circulation and react with A or B
antigens on the erythrocyte surface. In type A and B individuals naturally occurring
anti B and anti A isoantibodies largely are IgM molecules that do not cross placenta.
In contrast the alloantibodies present in type O individuals although IgM can be more
of IgG as well. For this reason ABO incompatibility is largely restricted to type O
1
Introduction
mothers with type A or B fetus. The presence of IgG anti A or anti B antibodies in
type O mothers also explains why hemolysis caused by ABO incompatibility
frequently occurs during first pregnancy without prior sensitization.9
ABO incompatible babies have double risk to develop jaundice requiring
treatment and 5-10 times increase risk of exchange transfusion.10
Kernicterus in such Newborns is preventable, provided excessive
hyperbilirubinemia for age is promptly identified and appropriately treated.3,11 With
the intent to facilitate such identification and treatment, universal screening for
severity of bilirubinemia before hospital discharge may predict, that extraordinary
segment of the neonatal population which is at risk for excessive hyperbilirubinemia
during the first week after birth.12
Early discharge of healthy term newborns after delivery has become a
common practice because of medical and social reasons as well as economic
constraints.13, 14
Thus, the recognition, follow-up, and early treatment of jaundice has become
more difficult as a result of earlier discharge from the hospital. The American
Academy of Paediatrics (AAP) recommends that newborns discharged within 48
hours should have a follow-up visit after 2-3 days to detect significant jaundice and
other problems, 15 this recommendation is not possible in our country due to limited
follow up facilities in the community.
Phototherapy is now a viable alternative to the planned use of exchange
transfusion in the treatment of even moderate to severe HDN.16 Phototherapy is
2
Introduction
widely accepted as a relatively safe and effective method for treatment of neonatal
Hyperbilirubinemia.17
Since Allen and Diamond published their well known treatise on Rh
isoimmunisation in 1958, it has been recognised that the level of cord bilirubin is of
considerable value in predicting the severity of subsequent haemolysis. Because of the
relative infrequency of severe ABO disease, the urgency for predictive criteria in this
disease has not seemed great, and there has been a tendency to presume that the
criteria for Rh disease could be applied to ABO incompatibility.18
Predictive criteria used in Rh isoimmunity cannot be applied to ABO
incompatibility as there are several differences.
(1) Hyperbilirubinemia when it occurs, is rarely associated with significant
anemia.19
(2) Anti-A and anti-B antibodies are normally present in maternal serum and
normally reach the foetus.8, 19
(3) In hetrospecific pregnancies the maternal antibody patterns during the
period of gestation show no more response than those of the homospecific group, up
to the time of delivery. Changes in level of antibody occurs only after delivery in the
hetrospecific group.8
(4) There is no cumulative effect on serum antibody levels, or on the foetus in
subsequent hetrospecific pregnancies, in a manner comparable to progression of Rh
incompatibility.18
(5)Though a positive Coombs test is often weak and there is unacceptably high
number of false negative results.19
3
Introduction
Concept of prediction of significant jaundice, as early as at birth, offers an
attractive option to pick up neonates at risk of NH. A Total serum bilirubin level of
≥15 mg/dl is found in 3% of normal term babies.20 The incidence of
hyperbilirubinemia depends on regional variations, ethnic makeup of the
population,21,22 laboratory variability in the measurement of bilirubin, and the
incidence of breastfeeding.23 Several investigators have tried to find a simple marker
to predict hyperbilirubinemia in newborns. Some of them used transcutaneous
bilirubin measurement24-30, and ETCOc measurement31-32 CBB estimation,18, 51-54, 56-71
predischarge hour specific bilirubin estimation,12 to predict the subsequent course of
Jaundice.
Despite the failure to detect a prenatal increase in maternal antibody levels
there is no doubt that intrauterine haemolysis must take place in ABO incompatibility
and cord blood bilirubin levels are often considerably raised.18
There is an obvious need to develop simple predictive guidelines that will
enable the physicians to predict or to identify which of the early discharged newborns
will develop significant hyperbilirubinemia, and thereby minimize the risk of bilirubin
dependent brain damage.
The present study was designed to evaluate the predictive value of cord
bilirubin levels in hetrospecific pregnancies, involving group O-mothers and A-or B
term babies in rural Bangalore with subsequent hyperbilirubinemia.
4
Objectives
OBJECTIVES
1. The present study was conducted to correlate the Cord Blood Bilirubin level
with subsequent Neonatal Hyperbilirubinemia in new born with a setting of
ABO incompatibility.
2. To predict the risk of jaundice, in order to implement early treatment and there
by minimize the risk of Bilirubin dependent brain damage.
5
Review of Literature
REVIEW OF LITERATURE
HISTORY REVIEW
Neonatal jaundice must have been noticed by caregivers through the centuries,
but the scientific description and study of this phenomenon seem to have started in the
last half of the 18th century. In 1785 Jean Baptiste Thimote´e Baumes was awarded a
prize from the University of Paris for his work describing the clinical course in 10
jaundiced infants33.
The work by Jacques Hervieux, which he defended for his doctor of medicine
degree in 1847, was, in many respects, a landmark. Having dismissed most of the
theories and work of his predecessors, a number of his clinical observations are still
thought to be accurate today. 33
His Clinical and Epidemiological Observations on Neonatal Jaundice are
1. The cause of neonatal jaundice is not known, but one can state that jaundice in
the neonate is a manifestation of a recently established function that for a
limited time exceeds its physiological limits.
2. Neonatal jaundice is a physiological condition.
3. Neonatal jaundice is, by itself, never fatal
4. Neonatal jaundice appears during the first 2 to 4 days of life and lasts for 1 to
2 weeks. It never reappears in the following months.
5. There is a cephalocaudal progression in the appearance of jaundice the
extremities are always last to be affected. When jaundice disappears, the order
is reversed.
6
6. Neonatal jaundice is very common; approximately two thirds of all infants are
affected. The prognosis in the absence of complicating conditions is benign.
7. Jaundice is not seen in foundlings who are wet-nursed, or in infants nursed by
a woman who gave birth a long time ago.
8. The most frequent complicating conditions are scleredema, diarrhoea, and
thrush.
9. Treatment consists of combating the complicating conditions. Isolated
neonatal jaundice does not need treatment.
10. In neonatal jaundice, the yellow colour is found throughout the tissues of the
body, including the brain. Hervieux described brain jaundice in 31 of 44 cases
of neonatal jaundice. In all of these cases, clinical jaundice had been at its
peak at the time of death. He described the intensity of the brain jaundice as
variable. Some brains were quite uniformly stained, while in other brains some
regions were more heavily stained than others. It is noteworthy that he found
the cerebrospinal fluid to be jaundiced in all cases. 33
In 1847, Virchow suggested that the excessive destruction of red blood cells in
the first week of life is the basic cause of jaundice.34
Molisan demonstrated by transfusion experiments that erythrocytes of new born
break down twice as rapidly as compared to adults.34
The first description of the pathoanatomical picture of Kernicterus may belong to
Johannes Orth. Orth an assistant to Virchow, in his article, which primarily focused
on pigment crystals in various organs, he described a term female infant who was
7
born nonicteric, but who became jaundiced soon after birth. The child died at two
days of age with very pronounced jaundice, which was apparently her only
sign/symptom. At autopsy all organs were found to be jaundiced, but with an
underlying pallor that may perhaps point to the existence of anaemia. The brain was
intensely yellow, but with much more intense staining of the basal ganglia, the wall of
the third and fourth ventricles, the hippocampus, and the central parts of the
cerebellum. On microscopic examination of the latter, the granular layer was found to
be heavily stained. Orth also noted that although neurons of the basal ganglia were
stained, the glial elements were not. 33 Orth finally speculated that the intense jaundice
in this infant might have had a hematologic causes, a speculation, which, in the light
of later knowledge, may well have been precisely on target. 33
Christian Georg Schmorl coined the term Kernicterus (Jaundice of the nuclei),
which has subsequently been used both to describe a pathoanatomical picture seen at
autopsy in those who died, as well as a neurological syndrome in survivors of extreme
Jaundice. 33 In his landmark paper Schmorl described his findings from the autopsies
of 280 neonates, of whom 120 were Jaundiced at the time of death. In the majority of
these cases (114/120), he found the brain to be diffusely yellow. He noted that the
intensity of the brain colour paralleled that of the face, which is often the most
intensely Jaundiced part of an infant’s body, as also described by Hervieux. 33
In the brains that Schmorl examined, the Jaundiced nuclei were very sharply
demarcated and, therefore, contrasted clearly with the colour of the surrounding
tissue. Because of this sharp demarcation and the predilection for staining of the
nuclei, Schmorl proposed the term Kernicterus. He further suggested that the yellow
8
colour was not simply attributable to saturation of the tissue with bile pigments, such
as was the case (he believed) with eg, skin, but to binding of the bile pigments to
specific structural elements in the tissue. Microscopic examination of the tissue
supported this hypothesis. Some neurons in the nuclei were strongly coloured, while
others had a paler yellow colour. These latter cells exhibited changes that suggested
that they were in the process of dying. 33
Beneke in 1907, was the first to suggest that septicaemia might play an important
role in icterus gravis neonatorum, and he theorized that the pigmentation of brain
tissue was caused by a peculiar attraction of bile pigments to ganglion cells leading to
their necrosis, damage to the ganglion cells by the bile salts which then became
pigmented, or ischemic or the traumatic insult that allowed the cells to become
pigmented.34
As early as 1913, there was description of children who survived severe neonatal
Jaundice with resultant mental retardation and neuromuscular dysfunction, with the
Jaundice being considered the causal agent (Guthrie, 1913; Spiller, 1915).34
In 1916, Dutch Biochemists, Van Den Bergh and Muller, observed that serum
from patients with haemolytic Jaundice can be differentiated from the serum of
patients with obstructive Jaundice on the basis of chemical reactions. They observed
that haemolytic serum did not react promptly with diazotised sulphanilic acid except
in presence of alcohol while the other serum reacted in an aqueous solution.34
9
In 1932, Diamond and colleagues recognized that generalized oedema of the
foetus (Hydrops fetalis), icterus gravis and congenital anaemia of the newborn were
all in fact a part of single condition which they termed “isoimmunisation fetalis”.35
In 1944, Halbrecht coined the term “Icterus praecox” for Jaundice developed
within 24 hours of birth.36
In 1946, they introduced the technique of alternate removal and administration of
blood for each transfusion by umbilical vein catheterization. Allen et al in 1950
showed effectiveness of exchange transfusion as a protection from Kernicterus.35
In 1952, Crigler and Najjar in the publication describing congenital familial non
haemolytic Jaundice with Kernicterus not only defined a new disease but also
advanced the understanding of Kernicterus as a process related more to elevated
unconjugated bilirubin levels than to specific blood group incompatibilities or even
hemolysis.34
In 1958, Cremer and associates from Rochform hospital in Essex, published their
report of the successful use of phototherapy for the treatment of neonatal Jaundice.
The initiator of phototherapy was a staff nurse of the above hospital, who noticed that
babies whose uncovered parts were less yellow when compared to covered parts of
body on exposure to sunlight.37
10
FETAL BILIRUBIN METABOLISM
Bilirubin is detected in normal amniotic fluid as early as 12 weeks of
gestation, but usually disappears by 36- 37 weeks.20
In early life bilirubin binds to fetoprotein and liver plays a minor role in
excretion. During the neonatal period, metabolism of bilirubin is in transition from the
foetal stage during which the placenta is the principal route of elimination of the lipid-
soluble, unconjugated bilirubin to the adult stage, during which the water-soluble
conjugated form is excreted from hepatic cells into the biliary system and
gastrointestinal tract.2
Uridine diphosphoglucuronyl transferase (UDPGT) is detectable at 18 – 20
weeks. UDPGT levels in full term and preterm neonates are usually less than 0.1% of
adult values. Adult value of this enzyme activity is demonstrable only by 6–14 weeks
of postnatal life.38
NEONATAL BILURUBIN METABOLISM
Normally destroyed RBC’s account for nearly 75% of daily bilirubin
production in the newborn. Breakdown of 1gm of haemoglobin usually yields 35 mgs
of bilirubin and neonates produce nearly 8- 10 mgs/ kg/ day of bilirubin which is
more than two times as compared to adult 3-4/ mgs/ kg/ day.20,38
Bilirubin is the end product of catabolism of iron protoporphyrins or heme,
haemoglobin being the major source for the same. First step in bilirubin production
involves removal of iron and protein moiety, followed by oxidative process catalyzed
by the enzyme microsomal heme oxygenase and equimolar amount of carbon
monoxide and biliverdin are formed. This enzyme heme oxygenase is called the rate
11
limiting enzyme in bilirubin metabolism. Biliverdin is then reduced to bilirubin by
biliverdin reductase.39
In step 2, extra hepatic bilirubin is bound to serum albumin and delivered to
the liver. Fraction of unbound bilirubin in plasma may increase in severe haemolytic
disease or when protein binding drugs displace bilirubin from albumin.39
In step 3 when the bilirubin albumin complex reaches plasma membrane of
hepatocytes a proportion of bilirubin is transferred across cell membrane of
hepatocytes, where it binds to ligandin and probably other cytosolic-binding
proteins.39
In step 4, conjugation with one or two molecules of glucuronic acid by
UDPGT in the endoplasmic reticulum occurs and generates bilirubin
monoglucuronides and diglucuronides, which are water soluble, are readily excreted
into bile. Hepatic uptake, conjugation and excretion of bilirubin is limited due to
transient deficiency of Y and Z acceptor proteins and UDPGT enzyme in the
newborn.38, 39
In step 5 most bilirubin glucuronides are deconjugated by the bacterial β-
glucuronidase and degraded to colourless urobilinogen. Due to paucity of bacterial
flora in the gut and over activity of intestinal β-glucuronidase enzyme the conjugated
bilirubin entering the duodenum is rapidly deconjugated and recirculated in the blood
and delivered to the liver for reconjugation through enterohepatic circulation.38, 39
12
FIGURE I: BILIRUBIN METABOLISM AND ELIMINATION39
13
CAUSES OF UNCONJUGATED HYPERBILIRUBINEMIA34
A. Excessive production of Bilirubin (haemolytic disease of newborn)
1. Blood Group heterospecificity (Incompatibility)
a. Rh Isoimmunisation
b. ABO incompatibility
c. Minor blood group incompatibility
2. Red blood cell enzyme abnormalities
a. Glucose 6-phosphate dehydrogenase deficiency

b. Pyruvate kinase deficiency
3. Sepsis
4. Red blood cell membrane defects
a. Hereditary Spherocytosis
b. Elliptocytosis
c. Poikilocytosis
5. Extra vascular blood
6. Polycythemia
B. Impaired conjugation or excretion
1. Hormonal Deficiency
a. Hypothyroidism
b. Hypopituitarism
2. Disorders of bilirubin metabolism
a. Criggler-Najjar syndrome type- I

b. Criggler-Najjar syndrome type- II (Arias Disease)
c. Gilbert disease
d. Lucey- Driscoll syndrome
3. Enhanced enterohepatic circulation
a. Intestinal obstruction, Pyloric Stenosis

b. Illeus, Meconium plugging, Cystic fibrosis
14
CAUSES OF JAUNDICE ON THE BASIS OF AGE OF ONSET.40

WITHIN 24 HOURS OF BIRTH
Rh and ABO incompatibility.
Glucose 6-phosphate dehydrogenase deficiency.
Pyruvate kinase deficiency.
Infections: Bacterial, TORCH.
Criggler-Najjar syndrome type- I.
Drugs to Mother Vit-K, salicylate, etc.
24-72 HOURS AFTER BIRTH

Physiological Jaundice
Rh and ABO incompatibility
Polycythemia.
Extra vascular bleed.
Breast feeding Jaundice.
Neonatal sepsis.
Enhanced enterohepatic circulation.
AFTER 72 HOURS OF BIRTH

Neonatal sepsis.
Neonatal hepatitis.
Hypothyroidism.
Hypopituitarism.
Galactosemia..
Criggler-Najjar syndrome type – II.
Gilbert disease.
15
HIGH RISK FACTORS OF JAUNDICE2, 20, 40
• Prematurity.
• Low birth weight.
• Blood group incompatibility.
• Perinatal asphyxia.
• Infant of diabetic mother.
• Intrapartum use of oxytocin.
• Problem in breastfeeding.
• H/o Jaundice in previous siblings.
• Cephalhematoma or significant bruising.
HAEMOLYTIC DISEASE OF NEWBORN.
The American Academy of paediatrics lists blood group incompatibility with
positive direct antiglobin test (DAT) as one of the four most important risk factors for
severe hyperbilirubinemia; the other factors being high risk zone predischarge total
serum bilirubin levels; Jaundice in the first 24 hrs of life and gestational age (GA) 35-
36 weeks.15
APPROACH TO A JAUNDICED NEWBORN.40
• Identify “high risk” newborns at delivery likely to develop Jaundice.
• Ensure appropriate follow up for Jaundice.
•Emphasize need for early, exclusive breast feeds and ensure adequacy of breast
feeding.
• Assess clinical condition (well or ill)
• Ascertain birth weight & gestation
• Evaluate Jaundice with post-natal age in hours
16
• Perform systematic evaluation – history and physical examination.
• Decide whether Jaundice is physiological or pathological
• If physiological and baby well, only observation is required
• If deeply Jaundiced, look for signs of bilirubin encephalopathy (lethargy, poor,
feeding, shrill cry, asymmetric Moro reflex, hypertonia, opisthotonus or convulsions)
• If Jaundice is pathological perform lab tests.
• Initiate appropriate measures to reduce elevated bilirubin
• Counsel parents.
CLINICAL ASSESMENT OF NEONATAL JAUNDICE
Clinicians should ensure that all infants are routinely monitored for the
development of Jaundice, and nurseries should have established protocols for the
assessment of Jaundice. Jaundice should be assessed whenever the infant’s vital signs
are measured but no less than every 8 to 12 hours. In newborn infants, Jaundice can
be detected by blanching the skin with digital pressure, revealing the underlying
colour of the skin and subcutaneous tissue. The assessment of Jaundice must be
performed in a well-lit room or, preferably, in day light or at a window. Jaundice is
usually seen first in the face and progresses caudally to the trunk and extremities, but
visual estimation of bilirubin levels from the degree of Jaundice can lead to errors15
17
FIGURE II: ALGORITHM FOR THE MANAGEMENT OF
JAUNDICE IN NEWBORN20
18
COMPLICATIONS OF NEONATAL JAUNDICE
The precise blood level above which indirect-reacting bilirubin or free
bilirubin will be toxic for an individual infant is unpredictable, but Kernicterus is rare
in healthy term infants and in the absence of haemolysis if the serum level is <25
mg/dl. In previously healthy, predominantly breast-fed term infants, Kernicterus has
developed when bilirubin levels exceed 30 mg/dl. The duration of exposure needed to
produce toxic effects is unknown. Little evidence suggests that a level of indirect
bilirubin <25 mg/dl affects the IQ of healthy term infants without haemolytic disease.2
Bilirubin encephalopathy describes the clinical central nervous system
findings caused by bilirubin toxicity to the basal ganglia and various brainstem
nuclei.20
To avoid confusion and encourage greater consistency in the literature, the
AAP committee recommends that in infants the term “acute bilirubin encephalopathy”
be used to describe the acute manifestations of bilirubin toxicity seen in the first
weeks after birth and that the term “Kernicterus” be reserved for the chronic and
permanent clinical sequelae of bilirubin toxicity.15
CLINICAL FEATURES OF BILIRUBIN ENCEPHALOPATHY
Signs and symptoms of Kernicterus usually appear 2–5 days after birth in term
infants and as late as the 7th day in premature infants, but hyperbilirubinemia may
lead to encephalopathy at any time during the neonatal period. The early signs are
subtle and indistinguishable from those of sepsis, asphyxia, hypoglycaemia,
intracranial haemorrhage, and other acute systemic illnesses in a neonate.2
19
TABLE I:
CLINICAL FEATURES OF BILIRUBIN ENCEPHALOPATHY2,20
ACUTE FORM
Phase 1 (1st 1–2 days):
poor sucking, stupor, hypotonia, seizures
Phase 2 (middle of 1st wk):
hypertonia of extensor muscles, opisthotonos, retrocollis, fever
Phase 3 (after the 1st wk):
hypertonia
CHRONIC FORM
First year:
hypotonia, active deep tendon reflexes,
obligatory tonic neck reflexes, delayed motor skills
After 1st yr:
movement disorders (choreoathetosis, ballismus, tremor),
limitation of upward gaze, sensorineural hearing loss,
dental dysplasia and intellectual deficits.
20
TREATMENT
The aim of therapy is to ensure that serum bilirubin is kept at a safe level and
neurological damage is prevented.
Reduction of STB levels and prevention of neurotoxicity can be achieved by
phototherapy, Pharmacotherapy and exchange transfusion.
Principles of treatment in Jaundiced infants according to 2006 IAP NNF
guidelines are40
1. Treatment decisions are based on total serum bilirubin.
2. Gestation is more important than birth weight of the baby. A higher cut
off can be used for a small for date baby.
3. Post natal age in hours should be considered when deciding treatment
4. Sick baby refers to presence of asphyxia, hypothermia, sepsis, acidosis,
hypoxia, hypercapnia and evidence of haemolysis.
PHOTOTHERAPY
Phototherapy was first introduced in the treatment of neonatal
hyperbilirubinemia in the late 1950s.37 The goal of therapy is to lower the
concentration of circulating bilirubin or keep it from increasing. Phototherapy
achieves this by using light energy to change the shape and structure of bilirubin,
converting it to molecules that can be excreted even when normal conjugation is
deficient.2, 20
Bilirubin absorbs light most strongly in the blue region of the spectrum near
460 nm (Figure III), a region in which penetration of tissue by light increases
markedly with increasing wavelength. The rate of formation of bilirubin

21
photoproducts is highly dependent on the intensity and wavelengths of the light used.
Taking these factors into account, lamps with output predominantly in the 460 to 490
nm blue region of the spectrum are probably the most effective for treating
hyperbilirubinemia.17,41
Combination of 2 special blue and 4-6 white fluorescent tubes to be used. The
blue tubes must have the serial number F20T12/BB to be a special phototherapy
lights. This combination would deliver 12 µw/cm2/nm.17,41
The absorption of light by the normal form of bilirubin (4Z, 15Z-bilirubin)
generates transient excited-state bilirubin molecules. These fleeting intermediates can
react with oxygen to produce colourless products of lower molecular weight, or they
can undergo rearrangement to become structural isomers (lumirubins) or isomers in
which the configuration of at least one of the two Z-configuration double bonds has
changed to an E configuration. Configurational isomerisation is reversible and much
faster than structural isomerisation, which is irreversible. Both occur much more
quickly than photo oxidation. The photo isomers are less lipophilic than the 4Z, 15Z
form of bilirubin and can be excreted unchanged in bile without undergoing
glucuronidation. Lumirubin isomers can also be excreted in urine. Photo oxidation
products are excreted mainly in urine. Once in bile, configurational isomers revert
spontaneously to the natural 4Z, 15Z form of bilirubin.17, 41
22
FIGURE III: IMPORTANT FACTORS IN THE EFFICACY OF
PHOTOTHERAPHY41
Distance of the phototherapy unit should be as close to the baby as possible ensuring
euthermia. Hyperthermia makes the phototherapy less effective.17, 41
On an average, for infants of more than 35 weeks’ gestation readmitted for
phototherapy, intensive phototherapy can produce a decrement of 30% to 40% in the

23
initial bilirubin level by 24 hours after initiation of phototherapy. The most significant
decline will occur in the first 4 to 6 hours. With standard phototherapy systems, a
decrease of 6% to 20% of the initial bilirubin level can be expected in the first 24
hours.17, 41
CARE OF A NEWBORN RECEIVING PHOTOTHERAPY40
• The eyes should be covered during phototherapy.
• Breast feeding on demand is continued. More frequent breast feeds or 10-20% extra
IV fluids are provided.
• Adequacy of hydration is checked by urine colour and frequency, skin turgor mucous
membrane and weight.
• Assess and record urine and stool pattern.
• Frequent change of posture is necessary.
• Temperature is monitored every 3-4 hrs, Avoid hypo or hyperthermia.
• Daily baby is weighed.
• TSB is measured every 12 hrs or 4-6 hourly if severely Jaundiced.
•Monitor for adverse effects of phototherapy: Dehydration, loose stools, hyperthermia/
hypothermia, erythematous rash and bronze baby syndrome.
SIDE EFFECTS OF PHOTOTHERAPY2, 17,20
Retinal damage, Passage of loose green stools.
Hyperthermia, Dehydration.
Hypocalcaemia, Bronze baby.
Flea-bite rash, Opening up of PDA in preterm.
Increase in mean cerebral blood flow velocity.

