"TO STUDY THE EFFECTIVENESS OF CORD

BLOOD ALBUMIN AS A PREDICTOR OF

NEONATAL JAUNDICE”

Submitted by 
Dr. MURALI. S. M. MBBS

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. VENKATAMURTHY. M. MBBS, MD
PROFESSOR

DEPARTMENT OF PEDIATRICS,
ADICHUNCHANAGIRI INSTITUTE OF MEDICAL SCIENCES,
B.G. NAGARA, NAGAMANGALA TALUK, MANDYA DIST. KARNATAKA

2014

i
 RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES,

KARNATAKA, BANGALORE

DECLARATION BY THE CANDIDATE

I hereby declare that this dissertation/thesis entitled “TO STUDY THE

EFFECTIVENESS OF CORD BLOOD ALBUMIN AS A PREDICTOR OF

NEONATAL JAUNDICE” is a bonafide and genuine research work carried out by

me under the guidance of Dr. VENKATAMURTHY. M. MBBS, MD, Professor,

Department of Pediatrics, Adichunchanagiri Institute of Medical Sciences, B.G.

Nagara, Nagamangala Taluk, Mandya District, Karnataka.

I submit this dissertation to Rajiv Gandhi University of Health Sciences,

Bangalore, Karnataka, in partial fulfillment of the regulation for the award of the

degree of Doctor of Medicine in Pediatrics.

This dissertation has not been submitted to any other University for the award

of any degree or diploma.

ii
RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES,
KARNATAKA, BANGALORE

CERTIFICATE BY THE GUIDE

This is to certify that this dissertation titled “TO STUDY THE

EFFECTIVENESS OF CORD BLOOD ALBUMIN AS A PREDICTOR OF

NEONATAL JAUNDICE” is a bonafide research work done by Dr. MURALI.

S.M., Postgraduate student, Department of Pediatrics, Adichunchanagiri Institute of

Medical Sciences, B.G. Nagara, Nagamangala Taluk, Mandya District, Karnataka, in

partial fulfillment of the requirement for the degree of Doctor of Medicine in

Pediatrics.

iii
RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES,
KARNATAKA, BANGALORE

ENDORSEMENT BY THE HOD, PRINCIPAL/HEAD OF

THE INSTITUTION

This is to certify that this dissertation entitled “TO STUDY THE

EFFECTIVENESS OF CORD BLOOD ALBUMIN AS A PREDICTOR OF

NEONATAL JAUNDICE” is a bonafide research work done by Dr. MURALI.

S.M., Postgraduate Student in Pediatrics, Adichunchanagiri Institute of Medical

Sciences, B.G. Nagara, Mandya Disrtict, Karnataka, under the guidance of

Dr. VENKATAMURTHY. M. MBBS, MD., Professor, Department of Pediatrics,

Adichunchanagiri Institute of Medical Sciences, B.G. Nagara, Mandya District.

Karnataka, in partial fulfillment of the requirement for the degree of Doctor of

Medicine in Pediatrics.

iv
RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES,
KARNATAKA, BANGALORE

COPYRIGHT

DECLARATION BY THE CANDIDATE

I hereby declare that the Rajiv Gandhi University of Health Sciences,

Karnataka, shall have all rights to preserve, use and disseminate this

dissertation/thesis in print or electronic format for the academic/ research purpose.

© Rajiv Gandhi University of Health Sciences, Karnataka, Bangalore

v
 ACKNOWLEDGEMENT

With great reverence, I extend my deep sense of gratitude to my respected

guide and teacher Dr. VENKATAMURTHY. M. MD, Professor, Department of

Pediatrics, Adichunchanagiri Institute of Medical Sciences, B.G. Nagara, for his

advice and able guidance, constant inspiration, constructive criticism and novel

sugesstions, without whose initiative and enthusiasm, this study would not have been

completed.

I also extend my sincere thanks to Dr. SHIVAPRAKASH N.C. MD, Professor

and Head, Department of Pediatrics, Adichunchanagiri Institute of Medical Sciences,

B.G. Nagara, for his valuable guidance, encouragement and suggestion during this

dissertation.

I extend my sincere thanks to Dr. NISARGA. R. MD, Professor, Department of

Pediatrics, Adichunchanagiri Institute of Medical Sciences, B.G. Nagara, for his

valuable guidance, encouragement and suggestion during this dissertation.

I sincerely thank Dr. VIJAYADEVA. MD Former Professor of Pediatrics,

Adichunchanagiri Institute of Medical Sciences, B.G. Nagara. Who had guided me

directly or indirectly during the study.

I extend my sincere thanks to Dr. SIDDARAJU.M.L. MD, Professor,

Department of Pediatrics, Adichunchanagiri Institute of Medical Sciences, B.G.

Nagara, for his valuable guidance, encouragement and suggestion during this

dissertation.

vi
 I would like to thank Dr M.G. SHIVARAMU. MD, THE PRINCIPAL,

Adichunchanagiri Institute of Medical Sciences, B.G. Nagara, for permitting me to

utilize the college and hospital facilities for the study.

I also sincerely thank Dr. SUGUNA. S, Dr. SUNILKUMAR. P, Dr.

HARICHARAN, and Dr. VIJAYKUMAR, for their constant encouragement and

guidance.

I would like to thank Dr. SWETHA.S.RAO, Dr. RANJIT BABY JOSEPH,

Dr. HEMACHANDRA REDDY, Dr. SHINY VEETUS and Dr. RACHANA.G,

my colleague for his/her support and encouragement.

I thank my fellow postgraduates Dr. UDAY SHANKAR, Dr.

RAGAVENDRA, Dr. VENUGOPAL, Dr. SUMAN FATIMA, Dr. SWETHA

AGARWAL, and Dr. MAMATHA. S, for their help and suggestions during this

work.

I thank Dr. K.P. Suresh, Scientist (Biostatistics) for his valuable support in the

statistical analysis.

I will be failing in my duty, if I do not express my gratitude to all those

newborns and parents who gave consent to be subjects of this study.

Finally, I would like to thank Almighty God, my parents and family members,

whose constant blessings, inspiration and support have been with me always.

vii
 LIST OF ABBREVIATIONS USED

ATP → Adenosine Tri Phosphate

BEAR → Brain Evoked Auditory Response

CB → Conjugated Bilirubin

CPD → Citrate Phosphate Dextrose

CS → Caesarean Section

CSA → Cord Serum Albumin

DCT → Direct Coomb Test

DIC → Disseminated Intra Vascular Coagulation

ExT → Exchange Transfusion

ETCOc → End Tidal Carbon Monoxide

G6PD → Glucose-6-Phosphate Dehydrogenase

ICT → Indirect Coomb Test

NH → Neonatal Hyperbilirubinemia.

PT → Phototherapy.

RBC → Red Blood Cell

TcB → Trans Cutaneous Bilirubin

TSB → Total Serum Bilirubin

UCB → Unconjugated Bilirubin

UDPG-T → Uridine Di Phosphate Glucuronyl Transferase

VD → Vaginal Delivery

NPV → Negative Predictive value.

PPV → Positive predictive value.

viii
 ABSTRACT

BACKGROUND

Neonatal Hyperbilirubinemia (NH) is commonest abnormal physical finding

during the first week of life. NH affects nearly 60% of term and 80% of preterm

neonates during first week of life. Early discharge of healthy term newborns has

become a common practice, because of medical reasons like prevention of nosocomial

infections, social reasons like in early naming ceremony, and also due to economical

constrains. In significant number (6.5%) of newborns, Neonatal Hyperbilirubinemia

(NH) is the most common cause for readmission during the early neonatal period.

There are reports of bilirubin induced brain damage occurred in healthy term infants

even without hemolysis and the sequalae could be serious.

OBJECTIVE

To predict the development of Neonatal Hyperbilirubinemia at birth using

Cord Serum Albumin as a risk indicator.

METHOD

Observation study was performed on 174 healthy term newborns. Cord blood

was collected from the healthy term newborns delivered either vaginally or cesarean

section for cord serum albumin level measurements. Total serum bilirubin and direct

serum bilirubin were measured during 72-96 hours of life with serum sampling of

peripheral venous blood. Newborn was assessed clinically daily for Neonatal

Hyperbilirubinemia or for any other complication during the study period.

ix
RESULT

Study cohort is grouped into Group1, Group2 and Group 3 based on Cord

Serum Albumin level ≤ 2.8g/dl, 2.9-3.3g/dl and ≥ 3.4g/dl, respectively. In these

groups, newborns with total serum bilirubin level ≥17mg/dl after 72 hours are taken

as Neonatal Hyperbilirubinemia, requiring interventions like phototherapy or

exchange transfusion. Statistical analysis done for correlation of cord serum albumin

with neonatal hyperbilirubinemia. It showed that cord serum albumin level ≤ 2.8g/dl

is critical, as it was seen in 95% (sensitivity) of newborn who developed neonatal

hyperbilirubinemia. In cord serum albumin group ≥ 3.4g/dl, none of the newborn

developed neonatal hyperbilirubinemia.