24
Decrease in renal blood flow velocity.
Increase in renal vascular resistance.
EXCHANGE TRANSFUSION
Exchange transfusion is the most rapid method for lowering serum bilirubin
concentrations. This treatment is rarely needed when intensive phototherapy is
effective. The procedure removes partially haemolysed and antibody-coated
erythrocytes and replaces them with uncoated donor red blood cells that lack the
sensitising antigen.42
The appearance of clinical signs suggesting Kernicterus is an indication for
exchange transfusion at any level of serum bilirubin. Double volume exchange
transfusion (170 ml/ kg) is performed if intensive phototherapy has failed to reduce
bilirubin levels to a safe range and if the risk of Kernicterus exceeds the risk of the
procedure.2
Blood for exchange transfusion is modified whole blood (red cells and
plasma) cross matched against the mother and compatible with the infant.20
Exchange transfusion should be done in small aliquots of 5 – 10 ml.2, 20, 34, 42
EXCHANGE TRANSFUSION IS DONE BY TWO METHODS2,20,34,42
a) Push and pull technique: Central access usually through umbilical venous
catheter.
b) Isovolumetric exchange with simultaneous infusion of donor blood through
venous line and removal of baby’s blood through arterial line.
25
POTENTIAL COMPLICATIONS FROM EXCHANGE TRANSFUSION2,20,34,42
1. Metabolic
a. Hypocalcaemia
b. Hypoglycaemia
c. Hyperglycaemia
d. Hyperkalaemia
2. Cardio respiratory
a. Apnoea.
b. Bradycardia.
c. Hypotension.
d. Hypertension.
e. Hematologic.
f. Thrombocytopenia.
g. Dilutional coagulopathy.
h. Neutropenia.
i. Disseminated Intravascular coagulation.
3. Vascular Catheter Related
a. Vasospasm.
b. Thrombosis.
c. Embolization.
d. Gastrointestinal.
e. Feeding intolerance.
f. Ischemic injury.
g. Necrotizing enterocolitis.
26
4. Infection
a. Omphalitis
b. Septicemia
CHOICE OF BLOOD FOR EXCHANGE TRANSFUSION2, 20, 34, 42
Rh isoimmunisation: In emergency situation use O Rh negative cells. Ideal is to use O
Rh negative blood suspended in AB plasma. Cross matched baby’s blood group but
Rh negative can also be used.
ABO incompatibility: Blood group O types (Rh compatible) with baby. Ideal is to use
blood group O (Rh compatible) suspended in AB plasma.
Other situations: Cross-matched baby’s blood group.
PHARMACOTHERAPY
PREVENTION OF HEMOLYSIS BY INTRAVENOUS IMMUNOGLOBULIN
The administration of intravenous immunoglobulin is an adjunctive treatment
for hyperbilirubinemia due to isoimmune haemolytic disease. Its use is recommended
when serum bilirubin is approaching exchange levels despite maximal interventions
including phototherapy. Intravenous immunoglobulin (IVIG) (0.5–1.0 g/kg/dose;
repeat in 12 hr) has been shown to reduce the need for exchange transfusion in both
ABO and Rh haemolytic disease, presumably by reducing hemolysis.2,34,44.It may well
be justified to electively use IVIG in a small number of selected patients with HDN
where the likelihood of exchange transfusion is great-that is neonate with Rh disease
27
unmodified by antenatal treatment or neonate with potential ABO HDN where a
previous sibling has suffered from severe disease requiring exchange transfusion.43
INHIBITORS OF BILIRUBIN FORMATION:METALLOPORPHYRINS
These are structural analogues of the heme molecule in which the central iron
molecule has been replaced with other metallic ions including tin, zinc, manganese
and chromium. The metalloporphyrins Sn-mesoporphyrin (SnMP) offers promise as a
drug candidate. The proposed mechanism of action is by competitive enzymatic
inhibition of the rate limiting conversion of heme-protein to biliverdin (an
intermediate metabolite to the production of unconjugated bilirubin) by heme-
oxygenase. A single intramuscular dose of 6 mg/ kg on the 1st day of life may reduce
the need for phototherapy. Complications from metalloporphyrins include transient
erythema if the infant is receiving phototherapy.2, 34, 44
BILIRUBIN TRANSPORT: ALBUMIN INFUSION
Bilirubin bound to albumin is relatively innocuous, as it cannot diffuse across
the blood brain barrier. The amount of free bilirubin (unbound) doubles when TSB
level reaches 15- 20 mg/dl, quadruples at 25 mg/ dl and increases 8 folds at 30 mg/ dl.
Before an exchange transfusion, one may consider an albumin infusion (1 g/kg).34,44
INDUCERS OF LIVER ENZYMES: PHENOBARBITONE
Phenobarbitone enhances bilirubin clearance by liver by increasing its uptake,
increasing the intracellular concentration of ligandin, increasing its conjugation by
UDPGT and increasing the excretion of conjugated bilirubin by increasing bile flow.34
28
Dosage 2.5-5mg/kg/day BD. The main drawback with the use of
phenobarbitone is its latent period. It exerts its effect after 1- 3 days and adjuvant
therapy in the form of phototherapy is usually required in the first 48- 72 hours.44
PREDICTION OF NEONATAL HYPERBILIRUBINEMIA
Johnson and Brown suggested that shorter hospital stays, decreased vigilance
in diagnosing Jaundice and lack of physician compliance with current guidelines may
account for re-emergence of severe hyperbilirubinemia and Kernicterus.12Since 1991,
there have been several articles published on re-emergence of Kernicterus in full term
infants.3,45,46
Jaundice appears in 60% of term newborns and 80% of preterm infants by the
first week of life. Up to 4% of term newborns who are readmitted to the hospital
during their first week of life, approximately 85% are readmitted for Jaundice. If left
unrecognized and untreated, hyperbilirubinemia can have dire consequences.
Overproduction and reduced removal of bilirubin may elevate serum bilirubin levels
(hyperbilirubinemia) to toxic levels that present the threat of brain damage
(Kernicterus).47
Kernicterus, resulting from the deposition of unconjugated bilirubin in brain
cells, is clinically characterized by convulsions, opisthotonus, hypotonia, high pitched
cry, and fever. Because of effective diagnosis and treatment, Kernicterus has become
a rare event. It is of concern, however that this rare event, while still infrequent, is
becoming more common. Catz and colleagues recounted that in the United States,
29
between 1991 and 1995, there were reports of 22 cases of term or near-term infants
who had developed Kernicterus after being discharged within 48 hours of birth.Of
these cases 95% (n = 21) had been breastfed, 23% (n = 5) were glucose 6- phosphate
dehydrogenase deficient, and others had identifiable risk factors such as bruising,
ABO haemolytic disease , or other causes of hemolysis.13,.47
The current list of identified risk factors to recognize infants who are likely to
require treatment for hyperbilirubinemia is not adequate. While Jaundice per se is not
always preventable, nonetheless, early detection of threatening bilirubin levels
permits initiation of phototherapy and prevents higher risk and higher cost exchange
transfusion therapy or Kernicterus. Early discharge complicates the ability to measure
both the level of serum bilirubin and the rate of increase. 47
The trend toward shorter hospital stay was evident even before the recent
influence of insurance and managed care plans. In the past decade, however this trend
has increased rapidly.47
Hyperbilirubinemia is the commonest cause for readmission to the hospital
after early discharge.48-50
Palmer et al (1983), presented a review of Jaundiced newborn infants during
the 10-year period to 1980. Included were those whose serum bilirubin level was 9
mg/dl or more. Of 41,057 live births, 4,406 (10.7%) infants had hyperbilirubinemia.
The most common (19.9;%) aetiological factor was prematurity, followed by ABO
isoimmunisation 7.1%;sepsis 3.4%; Rhesus isoimmunisation 2.7%; bruising 2.2%;
multifactorial 1.0% and glucose-6-phosphate dehydrogenase deficiency 0.5%.

30
Treatment was not undertaken in 2,855 (64.7%) infants, but 1,419 (32.2%) received
phototherapy alone, 122 (2.7%) infants received both exchange transfusion and
phototherapy and 10 (0.2%) infants received exchange transfusion alone. Of the
infants requiring exchange transfusion 50.0% had Rhesus isoimmunisation, 28.0%
ABO isoimmunisation, 10.6% Jaundice of prematurity and the remainder were due to
a variety of causes.51
Rosenfeld J et al (1986) reported that Infants with cord bilirubin levels less
than 2.0 mg/dl have only a 4 percent chance of developing hyperbilirubinemia and a
1.4 percent chance of needing phototherapy. However, if serum cord bilirubin levels
are more than 2.0 mg/dl, the infant has a 25 percent chance of developing subsequent
hyperbilirubinemia.52
Knudsen A et al (1989) found that if cord bilirubin was below 1.17 mg/dl,
2.9% became Jaundiced as opposed to 85% if cord bilirubin was above 2.3 mg/dl.
Furthermore, 57% of Jaundiced infants with cord bilirubin above 2.3 mg/dl required
phototherapy, but only 9% if cord bilirubin was 2.3 mg/dl or lower (p< 0.003). Since
the ability of plasma to bind bilirubin in cord blood from Jaundiced and non-
Jaundiced infants showed no significant differences, the increased cord bilirubin
among infants who later became Jaundiced is presumably caused by increased fetal
bilirubin production or decreased removal of bilirubin from the fetal circulation.53
Ho NK, et al. (1991), reported a 4-year experience (1986-1989) of neonatal
Jaundice. Babies who have received some form of treatment such as phototherapy are
considered as cases of neonatal Jaundice. However, the incidence of

31
hyperbilirubinemia (defined as serum bilirubin level of 15 mg/dl or greater) fell from
3.23% to 2.11% of all live births.54ABO Incompatibility, glucose-6-phosphate
dehydrogenase (G6PD) deficiency and low birth weights (LBW) remain as the
common aetiological factors of neonatal Jaundice.55
Rataj, et a.l 1994, investigated 800 healthy full-term newborns and reported
that if cord bilirubin was under 1 mg% the Jaundice occurred in 2.4% newborns,
where as 89% of the infants with cord bilirubin above 2.5 mg% became Jaundiced.56
Awasthi, et al. (1998), conducted a prospective cohort study of 274 neonates
born in North India and predicted that occurrence of peak serum bilirubin level >15
mg/dl between second to fifth postnatal day by using serum bilirubin level measured
between 18 to 24 hrs of life. The main outcome measures were hyperbilirubinemia
and phototherapy. Hyperbilirubinemia was found in 12.8% babies using a cut-off
>3.99 mg/dl with sensitivity and specificity of 67%. Using serum bilirubin levels
estimated at 18-24 hrs of life as the “prediction test”, approximately two-third of the
neonates were test negative and had one in ten chances of readmission for treatment
of hyperbilirubinemia, if discharged early.57
Alpay, et al. (2000), followed up a total of 498 healthy term newborns
daily with serum total bilirubin measurements for the first 5 days of life, and cases
with TSB of >17 mg/dl after 24 hours of life were defined to have significant
hyperbilirubinemia. No newborns had a TSB level of >17 mg/dl in the first 72 hours
of life. Sixty of 498 cases (12.05%) had significant hyperbilirubinemia after 72 hours
of life, and these cases had significantly higher bilirubin levels than those who did not
develop significant hyperbilirubinemia on each of the first 5 days’ measurements. Of
the 206 newborns who had a TSB level of >6 mg/dl in the first 24 hours, 54 (26.21%)
32
developed significant hyperbilirubinemia, whereas only 6 of the 292 newborns
(2.05%) who had a TSB level of <6 mg/dl on the first day developed significant
hyperbilirubinemia. A mean TSB level of >6 mg/dl on the first day had the highest
sensitivity (90%). At this critical serum bilirubin value, the negative predictive value
was very high (97.9%) and the positive predictive value was fairly low (26.2%). The
use of the critical bilirubin level of 6 mg/dl in the first 24 hours of life can predict
nearly all of the term newborns who will have significant hyperbilirubinemia and
could determine all those who will require a phototherapy treatment later during the
first days of life.58
Agarwal, et al. (2002), conducted a study on 220 infants. All infants were
exclusively breastfed. Clinically detectable Jaundice was present in 164(77%) and
hyperbilirubinemia occurred in 22(10.3%) infants. Study predicted that infants with
total serum bilirubin levels lesser than 6 mg/dl at 24 ± 6 hours would not develop
Suchonska, et al. (2004), investigated 187 healthy, full-term newborns in good
general condition. Newborns with serological incompatibility were not included into
the study. In 155 (83%) cases babies were born through normal vaginal delivery, in 32
(17%) by Caesarean section. The umbilical blood was taken immediately after
delivery and the venous blood on the 3rd day of life to determine concentration of
bilirubin. 3rd day Bilirubin values lower than 12.9 mg% were considered
physiological. Hyperbilirubinemia was recognized when the concentration of bilirubin
was over 12.9 mg%. Pearson test was used to estimate the correlation between
bilirubin value in the umbilical blood and the venous blood. The mean value of total
bilirubin in the umbilical blood was 1.30 mg% +/- 0.47 and in venous blood on the
3rd day of life 8.07 mg% +/- 3.08. No one with umbilical bilirubin concentration
33
lower than 1 mg% developed hyperbilirubinemia. They concluded that concentration
of bilirubin in the umbilical blood can be useful indicator of risk of icterus in
newborns. Special care is needed for newborns whose concentration of bilirubin in
umbilical blood is over 1 mg%.60
Bernaldo et al (2004) predicted that Blood incompatibility between mother
and child was a predictor for the appearance of hyperbilirubinemia that required
treatment. Considering a cut-off point of 2.0 mg/dl, 53% of the newborns who had
greater unconjugated bilirubin levels in cord blood would reach levels requiring
phototherapy by the third day of life. In addition, they also concluded that the
presence of mother/child blood group incompatibility was statistically significant for
the occurrence of unconjugated bilirubin serum levels that were indicative of
phototherapy treatment during the same three-day period.61
Kupfer et al (2005) investigated the predictive value of umbilical cord serum
bilirubin (CBB) for the postnatal course of bilirubinemia in healthy term and near-
term newborns. Term appropriate-for-gestational-age (AGA; n=1100), small-for-
gestational-age (SGA; n=163) and near-term infants (GA 34–36 wk; n=78) were
included and separated according to their CBB levels, starting from <1.1 (group 1),
1.1–<1.7 (2), 1.7–2.3 (3) and >2.3 (4) mg/dl. The newborns were followed for at least
5 postnatal days, and CBB values were correlated with the development of
hyperbilirubinemia and phototherapy (PT) treatment which showed a clear relation
between CBB and the development of hyperbilirubinemia in all three patient
populations. None of the 75 AGA patients of group 1 developed postnatal bilirubin
values above 17.6 mg/dl, whereas 0.3, 3.4 and 8.6% of the patients in groups 2–4,
respectively, did so. The frequency of phototherapy increased from 0% in group 1 up

34
to 9.6% in group 4. For the prediction of further need of phototherapy using a CBB
cut-off level of 1.7 mg/dl, they found a sensitivity of 90% and a negative predictive
value of 99.1%, indicating that all patients with CBB values below 1.7 mg/dl
(443/1100 or 40.2%) were at a very low risk of developing dangerous
hyperbilirubinemia. Similar results were obtained in SGA children with a sensitivity
of 94.1% and a negative predictive value of 98.6%. In comparison to term newborns,
they generally found higher bilirubin values in preterms. A total of 6.4% of preterm
children developed bilirubin values over 17.6 mg/dl, compared with 3% of term
children, and 47.4% of preterms had to be treated with phototherapy. Predicting the
need of phototherapy by using a CBB cut-off level of 1.7 mg/dl revealed a sensitivity
of 70.3% and a negative predictive value of 65.6%.62
Sun, et al (2007), Investigated 523 healthy term newborns. The cord blood
total serum bilirubin concentration and the serum albumin concentration were
determined. The infants were aligned into four groups according to their CBB levels,
starting from < 1.7 mg/dl (group 1); ≥1.7 mg/dl (group 2); ≥2.1 mg/dl (group 3); ≥2.4
mg/dl (group 4). The frequency of hyperbilirubinemia and phototherapy (PT) were
compared among the four groups. An analysis of CBB as a predictor of later
development of Jaundice was performed. The characteristics of the infants who
became Jaundiced (Jaundiced group) were compared with the normal infants (non-
Jaundiced group). The frequency of patients with hyperbilirubinemia or phototherapy
increased with increasing CBB levels. For the prediction of TCB ≥25 using a UCS
bilirubin cut-off level, such as ≥2 mg/dl, a positive predictive value of 45.68% and
sensitivity of 68.27% was found. It is significant to predict neonatal Jaundice by CBB
levels (P < 0.001). In the Jaundiced group (TCB ≥25) CBB levels were significantly
35
higher than those in the non-Jaundiced group (t = 10.96, P < 0.001). No significant
differences were found in the cord blood serum albumin concentration (t = 2.38, P >
0.05), the gestational age (t = -0.90, P > 0.05), and birth weight (t = 0.10, P > 0.05)
between the Jaundiced and non-Jaundiced groups.63
Randev S, et a.l (2010), concluded that first day TSB estimation can serve as a
reliable screening test for neonates at risk for subsequent hyperbilirubinemia.
Neonates with the first day TSB <6.4 mg/dl have minimum risk of subsequent
Nair, et al. reported that 29.5% babies developed hyperbilirubinemia and
17.65% of them were ABO Incompatible group.65 Some of the similar predictive
study done in ABO incompatibility as well.
Robinson, et al. in (1960), study observed that cord bilirubin level above
3mg/dl were suggestive of significant Jaundice.66
H.M Risemberg et al in (1977) found association of cord bilirubin and severity
of hyperbilirubinemia in ABO (Heterospecific pregnancies) The study group had 91
new borns of hetrospecific pregnancies, and 30 term infants of homospecific were
used as controls. Of the 91 patients included in the study 13(14%) developed severe
hyperbilirubinemia serum bilirubin level > 16 mg/dl at 12-36 hrs of life and with the
exception of one patient cord blood bilirubin levels were > 4mg/dl in all cases. All of
these babies required exchange transfusion. 17% of infants who developed moderate
hyperbilirubinemia the cord bilirubin level was < 4mg/dl and none required exchange
transfusion .69 did not develop significant hyperbilirubinemia at 36hrs of life. In all
these cord blood level was < 4mg/dl.18
36
Haque K N, (1978), found there are no definite criteria of ABO haemolytic
disease that could predict immediately after birth which infant may require treatment
for hyperbilirubinemia.67
Whyte.J.Graham H, in (1981) studied 71 ABO incompatible infants and equal
number of control to ascertain which cord blood test reliably predict the severity of
ABO HDN, the modified DAT was positive in all the infants who required treatment
for haemolytic Jaundice and all DAT positive children showed evidence of impending
haemolytic anaemia or compensated haemolysis in cord or capillary blood. Cord
serum bilirubin has some predictive value particularly when level exceed 85
mu/mol/litre (5mg/dl) but it was less reliable indicator and had greater value if used in
association with DAT.68
Chen J Y, Ling UP in 1994 studied in Taiwan found ABO incompatible
newborn infants with maternal IgG anti A or anti B titres ≥ or 512X , cord bilirubin
levels ≥ 4mg/dl or positive DCT of cord blood represent a “high risk” category and
should be placed in hospital where frequent Re-evaluation and appropriate therapy are
available.69
Sarici, et al. in (2002) observed a total of 136 healthy term newborns with
ABO (O-A or O-B) blood group incompatibility were followed prospectively with
daily serum total bilirubin measurements for the first 5 days of life. Newborns with
serum total bilirubin levels of ≥5 mg/dL and an increase in serum total bilirubin
concentration of >0.5 mg/dL/h in the first 24 hours, ≥12 mg/dL on day 2, ≥15 mg/dL
on day 3, and ≥17 mg/dL on days 4 and 5 were defined to have significant
hyperbilirubinemia and were started on phototherapy treatment. The additional
assessment of the predictive ability of the sixth-hour serum total bilirubin value in
determining the development of significant hyperbilirubinemia was made on the basis

37
of the placement of any of the first 5 day’s serum bilirubin measurements in the ≥90th
percentile of the study population. Results were twenty nine newborns (21.3%) had
significant hyperbilirubinemia.70
There were significant differences between the newborns who did and the
newborns who did not develop significant hyperbilirubinemia with respect to the
reticulocyte count (4.39 +/- 3.46% vs 2.95 +/- 1.63) and the presence of a direct
antiglobulin test positivity (6 of 23 vs 0 of 107) and a sibling with neonatal Jaundice
(6 of 23 vs 5 of 102). A mean serum bilirubin level of > or =4 mg/dL at the sixth hour
of life was determined to have the highest sensitivity (86.2%) and negative predictive
value (94.5%) and a positive predictive value of 39.7% to predict the newborns who
would develop significant hyperbilirubinemia.70
Covas Mdel C, et al in (2009), observed serum bilirubin at 24-36 hours of life
might contribute to identify those term newborns with ABO incompatibility that have
the highest risk of developing Jaundice.71
Azma RZ et al in a study published in 2011of 214 cases with 114 of them
ABO Incompatible, were of the conclusion that level of cord blood total bilirubin
≥2.5mg/dl was not shown to have a good prediction of significant hyperbilirubinemia
in ABO incompatibility.73
PREDISCHARGE HOUR SPECIFIC BILIRUBIN ESTIMATION
Bhutani and colleagues generated a percentile based bilirubin normogram
using hour specific predischarge TSB levels from a racially diverse group of term
healthy newborns with no Rh and ABO incompatibility who did not need
phototherapy before 60 hours of age and of whom 60% were breastfed. The risk of
38
significant hyperbilirubinemia (TSB greater than 17 mg/dL) for predischarge TSB
above the 95th percentile (high risk zone) was 57%, for infants with TSB between
75th and 95th percentiles (high intermediate risk) it was 13%, for infants with TSB
between 40th and 75th percentile (low intermediate risk zone) it was 2.1% and for
infants with TSB below the 40th percentile (low risk) it was zero
FIGURE NO IV.
Risk designation of term and near-term well newborns based on their hour specific
serum bilirubin values. The high-risk zone is designated by the 95th percentile track.
The intermediate-risk zone is subdivided to upper- and lower-risk zones by the 75th
percentile track. The low-risk zone has been electively and statistically defined by the
40th percentile track. (Dotted extensions are based on <300 TSB values/epoch).
The advantage is that hour-specific TSB before hospital discharge can predict
which newborn is at high, intermediate or low risk for developing clinically
significant hyperbilirubinemia (specifically defined as TSB levels ≥95th percentile for
age in hours). Risk designation and subsequent increase or decrease of TSB can be
39
easily monitored on an hour-specific percentile based predictive bilirubin normogram.
A predischarge total serum bilirubin measured as a universal policy would facilitate
targeted intervention and follow-up in a safe, cost-effective manner. In conjunction
with bilirubin practice parameter of the American Academy of Pediatrics, it could
reduce the potential risk for bilirubin induced neurologic dysfunction.12
40
Methodology
METHODOLOGY
This study was performed at the Department of Pediatrics of M.V.J. Medical
College & Research Hospital. Eligible 200 healthy full-term newborns, delivered at
this hospital were prospectively enrolled in the study. The study was approved by the
Research Ethics Committee of M.V.J. Medical College and Research Hospital.
INCLUSION CRITERIA
1. Healthy full term Newborns of blood group A or B Positive born to Mothers
with O positive blood group.
EXCLUSION CRITERIA
1. Rhesus blood factor incompatibility.
2. Blood group O positive babies
3. Significant illness requiring NICU admission.
4. Major congenital malformations.
5. Chronic maternal illness (like DM)
6. Those who didn’t give consent for follow up
METHOD OF COLLECTION OF DATA
An informed consent was obtained from the parents of the newborn before
enrolling them in the study. Demographic profile and relevant information of was
collected by using structured Proforma by interviewing the mother. Gestational age
was assessed by New Ballard score. CBB was estimated. Serum Bilirubin estimation
was done at 72 hours of age. All babies were daily assessed for Jaundice and its
severity.
41
Methodology
LABORATORY INVESTIGATION:
1. Cord blood (2ml) was collected from placental side after its separation and
subjected to following investigation.
a. Blood group
b. Total and Direct Serum Bilirubin.
c. Haemoglobin and Packed Cell Volume
2. Venous blood samples were collected from the baby at 72 hours of life. These
samples were subjected to following investigation
a. Total and Direct Serum Bilirubin.
b. Haemoglobin and Packed Cell Volume
Serum bilirubin estimation was done by Diazo method. This method for Bilirubin
estimation is based on principle that Bilirubin reacts with Diazotised Sulphanilic acid
in acidic medium to form pink coloured Azobilirubin with absorbance directly
proportional to Bilirubin concentration. Direct Bilirubin, being water soluble directly
reacts in acidic medium. However indirect or unconjugated Bilirubin is solubilised
using a surfactant and then it reacts similar to direct Bilirubin.
42
Results
RESULTS
Prospective clinical study consisted of 200 healthy term newborns delivered in M.V.J.M C &
RH. Significant Jaundice was defined as TSB ≥ 15 mg/ dl at 72 hours of life.

life
Incidence of Significant hyperbilirubinemia in our study population is 11%
TABLE 2
STUDY POPULATION AND SIGNIFICANT JAUNDICE
SIGNIFICANT JAUNDICE
TOTAL NUMBER PERCENTAGE
200 22 11%
GRAPH I
11%
89%
Significant Jaundice Insignificant
43
Results
TABLE 3
PARITY OF MOTHERS
(N = 200)
Number of
Parity Total %
mothers
• Primi 116 58.0
• Multi 84 42.0
Total 200 100.0
GRAPH II
MATERNAL PARITY
· Multi
· Primi
0 20 40 60 80 100 120 140
Healthy mothers with O positive group were included. The Parity of mothers
of 200 neonates is shown in the above table. Primigravida were 58% (n=116) and
Multigravida constituted 42% (n= 84).
44
Results
TABLE 4
DISTRIBUTION
ISTRIBUTION OF NEONA
NEONATES ACCORDING
DING TO SEX
Gender of neonates Number of neonates Total %
Male 108 54%

%
Female 92 46%
%
GRAPH III
DISTRIBUTION OF NEONATE
NEONATES ACCORDING TO SEX
110
105
100
108
95
90
92
85
80
· Male · Female
Male babies were 54% (n=108) and female babies were 46% (n=92).
45
Results
TABLE 5
DISTRIBUTION
BUTION OF NEONATES A
ACCORDING TO BIRTH WEIGHT
Birth weight in kgs. Number of neonates Total %
2.50--3.00 145 72.5
3.01--3.50 53 26.5
3.51--4.00 2 1
GRAPH IV
DISTRIBUTION OF NEONATES ACCORDING TO BIRTH WEIGHT
160
140
120
100
80 145
60
40
53
20
2
0
2.50
2.50-3.00 3.01-3.50 3.51-4.00
Babies with birth weight between 2.5

2.5-3.0 kg were 145 (72.5%); between 3.01-
3.5 kg had 53 babies (26.5%) and above 3.5 constituted only 2 (1%).
%)
46
Results
TABLE 6
DISTRIBUTION OF NEONATES ACCORDING TO BLOOD GROUP
Blood group of
Number of neonates Total %
neonates
A+ 88 44
B+ 112 56
GRAPH V
Blood group
88
A
112
B
Among the newborns in our study, blood group B was more common (56%)
47
Results
TABLE 7
SIGNIFICANT JAUNDICE IN RELATION TO BLOOD GROUPS A AND B
Newborns with
Blood group Significant Jaundice in
Significant
%
Jaundice
A (n=88) 9 10.22%
B (n=112) 13 11.06%
GRAPH VI
BLOOD GROUP
GROUPS AND SIGNIFICANT JAUNDICE
Newborns with Significant jaundice
11.06%
11.20%
11.00%
10.80%
10.60%
10.22%
10.40%
10.20%
10.00%
9.80%
A (n=88) B (n=112)
The incidence of ssignificant Jaundice was almost the same in Blood groups
type A and type B, (p=0.757) which is not significant
48
Results
TABLE 8
SEX DISTRIBUTION IN SIGNIFICANT HYPERBILIRUBINEMIA

IRUBINEMIA
Number of neonates
SEX with significant Total %
Jaundice
MALE (n=108) 14 12.9%
FEMALE (n= 92) 8 8.7%.

8.7%
GRAPH VII

IRUBINEMIA
14
Number of neonates
12 with significant
jaundice
10
14
8
8
6
0
MALE (n=108) FEMALE (n= 92)
Significant Jaundice was non-significantly more in male babies (12.9

12.9%) as compared
to female babies (8.7%).

%).(p=0.336)
49
Results
TABLE 9
BILIRUBIN, HAEMOGLOBIN AND PCV PROFILE OF THE STUDY
POPULATION
Parameters Minimum Maximum Mean SD
Cord Blood Total

0.6 4.7 2.3 0.7
Bilirubin (mg/dl)
Postnatal 72 hours
2.4 19.7 11.1 2.8
Bilirubin (mg/dl)
Haemoglobin
12.0 20 15.6 1.2
(gm/dl)
PCV
28 60 43.6 4.1
Postnatal 72 hours
12.5 18.0 14.6 1.2
Haemoglobin (gm/dl)
Postnatal 72 hours
PCV 34 55 42.9 3.5
Mean cord bilirubin level was 2.3 mg/dl (range: 0.60- 4.7, SD- 0.7), the mean
total bilirubin at Postnatal 72 hours was 11.1 mg/dl (range: 2.40- 19.7, SD- 2.8).
Mean cord haemoglobin was 15.6 gm% (range: 12.00- 20.00, SD- 1.2) and the
mean haemoglobin at Postnatal 72 hours was 14.6gm% (range: 12.50- 18.00, SD- 1.2).
Mean cord PCV was 43.6% (range: 28.00- 60.00, SD- 4.1) and the mean PCV
at Postnatal 72 hours was 42.9% (range: 34.00- 55.00, SD- 3.5).
50
Results
TABLE 10
COMPARATIVE EVALUATIONS OF CORD AND POSTNATAL 72 HOURS
TOTAL BILIRUBIN, HAEMOGLOBIN AND PCV
Cord Postnatal 72 hours
Total Bilirubin
2.3±0.7 11.1±2.8
(mg/dl)
Haemoglobin
15.60±1.2 14.6±1.2
(gm/dl)
PCV
43.6±4.1 42.9±3.5
Mean cord bilirubin level was 2.3 mg/dl, mean total bilirubin at Postnatal 72
hours was 11.1 mg/dl.
Mean cord haemoglobin was 15.60 gm% compared to the mean haemoglobin
of 14.6 gm% at postnatal 72 hours.
Mean cord PCV was 43.6% and the Postnatal 72 hour mean PCV was 42.9%
51
Results
TABLE 11
DIAGNOSTIC PREDICTABILITY OF CORD BLOOD BILIRUBIN FOR
SIGNIFICANT HYPERBILIRUBINEMIA
(TOTAL
TOTAL BILIRUBIN OF ≥3.5 mg/dl AT 72 HOUR)
HOUR
CORD BILIRUBIN SIGNIFICANT INSIGNIFICANT
JAUNDICE JAUNDICE
≥3.5 18 1
<3.5 4 177
GRAPH VIII
CORD BLOOD BILIRUBIN AND SIGNIFICANT HYPERBILIRUBINEMIA

HYPERBIL
177
180
160
140
120
100
80 ≥3.5mg%
60
18 <3.5mg%
40 4 1
20
0
JAUNDICE
SIGNIFICANT JAUNDICE INSIGNIFICANT
18 newborns out of 22 who developed significant Jaundice had CBB ≥3.5mg/dl. Only
1 newborn out of 178 who did not develop significant Jaundice had a total CBB
≥3.5mg/dl
52
Results
TABLE 12
PREDICTABILITY OF CORD BLOOD BILIRUBIN FOR
HYPERBILIRUBINEMIA
True Positive n= 18
False Positive n= 4
False negative n= 1
True negative n= 177
Sensitivity (%) 94.7%
Specificity (%) 97.7%
PPV (%) 81.8%
NPV (%) 99.4%
True Positive: 18 Newborns with CBB ≥ 3.5mg/dl who developed significant
Jaundice at post natal 72 hours.
True Negative: 177 newborns with CBB < 3.5mg/dl who did not develop significant
Jaundice.
53
Results
False Positive: 4 Newborns with CBB ≥ 3.5mg/dl who did not develop significant
False Negative: 1 Newborn with CBB <3.5mg/dl who developed significant Jaundice
at post natal 72 hours.
Sensitivity: If a neonate develops significant hyperbilirubinemia, the probability that
the cord bilirubin was higher than 3.5 mg/dl was 94.7%.
Specificity: The probability that the cord bilirubin was <3.5 mg/dl was 97% in a Non
hyperbilirubinemic neonate.
Positive Predictive Value: In the present study, the probability that a neonate with
cord bilirubin ≥ 3.5 mg/dl would later develop hyperbilirubinemia was 81.8%.
Negative Predictive Value: The probability that a neonate with cord bilirubin <3.5
mg/dl would not develop hyperbilirubinemia was 99.4%.
54
Discussion
DISCUSSION
ABO Incompatibility is the most common materno-fetal blood group
incompatibility which is usually a problem of the neonate rather than the foetus.
Anaemia in the neonatal period is usually mild. The main clinical problem is Jaundice
in the first 24 hours of life (icterus praecox). Approximately 50% of cases occur in
first newborn infants. There is no predictable pattern of recurrence in subsequent
infants. Our study hypothesis was that a high serum bilirubin level at birth would also
predict a high peak later in life. Our aim was to find a correlation of CBB level with
subsequent NH in A and B blood group babies born to O blood group mothers and to
find a cut-off level of CBB for predicting the development of NH. We chose cord
bilirubin because it is a non-invasive way and the results are available within few
hours after birth and estimation of bilirubin can be done even in resource limited rural
areas in contrast to other studies like DAT, IgG anti A or anti B titres.
The diagnosis of ABO haemolytic disease depends on the clinical, serological
and biochemical findings in the newborn. Hydrops fetalis in association with ABO
incompatibility is extremely rare and has been reported in two cases72. Micro
spherocytosis is the most prominent feature of ABO haemolytic disease. Coombs test
in ABO incompatible infants does not necessarily indicate disease. It has been
observed that 1/3rd of babies born to O group mothers had a positive DAT.
Development of safe marker will help in preventing fatal outcome due to Jaundice.
To address this issue AAP recommends that follow up should be provided to
all neonates discharged less than 48 hours after birth by a health care professional in
an office, clinic, or at home within 2 to 3 days of discharge. Compliance with this

55
Discussion
advice may not be easy however, particularly in rural or lower socioeconomic areas,
and given the rarity of Kernicterus, it will be very difficult, if not possible to
document the benefits of this policy. Experience suggests that asking mothers to
observe infants for the development of Jaundice is not satisfactory. Despite such
instructions, it is difficult for many parents to recognize significant Jaundice.
Currently we do not have a reliable method of anticipating such levels of
hyperbilirubinemia. It is possible that closer, and more frequent, follow up after birth
and discharge from the hospital might prevent some of these unfortunate outcomes,
but rare, sporadic cases of Kernicterus may not be preventable unless we adopt an
approach to surveillance of the newborn that is substantially more rigorous than has
been practiced. The feasibility, costs, risks and benefits of such an approach need to
be determined.
Reliable predictors can reduce hospital stay for normal babies resulting in
discharge and identifying at risk or high risk neonates likely to develop pathological
Jaundice. These neonates would need close monitoring so that potential risk for
bilirubin induced brain damage can be reduced amongst term healthy newborn
discharged early from hospital.
Several factors are recognised as early predictors both individually and in
combination in predicting significant Jaundice in ABO incompatibility, those
includes IgG anti A or anti B titres in maternal serum, Coombs test, serum bilirubin,
cord bilirubin, retculocyte count.
Keeping these factors in consideration our study was conducted on term
healthy neonates with A or B blood group born to O positive healthy mothers,
56
Discussion
outcome was hyperbilirubinemia we have considered peak serum bilirubin levels ≥
15mg/dl at 72 hrs of age as significant Jaundice since specific treatment is considered
at or above this level.
TABLE 13:
COMPARISON OF CORD SERUM BILIRUBIN AND SIGNIFICANT
JAUNDICE IN ABO INCOMPATIBILITY
No. Of Umbilical cord bilirubin as

Studies Year
Cases predictor
Robinson et al66 1960 - >3mg/dl
H.M.Risemberg18 1977 71 >4mg/dl
K N Haque67 1978 - No correlation
White J G.68 1981 - >85mmol/l (5mg/dl)
Simpson et al77 1999 71 >2.5mg/dl.
Azma RZ73 2011 114 ≥2.5mg/dl No correlation
Present study 2011 200 ≥3.5mg/dl
Other studies also reported the relation between raising levels of cord bilirubin
and increased incidence of significant hyperbilirubinemia. Thus from the above table
it can be seen that different authors have used different cut off value for predicting
significant hyperbilirubinemia and some have found CBB cannot be used as a
prediction of subsequent hyperbilirubinemia.
57
Discussion
This variability is mainly because of technical error in estimating bilirubin
levels, sample size, cut off value decided for significant hyperbilirubinemia, as many
studies were done before the Bhutani hour specific normogram were introduced.
Hence the need for a local laboratory to define the cut off value becomes all the more
important.
In the present study significant Jaundice was seen equally in both O-B or O-A
blood group, The literature is inconsistent with regard to the degree of haemolysis and
the incidence and severity of hyperbilirubinemia among O-A and O-B pairs. Some
Literature review shows that significant Jaundice was more severe in OA
combination.12 Kaplan et al study using ETCOc as predictor for hyperbilirubinemia
showed O-B blood group had more significant and severity of Jaundice 74. Our study
showed a positive correlation only and observations were not statistically significant.
Significant Jaundice was slightly more in male babies (12.9%) as compared to
female babies (8.7%) though it was not significant statistically. Literature review
reported variable sex distribution with some stating disease as more common in
female babies and some males.12,75 Hodr R, in 1989 observed that among neonates
treated successfully by phototherapy, boys prevailed significantly and there was
significantly higher prevalence of girls among the most severe forms of ABO
haemolytic disease75. Dufour DR, in a retrospective analysis of 254 cases found that
sex, race, gravidity, birth weight and blood type of the infant did not have any
significant relationships to outcome76. In our study also none of these variables were
statistically significant.
58
Discussion
In the present study using serum bilirubin levels ≥ 3.5 mg/dL in the cord
blood, hyperbilirubinemia could be predicted with sensitivity of 94.7%, specificity of
97.7%, and Positive Predictive Value of 81.8%. The Negative Predictive Value is
99.4%. The correlation between cord bilirubin and development of significant
Jaundice in the postnatal 72 hours showed a positive correlation according to Karl
Pearson’s correlation coefficient method is (r = 0.37).
59
Conclusion
CONCLUSION
introduction of anti-D Prophylaxis, ABO incompatibility is now the major cause of
immune haemolytic disease of new born(HDN) various studies has shown ABO
incompatibility occurs in 15-25% of all pregnancies and it was in every 10th newborn
that this incompatibility became manifest as a haemolytic disease requiring treatment
ABO incompatible babies have double the risk to develop Jaundice requiring
treatment and 5-10 times increased risk of exchange transfusion.
Early identification of newborn at risk for significant hyperbilirubinemia by
using simple predictors can help to prevent possible bilirubin induced neurological
dysfunction.
A 99.4% Negative Predictive Value in the present study suggests that in
healthy Term babies with ABO without Rh incompatibility Cord Blood Bilirubin <
3.5 mg/dl can help to identify those newborns who are unlikely to require further
evaluation and intervention. Babies with Cord Blood Bilirubin level ≥ 3.5 mg/dl
should be followed more frequently to reduce mortality and morbidity due to
Neonatal hyperbilirubinemia.
As a speculation, one may consider the umbilical cord blood to be a kind of ‘file’ for
the newborn. As such it could be collected, stored and used for further analysis of
unconjugated bilirubin levels, should a slightly or moderately Jaundiced child be
considered early discharge from hospital. Such a proposal may therefore constitute an
additional predictive method that is available for evaluating the occurrence of severe
60
Conclusion
hyperbilirubinemia by third day of life. In association with other resources that were
already available this proposal may help in assuring safer early discharge
Our study had homogenous local rural population unlike heterogeneous group
of neonate from Cosmopolitan Urban Bangalore. This is the strength of our study. It
means that the Prediction test developed by us can be applied to the neonates of
Hoskote’s local rural population on whom it was developed.
Thus prediction of neonatal hyperbilirubinemia will have widespread
implication especially in our rural setup where there are limited resources and few
hospital beds.
Healthy newborns at low risk for hyperbilirubinemia can be discharged early
from the hospital.
61
Summary
SUMMARY
• The study group consisted of 200 full term neonates delivered in M.V.J.MC &
RH with ABO incompatibility
• Cord blood bilirubin and Total Serum Bilirubin at 72 hours of age was
estimated for all neonates.
• Incidence of significant hyperbilirubinemia ( TSB >15 mg/ dl at 72 hours of
age ) in our study population is 11%
• Male were slightly more affected than the female newborns in the significant
Jaundice group. (M:F ::1.4:1 ). But this was not statistically significant.
• The incidence of significant Jaundice was more or less equal in A-blood group
and B-blood group newborns.
• There were no statistical significant differences between the cases who had
cord bilirubin level <3.5 mg/dl and ≥3.5 mg/dl with respect to various factors
that may be associated with the risk of hyperbilirubinemia, such as gender,
gestational age, birth weight and blood group
• Mean cord bilirubin level was 2.3±0.7 mg/dl. Mean total bilirubin at 72 hours
of post natal age was 11.1±2.8 mg/dl.
• There was a positive correlation between cord bilirubin and third postnatal day
serum bilirubin.
• Using cord bilirubin level of ≥ 3.5 mg/dl, Hyperbilirubinemia can be predicted
with sensitivity of 94.7%, specificity of 97.7 %, and positive predictive value
of 81.8% and negative predictive value of 99.4%.
62
Summary
• Healthy term babies with ABO incompatibility with Cord Blood Bilirubin
<3.5 mg/dl are unlikely to require further evaluation and intervention hence
these newborns can be discharged with assurance to Parents.
• The babies who are discharged with a CBB level ≥ 3.5 mg/dl should have
unfailing frequent follow ups in the postnatal 1st week. A clearly written
description of neonatal hyperbilirubinemia including risks, what to look for,
and when to call or bring the infant back should be given to parents whose
babies are discharged early.
CBB <3.5 mg/dl seems a “cost effective” screening method for early
discharge of newborns.
63
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71
Annexure
ANNEXURE I – PHOTOGRAPH
Photograph I: Visual assessment of Jaundice
72
Annexure
ANNEXURE II – PROFORMA
MVJ MEDICAL COLLEGE AND RESEARCH HOSPITAL
HOSKOTE, BANGALORE DEPARTMENT OF PEDIATRICS
Correlation of Cord Blood Bilirubin with Neonatal Hyperbilirubinemia in
New borns with a setting of ABO Incompatibility
Mother’s Name: Case No:
Age of the Mother: Sex of the Baby:
Date of Delivery: I.P Number of the Baby:
Gravida: Gestational Age: Birth weight:
INVESTIGATIONS:
Blood Group of the Mother: Blood Group of the Baby:
Cord 12hrs 24hrs 72hrs
Total bilirubin
Direct bilirubin
Indirect bilirubin
Haemoglobin
Haematocrit
73
Annexure
ANNEXURE III – MASTER CHART
KEY TO MASTER CHART
B/W ------- Birth weight
CBB ------- Cord blood bilirubin
CHb ------- Cord blood haemoglobin
DOB ------- Date of Birth
D3 ------- Day three
F ------- Female
G ------- Gravida
Hb ------- Haemoglobin
I.P.No ------- In patient number
Kg ------ Kilogram
M ------ Male
Mg ------ Milligram
PCV ------ Packed cell volume
Sl: No. ------ Serial Number
Yrs – years.
74
Blood
Sl:No Sex of baby IP :NO DOB Gravida B/W in group CBB D3-bilirubin CHb/PCV D3-Hb/PCV
BABY Kgs baby
01 F 128030 02-09-10 Primi 2.975 B+ 2.5 14.5 16/42 14.2/42.6