CONCLUSION

There is a correlation between Cord serum albumin level and neonatal

hyperbilirubinemia in healthy term newborns. Cord serum albumin level of ≤2.8 g/dl

can predict the development of neonatal hyperbilirubinemia.

KEYWORDS : Cord Serum Albumin, Neonatal Hyperbilirubinemia, Prediction and

Newborns.

x
 TABLE OF CONTENTS

Sl No. TITLE PAGE No.

1. INTRODUCTION 1-2

2. AIMS AND OBJECTIVES 3

3. REVIEW OF LITERATURE 4-41

4. METHODOLOGY 42-45

5. RESULTS AND OBSERVATIONS 46-67

6. DISCUSSION 68-74

7. CONCLUSION 75-77

8. SUMMARY 78-79

9. BIBLIOGRAPHY 80-86

10. ANNEXURE 87-100

• PROFORMA 87-88

• SATISTICAL METHODS 89-93

• KEY TO MASTER CHART 94

• MASTER CHART 95-100

xi
 LIST OF TABLES

Sl No. Tables Page No.

1. Kramer’s Dermal staining for clinical assessment of jaundice 21

2. Gender distribution of newborns 46

3. Mode of delivery 47

4. Maternal weight 48

5. Oxytocin administration in mother 49

6. Maternal blood group 50

7. Birth weight (kg) distribution in study group 51

8. Grouped based on Cord Serum Albumin (g/dl) level. 52

9. Distribution of Newborn Blood Group in the study 53

10. Distribution of Total Serum Bilirubin (mg/dl) of newborn 54

studied

11. Distribution of Phototherapy requirement for Neonatal 55

Hyperbilirubinemia in the study.

12. Need for Exchange Transfusion in the study 56

13. Comparision table of Gender distribution and Cord Serum 57

Albumin level.

14. Comparison of birth weight with cord serum albumin level. 58

15. Comparison of Maternal weight with Cord serum albumin 59

level.

16. Comparision of oxytocin administration in mothers with cord 60

serum albumin level

17. Comparison of Need for Phototherapy with Cord Serum 61

Albumin level

18. Comparison of Need for Exchange Transfusion with Cord 62

Serum Albumin level.

19. Correlation of Clinical Variable with Need for Phototherapy. 63

20. Diagnostic Predictability of Cord Serum Albumin levels for 67

Neonatal Hyperbilirubinemia..

xii
21. Comparison of Gender Predilection for Neonatal 69
Hyperbilirubinemia outcome in other studies.

22. Comparison of Mode of delivery with Neonatal 70

Hyperbilirubinemia outcome in other studies.

23. Comparison of Incidence of NH with other Studies. 72

24. Comparison of CSA level as risk indicator for NH in other 73

studies.

xiii
 LIST OF FIGURES

Sl No. Figures Page No.

1. Bilirubin metabolism 9

2. Schematic approach to the diagnosis of neonatal jaundice 23

Guidelines for phototherapy in hospitalized infants of 35 or
3. 25
more weeks’ gestation
Guidelines for exchange transfusion in hospitalized infants of
4. 26
35 or more weeks’ gestation

5. Important factors in efficacy of phototherapy. 31

Risk designation of term and near-term well newborns based
6. 39
on their hour-specific serum bilirubin values.
Autoanalyser Machine used for cord serum albumin
7. 44
estimation.

8. Anitsera for identification of blood group. 45

xiv
 LIST OF GRAPHS

Sl No. Figures Page No.

1. Gender distribution of newborns 46
2. Distribution of Mode of delivery in Study cohort 47
3. Distribution of Maternal Weight in the present Study. 48
4. Oxytocin administered to Mothers in the study cohort. 49
5. Distribution of Maternal Blood Group in Study Cohort. 50
6. Distribution of Birth weight of Newborn in the Study cohort. 51
7. Cord Serum Albumin levels in the Study Groups. 52
8. Distribution of Newborn Blood Group in Study Cohort. 53
9. Distribution of TSB estimated in postnatal life. 54
10. Neonatal Hyperbilirubinemia Treated with Phototherapy. 55
11. Need for Exchange Transfusion in Study Cohort. 56
Comparison of Gender distribution and CSA level in Study
12. 57
cohort.
13. Comparison of Birth weight of newborn with CSA level. 58
14. Correlation of Maternal weight with CSA levels in Neonates. 59
Correlation of oxytocin administration in mother with cord
15. 60
serum albumin level in neonates.
16. Correlation of CSA level with NH requiring PT. 62
17. Correlation of CSA level and NH requiring ExT. 64
18. Correlation of NH requiring PT with Gender Predilection. 64
Correlation of NH requiring PT with Mode of Delivery in this
19. 65
Study
Correlation of NH requiring PT with oxytocin use for
20. 65
induction of labour.