02 F 131872 20-10-10 Primi 3.17 A+ 2.4 13.2 18/42 16/38
03 F 132827 03-11-10 Multi 3.5 B+ 2.2 12 18/39 18/55
04 M 132999 06-11-10 Primi 2.7 B+ 2.8 16.1 15.5/44 15/45
05 M 133237 10-11-10 Primi 2.94 A+ 2.3 13 16/42 16/48
06 F 133334 11-11-10 Multi 2.96 A+ 2.3 12.4 15/35 15/48
07 F 134141 20-11-10 Primi 2.565 B+ 2.4 12 15/51 16/48
08 M 134784 28-11-10 Multi 3.294 A+ 2.8 10.8 20/60 18/52
09 M 135754 10-12-10 Primi 2.62 A+ 1.5 9.8 16.2/48.4 16/48
10 F 135835 11-12-10 Multi 2.5 B+ 2.1 10.6 17/51 16/48
11 F 135868 11-12-10 Primi 2.6 A+ 2 8.4 19/48 18/48
12 M 136883 24-12-10 Primi 2.8 B+ 2.1 10 18/46 15/42
13 F 136893 26-12-10 Primi 2.5 B+ 2.1 11 14/46 14.1/48
14 M 136908 26-12-10 Multi 3.5 B+ 2.5 12.8 18/42 16/42
15 M 137934 06-01-11 Primi 2.8 A+ 1.9 11.8 16/48 16/46
16 M 138632 08-01-11 Multi 3.335 B+ 3.7 16 15/45 14/45
17 M 138748 18-01-11 Multi 3.05 A+ 1.9 12.2 14/42 16.5/50
18 F 139184 27-01-11 Primi 2.71 B+ 2.1 13.6 16.6/44 15/42
19 F 139185 27-01-11 Multi 3.6 B+ 2.1 12.6 15.2/42 16.4/48
20 M 139444 01-0211 Primi 3.42 B+ 3.6 15 15/46 15.2/44
21 F 140035 02-01-11 Multi 2.705 A+ 2.5 10 15.4/47 15/44
22 F 140310 03-02-11 Multi 2.73 B+ 2.3 11.3 16/50 15/46
23 M 140422 06-02-11 Primi 2.7 B+ 1.8 9 14.4/49.4 13.4/44
24 F 140486 09-02-11 Primi 3.4 B+ 2.6 12 16.4/50 16/48
25 F 140901 11-02-11 Multi 2.8 A+ 2.7 12 16/42 14.4/48
26 F 140904 12-02-11 Primi 2.945 A+ 2.2 7.8 15.6/48 14.2/46
27 F 141017 13-02-11 Multi 2.7 B+ 4.7 17 15.7/47.8 15.2/47.6
28 F 141207 15-02-11 Primi 2.5 B+ 1.8 7.5 15/46 16/48
29 M 142536 05-03-11 Multi 2.5 B+ 1.8 11.5 15.6/42 15/42
30 F 143361 15-03-11 Primi 2.75 B+ 1.6 6.1 14.7/46 14/44
31 F 143925 21-03-11 Primi 2.75 B+ 2.6 10 10/28 14.2/36
32 F 144207 24-03-11 Primi 2.9 A+ 1.7 12.3 15/42 16/42
75
Blood
BABY Kgs baby
33 M 144622 29-03-11 Multi 2.6 B+ 1.8 10.8 15/41 14.5/42
34 M 144625 30-03-11 Multi 2.76 A+ 2 10 16.2/51 14/42
35 F 145014 07-04-11 Primi 3.23 B+ 3.6 15 16/50 15/48
36 M 145018 07-04-11 Primi 2.88 A+ 3.8 15.6 13/42 13/40
37 F 145342 07-04-11 Primi 2.54 A+ 2.4 10.8 16/42 14/40
38 M 145585 09-04-11 Primi 2.6 A+ 2.2 10.2 17/50 15/48
39 F 145589 10-04-11 Multi 3.56 B+ 3 12 16/42 15.3/42
40 F 146416 21-04-11 Primi 2.7 A+ 2.7 10.6 17/40 14/40
41 M 146671 26-04-11 Multi 2.86 A+ 1.9 12.7 15/42 15/41
42 M 147136 27-04-11 Primi 3.1 B+ 2.5 10.4 17/40 15/40
43 M 147162 01-05-11 Primi 2.5 A+ 2.4 9 15/42 15/40
44 M 147308 03-05-11 Multi 2.75 B+ 1.9 10 17/42 14/41
45 F 147570 10-05-11 Primi 3.4 A+ 3.7 16.4 16/40 14/40
46 M 147590 10-05-11 Multi 2.94 B+ 2.1 13.1 17/44 15/42
47 F 148868 21-05-11 Primi 2.62 A+ 2.6 12 17.2/32.5 16.2/34
48 M 149094 25-05-11 Multi 2.5 B+ 4 17.6 16/42 16/40
49 F 149288 25-05-11 Multi 2.8 B+ 3.6 16.3 14/49 13/47
50 M 150119 03-06-11 Primi 3.09 B+ 2.1 10.4 12.4/39.7 13/42
51 F 150281 05-06-11 Primi 3.2 A+ 1.9 9.6 17/49.8 17/49
52 M 150686 09-06-11 Multi 3.04 B+ 2.1 11.8 16/42 16/42
53 M 150989 17-06-11 Primi 2.52 A+ 3.8 18.1 17/42 16/41
54 M 152126 26-06-11 Multi 2.8 B+ 1.4 7.8 16/42 15/41
55 M 152269 27-06-11 Primi 2.9 A+ 2.2 11.8 15.6/49 14/48
56 F 152337 29-06-11 Multi 2.65 B+ 2 8.6 16.8/47 15/46
57 M 152752 02-07-11 Multi 3.2 B+ 3.9 15 15/47 14.8/46
58 M 153291 09-07-11 Multi 2.6 B+ 2.3 15.3 14.8/53 15/44
59 M 153386 11-07-08 Primi 2.8 B+ 1.3 9.5 14.8/44 14/43
60 F 153723 13-07-11 Multi 3.25 A+ 3.7 15.2 14.3/42 14/43
61 M 153927 16-07-11 Primi 3.2 A+ 1.8 14.3 15/44 15/42
62 F 153828 16-07-11 Multi 2.86 B+ 2 11.9 14.3/44 14.2/44
63 F 154134 18-07-11 Primi 2.51 B+ 1.8 6.4 15/48 14.5/44
64 M 154452 21-07-11 Primi 2.5 A+ 2.3 10.2 14.6/47 14.5/47
65 M 154468 21-07-11 Primi 2.6 A+ 1.5 7.8 15/46 14.5/42
66 F 154912 26-07-11 Primi 2.9 B+ 2.6 14 15/43 14/42
67 F 155032 27-07-11 Primi 2.8 A+ 3.1 10.5 15/47 13/44
68 F 155138 28-07-11 Multi 2.75 B+ 2.5 12 15/42 14.3/41
69 F 155233 29-07-11 Primi 3.08 A+ 2.5 11.4 14.3/44 14/41
70 F 155421 02-08-11 Multi 2.7 B+ 1.8 10 14.3/48 14/42
71 F 155667 03-08-11 Multi 2.8 B+ 2.2 8.3 14.2/44 14/42
72 F 156018 07-08-11 Primi 2.985 B+ 2.1 10.7 13.4/46 13/42
76
Blood
BABY Kgs baby
73 M 156243 09-08-11 Multi 2.8 A+ 2 11 15/42 15/40
74 M 156352 10-08-11 Multi 2.935 B+ 1.8 9.3 14/42 13/40
75 M 157336 22-08-11 Primi 3.5 A+ 2.4 12.4 15/42 14/43
76 F 158616 08-09-11 Multi 2.75 A+ 2.3 10.4 14/42 13/44
77 F 158822 11-09-11 Primi 2.6 A+ 2.1 9.4 17/40 16/40
78 F 158990 12-09-11 Primi 3.245 A+ 3.8 15.4 15.3/44 14/42
79 F 159003 14-09-11 Primi 2.675 B+ 2.6 13 15/42 13.4/40
80 F 159367 15-09-11 Primi 2.5 B+ 2.5 11 14.4/47 13/42
81 M 159705 17-09-11 Primi 3.25 B+ 2.3 12.4 15/40 14/40
82 M 159843 21-09-11 Multi 3.5 A+ 1.8 8.6 13.8/48 13/42
83 M 160031 21-09-11 Primi 3.34 B+ 1.2 7.2 15/44 13/42
84 M 160067 21-09-11 Multi 2.65 A+ 2.3 9 15.2/45 13/43
85 F 160446 22-09-11 Primi 3.2 B+ 1.7 11.2 15/41 13/40
86 M 160689 27-09-11 Multi 3.14 B+ 2.3 10.8 14.5/52 12.5/47
87 F 160828 29-09-11 Primi 2.6 B+ 2.8 12 14.5/48 13/46
88 F 160840 02-10-11 Multi 2.67 B+ 3.2 13 15/46 13/42
89 M 161189 03-10-11 Primi 3.06 B+ 3.1 13 15/42 13/40
90 M 161328 06-10-11 Multi 2.93 A+ 3.2 13.4 15/46 15/44
91 M 161563 08-10-11 Primi 2.56 A+ 2.1 13 14.3/44 13.5/40
92 M 161736 10-10-11 Multi 2.5 A+ 2.5 10.4 16/42 13/40
93 M 162153 14-10-11 Primi 2.6 B+ 2.4 11 13/42 13/40
94 F 162286 15-10-11 Multi 2.9 B+ 2.7 10.8 13.6/40 13/42
95 M 162690 19-10-11 Multi 2.5 B+ 3.7 16 15/42 14/40
96 M 162696 20-10-11 Primi 3.325 A+ 1.6 8 13/40 12.5/42
97 M 163055 23-10-11 Primi 3.47 A+ 2.8 12 14/44 13/42
98 M 163300 28-10-11 Primi 3.25 A+ 3 12.3 13.5/42 13/40
99 M 163813 02-11-11 Multi 2.6 B+ 2.3 8.6 15/40 13/40
100 M 163822 06-11-11 Multi 2.9 A+ 2.4 11.5 17/42 13/42
101 F 164155 07-11-11 Primi 2.61 B+ 2.6 14.3 14.3/44 13.5/40
102 M 164425 09-11-11 Multi 2.72 B+ 2.2 11.2 16/47 15/44
103 M 164630 12-11-11 Primi 2.5 B+ 2.3 11.1 16/48 13/46
104 M 164780 14-11-11 Multi 2.9 A+ 2.5 15.6 15/40 14/42
105 M 164784 14-11-11 Primi 2.5 A+ 1.8 11 16/48 14/47
106 F 165566 21-11-11 Primi 2.6 A+ 1.6 9 17/46 15/42
107 M 165906 24-11-11 Multi 3.1 B+ 2.3 11 17/48 15/42
108 M 165912 24-11-11 Primi 2.85 A+ 1 7.6 16/47 14/42
109 F 166019 25-11-11 Multi 2.76 A+ 1.5 7 18/48 15/47
110 F 166126 26-11-11 Multi 2.7 A+ 2.4 10.6 16/42 13/40
111 M 166278 28-11-11 Primi 2.6 B+ 1.8 9 16/45 15/40
112 M 166640 01-12-11 Primi 2.71 B+ 2 10 17/40 15/40
77
Blood
BABY Kgs baby
113 M 166641 01-12-11 Primi 2.71 A+ 1 6 16/40 13/40
114 M 167013 05-12-11 Multi 3.055 B+ 1.6 9.6 17/47 14/42
115 F 167030 06-12-11 Primi 2.5 B+ 1 11 17.2/42 15/40
116 F 167048 06-12-11 Primi 2.75 A+ 2.8 12 17/44 15/42
117 F 167610 12-12-11 Primi 2.5 B+ 3.7 19.5 16/41 15/42
118 M 167859 14-12-11 Primi 2.55 B+ 2.6 15 17/42 16/41
119 F 168485 20-12-11 Multi 3.325 A+ 3.7 17 16/42 15/40
120 F 168583 24-12-11 Primi 3.35 B+ 1 5.6 15/41 15/42
121 M 168987 26-12-11 Primi 2.6 A+ 3.4 14 15/42 15/40
122 F 169436 29-12-11 Primi 2.505 B+ 2.6 12 16/40 15/40
123 F 169673 02-01-12 Multi 2.75 A+ 1.8 9.8 16/40 14/40
124 M 169930 03-01-12 Multi 2.54 A+ 2 12.6 15/40 14/41
125 F 170139 05-01-12 Primi 3.2 A+ 1.4 9 15/41 15/40
126 M 170163 05-01-12 Multi 2.75 A+ 2.6 11.4 14/36 13/37
127 M 170379 07-01-12 Primi 2.8 B+ 2.4 12 15/40 13/48
128 F 171557 19-01-12 Multi 3.13 B+ 3.2 14 15/46 13/46
129 M 172156 26-01-12 Primi 2.55 B+ 2.6 14.5 14/38 14/39
130 F 172157 26-01-12 Primi 2.7 A+ 3.1 12 15/38 15/36
131 F 172288 28-01-12 Multi 2.6 A+ 2.2 11.6 15/40 15/40
132 M 172383 28-01-12 Primi 2.715 A+ 2 9.6 15/42 15/40
133 M 172402 29-01-12 Primi 2.68 B+ 3.2 12.2 16/40 13/37
134 F 172532 30-01-12 Multi 2.62 B+ 2.1 11 15/40 15/40
135 M 172775 01-02-12 Primi 2.89 B+ 2 10 16/44 15/42
136 F 173232 06-02-12 Primi 2.93 B+ 1.8 8.9 16/40 15/40
137 F 173244 08-02-12 Primi 2.535 A+ 1.6 6.4 16/41 13/40
138 M 174054 14-02-12 Multi 2.705 A+ 2.4 11.2 15/40 14/40
139 M 174074 15-02-12 Multi 3.03 B+ 2.2 12.5 15/42 14/40
140 M 174531 18-02-12 Primi 3.19 A+ 2 8.6 16/40 16/42
141 F 174552 18-02-12 Primi 2.6 B+ 2.5 9.8 16/40 15/40
142 M 174678 21-02-12 Primi 2.8 B+ 2 8.6 16/40 15/40
143 F 174691 21-02-12 Multi 2.68 A+ 3.7 11.5 16/40 14/42
144 M 175135 25-02-12 Primi 3.1 B+ 1.7 14.3 15/40 14/36
145 M 175288 27-02-12 Multi 3.25 B+ 1.7 11.2 15/40 14/40
146 M 175389 28-02-12 Primi 2.6 A+ 2 11.1 14/40 13/40
147 M 175491 29-02-12 Primi 2.8 A+ 3.9 16.8 15/42 13/41
148 M 176000 29-02-12 Primi 2.7 B+ 1.5 13.3 16/42 13/40
149 M 176199 07-03-12 Primi 2.73 B+ 2.2 14.1 16/42 15/40
150 M 176299 07-03-12 Multi 2.5 A+ 2.7 12.3 13/40 13/40
151 M 176306 08-03-12 Primi 2.55 B+ 2.4 13.6 16/42 14.2/42.6
152 M 176320 09-03-12 Multi 3.325 B+ 2.2 10.3 18/42 16/38
78
Blood
BABY Kgs baby
153 F 176418 11-03-12 Multi 3.35 B+ 0.6 8.2 18/39 18/55
154 M 176710 14-03-12 Primi 3.14 B+ 2.2 8.9 15.5/44 15/45
155 F 176791 14-03-12 Primi 2.6 B+ 1 10.3 16/42 16/48
156 M 176800 15-03-12 Primi 2.67 A+ 1.4 5.9 15/35 15/48
157 F 176805 16-03-12 Primi 2.56 B+ 2 11.4 16.2/48.4 16/48
158 M 177362 19-03-12 Primi 2.5 B+ 1.9 14.6 17/51 16/48
159 F 177448 19-03-12 Multi 2.6 A+ 1.7 9 19/48 18/48
160 F 177493 20-03-12 Primi 2.9 A+ 1.8 7.2 17/40 14/40
161 M 177510 20-03-12 Multi 2.5 A+ 1.9 9.8 15/42 15/41
162 M 177617 21-03-12 Primi 3.325 B+ 2.2 10.4 17/40 15/40
163 F 177771 22-03-12 Multi 3.47 A+ 1.8 9.4 15/42 15/40
164 M 177740 22-03-12 Primi 3.25 B+ 2.9 14 17/42 14/41
165 M 177846 23-03-12 Primi 2.6 B+ 1.8 8.9 16/40 14/40
166 F 177867 24-03-12 Primi 2.9 A+ 2.1 11.2 17/44 15/42
167 M 178135 27-03-12 Multi 2.61 A+ 1.7 12 17.2/32.5 16.2/34
168 F 178146 27-03-12 Multi 2.72 A+ 2 10 16/42 16/40
169 M 178392 30-03-12 Primi 2.5 B+ 1.2 3.9 14/49 13/47
170 M 178511 01-04-12 Multi 2.5 B+ 2.1 11 12.4/39.7 13/42
171 M 178605 02-04-12 Primi 3.325 B+ 1.4 8.3 17/49.8 17/49
172 F 178773 02-04-12 Multi 3.47 B+ 1.6 9.6 16/42 16/42
173 M 178785 03-04-12 Primi 3.25 B+ 1.4 7.1 17/42 16/41
174 M 178786 03-04-12 Multi 2.6 B+ 3 14.3 16/42 15/41
175 F 178617 04-04-12 Primi 2.9 B+ 2.5 9 15.6/49 14/48
176 F 178926 06-04-12 Multi 2.61 A+ 1.4 7.2 16.8/47 15/46
177 F 179084 07-04-12 Multi 2.72 B+ 1.4 7.8 15/47 14.8/46
178 F 179481 10-04-12 Primi 2.7 A+ 1.6 9.4 14.8/53 15/44
179 M 179623 10-04-12 Primi 2.8 B+ 1.3 9.2 14.8/44 14/43
180 M 180583 20-04-12 Multi 2.985 B+ 2 11.2 14.3/42 14/43
181 F 180610 21-04-12 Primi 2.8 A+ 1.7 12.2 15/44 15/42
182 F 180612 23-04-12 Multi 2.935 B+ 1.4 3.4 15.7/47.8 15.2/47.6
183 M 180866 25-04-12 Primi 3.5 A+ 1.6 7.8 15/46 16/48
184 M 180905 25-04-12 Multi 2.75 B+ 2.5 13 15.6/42 15/42
185 F 181211 26-04-12 Primi 2.6 B+ 1.8 9.9 14.7/46 14/44
186 F 181212 28-04-12 Multi 3.245 A+ 2.3 10 14/38 14.2/36
187 M 181281 29-04-12 Primi 2.8 B+ 2.6 12 15/42 16/42
188 M 181433 30-04-12 Multi 2.6 A+ 1.8 8.6 15/41 14.5/42
189 F 181609 02-05-12 Primi 2.5 A+ 3 12 16.2/51 14/42
190 M 181746 03-05-12 Multi 3.01 A+ 3.5 15 17/42 13/42
191 F 181747 03-05-12 Multi 2.8 A+ 2.8 12 14.3/44 13.5/40
192 M 181748 03-05-12 Primi 2.76 B+ 2.8 12 16/47 15/44
79
Blood
BABY Kgs baby
193 M 181981 05-05-12 Primi 2.6 B+ 3.8 17 16/48 13/46
194 F 182002 05-05-12 Primi 2.5 A+ 1.6 6.8 15/40 14/42
195 M 182222 06-05-12 Multi 2.9 B+ 1.8 9.8 16/48 14/47
196 F 182261 07-05-12 Primi 2.6 B+ 1.8 10 17/46 15/42
197 F 182765 13-05-12 Primi 2.7 B+ 2.4 12 17/48 15/42
198 F 182902 15-05-12 Multi 3.5 A+ 1.1 5 16/47 14/42
199 F 183217 16-05-12 Multi 3.02 B+ 2.8 13 18/48 15/47
200 M 183721 20-05-12 Primi 3.0 A+ 2.2 11 16/48 15/47
80
CORRELATION OF CORD BLOOD BILIRUBIN AND
NEONATAL HYPERBILIRUBINEMIA IN NEWBORNS
WITH A SETTING OF ABO INCOMPATIBILITY
By
Dr. SAJJAD SANEEQ C.H
Dissertation Submitted to the
Rajiv Gandhi University of Health Sciences, Karnataka, Bangalore
In partial fulfillment
Of the requirements for the degree of
DOCTOR OF MEDICINE
In
PEDIATRICS
Under the guidance of
Dr. SANJEEV SHRINIVAS MANAGOLI
PROFESSOR
DEPARTMENT OF PEDIATRICS
M.V.J. MEDICAL COLLEGE AND RESEARCH HOSPITAL
DANDUPALAYA, BANGALORE
2012
i
ACKNOWLEDGMENT
It is with great privilege, I express my most humble and profound gratitude to
my Teacher and Guide Dr. SANJEEV SHRINIVAS MANAGOLI Professor
Department of Pediatrics. M.V.J. Medical College and Research Hospital for his
guidance, able supervision, valuable suggestions, cyber help and constant
encouragement throughout the study which facilitated the completion of this
dissertation. He has made me realize that there is no substitution for hard work and
revision for perfection.
I am thankful to Dr. B. RAVI CHANDER Professor, Head of the Department,
Department of Pediatrics, M.V.J. Medical College and Research Hospital for his
valuable suggestions and constant encouragement throughout the study which has
helped me greatly to expedite this dissertation and for his guidance, encouragement
and moral support during my career as a postgraduate, who taught me to take care of
simple things initially so that bigger issues gets solved by its own.
I express my deepest sense of gratitude to my eminent and esteemed teacher
Dr.T.S RAGHU RAMAN, Principal M.V.J. Medical College and Research Hospital
for permitting me to carry out this study, his unabated inspiration, constant support and
encouragement.
I am extremely grateful to Dr. M. J. Mohan and Mrs. Dharani Mohan, for
their kind co-operation, encouragement, moral support in conducting my study and for
providing a home away from home during my career as a postgraduate.
I am extremely grateful to all my distinguished Professors, Dr. Jaishree R.
Kamat, who helped me to take lot of responsibilities and showed importance of
discipline during major part of final year posting under her, Dr. Gopal for his vast
experience filled advices, Associate Professors, Dr. Poornima S and Dr. Santhosh
vi
for helping in literature search and timely advices. Assistant Professors, Senior
Residents and Junior Residents, staff nurses, of the Department of Pediatrics for
their kind co-operation and encouragement in conducting my study and for their
guidance, inspiration and moral support during my career as a postgraduate.
I am thankful to Dr. Gurumurthy, Professor, Head of the Department,
Department of Biochemistry, M.V.J. Medical College and Research Hospital, the
Faculty and the Technicians of Biochemistry for their constant support to complete
my study.
I thank my fellow Post graduates Dr. Amitoj, Dr. Kiran and post-graduate
colleagues in Pediatrics, both past and present, for their support and co-operation.
Most important of all I shall be failing in my duties if I do not thank all the
MOTHERS AND BABIES included in the study, without whom this study would
not have been possible.
I owe my gratitude to my Parents and my lovely Wife and Son whose love
and support constantly beholds me.
I certainly owe my thanks to all the people especially Paediatric Department
Assistant, Office Stenographer, Statistician, who have helped me directly or
indirectly in accomplishing this work.
Finally I thank god, for making all these wonderful people happen to me and
pray for continued blessing and success.
Date: Signature of candidate
Place: Dr. Sajjad Saneeq C.
vii
LIST OF ABBREVIATIONS
(In alphabetical order)
AAP : American Academy of Pediatrics
AGA : Appropriate for Gestational Age
CBB : Cord Blood Bilirubin
DAT : Direct Anti-globin Test
ETCOC : Corrected ambient carbon monoxide
gm : Gram
HDN : Haemolytic disease of newborn
LBW : Low Birth Weight
NH : Neonatal Hyperbilirubinemia
NICU : Neonatal Intensive Care Unit
NPV : Negative predictive value
PPV : Positive predictive value
PT : Phototherapy
Rh : Rhesus
SGA : Small for Gestational Age
TCB : Transcutaneous Bilirubin
TSB : Total serum bilirubin.
viii
ABSTRACT
Background and Objectives
The incidence of Rh D allo-immunization has decreased after the introduction
of anti-D prophylaxis, and so ABO incompatibility is now the major cause of immune
haemolytic disease of newborn (HDN). Various studies has shown ABO
incompatibility occurs in 15-20% of all pregnancies, and have double the risk to
develop jaundice requiring treatment, 5-10 times risk of exchange transfusion, and it
was in 1/10th of newborn that this incompatibility become manifested as HDN
requiring treatment. There is a recent trend of early discharge of the newborn after
birth. At the same time, it has been observed that Neonatal hyperbilirubinemia (NH) is
a significant cause (6.5%) for readmission to the hospital. Hence the present study was
conducted to correlate the Cord Blood Bilirubin (CBB) levels with subsequent NH in
newborns with setting of ABO incompatibility.
Methods
Study was performed at the Department of Pediatrics in a Rural Medical
College Hospital. Healthy term newborns (n=200) with A or B blood group born to
healthy mothers with blood group O positive, were prospectively enrolled in the study.
CBB was estimated. Postnatal Serum Bilirubin estimation was done at 72 hours.
Results
Significant NH in our study is 11%. Mean total bilirubin at postnatal 72 hours
was 11.1 mg/dl. Using CBB level of ≥ 3.5 mg/dl as a cut-off, NH can be correlated
ix
with sensitivity of 94.7%, specificity of 97.7 %, positive predictive value of 81.8 %
and negative predictive value of 99.4%
Interpretation & Conclusion
In the present study a Negative Predictive Value of 99.4% suggests that in
Healthy Term babies with ABO incompatibility having a CBB <3.5 mg/dl, are
unlikely to require further evaluation and intervention. These newborns can be
discharged with assurance to Parents. Whereas the babies who are discharged with a
CBB level ≥ 3.5 mg/dl should have unfailing frequent follow ups in the postnatal 1st
week.
Keywords
Newborn; Neonate; ABO incompatibility; Hyperbilirubinemia; Jaundice prediction;
Cord bilirubin
x
TABLE OF CONTENTS
SL. NO TOPICS PAGE NO
1 INTRODUCTION 1
2 OBJECTIVES 5
3 REVIEW OF LITERATURE 6
4 METHODOLOGY 41
5 RESULTS 43
6 DISCUSSION 55
7 CONCLUSION 60
8 SUMMARY 62
9 BIBLIOGRAPHY 64
10 ANNEXURE I – PHOTOGRAPHS 72
11 ANNEXURE II – PROFORMA 73
12 ANNEXURE III – MASTER CHART 74
xi
LIST OF TABLES
Sl.No Tables Pages

Clinical Features of Bilirubin Encephalopathy
1 20
Study population and Significant Jaundice

2 43
Parity of Mothers
3 44
Distribution of Neonates according to Sex.

4 45
Distribution of Neonates according to Birth weight

5 46
Distribution of Neonate according to Blood group

6 47
Significant Jaundice in relation to Blood group A&B

7 48
8 Sex distribution in Significant Hyperbilirubinemia. 49
Bilirubin, Haemoglobin and PCV profile of the Study

9 Population 50
Comparative evaluation of Cord and Postnatal 72hours,

10 Haemoglobin & PCV 51
Diagnostic predictability of Cord Blood Bilirubin for

11 Significant Hyperbilirubinemia. 52
Predictability of Cord Blood Bilirubin for

12 Hyperbilirubinemia 53
Comparison of Cord Serum Bilirubin and Significant

13 Jaundice in ABO incompatibility 57
xii
LIST OF GRAPHS
Sl.No Graphs Pages
I Study population and Significant Jaundice 43
II Maternal Parity 44
III Distribution of Neonates according to Sex 45
IV Distribution of Neonates according to Birth Weight 46
V Distribution of Neonates according to Blood Group 47
VI Blood Group and Significant Jaundice 48
VII Sex distribution in Significant Hyperbilirubinemia 49
Cord Blood Bilirubin and Significant

IX 52
Hyperbilirubinemia
xiii
LIST OF FIGURES
Sl. No Figure Pages
I Bilirubin Metabolism and Elimination 13
II Algorithm for the management of Jaundice in newborn 18
III Important factors in the efficacy of Phototherapy 23
Risk designation of Term and Near-term well Newborns

IV 39
based on their Hour Specific Serum Bilirubin Values.
xiv
LIST OF PHOTOGRAPHS
Sl.No Photograph Pages
Visual assessment of Neonatal

I
Hyperbilirubinemia
72
xv
Introduction
INTRODUCTION
Neonatal hyperbilirubinemia (NH) is a cause of concern for the parents as well
as for the pediatricians.1 It affects nearly 60% of term and 80% of preterm neonates
during first week of life 2
Neonatal hyperbilirubinemia is the most common reason for readmission after
early hospital discharge. Concerns regarding Jaundice have increased after reports of
bilirubin induced brain damage occurring in healthy term infants even without
hemolysis.3, 4
introduction of anti-D prophylaxis, ABO incompatibility is now the major cause of
immune hemolytic disease of new born (HDN) in developed countries.5,6
Approximately 20% of all pregnancies are associated with ABO
incompatibility between mother and the fetus and only less than 10% of all these
cases manifest ABO HDN.7 Clinically and almost exclusively ABO incompatibility
occurs in ‘A’ and ‘B’ blood group babies of ‘O’ positive mothers. These babies are
reported to be at high risk of severe hyperbilirubinemia (serum bilirubin level more
than 16mg/dl).8
Hemolysis associated with ABO incompatibility is due to the fact that
maternal anti A or anti B antibodies enter the fetal circulation and react with A or B
antigens on the erythrocyte surface. In type A and B individuals naturally occurring
anti B and anti A isoantibodies largely are IgM molecules that do not cross placenta.
In contrast the alloantibodies present in type O individuals although IgM can be more
of IgG as well. For this reason ABO incompatibility is largely restricted to type O
1
Introduction
mothers with type A or B fetus. The presence of IgG anti A or anti B antibodies in
type O mothers also explains why hemolysis caused by ABO incompatibility
frequently occurs during first pregnancy without prior sensitization.9
ABO incompatible babies have double risk to develop jaundice requiring
treatment and 5-10 times increase risk of exchange transfusion.10
Kernicterus in such Newborns is preventable, provided excessive
hyperbilirubinemia for age is promptly identified and appropriately treated.3,11 With
the intent to facilitate such identification and treatment, universal screening for
severity of bilirubinemia before hospital discharge may predict, that extraordinary
segment of the neonatal population which is at risk for excessive hyperbilirubinemia
during the first week after birth.12
Early discharge of healthy term newborns after delivery has become a
common practice because of medical and social reasons as well as economic
constraints.13, 14
Thus, the recognition, follow-up, and early treatment of jaundice has become
more difficult as a result of earlier discharge from the hospital. The American
Academy of Paediatrics (AAP) recommends that newborns discharged within 48
hours should have a follow-up visit after 2-3 days to detect significant jaundice and
other problems, 15 this recommendation is not possible in our country due to limited
follow up facilities in the community.
Phototherapy is now a viable alternative to the planned use of exchange
transfusion in the treatment of even moderate to severe HDN.16 Phototherapy is
2
Introduction
widely accepted as a relatively safe and effective method for treatment of neonatal
Hyperbilirubinemia.17
Since Allen and Diamond published their well known treatise on Rh
isoimmunisation in 1958, it has been recognised that the level of cord bilirubin is of
considerable value in predicting the severity of subsequent haemolysis. Because of the
relative infrequency of severe ABO disease, the urgency for predictive criteria in this
disease has not seemed great, and there has been a tendency to presume that the
criteria for Rh disease could be applied to ABO incompatibility.18
Predictive criteria used in Rh isoimmunity cannot be applied to ABO
incompatibility as there are several differences.
(1) Hyperbilirubinemia when it occurs, is rarely associated with significant
anemia.19
(2) Anti-A and anti-B antibodies are normally present in maternal serum and
normally reach the foetus.8, 19
(3) In hetrospecific pregnancies the maternal antibody patterns during the
period of gestation show no more response than those of the homospecific group, up
to the time of delivery. Changes in level of antibody occurs only after delivery in the
hetrospecific group.8
(4) There is no cumulative effect on serum antibody levels, or on the foetus in
subsequent hetrospecific pregnancies, in a manner comparable to progression of Rh
incompatibility.18
(5)Though a positive Coombs test is often weak and there is unacceptably high
number of false negative results.19
3
Introduction
Concept of prediction of significant jaundice, as early as at birth, offers an
attractive option to pick up neonates at risk of NH. A Total serum bilirubin level of
≥15 mg/dl is found in 3% of normal term babies.20 The incidence of
hyperbilirubinemia depends on regional variations, ethnic makeup of the
population,21,22 laboratory variability in the measurement of bilirubin, and the
incidence of breastfeeding.23 Several investigators have tried to find a simple marker
to predict hyperbilirubinemia in newborns. Some of them used transcutaneous
bilirubin measurement24-30, and ETCOc measurement31-32 CBB estimation,18, 51-54, 56-71
predischarge hour specific bilirubin estimation,12 to predict the subsequent course of
Jaundice.
Despite the failure to detect a prenatal increase in maternal antibody levels
there is no doubt that intrauterine haemolysis must take place in ABO incompatibility
and cord blood bilirubin levels are often considerably raised.18
There is an obvious need to develop simple predictive guidelines that will
enable the physicians to predict or to identify which of the early discharged newborns
will develop significant hyperbilirubinemia, and thereby minimize the risk of bilirubin
dependent brain damage.
The present study was designed to evaluate the predictive value of cord
bilirubin levels in hetrospecific pregnancies, involving group O-mothers and A-or B
term babies in rural Bangalore with subsequent hyperbilirubinemia.
4
Objectives
OBJECTIVES
1. The present study was conducted to correlate the Cord Blood Bilirubin level
with subsequent Neonatal Hyperbilirubinemia in new born with a setting of
ABO incompatibility.
2. To predict the risk of jaundice, in order to implement early treatment and there
by minimize the risk of Bilirubin dependent brain damage.
5
REVIEW OF LITERATURE
HISTORY REVIEW
Neonatal jaundice must have been noticed by caregivers through the centuries,
but the scientific description and study of this phenomenon seem to have started in the
last half of the 18th century. In 1785 Jean Baptiste Thimote´e Baumes was awarded a
prize from the University of Paris for his work describing the clinical course in 10
jaundiced infants33.
The work by Jacques Hervieux, which he defended for his doctor of medicine
degree in 1847, was, in many respects, a landmark. Having dismissed most of the
theories and work of his predecessors, a number of his clinical observations are still
thought to be accurate today. 33
His Clinical and Epidemiological Observations on Neonatal Jaundice are
1. The cause of neonatal jaundice is not known, but one can state that jaundice in
the neonate is a manifestation of a recently established function that for a
limited time exceeds its physiological limits.
2. Neonatal jaundice is a physiological condition.
3. Neonatal jaundice is, by itself, never fatal
4. Neonatal jaundice appears during the first 2 to 4 days of life and lasts for 1 to
2 weeks. It never reappears in the following months.
5. There is a cephalocaudal progression in the appearance of jaundice the
extremities are always last to be affected. When jaundice disappears, the order
is reversed.
6
6. Neonatal jaundice is very common; approximately two thirds of all infants are
affected. The prognosis in the absence of complicating conditions is benign.
7. Jaundice is not seen in foundlings who are wet-nursed, or in infants nursed by
a woman who gave birth a long time ago.
8. The most frequent complicating conditions are scleredema, diarrhoea, and
thrush.
9. Treatment consists of combating the complicating conditions. Isolated
neonatal jaundice does not need treatment.
10. In neonatal jaundice, the yellow colour is found throughout the tissues of the
body, including the brain. Hervieux described brain jaundice in 31 of 44 cases
of neonatal jaundice. In all of these cases, clinical jaundice had been at its
peak at the time of death. He described the intensity of the brain jaundice as
variable. Some brains were quite uniformly stained, while in other brains some
regions were more heavily stained than others. It is noteworthy that he found
the cerebrospinal fluid to be jaundiced in all cases. 33
In 1847, Virchow suggested that the excessive destruction of red blood cells in
the first week of life is the basic cause of jaundice.34
Molisan demonstrated by transfusion experiments that erythrocytes of new born
break down twice as rapidly as compared to adults.34
The first description of the pathoanatomical picture of Kernicterus may belong to
Johannes Orth. Orth an assistant to Virchow, in his article, which primarily focused
on pigment crystals in various organs, he described a term female infant who was
7
born nonicteric, but who became jaundiced soon after birth. The child died at two
days of age with very pronounced jaundice, which was apparently her only
sign/symptom. At autopsy all organs were found to be jaundiced, but with an
underlying pallor that may perhaps point to the existence of anaemia. The brain was
intensely yellow, but with much more intense staining of the basal ganglia, the wall of
the third and fourth ventricles, the hippocampus, and the central parts of the
cerebellum. On microscopic examination of the latter, the granular layer was found to
be heavily stained. Orth also noted that although neurons of the basal ganglia were
stained, the glial elements were not. 33 Orth finally speculated that the intense jaundice
in this infant might have had a hematologic causes, a speculation, which, in the light
of later knowledge, may well have been precisely on target. 33
Christian Georg Schmorl coined the term Kernicterus (Jaundice of the nuclei),
which has subsequently been used both to describe a pathoanatomical picture seen at
autopsy in those who died, as well as a neurological syndrome in survivors of extreme
Jaundice. 33 In his landmark paper Schmorl described his findings from the autopsies
of 280 neonates, of whom 120 were Jaundiced at the time of death. In the majority of
these cases (114/120), he found the brain to be diffusely yellow. He noted that the
intensity of the brain colour paralleled that of the face, which is often the most
intensely Jaundiced part of an infant’s body, as also described by Hervieux. 33
In the brains that Schmorl examined, the Jaundiced nuclei were very sharply
demarcated and, therefore, contrasted clearly with the colour of the surrounding
tissue. Because of this sharp demarcation and the predilection for staining of the
nuclei, Schmorl proposed the term Kernicterus. He further suggested that the yellow
8
colour was not simply attributable to saturation of the tissue with bile pigments, such
as was the case (he believed) with eg, skin, but to binding of the bile pigments to
specific structural elements in the tissue. Microscopic examination of the tissue
supported this hypothesis. Some neurons in the nuclei were strongly coloured, while
others had a paler yellow colour. These latter cells exhibited changes that suggested
that they were in the process of dying. 33
Beneke in 1907, was the first to suggest that septicaemia might play an important
role in icterus gravis neonatorum, and he theorized that the pigmentation of brain
tissue was caused by a peculiar attraction of bile pigments to ganglion cells leading to
their necrosis, damage to the ganglion cells by the bile salts which then became
pigmented, or ischemic or the traumatic insult that allowed the cells to become
pigmented.34
As early as 1913, there was description of children who survived severe neonatal
Jaundice with resultant mental retardation and neuromuscular dysfunction, with the
Jaundice being considered the causal agent (Guthrie, 1913; Spiller, 1915).34
In 1916, Dutch Biochemists, Van Den Bergh and Muller, observed that serum
from patients with haemolytic Jaundice can be differentiated from the serum of
patients with obstructive Jaundice on the basis of chemical reactions. They observed
that haemolytic serum did not react promptly with diazotised sulphanilic acid except
in presence of alcohol while the other serum reacted in an aqueous solution.34
9
In 1932, Diamond and colleagues recognized that generalized oedema of the
foetus (Hydrops fetalis), icterus gravis and congenital anaemia of the newborn were
all in fact a part of single condition which they termed “isoimmunisation fetalis”.35
In 1944, Halbrecht coined the term “Icterus praecox” for Jaundice developed
within 24 hours of birth.36
In 1946, they introduced the technique of alternate removal and administration of
blood for each transfusion by umbilical vein catheterization. Allen et al in 1950
showed effectiveness of exchange transfusion as a protection from Kernicterus.35
In 1952, Crigler and Najjar in the publication describing congenital familial non
haemolytic Jaundice with Kernicterus not only defined a new disease but also
advanced the understanding of Kernicterus as a process related more to elevated
unconjugated bilirubin levels than to specific blood group incompatibilities or even
hemolysis.34
In 1958, Cremer and associates from Rochform hospital in Essex, published their
report of the successful use of phototherapy for the treatment of neonatal Jaundice.
The initiator of phototherapy was a staff nurse of the above hospital, who noticed that
babies whose uncovered parts were less yellow when compared to covered parts of
body on exposure to sunlight.37
10
FETAL BILIRUBIN METABOLISM
Bilirubin is detected in normal amniotic fluid as early as 12 weeks of
gestation, but usually disappears by 36- 37 weeks.20
In early life bilirubin binds to fetoprotein and liver plays a minor role in
excretion. During the neonatal period, metabolism of bilirubin is in transition from the
foetal stage during which the placenta is the principal route of elimination of the lipid-
soluble, unconjugated bilirubin to the adult stage, during which the water-soluble
conjugated form is excreted from hepatic cells into the biliary system and
gastrointestinal tract.2
Uridine diphosphoglucuronyl transferase (UDPGT) is detectable at 18 – 20
weeks. UDPGT levels in full term and preterm neonates are usually less than 0.1% of
adult values. Adult value of this enzyme activity is demonstrable only by 6–14 weeks
of postnatal life.38
NEONATAL BILURUBIN METABOLISM
Normally destroyed RBC’s account for nearly 75% of daily bilirubin
production in the newborn. Breakdown of 1gm of haemoglobin usually yields 35 mgs
of bilirubin and neonates produce nearly 8- 10 mgs/ kg/ day of bilirubin which is
more than two times as compared to adult 3-4/ mgs/ kg/ day.20,38
Bilirubin is the end product of catabolism of iron protoporphyrins or heme,
haemoglobin being the major source for the same. First step in bilirubin production
involves removal of iron and protein moiety, followed by oxidative process catalyzed
by the enzyme microsomal heme oxygenase and equimolar amount of carbon
monoxide and biliverdin are formed. This enzyme heme oxygenase is called the rate
11
limiting enzyme in bilirubin metabolism. Biliverdin is then reduced to bilirubin by
biliverdin reductase.39
In step 2, extra hepatic bilirubin is bound to serum albumin and delivered to
the liver. Fraction of unbound bilirubin in plasma may increase in severe haemolytic
disease or when protein binding drugs displace bilirubin from albumin.39
In step 3 when the bilirubin albumin complex reaches plasma membrane of
hepatocytes a proportion of bilirubin is transferred across cell membrane of
hepatocytes, where it binds to ligandin and probably other cytosolic-binding
proteins.39
In step 4, conjugation with one or two molecules of glucuronic acid by
UDPGT in the endoplasmic reticulum occurs and generates bilirubin
monoglucuronides and diglucuronides, which are water soluble, are readily excreted
into bile. Hepatic uptake, conjugation and excretion of bilirubin is limited due to
transient deficiency of Y and Z acceptor proteins and UDPGT enzyme in the
newborn.38, 39
In step 5 most bilirubin glucuronides are deconjugated by the bacterial β-
glucuronidase and degraded to colourless urobilinogen. Due to paucity of bacterial
flora in the gut and over activity of intestinal β-glucuronidase enzyme the conjugated
bilirubin entering the duodenum is rapidly deconjugated and recirculated in the blood
and delivered to the liver for reconjugation through enterohepatic circulation.38, 39
12
FIGURE I: BILIRUBIN METABOLISM AND ELIMINATION39
13
CAUSES OF UNCONJUGATED HYPERBILIRUBINEMIA34
A. Excessive production of Bilirubin (haemolytic disease of newborn)
1. Blood Group heterospecificity (Incompatibility)
a. Rh Isoimmunisation
b. ABO incompatibility
c. Minor blood group incompatibility
2. Red blood cell enzyme abnormalities
a. Glucose 6-phosphate dehydrogenase deficiency

b. Pyruvate kinase deficiency
3. Sepsis
4. Red blood cell membrane defects
a. Hereditary Spherocytosis
b. Elliptocytosis
c. Poikilocytosis
5. Extra vascular blood
6. Polycythemia
B. Impaired conjugation or excretion
1. Hormonal Deficiency
a. Hypothyroidism
b. Hypopituitarism
2. Disorders of bilirubin metabolism
a. Criggler-Najjar syndrome type- I

b. Criggler-Najjar syndrome type- II (Arias Disease)
c. Gilbert disease
d. Lucey- Driscoll syndrome
3. Enhanced enterohepatic circulation
a. Intestinal obstruction, Pyloric Stenosis

b. Illeus, Meconium plugging, Cystic fibrosis
14
CAUSES OF JAUNDICE ON THE BASIS OF AGE OF ONSET.40

WITHIN 24 HOURS OF BIRTH
Rh and ABO incompatibility.
Glucose 6-phosphate dehydrogenase deficiency.
Pyruvate kinase deficiency.
Infections: Bacterial, TORCH.
Criggler-Najjar syndrome type- I.
Drugs to Mother Vit-K, salicylate, etc.
24-72 HOURS AFTER BIRTH

Physiological Jaundice
Rh and ABO incompatibility
Polycythemia.
Breast feeding Jaundice.
Neonatal sepsis.
AFTER 72 HOURS OF BIRTH

Neonatal sepsis.
Neonatal hepatitis.
Hypothyroidism.
Hypopituitarism.
Galactosemia..
Criggler-Najjar syndrome type – II.
Gilbert disease.
15
HIGH RISK FACTORS OF JAUNDICE2, 20, 40
• Prematurity.
• Low birth weight.
• Blood group incompatibility.
• Perinatal asphyxia.
• Infant of diabetic mother.
• Intrapartum use of oxytocin.
• Problem in breastfeeding.
• H/o Jaundice in previous siblings.
• Cephalhematoma or significant bruising.
HAEMOLYTIC DISEASE OF NEWBORN.
The American Academy of paediatrics lists blood group incompatibility with
positive direct antiglobin test (DAT) as one of the four most important risk factors for
severe hyperbilirubinemia; the other factors being high risk zone predischarge total
serum bilirubin levels; Jaundice in the first 24 hrs of life and gestational age (GA) 35-
36 weeks.15
APPROACH TO A JAUNDICED NEWBORN.40
• Identify “high risk” newborns at delivery likely to develop Jaundice.
• Ensure appropriate follow up for Jaundice.
•Emphasize need for early, exclusive breast feeds and ensure adequacy of breast
feeding.
• Assess clinical condition (well or ill)
• Ascertain birth weight & gestation
• Evaluate Jaundice with post-natal age in hours
16
• Perform systematic evaluation – history and physical examination.
• Decide whether Jaundice is physiological or pathological
• If physiological and baby well, only observation is required
• If deeply Jaundiced, look for signs of bilirubin encephalopathy (lethargy, poor,
feeding, shrill cry, asymmetric Moro reflex, hypertonia, opisthotonus or convulsions)
• If Jaundice is pathological perform lab tests.
• Initiate appropriate measures to reduce elevated bilirubin
• Counsel parents.
CLINICAL ASSESMENT OF NEONATAL JAUNDICE
Clinicians should ensure that all infants are routinely monitored for the
development of Jaundice, and nurseries should have established protocols for the
assessment of Jaundice. Jaundice should be assessed whenever the infant’s vital signs
are measured but no less than every 8 to 12 hours. In newborn infants, Jaundice can
be detected by blanching the skin with digital pressure, revealing the underlying
colour of the skin and subcutaneous tissue. The assessment of Jaundice must be
performed in a well-lit room or, preferably, in day light or at a window. Jaundice is
usually seen first in the face and progresses caudally to the trunk and extremities, but
visual estimation of bilirubin levels from the degree of Jaundice can lead to errors15
17
FIGURE II: ALGORITHM FOR THE MANAGEMENT OF
JAUNDICE IN NEWBORN20
18
COMPLICATIONS OF NEONATAL JAUNDICE
The precise blood level above which indirect-reacting bilirubin or free
bilirubin will be toxic for an individual infant is unpredictable, but Kernicterus is rare
in healthy term infants and in the absence of haemolysis if the serum level is <25
mg/dl. In previously healthy, predominantly breast-fed term infants, Kernicterus has
developed when bilirubin levels exceed 30 mg/dl. The duration of exposure needed to
produce toxic effects is unknown. Little evidence suggests that a level of indirect
bilirubin <25 mg/dl affects the IQ of healthy term infants without haemolytic disease.2
Bilirubin encephalopathy describes the clinical central nervous system
findings caused by bilirubin toxicity to the basal ganglia and various brainstem
nuclei.20
To avoid confusion and encourage greater consistency in the literature, the
AAP committee recommends that in infants the term “acute bilirubin encephalopathy”
be used to describe the acute manifestations of bilirubin toxicity seen in the first
weeks after birth and that the term “Kernicterus” be reserved for the chronic and
permanent clinical sequelae of bilirubin toxicity.15
CLINICAL FEATURES OF BILIRUBIN ENCEPHALOPATHY
Signs and symptoms of Kernicterus usually appear 2–5 days after birth in term
infants and as late as the 7th day in premature infants, but hyperbilirubinemia may
lead to encephalopathy at any time during the neonatal period. The early signs are
subtle and indistinguishable from those of sepsis, asphyxia, hypoglycaemia,
intracranial haemorrhage, and other acute systemic illnesses in a neonate.2
19
TABLE I:
CLINICAL FEATURES OF BILIRUBIN ENCEPHALOPATHY2,20
ACUTE FORM
Phase 1 (1st 1–2 days):
poor sucking, stupor, hypotonia, seizures
Phase 2 (middle of 1st wk):
hypertonia of extensor muscles, opisthotonos, retrocollis, fever
Phase 3 (after the 1st wk):
hypertonia
CHRONIC FORM
First year:
hypotonia, active deep tendon reflexes,
obligatory tonic neck reflexes, delayed motor skills
After 1st yr:
movement disorders (choreoathetosis, ballismus, tremor),
limitation of upward gaze, sensorineural hearing loss,
dental dysplasia and intellectual deficits.
20
TREATMENT
The aim of therapy is to ensure that serum bilirubin is kept at a safe level and
neurological damage is prevented.
Reduction of STB levels and prevention of neurotoxicity can be achieved by
phototherapy, Pharmacotherapy and exchange transfusion.
Principles of treatment in Jaundiced infants according to 2006 IAP NNF
guidelines are40
1. Treatment decisions are based on total serum bilirubin.
2. Gestation is more important than birth weight of the baby. A higher cut
off can be used for a small for date baby.
3. Post natal age in hours should be considered when deciding treatment
4. Sick baby refers to presence of asphyxia, hypothermia, sepsis, acidosis,
hypoxia, hypercapnia and evidence of haemolysis.
PHOTOTHERAPY
Phototherapy was first introduced in the treatment of neonatal
hyperbilirubinemia in the late 1950s.37 The goal of therapy is to lower the
concentration of circulating bilirubin or keep it from increasing. Phototherapy
achieves this by using light energy to change the shape and structure of bilirubin,
converting it to molecules that can be excreted even when normal conjugation is
deficient.2, 20
Bilirubin absorbs light most strongly in the blue region of the spectrum near
460 nm (Figure III), a region in which penetration of tissue by light increases
markedly with increasing wavelength. The rate of formation of bilirubin

21
photoproducts is highly dependent on the intensity and wavelengths of the light used.
Taking these factors into account, lamps with output predominantly in the 460 to 490
nm blue region of the spectrum are probably the most effective for treating
hyperbilirubinemia.17,41
Combination of 2 special blue and 4-6 white fluorescent tubes to be used. The
blue tubes must have the serial number F20T12/BB to be a special phototherapy
lights. This combination would deliver 12 µw/cm2/nm.17,41
The absorption of light by the normal form of bilirubin (4Z, 15Z-bilirubin)
generates transient excited-state bilirubin molecules. These fleeting intermediates can
react with oxygen to produce colourless products of lower molecular weight, or they
can undergo rearrangement to become structural isomers (lumirubins) or isomers in
which the configuration of at least one of the two Z-configuration double bonds has
changed to an E configuration. Configurational isomerisation is reversible and much
faster than structural isomerisation, which is irreversible. Both occur much more
quickly than photo oxidation. The photo isomers are less lipophilic than the 4Z, 15Z
form of bilirubin and can be excreted unchanged in bile without undergoing
glucuronidation. Lumirubin isomers can also be excreted in urine. Photo oxidation
products are excreted mainly in urine. Once in bile, configurational isomers revert
spontaneously to the natural 4Z, 15Z form of bilirubin.17, 41
22
FIGURE III: IMPORTANT FACTORS IN THE EFFICACY OF
PHOTOTHERAPHY41
Distance of the phototherapy unit should be as close to the baby as possible ensuring
euthermia. Hyperthermia makes the phototherapy less effective.17, 41
On an average, for infants of more than 35 weeks’ gestation readmitted for
phototherapy, intensive phototherapy can produce a decrement of 30% to 40% in the

23
initial bilirubin level by 24 hours after initiation of phototherapy. The most significant
decline will occur in the first 4 to 6 hours. With standard phototherapy systems, a
decrease of 6% to 20% of the initial bilirubin level can be expected in the first 24
hours.17, 41
CARE OF A NEWBORN RECEIVING PHOTOTHERAPY40
• The eyes should be covered during phototherapy.
• Breast feeding on demand is continued. More frequent breast feeds or 10-20% extra
IV fluids are provided.
• Adequacy of hydration is checked by urine colour and frequency, skin turgor mucous
membrane and weight.
• Assess and record urine and stool pattern.
• Frequent change of posture is necessary.
• Temperature is monitored every 3-4 hrs, Avoid hypo or hyperthermia.
• Daily baby is weighed.
• TSB is measured every 12 hrs or 4-6 hourly if severely Jaundiced.
•Monitor for adverse effects of phototherapy: Dehydration, loose stools, hyperthermia/
hypothermia, erythematous rash and bronze baby syndrome.
SIDE EFFECTS OF PHOTOTHERAPY2, 17,20
Retinal damage, Passage of loose green stools.
Hyperthermia, Dehydration.
Hypocalcaemia, Bronze baby.
Flea-bite rash, Opening up of PDA in preterm.
Increase in mean cerebral blood flow velocity.

24
Decrease in renal blood flow velocity.
Increase in renal vascular resistance.
EXCHANGE TRANSFUSION
Exchange transfusion is the most rapid method for lowering serum bilirubin
concentrations. This treatment is rarely needed when intensive phototherapy is
effective. The procedure removes partially haemolysed and antibody-coated
erythrocytes and replaces them with uncoated donor red blood cells that lack the
sensitising antigen.42
The appearance of clinical signs suggesting Kernicterus is an indication for
exchange transfusion at any level of serum bilirubin. Double volume exchange
transfusion (170 ml/ kg) is performed if intensive phototherapy has failed to reduce
bilirubin levels to a safe range and if the risk of Kernicterus exceeds the risk of the
procedure.2
Blood for exchange transfusion is modified whole blood (red cells and
plasma) cross matched against the mother and compatible with the infant.20
Exchange transfusion should be done in small aliquots of 5 – 10 ml.2, 20, 34, 42
EXCHANGE TRANSFUSION IS DONE BY TWO METHODS2,20,34,42
a) Push and pull technique: Central access usually through umbilical venous
catheter.
b) Isovolumetric exchange with simultaneous infusion of donor blood through
venous line and removal of baby’s blood through arterial line.
25
POTENTIAL COMPLICATIONS FROM EXCHANGE TRANSFUSION2,20,34,42
1. Metabolic
a. Hypocalcaemia
b. Hypoglycaemia
c. Hyperglycaemia
d. Hyperkalaemia
2. Cardio respiratory
a. Apnoea.
b. Bradycardia.
c. Hypotension.
d. Hypertension.
e. Hematologic.
f. Thrombocytopenia.
g. Dilutional coagulopathy.
h. Neutropenia.
i. Disseminated Intravascular coagulation.
3. Vascular Catheter Related
a. Vasospasm.
b. Thrombosis.
c. Embolization.
d. Gastrointestinal.
e. Feeding intolerance.
f. Ischemic injury.
g. Necrotizing enterocolitis.
26
4. Infection
a. Omphalitis
b. Septicemia
CHOICE OF BLOOD FOR EXCHANGE TRANSFUSION2, 20, 34, 42
Rh isoimmunisation: In emergency situation use O Rh negative cells. Ideal is to use O
Rh negative blood suspended in AB plasma. Cross matched baby’s blood group but
Rh negative can also be used.
ABO incompatibility: Blood group O types (Rh compatible) with baby. Ideal is to use
blood group O (Rh compatible) suspended in AB plasma.
Other situations: Cross-matched baby’s blood group.
PHARMACOTHERAPY
PREVENTION OF HEMOLYSIS BY INTRAVENOUS IMMUNOGLOBULIN
The administration of intravenous immunoglobulin is an adjunctive treatment
for hyperbilirubinemia due to isoimmune haemolytic disease. Its use is recommended
when serum bilirubin is approaching exchange levels despite maximal interventions
including phototherapy. Intravenous immunoglobulin (IVIG) (0.5–1.0 g/kg/dose;
repeat in 12 hr) has been shown to reduce the need for exchange transfusion in both
ABO and Rh haemolytic disease, presumably by reducing hemolysis.2,34,44.It may well
be justified to electively use IVIG in a small number of selected patients with HDN
where the likelihood of exchange transfusion is great-that is neonate with Rh disease
27
unmodified by antenatal treatment or neonate with potential ABO HDN where a
previous sibling has suffered from severe disease requiring exchange transfusion.43
INHIBITORS OF BILIRUBIN FORMATION:METALLOPORPHYRINS
These are structural analogues of the heme molecule in which the central iron
molecule has been replaced with other metallic ions including tin, zinc, manganese
and chromium. The metalloporphyrins Sn-mesoporphyrin (SnMP) offers promise as a
drug candidate. The proposed mechanism of action is by competitive enzymatic
inhibition of the rate limiting conversion of heme-protein to biliverdin (an
intermediate metabolite to the production of unconjugated bilirubin) by heme-
oxygenase. A single intramuscular dose of 6 mg/ kg on the 1st day of life may reduce
the need for phototherapy. Complications from metalloporphyrins include transient
erythema if the infant is receiving phototherapy.2, 34, 44
BILIRUBIN TRANSPORT: ALBUMIN INFUSION
Bilirubin bound to albumin is relatively innocuous, as it cannot diffuse across
the blood brain barrier. The amount of free bilirubin (unbound) doubles when TSB
level reaches 15- 20 mg/dl, quadruples at 25 mg/ dl and increases 8 folds at 30 mg/ dl.
Before an exchange transfusion, one may consider an albumin infusion (1 g/kg).34,44
INDUCERS OF LIVER ENZYMES: PHENOBARBITONE
Phenobarbitone enhances bilirubin clearance by liver by increasing its uptake,
increasing the intracellular concentration of ligandin, increasing its conjugation by
UDPGT and increasing the excretion of conjugated bilirubin by increasing bile flow.34
28
Dosage 2.5-5mg/kg/day BD. The main drawback with the use of
phenobarbitone is its latent period. It exerts its effect after 1- 3 days and adjuvant
therapy in the form of phototherapy is usually required in the first 48- 72 hours.44
PREDICTION OF NEONATAL HYPERBILIRUBINEMIA
Johnson and Brown suggested that shorter hospital stays, decreased vigilance
in diagnosing Jaundice and lack of physician compliance with current guidelines may
account for re-emergence of severe hyperbilirubinemia and Kernicterus.12Since 1991,
there have been several articles published on re-emergence of Kernicterus in full term
infants.3,45,46
Jaundice appears in 60% of term newborns and 80% of preterm infants by the
first week of life. Up to 4% of term newborns who are readmitted to the hospital
during their first week of life, approximately 85% are readmitted for Jaundice. If left
unrecognized and untreated, hyperbilirubinemia can have dire consequences.
Overproduction and reduced removal of bilirubin may elevate serum bilirubin levels
(hyperbilirubinemia) to toxic levels that present the threat of brain damage
(Kernicterus).47
Kernicterus, resulting from the deposition of unconjugated bilirubin in brain
cells, is clinically characterized by convulsions, opisthotonus, hypotonia, high pitched
cry, and fever. Because of effective diagnosis and treatment, Kernicterus has become
a rare event. It is of concern, however that this rare event, while still infrequent, is
becoming more common. Catz and colleagues recounted that in the United States,
29
between 1991 and 1995, there were reports of 22 cases of term or near-term infants
who had developed Kernicterus after being discharged within 48 hours of birth.Of
these cases 95% (n = 21) had been breastfed, 23% (n = 5) were glucose 6- phosphate
dehydrogenase deficient, and others had identifiable risk factors such as bruising,
ABO haemolytic disease , or other causes of hemolysis.13,.47
The current list of identified risk factors to recognize infants who are likely to
require treatment for hyperbilirubinemia is not adequate. While Jaundice per se is not
always preventable, nonetheless, early detection of threatening bilirubin levels
permits initiation of phototherapy and prevents higher risk and higher cost exchange
transfusion therapy or Kernicterus. Early discharge complicates the ability to measure
both the level of serum bilirubin and the rate of increase. 47
The trend toward shorter hospital stay was evident even before the recent
influence of insurance and managed care plans. In the past decade, however this trend
has increased rapidly.47
Hyperbilirubinemia is the commonest cause for readmission to the hospital
after early discharge.48-50
Palmer et al (1983), presented a review of Jaundiced newborn infants during
the 10-year period to 1980. Included were those whose serum bilirubin level was 9
mg/dl or more. Of 41,057 live births, 4,406 (10.7%) infants had hyperbilirubinemia.
The most common (19.9;%) aetiological factor was prematurity, followed by ABO
isoimmunisation 7.1%;sepsis 3.4%; Rhesus isoimmunisation 2.7%; bruising 2.2%;
multifactorial 1.0% and glucose-6-phosphate dehydrogenase deficiency 0.5%.

30
Treatment was not undertaken in 2,855 (64.7%) infants, but 1,419 (32.2%) received
phototherapy alone, 122 (2.7%) infants received both exchange transfusion and
phototherapy and 10 (0.2%) infants received exchange transfusion alone. Of the
infants requiring exchange transfusion 50.0% had Rhesus isoimmunisation, 28.0%
ABO isoimmunisation, 10.6% Jaundice of prematurity and the remainder were due to
a variety of causes.51
Rosenfeld J et al (1986) reported that Infants with cord bilirubin levels less
than 2.0 mg/dl have only a 4 percent chance of developing hyperbilirubinemia and a
1.4 percent chance of needing phototherapy. However, if serum cord bilirubin levels
are more than 2.0 mg/dl, the infant has a 25 percent chance of developing subsequent
Knudsen A et al (1989) found that if cord bilirubin was below 1.17 mg/dl,
2.9% became Jaundiced as opposed to 85% if cord bilirubin was above 2.3 mg/dl.
Furthermore, 57% of Jaundiced infants with cord bilirubin above 2.3 mg/dl required
phototherapy, but only 9% if cord bilirubin was 2.3 mg/dl or lower (p< 0.003). Since
the ability of plasma to bind bilirubin in cord blood from Jaundiced and non-
Jaundiced infants showed no significant differences, the increased cord bilirubin
among infants who later became Jaundiced is presumably caused by increased fetal
bilirubin production or decreased removal of bilirubin from the fetal circulation.53
Ho NK, et al. (1991), reported a 4-year experience (1986-1989) of neonatal
Jaundice. Babies who have received some form of treatment such as phototherapy are
considered as cases of neonatal Jaundice. However, the incidence of

31
hyperbilirubinemia (defined as serum bilirubin level of 15 mg/dl or greater) fell from
3.23% to 2.11% of all live births.54ABO Incompatibility, glucose-6-phosphate
dehydrogenase (G6PD) deficiency and low birth weights (LBW) remain as the
common aetiological factors of neonatal Jaundice.55
Rataj, et a.l 1994, investigated 800 healthy full-term newborns and reported
that if cord bilirubin was under 1 mg% the Jaundice occurred in 2.4% newborns,
where as 89% of the infants with cord bilirubin above 2.5 mg% became Jaundiced.56
Awasthi, et al. (1998), conducted a prospective cohort study of 274 neonates
born in North India and predicted that occurrence of peak serum bilirubin level >15
mg/dl between second to fifth postnatal day by using serum bilirubin level measured
between 18 to 24 hrs of life. The main outcome measures were hyperbilirubinemia
and phototherapy. Hyperbilirubinemia was found in 12.8% babies using a cut-off
>3.99 mg/dl with sensitivity and specificity of 67%. Using serum bilirubin levels
estimated at 18-24 hrs of life as the “prediction test”, approximately two-third of the
neonates were test negative and had one in ten chances of readmission for treatment
of hyperbilirubinemia, if discharged early.57
Alpay, et al. (2000), followed up a total of 498 healthy term newborns
daily with serum total bilirubin measurements for the first 5 days of life, and cases
with TSB of >17 mg/dl after 24 hours of life were defined to have significant
hyperbilirubinemia. No newborns had a TSB level of >17 mg/dl in the first 72 hours
of life. Sixty of 498 cases (12.05%) had significant hyperbilirubinemia after 72 hours
of life, and these cases had significantly higher bilirubin levels than those who did not
develop significant hyperbilirubinemia on each of the first 5 days’ measurements. Of
the 206 newborns who had a TSB level of >6 mg/dl in the first 24 hours, 54 (26.21%)
32
developed significant hyperbilirubinemia, whereas only 6 of the 292 newborns
(2.05%) who had a TSB level of <6 mg/dl on the first day developed significant
hyperbilirubinemia. A mean TSB level of >6 mg/dl on the first day had the highest
sensitivity (90%). At this critical serum bilirubin value, the negative predictive value
was very high (97.9%) and the positive predictive value was fairly low (26.2%). The
use of the critical bilirubin level of 6 mg/dl in the first 24 hours of life can predict
nearly all of the term newborns who will have significant hyperbilirubinemia and
could determine all those who will require a phototherapy treatment later during the
first days of life.58
Agarwal, et al. (2002), conducted a study on 220 infants. All infants were
exclusively breastfed. Clinically detectable Jaundice was present in 164(77%) and
hyperbilirubinemia occurred in 22(10.3%) infants. Study predicted that infants with
total serum bilirubin levels lesser than 6 mg/dl at 24 ± 6 hours would not develop
Suchonska, et al. (2004), investigated 187 healthy, full-term newborns in good
general condition. Newborns with serological incompatibility were not included into
the study. In 155 (83%) cases babies were born through normal vaginal delivery, in 32
(17%) by Caesarean section. The umbilical blood was taken immediately after
delivery and the venous blood on the 3rd day of life to determine concentration of
bilirubin. 3rd day Bilirubin values lower than 12.9 mg% were considered
physiological. Hyperbilirubinemia was recognized when the concentration of bilirubin
was over 12.9 mg%. Pearson test was used to estimate the correlation between
bilirubin value in the umbilical blood and the venous blood. The mean value of total
bilirubin in the umbilical blood was 1.30 mg% +/- 0.47 and in venous blood on the
3rd day of life 8.07 mg% +/- 3.08. No one with umbilical bilirubin concentration
33
lower than 1 mg% developed hyperbilirubinemia. They concluded that concentration
of bilirubin in the umbilical blood can be useful indicator of risk of icterus in
newborns. Special care is needed for newborns whose concentration of bilirubin in
umbilical blood is over 1 mg%.60
Bernaldo et al (2004) predicted that Blood incompatibility between mother
and child was a predictor for the appearance of hyperbilirubinemia that required
treatment. Considering a cut-off point of 2.0 mg/dl, 53% of the newborns who had
greater unconjugated bilirubin levels in cord blood would reach levels requiring
phototherapy by the third day of life. In addition, they also concluded that the
presence of mother/child blood group incompatibility was statistically significant for
the occurrence of unconjugated bilirubin serum levels that were indicative of
phototherapy treatment during the same three-day period.61
Kupfer et al (2005) investigated the predictive value of umbilical cord serum
bilirubin (CBB) for the postnatal course of bilirubinemia in healthy term and near-
term newborns. Term appropriate-for-gestational-age (AGA; n=1100), small-for-
gestational-age (SGA; n=163) and near-term infants (GA 34–36 wk; n=78) were
included and separated according to their CBB levels, starting from <1.1 (group 1),
1.1–<1.7 (2), 1.7–2.3 (3) and >2.3 (4) mg/dl. The newborns were followed for at least
5 postnatal days, and CBB values were correlated with the development of
hyperbilirubinemia and phototherapy (PT) treatment which showed a clear relation
between CBB and the development of hyperbilirubinemia in all three patient
populations. None of the 75 AGA patients of group 1 developed postnatal bilirubin
values above 17.6 mg/dl, whereas 0.3, 3.4 and 8.6% of the patients in groups 2–4,
respectively, did so. The frequency of phototherapy increased from 0% in group 1 up

34
to 9.6% in group 4. For the prediction of further need of phototherapy using a CBB
cut-off level of 1.7 mg/dl, they found a sensitivity of 90% and a negative predictive
value of 99.1%, indicating that all patients with CBB values below 1.7 mg/dl
(443/1100 or 40.2%) were at a very low risk of developing dangerous
hyperbilirubinemia. Similar results were obtained in SGA children with a sensitivity
of 94.1% and a negative predictive value of 98.6%. In comparison to term newborns,
they generally found higher bilirubin values in preterms. A total of 6.4% of preterm
children developed bilirubin values over 17.6 mg/dl, compared with 3% of term
children, and 47.4% of preterms had to be treated with phototherapy. Predicting the
need of phototherapy by using a CBB cut-off level of 1.7 mg/dl revealed a sensitivity
of 70.3% and a negative predictive value of 65.6%.62
Sun, et al (2007), Investigated 523 healthy term newborns. The cord blood
total serum bilirubin concentration and the serum albumin concentration were
determined. The infants were aligned into four groups according to their CBB levels,
starting from < 1.7 mg/dl (group 1); ≥1.7 mg/dl (group 2); ≥2.1 mg/dl (group 3); ≥2.4
mg/dl (group 4). The frequency of hyperbilirubinemia and phototherapy (PT) were
compared among the four groups. An analysis of CBB as a predictor of later
development of Jaundice was performed. The characteristics of the infants who
became Jaundiced (Jaundiced group) were compared with the normal infants (non-
Jaundiced group). The frequency of patients with hyperbilirubinemia or phototherapy
increased with increasing CBB levels. For the prediction of TCB ≥25 using a UCS
bilirubin cut-off level, such as ≥2 mg/dl, a positive predictive value of 45.68% and
sensitivity of 68.27% was found. It is significant to predict neonatal Jaundice by CBB
levels (P < 0.001). In the Jaundiced group (TCB ≥25) CBB levels were significantly
35
higher than those in the non-Jaundiced group (t = 10.96, P < 0.001). No significant
differences were found in the cord blood serum albumin concentration (t = 2.38, P >
0.05), the gestational age (t = -0.90, P > 0.05), and birth weight (t = 0.10, P > 0.05)
between the Jaundiced and non-Jaundiced groups.63
Randev S, et a.l (2010), concluded that first day TSB estimation can serve as a
reliable screening test for neonates at risk for subsequent hyperbilirubinemia.
Neonates with the first day TSB <6.4 mg/dl have minimum risk of subsequent
Nair, et al. reported that 29.5% babies developed hyperbilirubinemia and
17.65% of them were ABO Incompatible group.65 Some of the similar predictive
study done in ABO incompatibility as well.
Robinson, et al. in (1960), study observed that cord bilirubin level above
3mg/dl were suggestive of significant Jaundice.66
H.M Risemberg et al in (1977) found association of cord bilirubin and severity
of hyperbilirubinemia in ABO (Heterospecific pregnancies) The study group had 91
new borns of hetrospecific pregnancies, and 30 term infants of homospecific were
used as controls. Of the 91 patients included in the study 13(14%) developed severe
hyperbilirubinemia serum bilirubin level > 16 mg/dl at 12-36 hrs of life and with the
exception of one patient cord blood bilirubin levels were > 4mg/dl in all cases. All of
these babies required exchange transfusion. 17% of infants who developed moderate
hyperbilirubinemia the cord bilirubin level was < 4mg/dl and none required exchange
transfusion .69 did not develop significant hyperbilirubinemia at 36hrs of life. In all
these cord blood level was < 4mg/dl.18
36
Haque K N, (1978), found there are no definite criteria of ABO haemolytic
disease that could predict immediately after birth which infant may require treatment
for hyperbilirubinemia.67
Whyte.J.Graham H, in (1981) studied 71 ABO incompatible infants and equal
number of control to ascertain which cord blood test reliably predict the severity of
ABO HDN, the modified DAT was positive in all the infants who required treatment
for haemolytic Jaundice and all DAT positive children showed evidence of impending
haemolytic anaemia or compensated haemolysis in cord or capillary blood. Cord
serum bilirubin has some predictive value particularly when level exceed 85
mu/mol/litre (5mg/dl) but it was less reliable indicator and had greater value if used in
association with DAT.68
Chen J Y, Ling UP in 1994 studied in Taiwan found ABO incompatible
newborn infants with maternal IgG anti A or anti B titres ≥ or 512X , cord bilirubin
levels ≥ 4mg/dl or positive DCT of cord blood represent a “high risk” category and
should be placed in hospital where frequent Re-evaluation and appropriate therapy are
available.69
Sarici, et al. in (2002) observed a total of 136 healthy term newborns with
ABO (O-A or O-B) blood group incompatibility were followed prospectively with
daily serum total bilirubin measurements for the first 5 days of life. Newborns with
serum total bilirubin levels of ≥5 mg/dL and an increase in serum total bilirubin
concentration of >0.5 mg/dL/h in the first 24 hours, ≥12 mg/dL on day 2, ≥15 mg/dL
on day 3, and ≥17 mg/dL on days 4 and 5 were defined to have significant
hyperbilirubinemia and were started on phototherapy treatment. The additional
assessment of the predictive ability of the sixth-hour serum total bilirubin value in
determining the development of significant hyperbilirubinemia was made on the basis

37
of the placement of any of the first 5 day’s serum bilirubin measurements in the ≥90th
percentile of the study population. Results were twenty nine newborns (21.3%) had
significant hyperbilirubinemia.70
There were significant differences between the newborns who did and the
newborns who did not develop significant hyperbilirubinemia with respect to the
reticulocyte count (4.39 +/- 3.46% vs 2.95 +/- 1.63) and the presence of a direct
antiglobulin test positivity (6 of 23 vs 0 of 107) and a sibling with neonatal Jaundice
(6 of 23 vs 5 of 102). A mean serum bilirubin level of > or =4 mg/dL at the sixth hour
of life was determined to have the highest sensitivity (86.2%) and negative predictive
value (94.5%) and a positive predictive value of 39.7% to predict the newborns who
would develop significant hyperbilirubinemia.70
Covas Mdel C, et al in (2009), observed serum bilirubin at 24-36 hours of life
might contribute to identify those term newborns with ABO incompatibility that have
the highest risk of developing Jaundice.71
Azma RZ et al in a study published in 2011of 214 cases with 114 of them
ABO Incompatible, were of the conclusion that level of cord blood total bilirubin
≥2.5mg/dl was not shown to have a good prediction of significant hyperbilirubinemia
in ABO incompatibility.73
PREDISCHARGE HOUR SPECIFIC BILIRUBIN ESTIMATION
Bhutani and colleagues generated a percentile based bilirubin normogram
using hour specific predischarge TSB levels from a racially diverse group of term
healthy newborns with no Rh and ABO incompatibility who did not need
phototherapy before 60 hours of age and of whom 60% were breastfed. The risk of
38
significant hyperbilirubinemia (TSB greater than 17 mg/dL) for predischarge TSB
above the 95th percentile (high risk zone) was 57%, for infants with TSB between
75th and 95th percentiles (high intermediate risk) it was 13%, for infants with TSB
between 40th and 75th percentile (low intermediate risk zone) it was 2.1% and for
infants with TSB below the 40th percentile (low risk) it was zero
FIGURE NO IV.
Risk designation of term and near-term well newborns based on their hour specific
serum bilirubin values. The high-risk zone is designated by the 95th percentile track.
The intermediate-risk zone is subdivided to upper- and lower-risk zones by the 75th
percentile track. The low-risk zone has been electively and statistically defined by the
40th percentile track. (Dotted extensions are based on <300 TSB values/epoch).
The advantage is that hour-specific TSB before hospital discharge can predict
which newborn is at high, intermediate or low risk for developing clinically
significant hyperbilirubinemia (specifically defined as TSB levels ≥95th percentile for
age in hours). Risk designation and subsequent increase or decrease of TSB can be
39
easily monitored on an hour-specific percentile based predictive bilirubin normogram.
A predischarge total serum bilirubin measured as a universal policy would facilitate
targeted intervention and follow-up in a safe, cost-effective manner. In conjunction
with bilirubin practice parameter of the American Academy of Pediatrics, it could
reduce the potential risk for bilirubin induced neurologic dysfunction.12
40
Methodology
METHODOLOGY
This study was performed at the Department of Pediatrics of M.V.J. Medical
College & Research Hospital. Eligible 200 healthy full-term newborns, delivered at
this hospital were prospectively enrolled in the study. The study was approved by the
Research Ethics Committee of M.V.J. Medical College and Research Hospital.
INCLUSION CRITERIA
1. Healthy full term Newborns of blood group A or B Positive born to Mothers
with O positive blood group.
EXCLUSION CRITERIA
1. Rhesus blood factor incompatibility.
2. Blood group O positive babies
3. Significant illness requiring NICU admission.
4. Major congenital malformations.
5. Chronic maternal illness (like DM)
6. Those who didn’t give consent for follow up
METHOD OF COLLECTION OF DATA
An informed consent was obtained from the parents of the newborn before
enrolling them in the study. Demographic profile and relevant information of was
collected by using structured Proforma by interviewing the mother. Gestational age
was assessed by New Ballard score. CBB was estimated. Serum Bilirubin estimation
was done at 72 hours of age. All babies were daily assessed for Jaundice and its
severity.
41
Methodology
LABORATORY INVESTIGATION:
1. Cord blood (2ml) was collected from placental side after its separation and
subjected to following investigation.
a. Blood group
b. Total and Direct Serum Bilirubin.
c. Haemoglobin and Packed Cell Volume
2. Venous blood samples were collected from the baby at 72 hours of life. These
samples were subjected to following investigation
a. Total and Direct Serum Bilirubin.
b. Haemoglobin and Packed Cell Volume
Serum bilirubin estimation was done by Diazo method. This method for Bilirubin
estimation is based on principle that Bilirubin reacts with Diazotised Sulphanilic acid
in acidic medium to form pink coloured Azobilirubin with absorbance directly
proportional to Bilirubin concentration. Direct Bilirubin, being water soluble directly
reacts in acidic medium. However indirect or unconjugated Bilirubin is solubilised
using a surfactant and then it reacts similar to direct Bilirubin.
42
Results
RESULTS
Prospective clinical study consisted of 200 healthy term newborns delivered in M.V.J.M C &
RH. Significant Jaundice was defined as TSB ≥ 15 mg/ dl at 72 hours of life.

life
Incidence of Significant hyperbilirubinemia in our study population is 11%
TABLE 2
SIGNIFICANT JAUNDICE
TOTAL NUMBER PERCENTAGE
200 22 11%
GRAPH I
11%
89%
Significant Jaundice Insignificant
43
Results
TABLE 3
PARITY OF MOTHERS
(N = 200)
Number of
Parity Total %
mothers
• Primi 116 58.0
• Multi 84 42.0
Total 200 100.0
GRAPH II
MATERNAL PARITY
· Multi
· Primi
0 20 40 60 80 100 120 140
Healthy mothers with O positive group were included. The Parity of mothers
of 200 neonates is shown in the above table. Primigravida were 58% (n=116) and
Multigravida constituted 42% (n= 84).
44
Results
TABLE 4
DISTRIBUTION
ISTRIBUTION OF NEONA
NEONATES ACCORDING
DING TO SEX
Gender of neonates Number of neonates Total %
Male 108 54%

%
Female 92 46%
%
GRAPH III
DISTRIBUTION OF NEONATE
NEONATES ACCORDING TO SEX
110
105
100
108
95
90
92
85
80
· Male · Female
Male babies were 54% (n=108) and female babies were 46% (n=92).
45
Results
TABLE 5
DISTRIBUTION
BUTION OF NEONATES A
ACCORDING TO BIRTH WEIGHT
Birth weight in kgs. Number of neonates Total %
2.50--3.00 145 72.5
3.01--3.50 53 26.5
3.51--4.00 2 1
GRAPH IV
DISTRIBUTION OF NEONATES ACCORDING TO BIRTH WEIGHT
160
140
120
100
80 145
60
40
53
20
2
0
2.50
2.50-3.00 3.01-3.50 3.51-4.00
Babies with birth weight between 2.5

2.5-3.0 kg were 145 (72.5%); between 3.01-
3.5 kg had 53 babies (26.5%) and above 3.5 constituted only 2 (1%).
%)
46
Results
TABLE 6
Blood group of
Number of neonates Total %
neonates
A+ 88 44
B+ 112 56
GRAPH V
Blood group
88
A
112
B
Among the newborns in our study, blood group B was more common (56%)
47
Results
TABLE 7
SIGNIFICANT JAUNDICE IN RELATION TO BLOOD GROUPS A AND B
Newborns with
Blood group Significant Jaundice in
Significant
%
Jaundice
A (n=88) 9 10.22%
B (n=112) 13 11.06%
GRAPH VI
BLOOD GROUP
GROUPS AND SIGNIFICANT JAUNDICE
Newborns with Significant jaundice
11.06%
11.20%
11.00%
10.80%
10.60%
10.22%
10.40%
10.20%
10.00%
9.80%
A (n=88) B (n=112)
The incidence of ssignificant Jaundice was almost the same in Blood groups
type A and type B, (p=0.757) which is not significant
48
Results
TABLE 8

IRUBINEMIA
Number of neonates
SEX with significant Total %
Jaundice
MALE (n=108) 14 12.9%
FEMALE (n= 92) 8 8.7%.

8.7%
GRAPH VII

IRUBINEMIA
14
Number of neonates
12 with significant
jaundice
10
14
8
8
6
0
MALE (n=108) FEMALE (n= 92)
Significant Jaundice was non-significantly more in male babies (12.9

12.9%) as compared
to female babies (8.7%).

%).(p=0.336)
49
Results
TABLE 9
BILIRUBIN, HAEMOGLOBIN AND PCV PROFILE OF THE STUDY
POPULATION
Parameters Minimum Maximum Mean SD
Cord Blood Total

0.6 4.7 2.3 0.7
Bilirubin (mg/dl)
Postnatal 72 hours
2.4 19.7 11.1 2.8
Bilirubin (mg/dl)
Haemoglobin
12.0 20 15.6 1.2
(gm/dl)
PCV
28 60 43.6 4.1
Postnatal 72 hours
12.5 18.0 14.6 1.2
Haemoglobin (gm/dl)
Postnatal 72 hours
PCV 34 55 42.9 3.5
Mean cord bilirubin level was 2.3 mg/dl (range: 0.60- 4.7, SD- 0.7), the mean
total bilirubin at Postnatal 72 hours was 11.1 mg/dl (range: 2.40- 19.7, SD- 2.8).
Mean cord haemoglobin was 15.6 gm% (range: 12.00- 20.00, SD- 1.2) and the
mean haemoglobin at Postnatal 72 hours was 14.6gm% (range: 12.50- 18.00, SD- 1.2).
Mean cord PCV was 43.6% (range: 28.00- 60.00, SD- 4.1) and the mean PCV
at Postnatal 72 hours was 42.9% (range: 34.00- 55.00, SD- 3.5).
50
Results
TABLE 10
COMPARATIVE EVALUATIONS OF CORD AND POSTNATAL 72 HOURS
TOTAL BILIRUBIN, HAEMOGLOBIN AND PCV
Cord Postnatal 72 hours
Total Bilirubin
2.3±0.7 11.1±2.8
(mg/dl)
Haemoglobin
15.60±1.2 14.6±1.2
(gm/dl)
PCV
43.6±4.1 42.9±3.5
Mean cord bilirubin level was 2.3 mg/dl, mean total bilirubin at Postnatal 72
hours was 11.1 mg/dl.
Mean cord haemoglobin was 15.60 gm% compared to the mean haemoglobin
of 14.6 gm% at postnatal 72 hours.
Mean cord PCV was 43.6% and the Postnatal 72 hour mean PCV was 42.9%
51
Results
TABLE 11
DIAGNOSTIC PREDICTABILITY OF CORD BLOOD BILIRUBIN FOR
SIGNIFICANT HYPERBILIRUBINEMIA
(TOTAL
TOTAL BILIRUBIN OF ≥3.5 mg/dl AT 72 HOUR)
HOUR
CORD BILIRUBIN SIGNIFICANT INSIGNIFICANT
JAUNDICE JAUNDICE
≥3.5 18 1
<3.5 4 177
GRAPH VIII
CORD BLOOD BILIRUBIN AND SIGNIFICANT HYPERBILIRUBINEMIA

HYPERBIL
177
180
160
140
120
100
80 ≥3.5mg%
60
18 <3.5mg%
40 4 1
20
0
JAUNDICE
SIGNIFICANT JAUNDICE INSIGNIFICANT
18 newborns out of 22 who developed significant Jaundice had CBB ≥3.5mg/dl. Only
1 newborn out of 178 who did not develop significant Jaundice had a total CBB
≥3.5mg/dl
52
Results
TABLE 12
PREDICTABILITY OF CORD BLOOD BILIRUBIN FOR
HYPERBILIRUBINEMIA
True Positive n= 18
False Positive n= 4
False negative n= 1
True negative n= 177
Sensitivity (%) 94.7%
Specificity (%) 97.7%
PPV (%) 81.8%
NPV (%) 99.4%
True Positive: 18 Newborns with CBB ≥ 3.5mg/dl who developed significant
True Negative: 177 newborns with CBB < 3.5mg/dl who did not develop significant
Jaundice.
53
Results
False Positive: 4 Newborns with CBB ≥ 3.5mg/dl who did not develop significant
False Negative: 1 Newborn with CBB <3.5mg/dl who developed significant Jaundice
at post natal 72 hours.
Sensitivity: If a neonate develops significant hyperbilirubinemia, the probability that
the cord bilirubin was higher than 3.5 mg/dl was 94.7%.
Specificity: The probability that the cord bilirubin was <3.5 mg/dl was 97% in a Non
hyperbilirubinemic neonate.
Positive Predictive Value: In the present study, the probability that a neonate with
cord bilirubin ≥ 3.5 mg/dl would later develop hyperbilirubinemia was 81.8%.
Negative Predictive Value: The probability that a neonate with cord bilirubin <3.5
mg/dl would not develop hyperbilirubinemia was 99.4%.
54
Discussion
DISCUSSION
ABO Incompatibility is the most common materno-fetal blood group
incompatibility which is usually a problem of the neonate rather than the foetus.
Anaemia in the neonatal period is usually mild. The main clinical problem is Jaundice
in the first 24 hours of life (icterus praecox). Approximately 50% of cases occur in
first newborn infants. There is no predictable pattern of recurrence in subsequent
infants. Our study hypothesis was that a high serum bilirubin level at birth would also
predict a high peak later in life. Our aim was to find a correlation of CBB level with
subsequent NH in A and B blood group babies born to O blood group mothers and to
find a cut-off level of CBB for predicting the development of NH. We chose cord
bilirubin because it is a non-invasive way and the results are available within few
hours after birth and estimation of bilirubin can be done even in resource limited rural
areas in contrast to other studies like DAT, IgG anti A or anti B titres.
The diagnosis of ABO haemolytic disease depends on the clinical, serological
and biochemical findings in the newborn. Hydrops fetalis in association with ABO
incompatibility is extremely rare and has been reported in two cases72. Micro
spherocytosis is the most prominent feature of ABO haemolytic disease. Coombs test
in ABO incompatible infants does not necessarily indicate disease. It has been
observed that 1/3rd of babies born to O group mothers had a positive DAT.
Development of safe marker will help in preventing fatal outcome due to Jaundice.
To address this issue AAP recommends that follow up should be provided to
all neonates discharged less than 48 hours after birth by a health care professional in
an office, clinic, or at home within 2 to 3 days of discharge. Compliance with this

55
Discussion
advice may not be easy however, particularly in rural or lower socioeconomic areas,
and given the rarity of Kernicterus, it will be very difficult, if not possible to
document the benefits of this policy. Experience suggests that asking mothers to
observe infants for the development of Jaundice is not satisfactory. Despite such
instructions, it is difficult for many parents to recognize significant Jaundice.
Currently we do not have a reliable method of anticipating such levels of
hyperbilirubinemia. It is possible that closer, and more frequent, follow up after birth
and discharge from the hospital might prevent some of these unfortunate outcomes,
but rare, sporadic cases of Kernicterus may not be preventable unless we adopt an
approach to surveillance of the newborn that is substantially more rigorous than has
been practiced. The feasibility, costs, risks and benefits of such an approach need to
be determined.
Reliable predictors can reduce hospital stay for normal babies resulting in
discharge and identifying at risk or high risk neonates likely to develop pathological
Jaundice. These neonates would need close monitoring so that potential risk for
bilirubin induced brain damage can be reduced amongst term healthy newborn
discharged early from hospital.
Several factors are recognised as early predictors both individually and in
combination in predicting significant Jaundice in ABO incompatibility, those
includes IgG anti A or anti B titres in maternal serum, Coombs test, serum bilirubin,
cord bilirubin, retculocyte count.
Keeping these factors in consideration our study was conducted on term
healthy neonates with A or B blood group born to O positive healthy mothers,
56
Discussion
outcome was hyperbilirubinemia we have considered peak serum bilirubin levels ≥
15mg/dl at 72 hrs of age as significant Jaundice since specific treatment is considered
at or above this level.
TABLE 13:
COMPARISON OF CORD SERUM BILIRUBIN AND SIGNIFICANT
JAUNDICE IN ABO INCOMPATIBILITY
No. Of Umbilical cord bilirubin as

Studies Year
Cases predictor
Robinson et al66 1960 - >3mg/dl
H.M.Risemberg18 1977 71 >4mg/dl
K N Haque67 1978 - No correlation
White J G.68 1981 - >85mmol/l (5mg/dl)
Simpson et al77 1999 71 >2.5mg/dl.
Azma RZ73 2011 114 ≥2.5mg/dl No correlation
Present study 2011 200 ≥3.5mg/dl
Other studies also reported the relation between raising levels of cord bilirubin
and increased incidence of significant hyperbilirubinemia. Thus from the above table
it can be seen that different authors have used different cut off value for predicting
significant hyperbilirubinemia and some have found CBB cannot be used as a
prediction of subsequent hyperbilirubinemia.
57
Discussion
This variability is mainly because of technical error in estimating bilirubin
levels, sample size, cut off value decided for significant hyperbilirubinemia, as many
studies were done before the Bhutani hour specific normogram were introduced.
Hence the need for a local laboratory to define the cut off value becomes all the more
important.
In the present study significant Jaundice was seen equally in both O-B or O-A
blood group, The literature is inconsistent with regard to the degree of haemolysis and
the incidence and severity of hyperbilirubinemia among O-A and O-B pairs. Some
Literature review shows that significant Jaundice was more severe in OA
combination.12 Kaplan et al study using ETCOc as predictor for hyperbilirubinemia
showed O-B blood group had more significant and severity of Jaundice 74. Our study
showed a positive correlation only and observations were not statistically significant.
Significant Jaundice was slightly more in male babies (12.9%) as compared to
female babies (8.7%) though it was not significant statistically. Literature review
reported variable sex distribution with some stating disease as more common in
female babies and some males.12,75 Hodr R, in 1989 observed that among neonates
treated successfully by phototherapy, boys prevailed significantly and there was
significantly higher prevalence of girls among the most severe forms of ABO
haemolytic disease75. Dufour DR, in a retrospective analysis of 254 cases found that
sex, race, gravidity, birth weight and blood type of the infant did not have any
significant relationships to outcome76. In our study also none of these variables were
statistically significant.
58
Discussion
In the present study using serum bilirubin levels ≥ 3.5 mg/dL in the cord
blood, hyperbilirubinemia could be predicted with sensitivity of 94.7%, specificity of
97.7%, and Positive Predictive Value of 81.8%. The Negative Predictive Value is
99.4%. The correlation between cord bilirubin and development of significant
Jaundice in the postnatal 72 hours showed a positive correlation according to Karl
Pearson’s correlation coefficient method is (r = 0.37).
59
Conclusion
CONCLUSION
introduction of anti-D Prophylaxis, ABO incompatibility is now the major cause of
immune haemolytic disease of new born(HDN) various studies has shown ABO
incompatibility occurs in 15-25% of all pregnancies and it was in every 10th newborn
that this incompatibility became manifest as a haemolytic disease requiring treatment
ABO incompatible babies have double the risk to develop Jaundice requiring
treatment and 5-10 times increased risk of exchange transfusion.
Early identification of newborn at risk for significant hyperbilirubinemia by
using simple predictors can help to prevent possible bilirubin induced neurological
dysfunction.
A 99.4% Negative Predictive Value in the present study suggests that in
healthy Term babies with ABO without Rh incompatibility Cord Blood Bilirubin <
3.5 mg/dl can help to identify those newborns who are unlikely to require further
evaluation and intervention. Babies with Cord Blood Bilirubin level ≥ 3.5 mg/dl
should be followed more frequently to reduce mortality and morbidity due to
Neonatal hyperbilirubinemia.
As a speculation, one may consider the umbilical cord blood to be a kind of ‘file’ for
the newborn. As such it could be collected, stored and used for further analysis of
unconjugated bilirubin levels, should a slightly or moderately Jaundiced child be
considered early discharge from hospital. Such a proposal may therefore constitute an
additional predictive method that is available for evaluating the occurrence of severe
60
Conclusion
hyperbilirubinemia by third day of life. In association with other resources that were
already available this proposal may help in assuring safer early discharge
Our study had homogenous local rural population unlike heterogeneous group
of neonate from Cosmopolitan Urban Bangalore. This is the strength of our study. It
means that the Prediction test developed by us can be applied to the neonates of
Hoskote’s local rural population on whom it was developed.
Thus prediction of neonatal hyperbilirubinemia will have widespread
implication especially in our rural setup where there are limited resources and few
hospital beds.
Healthy newborns at low risk for hyperbilirubinemia can be discharged early
from the hospital.
61
Summary
SUMMARY
• The study group consisted of 200 full term neonates delivered in M.V.J.MC &
RH with ABO incompatibility
• Cord blood bilirubin and Total Serum Bilirubin at 72 hours of age was
estimated for all neonates.
• Incidence of significant hyperbilirubinemia ( TSB >15 mg/ dl at 72 hours of
age ) in our study population is 11%
• Male were slightly more affected than the female newborns in the significant
Jaundice group. (M:F ::1.4:1 ). But this was not statistically significant.
• The incidence of significant Jaundice was more or less equal in A-blood group
and B-blood group newborns.
• There were no statistical significant differences between the cases who had
cord bilirubin level <3.5 mg/dl and ≥3.5 mg/dl with respect to various factors
that may be associated with the risk of hyperbilirubinemia, such as gender,
gestational age, birth weight and blood group
• Mean cord bilirubin level was 2.3±0.7 mg/dl. Mean total bilirubin at 72 hours
of post natal age was 11.1±2.8 mg/dl.
• There was a positive correlation between cord bilirubin and third postnatal day
serum bilirubin.
• Using cord bilirubin level of ≥ 3.5 mg/dl, Hyperbilirubinemia can be predicted
with sensitivity of 94.7%, specificity of 97.7 %, and positive predictive value
of 81.8% and negative predictive value of 99.4%.
62
Summary
• Healthy term babies with ABO incompatibility with Cord Blood Bilirubin
<3.5 mg/dl are unlikely to require further evaluation and intervention hence
these newborns can be discharged with assurance to Parents.
• The babies who are discharged with a CBB level ≥ 3.5 mg/dl should have
unfailing frequent follow ups in the postnatal 1st week. A clearly written
description of neonatal hyperbilirubinemia including risks, what to look for,
and when to call or bring the infant back should be given to parents whose
babies are discharged early.
CBB <3.5 mg/dl seems a “cost effective” screening method for early
discharge of newborns.
63
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70. Sarici SU, Yurdakok M, Serdar MA, Oran O, Erdam G, Tekinalp G, et al. An
early (sixth hour) serum bilirubin measurement is useful in predicting the
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development of significant hyperbilirubinemia and severe ABO haemolytic
disease in selective high risk population of newborns with ABO incompatibility.
Pediatrics 2002 Apr; 109(4):e53.
71. Covas Mdel C, Medina MS, Ventura S, Gamero D, Giulliano A, Esandi ME, et al.
ABO haemolytic disease and developing of significant hyperbilirubinemia in term
newborns: early predictive factors. Arch Argent pediatr 2009;107:16-25.
72. Maura MD, Simon Hann AM, Devane SP.Hydrops fetalis due to ABO
incompatibility.Arch Dis Child 1988;78:220-21.
73. Azma RZ, Farisyah SMZ, Nurasykin Y, Noriya M, Nabeelah AK, Soopy, et al.
Prediction of significant neonatal Jaundice in babies with ABO incompatibility by
cord blood tests. Med Health 2011; 6(1)(suppl)292-3.
74. Kaplan M, Hammerman C, Vreman HJ, Wong RJ, Stevenson DK. Hemolysis and
hyperbilirubinemia in antiglobulin positive,direct ABO blood group heterospecific
neonates. J Pediatr 2010; 157:772-777.
75. Hodr R, ABO haemolytic disease: sex ratio and blood groups in the newborns
requiring treatment. Czech Med 1989; 12(3):125-33.
76. Dufour DR, Monoghan WP. ABO haemolytic disease of the newborn. A
retrospective analysis of 254 cases. Am J clin pathol 1980 Mar; 73:369-73.
77. Simpson, Deorari AK, Paul VK, Saxena R. Early prediction of pathological
Jaundice due to ABO haemolytic disease.cohort study. In: Abstract of scientific
papers-14th Annual convention of NNF, 1999 Nov 19-21; Bangalore, 7pp.
71
Annexure
ANNEXURE I – PHOTOGRAPH
Photograph I: Visual assessment of Jaundice
72
Annexure
ANNEXURE II – PROFORMA
MVJ MEDICAL COLLEGE AND RESEARCH HOSPITAL
HOSKOTE, BANGALORE DEPARTMENT OF PEDIATRICS
Correlation of Cord Blood Bilirubin with Neonatal Hyperbilirubinemia in
New borns with a setting of ABO Incompatibility
Mother’s Name: Case No:
Age of the Mother: Sex of the Baby:
Date of Delivery: I.P Number of the Baby:
Gravida: Gestational Age: Birth weight:
INVESTIGATIONS:
Blood Group of the Mother: Blood Group of the Baby:
Cord 12hrs 24hrs 72hrs
Total bilirubin
Direct bilirubin
Indirect bilirubin
Haemoglobin
Haematocrit
73
Annexure
ANNEXURE III – MASTER CHART
KEY TO MASTER CHART
B/W ------- Birth weight
CBB ------- Cord blood bilirubin
CHb ------- Cord blood haemoglobin
DOB ------- Date of Birth
D3 ------- Day three
F ------- Female
G ------- Gravida
Hb ------- Haemoglobin
I.P.No ------- In patient number
Kg ------ Kilogram
M ------ Male
Mg ------ Milligram
PCV ------ Packed cell volume
Sl: No. ------ Serial Number
Yrs – years.
74
Blood
BABY Kgs baby
01 F 128030 02-09-10 Primi 2.975 B+ 2.5 14.5 16/42 14.2/42.6

02 F 131872 20-10-10 Primi 3.17 A+ 2.4 13.2 18/42 16/38
03 F 132827 03-11-10 Multi 3.5 B+ 2.2 12 18/39 18/55
04 M 132999 06-11-10 Primi 2.7 B+ 2.8 16.1 15.5/44 15/45
05 M 133237 10-11-10 Primi 2.94 A+ 2.3 13 16/42 16/48
06 F 133334 11-11-10 Multi 2.96 A+ 2.3 12.4 15/35 15/48
07 F 134141 20-11-10 Primi 2.565 B+ 2.4 12 15/51 16/48
08 M 134784 28-11-10 Multi 3.294 A+ 2.8 10.8 20/60 18/52
09 M 135754 10-12-10 Primi 2.62 A+ 1.5 9.8 16.2/48.4 16/48
10 F 135835 11-12-10 Multi 2.5 B+ 2.1 10.6 17/51 16/48
11 F 135868 11-12-10 Primi 2.6 A+ 2 8.4 19/48 18/48
12 M 136883 24-12-10 Primi 2.8 B+ 2.1 10 18/46 15/42
13 F 136893 26-12-10 Primi 2.5 B+ 2.1 11 14/46 14.1/48
14 M 136908 26-12-10 Multi 3.5 B+ 2.5 12.8 18/42 16/42
15 M 137934 06-01-11 Primi 2.8 A+ 1.9 11.8 16/48 16/46
16 M 138632 08-01-11 Multi 3.335 B+ 3.7 16 15/45 14/45
17 M 138748 18-01-11 Multi 3.05 A+ 1.9 12.2 14/42 16.5/50
18 F 139184 27-01-11 Primi 2.71 B+ 2.1 13.6 16.6/44 15/42
19 F 139185 27-01-11 Multi 3.6 B+ 2.1 12.6 15.2/42 16.4/48
20 M 139444 01-0211 Primi 3.42 B+ 3.6 15 15/46 15.2/44
21 F 140035 02-01-11 Multi 2.705 A+ 2.5 10 15.4/47 15/44
22 F 140310 03-02-11 Multi 2.73 B+ 2.3 11.3 16/50 15/46
23 M 140422 06-02-11 Primi 2.7 B+ 1.8 9 14.4/49.4 13.4/44
24 F 140486 09-02-11 Primi 3.4 B+ 2.6 12 16.4/50 16/48
25 F 140901 11-02-11 Multi 2.8 A+ 2.7 12 16/42 14.4/48
26 F 140904 12-02-11 Primi 2.945 A+ 2.2 7.8 15.6/48 14.2/46
27 F 141017 13-02-11 Multi 2.7 B+ 4.7 17 15.7/47.8 15.2/47.6
28 F 141207 15-02-11 Primi 2.5 B+ 1.8 7.5 15/46 16/48
29 M 142536 05-03-11 Multi 2.5 B+ 1.8 11.5 15.6/42 15/42
30 F 143361 15-03-11 Primi 2.75 B+ 1.6 6.1 14.7/46 14/44
31 F 143925 21-03-11 Primi 2.75 B+ 2.6 10 10/28 14.2/36
32 F 144207 24-03-11 Primi 2.9 A+ 1.7 12.3 15/42 16/42
75
Blood
BABY Kgs baby
33 M 144622 29-03-11 Multi 2.6 B+ 1.8 10.8 15/41 14.5/42
34 M 144625 30-03-11 Multi 2.76 A+ 2 10 16.2/51 14/42
35 F 145014 07-04-11 Primi 3.23 B+ 3.6 15 16/50 15/48
36 M 145018 07-04-11 Primi 2.88 A+ 3.8 15.6 13/42 13/40
37 F 145342 07-04-11 Primi 2.54 A+ 2.4 10.8 16/42 14/40
38 M 145585 09-04-11 Primi 2.6 A+ 2.2 10.2 17/50 15/48
39 F 145589 10-04-11 Multi 3.56 B+ 3 12 16/42 15.3/42
40 F 146416 21-04-11 Primi 2.7 A+ 2.7 10.6 17/40 14/40
41 M 146671 26-04-11 Multi 2.86 A+ 1.9 12.7 15/42 15/41
42 M 147136 27-04-11 Primi 3.1 B+ 2.5 10.4 17/40 15/40
43 M 147162 01-05-11 Primi 2.5 A+ 2.4 9 15/42 15/40
44 M 147308 03-05-11 Multi 2.75 B+ 1.9 10 17/42 14/41
45 F 147570 10-05-11 Primi 3.4 A+ 3.7 16.4 16/40 14/40
46 M 147590 10-05-11 Multi 2.94 B+ 2.1 13.1 17/44 15/42
47 F 148868 21-05-11 Primi 2.62 A+ 2.6 12 17.2/32.5 16.2/34
48 M 149094 25-05-11 Multi 2.5 B+ 4 17.6 16/42 16/40
49 F 149288 25-05-11 Multi 2.8 B+ 3.6 16.3 14/49 13/47
50 M 150119 03-06-11 Primi 3.09 B+ 2.1 10.4 12.4/39.7 13/42
51 F 150281 05-06-11 Primi 3.2 A+ 1.9 9.6 17/49.8 17/49
52 M 150686 09-06-11 Multi 3.04 B+ 2.1 11.8 16/42 16/42
53 M 150989 17-06-11 Primi 2.52 A+ 3.8 18.1 17/42 16/41
54 M 152126 26-06-11 Multi 2.8 B+ 1.4 7.8 16/42 15/41
55 M 152269 27-06-11 Primi 2.9 A+ 2.2 11.8 15.6/49 14/48
56 F 152337 29-06-11 Multi 2.65 B+ 2 8.6 16.8/47 15/46
57 M 152752 02-07-11 Multi 3.2 B+ 3.9 15 15/47 14.8/46
58 M 153291 09-07-11 Multi 2.6 B+ 2.3 15.3 14.8/53 15/44
59 M 153386 11-07-08 Primi 2.8 B+ 1.3 9.5 14.8/44 14/43
60 F 153723 13-07-11 Multi 3.25 A+ 3.7 15.2 14.3/42 14/43
61 M 153927 16-07-11 Primi 3.2 A+ 1.8 14.3 15/44 15/42
62 F 153828 16-07-11 Multi 2.86 B+ 2 11.9 14.3/44 14.2/44
63 F 154134 18-07-11 Primi 2.51 B+ 1.8 6.4 15/48 14.5/44
64 M 154452 21-07-11 Primi 2.5 A+ 2.3 10.2 14.6/47 14.5/47
65 M 154468 21-07-11 Primi 2.6 A+ 1.5 7.8 15/46 14.5/42
66 F 154912 26-07-11 Primi 2.9 B+ 2.6 14 15/43 14/42
67 F 155032 27-07-11 Primi 2.8 A+ 3.1 10.5 15/47 13/44
68 F 155138 28-07-11 Multi 2.75 B+ 2.5 12 15/42 14.3/41
69 F 155233 29-07-11 Primi 3.08 A+ 2.5 11.4 14.3/44 14/41
70 F 155421 02-08-11 Multi 2.7 B+ 1.8 10 14.3/48 14/42
71 F 155667 03-08-11 Multi 2.8 B+ 2.2 8.3 14.2/44 14/42
72 F 156018 07-08-11 Primi 2.985 B+ 2.1 10.7 13.4/46 13/42
76
Blood
BABY Kgs baby
73 M 156243 09-08-11 Multi 2.8 A+ 2 11 15/42 15/40
74 M 156352 10-08-11 Multi 2.935 B+ 1.8 9.3 14/42 13/40
75 M 157336 22-08-11 Primi 3.5 A+ 2.4 12.4 15/42 14/43
76 F 158616 08-09-11 Multi 2.75 A+ 2.3 10.4 14/42 13/44
77 F 158822 11-09-11 Primi 2.6 A+ 2.1 9.4 17/40 16/40
78 F 158990 12-09-11 Primi 3.245 A+ 3.8 15.4 15.3/44 14/42
79 F 159003 14-09-11 Primi 2.675 B+ 2.6 13 15/42 13.4/40
80 F 159367 15-09-11 Primi 2.5 B+ 2.5 11 14.4/47 13/42
81 M 159705 17-09-11 Primi 3.25 B+ 2.3 12.4 15/40 14/40
82 M 159843 21-09-11 Multi 3.5 A+ 1.8 8.6 13.8/48 13/42
83 M 160031 21-09-11 Primi 3.34 B+ 1.2 7.2 15/44 13/42
84 M 160067 21-09-11 Multi 2.65 A+ 2.3 9 15.2/45 13/43
85 F 160446 22-09-11 Primi 3.2 B+ 1.7 11.2 15/41 13/40
86 M 160689 27-09-11 Multi 3.14 B+ 2.3 10.8 14.5/52 12.5/47
87 F 160828 29-09-11 Primi 2.6 B+ 2.8 12 14.5/48 13/46
88 F 160840 02-10-11 Multi 2.67 B+ 3.2 13 15/46 13/42
89 M 161189 03-10-11 Primi 3.06 B+ 3.1 13 15/42 13/40
90 M 161328 06-10-11 Multi 2.93 A+ 3.2 13.4 15/46 15/44
91 M 161563 08-10-11 Primi 2.56 A+ 2.1 13 14.3/44 13.5/40
92 M 161736 10-10-11 Multi 2.5 A+ 2.5 10.4 16/42 13/40
93 M 162153 14-10-11 Primi 2.6 B+ 2.4 11 13/42 13/40
94 F 162286 15-10-11 Multi 2.9 B+ 2.7 10.8 13.6/40 13/42
95 M 162690 19-10-11 Multi 2.5 B+ 3.7 16 15/42 14/40
96 M 162696 20-10-11 Primi 3.325 A+ 1.6 8 13/40 12.5/42
97 M 163055 23-10-11 Primi 3.47 A+ 2.8 12 14/44 13/42
98 M 163300 28-10-11 Primi 3.25 A+ 3 12.3 13.5/42 13/40
99 M 163813 02-11-11 Multi 2.6 B+ 2.3 8.6 15/40 13/40
100 M 163822 06-11-11 Multi 2.9 A+ 2.4 11.5 17/42 13/42
101 F 164155 07-11-11 Primi 2.61 B+ 2.6 14.3 14.3/44 13.5/40
102 M 164425 09-11-11 Multi 2.72 B+ 2.2 11.2 16/47 15/44
103 M 164630 12-11-11 Primi 2.5 B+ 2.3 11.1 16/48 13/46
104 M 164780 14-11-11 Multi 2.9 A+ 2.5 15.6 15/40 14/42
105 M 164784 14-11-11 Primi 2.5 A+ 1.8 11 16/48 14/47
106 F 165566 21-11-11 Primi 2.6 A+ 1.6 9 17/46 15/42
107 M 165906 24-11-11 Multi 3.1 B+ 2.3 11 17/48 15/42
108 M 165912 24-11-11 Primi 2.85 A+ 1 7.6 16/47 14/42
109 F 166019 25-11-11 Multi 2.76 A+ 1.5 7 18/48 15/47
110 F 166126 26-11-11 Multi 2.7 A+ 2.4 10.6 16/42 13/40
111 M 166278 28-11-11 Primi 2.6 B+ 1.8 9 16/45 15/40
112 M 166640 01-12-11 Primi 2.71 B+ 2 10 17/40 15/40
77
Blood
BABY Kgs baby
113 M 166641 01-12-11 Primi 2.71 A+ 1 6 16/40 13/40
114 M 167013 05-12-11 Multi 3.055 B+ 1.6 9.6 17/47 14/42
115 F 167030 06-12-11 Primi 2.5 B+ 1 11 17.2/42 15/40
116 F 167048 06-12-11 Primi 2.75 A+ 2.8 12 17/44 15/42
117 F 167610 12-12-11 Primi 2.5 B+ 3.7 19.5 16/41 15/42
118 M 167859 14-12-11 Primi 2.55 B+ 2.6 15 17/42 16/41
119 F 168485 20-12-11 Multi 3.325 A+ 3.7 17 16/42 15/40
120 F 168583 24-12-11 Primi 3.35 B+ 1 5.6 15/41 15/42
121 M 168987 26-12-11 Primi 2.6 A+ 3.4 14 15/42 15/40
122 F 169436 29-12-11 Primi 2.505 B+ 2.6 12 16/40 15/40
123 F 169673 02-01-12 Multi 2.75 A+ 1.8 9.8 16/40 14/40
124 M 169930 03-01-12 Multi 2.54 A+ 2 12.6 15/40 14/41
125 F 170139 05-01-12 Primi 3.2 A+ 1.4 9 15/41 15/40
126 M 170163 05-01-12 Multi 2.75 A+ 2.6 11.4 14/36 13/37
127 M 170379 07-01-12 Primi 2.8 B+ 2.4 12 15/40 13/48
128 F 171557 19-01-12 Multi 3.13 B+ 3.2 14 15/46 13/46
129 M 172156 26-01-12 Primi 2.55 B+ 2.6 14.5 14/38 14/39
130 F 172157 26-01-12 Primi 2.7 A+ 3.1 12 15/38 15/36
131 F 172288 28-01-12 Multi 2.6 A+ 2.2 11.6 15/40 15/40
132 M 172383 28-01-12 Primi 2.715 A+ 2 9.6 15/42 15/40
133 M 172402 29-01-12 Primi 2.68 B+ 3.2 12.2 16/40 13/37
134 F 172532 30-01-12 Multi 2.62 B+ 2.1 11 15/40 15/40
135 M 172775 01-02-12 Primi 2.89 B+ 2 10 16/44 15/42
136 F 173232 06-02-12 Primi 2.93 B+ 1.8 8.9 16/40 15/40
137 F 173244 08-02-12 Primi 2.535 A+ 1.6 6.4 16/41 13/40
138 M 174054 14-02-12 Multi 2.705 A+ 2.4 11.2 15/40 14/40
139 M 174074 15-02-12 Multi 3.03 B+ 2.2 12.5 15/42 14/40
140 M 174531 18-02-12 Primi 3.19 A+ 2 8.6 16/40 16/42
141 F 174552 18-02-12 Primi 2.6 B+ 2.5 9.8 16/40 15/40
142 M 174678 21-02-12 Primi 2.8 B+ 2 8.6 16/40 15/40
143 F 174691 21-02-12 Multi 2.68 A+ 3.7 11.5 16/40 14/42
144 M 175135 25-02-12 Primi 3.1 B+ 1.7 14.3 15/40 14/36
145 M 175288 27-02-12 Multi 3.25 B+ 1.7 11.2 15/40 14/40
146 M 175389 28-02-12 Primi 2.6 A+ 2 11.1 14/40 13/40
147 M 175491 29-02-12 Primi 2.8 A+ 3.9 16.8 15/42 13/41
148 M 176000 29-02-12 Primi 2.7 B+ 1.5 13.3 16/42 13/40
149 M 176199 07-03-12 Primi 2.73 B+ 2.2 14.1 16/42 15/40
150 M 176299 07-03-12 Multi 2.5 A+ 2.7 12.3 13/40 13/40
151 M 176306 08-03-12 Primi 2.55 B+ 2.4 13.6 16/42 14.2/42.6
152 M 176320 09-03-12 Multi 3.325 B+ 2.2 10.3 18/42 16/38
78
Blood
BABY Kgs baby
153 F 176418 11-03-12 Multi 3.35 B+ 0.6 8.2 18/39 18/55
154 M 176710 14-03-12 Primi 3.14 B+ 2.2 8.9 15.5/44 15/45
155 F 176791 14-03-12 Primi 2.6 B+ 1 10.3 16/42 16/48
156 M 176800 15-03-12 Primi 2.67 A+ 1.4 5.9 15/35 15/48
157 F 176805 16-03-12 Primi 2.56 B+ 2 11.4 16.2/48.4 16/48
158 M 177362 19-03-12 Primi 2.5 B+ 1.9 14.6 17/51 16/48
159 F 177448 19-03-12 Multi 2.6 A+ 1.7 9 19/48 18/48
160 F 177493 20-03-12 Primi 2.9 A+ 1.8 7.2 17/40 14/40
161 M 177510 20-03-12 Multi 2.5 A+ 1.9 9.8 15/42 15/41
162 M 177617 21-03-12 Primi 3.325 B+ 2.2 10.4 17/40 15/40
163 F 177771 22-03-12 Multi 3.47 A+ 1.8 9.4 15/42 15/40
164 M 177740 22-03-12 Primi 3.25 B+ 2.9 14 17/42 14/41
165 M 177846 23-03-12 Primi 2.6 B+ 1.8 8.9 16/40 14/40
166 F 177867 24-03-12 Primi 2.9 A+ 2.1 11.2 17/44 15/42
167 M 178135 27-03-12 Multi 2.61 A+ 1.7 12 17.2/32.5 16.2/34
168 F 178146 27-03-12 Multi 2.72 A+ 2 10 16/42 16/40
169 M 178392 30-03-12 Primi 2.5 B+ 1.2 3.9 14/49 13/47
170 M 178511 01-04-12 Multi 2.5 B+ 2.1 11 12.4/39.7 13/42
171 M 178605 02-04-12 Primi 3.325 B+ 1.4 8.3 17/49.8 17/49
172 F 178773 02-04-12 Multi 3.47 B+ 1.6 9.6 16/42 16/42
173 M 178785 03-04-12 Primi 3.25 B+ 1.4 7.1 17/42 16/41
174 M 178786 03-04-12 Multi 2.6 B+ 3 14.3 16/42 15/41
175 F 178617 04-04-12 Primi 2.9 B+ 2.5 9 15.6/49 14/48
176 F 178926 06-04-12 Multi 2.61 A+ 1.4 7.2 16.8/47 15/46
177 F 179084 07-04-12 Multi 2.72 B+ 1.4 7.8 15/47 14.8/46
178 F 179481 10-04-12 Primi 2.7 A+ 1.6 9.4 14.8/53 15/44
179 M 179623 10-04-12 Primi 2.8 B+ 1.3 9.2 14.8/44 14/43
180 M 180583 20-04-12 Multi 2.985 B+ 2 11.2 14.3/42 14/43
181 F 180610 21-04-12 Primi 2.8 A+ 1.7 12.2 15/44 15/42
182 F 180612 23-04-12 Multi 2.935 B+ 1.4 3.4 15.7/47.8 15.2/47.6
183 M 180866 25-04-12 Primi 3.5 A+ 1.6 7.8 15/46 16/48
184 M 180905 25-04-12 Multi 2.75 B+ 2.5 13 15.6/42 15/42
185 F 181211 26-04-12 Primi 2.6 B+ 1.8 9.9 14.7/46 14/44
186 F 181212 28-04-12 Multi 3.245 A+ 2.3 10 14/38 14.2/36
187 M 181281 29-04-12 Primi 2.8 B+ 2.6 12 15/42 16/42
188 M 181433 30-04-12 Multi 2.6 A+ 1.8 8.6 15/41 14.5/42
189 F 181609 02-05-12 Primi 2.5 A+ 3 12 16.2/51 14/42
190 M 181746 03-05-12 Multi 3.01 A+ 3.5 15 17/42 13/42
191 F 181747 03-05-12 Multi 2.8 A+ 2.8 12 14.3/44 13.5/40
192 M 181748 03-05-12 Primi 2.76 B+ 2.8 12 16/47 15/44
79
Blood
BABY Kgs baby
193 M 181981 05-05-12 Primi 2.6 B+ 3.8 17 16/48 13/46
194 F 182002 05-05-12 Primi 2.5 A+ 1.6 6.8 15/40 14/42
195 M 182222 06-05-12 Multi 2.9 B+ 1.8 9.8 16/48 14/47
196 F 182261 07-05-12 Primi 2.6 B+ 1.8 10 17/46 15/42
197 F 182765 13-05-12 Primi 2.7 B+ 2.4 12 17/48 15/42
198 F 182902 15-05-12 Multi 3.5 A+ 1.1 5 16/47 14/42
199 F 183217 16-05-12 Multi 3.02 B+ 2.8 13 18/48 15/47
200 M 183721 20-05-12 Primi 3.0 A+ 2.2 11 16/48 15/47
80

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CORRELATION OF CORD BLOOD BILIRUBIN AND

NEONATAL HYPERBILIRUBINEMIA IN NEWBORNS

It is with great privilege, I express my most humble and profound gratitude to

my Teacher and Guide Dr. SANJEEV SHRINIVAS MANAGOLI Professor

guidance, able supervision, valuable suggestions, cyber help and constant

encouragement throughout the study which facilitated the completion of this

revision for perfection.

I am thankful to Dr. B. RAVI CHANDER Professor, Head of the Department,

I express my deepest sense of gratitude to my eminent and esteemed teacher

I am extremely grateful to Dr. M. J. Mohan and Mrs. Dharani Mohan, for

providing a home away from home during my career as a postgraduate.

I am extremely grateful to all my distinguished Professors, Dr. Jaishree R.

Kamat, who helped me to take lot of responsibilities and showed importance of

guidance, inspiration and moral support during my career as a postgraduate.

I am thankful to Dr. Gurumurthy, Professor, Head of the Department,

Department of Biochemistry, M.V.J. Medical College and Research Hospital, the

not have been possible.

and support constantly beholds me.

I certainly owe my thanks to all the people especially Paediatric Department

Assistant, Office Stenographer, Statistician, who have helped me directly or

indirectly in accomplishing this work.

pray for continued blessing and success.

Date: Signature of candidate

Place: Dr. Sajjad Saneeq C.

AAP : American Academy of Pediatrics

AGA : Appropriate for Gestational Age

CBB : Cord Blood Bilirubin

DAT : Direct Anti-globin Test

ETCOC : Corrected ambient carbon monoxide

HDN : Haemolytic disease of newborn

LBW : Low Birth Weight

NICU : Neonatal Intensive Care Unit

NPV : Negative predictive value

PPV : Positive predictive value

SGA : Small for Gestational Age

TCB : Transcutaneous Bilirubin

TSB : Total serum bilirubin.

Background and Objectives

The incidence of Rh D allo-immunization has decreased after the introduction

haemolytic disease of newborn (HDN). Various studies has shown ABO

was in 1/10th of newborn that this incompatibility become manifested as HDN

newborns with setting of ABO incompatibility.

Study was performed at the Department of Pediatrics in a Rural Medical

Significant NH in our study is 11%. Mean total bilirubin at postnatal 72 hours

and negative predictive value of 99.4%

Interpretation & Conclusion

In the present study a Negative Predictive Value of 99.4% suggests that in

unlikely to require further evaluation and intervention. These newborns can be

Newborn; Neonate; ABO incompatibility; Hyperbilirubinemia; Jaundice prediction;

SL. NO TOPICS PAGE NO

12 ANNEXURE III – MASTER CHART 74

Sl.No Tables Pages

Study population and Significant Jaundice

Distribution of Neonates according to Sex.

Distribution of Neonates according to Birth weight

Distribution of Neonate according to Blood group

Significant Jaundice in relation to Blood group A&B

8 Sex distribution in Significant Hyperbilirubinemia. 49

Bilirubin, Haemoglobin and PCV profile of the Study

Comparative evaluation of Cord and Postnatal 72hours,

Diagnostic predictability of Cord Blood Bilirubin for

Predictability of Cord Blood Bilirubin for

Comparison of Cord Serum Bilirubin and Significant