Correlation of NH requiring PT with CSA level estimated at

21. 65
birth.
Correlation of NH requiring PT with ABO incompatibility in
22. 66
the Study Cohort.

CSA level as a Risk factor to Predict NH

23. 67

xv
 INTRODUCTION

Neonatal Hyperbilirubinemia (NH) is commonest abnormal physical finding

during the first week of life. Over two third of newborn babies develop clinical

jaundice. The physical finding like yellowish discoloration of the skin and sclera in

newborns is due to accumulation of unconjugated bilirubin. In most infants,

unconjugated hyperbilirubinemia reflects a normal physiological phenomenon.1

NH affects nearly 60% of term and 80% of preterm neonates during first week

of life. 6.1% of well term newborn have a serum bilirubin over 12.9 mg%. Serum

bilirubin over 15 mg% is found in 3% of normal term newborns. Neonatal

Hyperbilirubinemia (NH) is a cause of concern for the parents as well as for the

pediatricians.4

Early discharge of healthy term newborns after normal vaginal delivery has

become a common practice, because of medical reasons like prevention of nosocomial

infections, social reasons like in early naming ceremony, and also due to economical

constrains.

In significant number (6.5%) of babies, Neonatal Hyperbilirubinemia (NH) is

the most common cause for readmission during the early neonatal period.2 Up to 4%

of term newborns who are readmitted to the hospital during their first week of life,

approximately 85% are for jaundice.3

American Academy of pediatrics recommends that newborn discharged with

in 48 hours should have a follow-up visit after 48 to 72 hours for any significant

jaundice and other problems.5

1
 This recommendation is not appropriate for our country due to limited follow-

up facilities in the community. These babies may develop jaundice which may be over

looked or delay in recognition, unless the baby is closely monitored.

Concern of pediatrician regarding the early discharge are reports of bilirubin

induced brain damage occurred in healthy term infants even without hemolysis. The

sequalae could be serious as it may results in cerebral palsy, sensorineural deafness

and mental retardation.6,7.

NH recognition, follow-up, early treatment and prevention of bilirubin

induced encephalopathy has become more difficult as a result of earlier discharge

from the hospital. The treatment of severe NH by exchange transfusion is costly. It is

associated with complications, time consuming and requires skilled manpower. Early

treatment of jaundice with phototherapy is effective, simple and cheap.

Developing countries like India must be fully aware of this limitation on the

development of neonatal care, particularly neonatal intensive care. The ultimate aim

should be to benefit maximum number of newborn babies with cost effective

treatment protocol.

The concept of prediction offers an attractive option to pick up babies at risk

of neonatal hyperbilirubinemia. Physical examination is not a reliable measure of the

serum bilirubin.

By predicting the newborns at risk for significant NH early at birth, we can

design and implement the follow-up programme in these risk groups, cost effectively.

2
 OBJECTIVE OF THE STUDY

The present study is conducted to find out critical value of Cord Serum

albumin in predicting the subsequent development of significant neonatal

hyperbilirubinemia requiring interventions like phototherapy or exchange transfusion.

Thus the aim of the present study includes:

1. To study the association between various levels of cord serum albumin (CSA) and

significant neonatal hyperbilirubinemia requiring interventions like phototherapy

or exchange transfusion.

2. To predict the proportion of new born requiring intervention for NH

(phototherapy or exchange transfusion) based on cord serum albumin level at

birth.

3
 REVIEW OF LITERATURE

A. History Review

Jaundice is a well known clinical entity in the Indian Medicine (Ayurveda).

Since the Vedic Era (1500 BC – 800 BC) this disease has been described. Jaundice

has been mentioned among diseases in Atharvaveda. Ayurveda is based on “Tridosha

theory of disease” – Vata (wind), Pitta (gall) and Kapha (mucus). Charaka Samhita

(200AD) described one of the first references to skin icterus. Jaundice (kamale) is a

specific condition, which arises due to aggravation of bile.

Greek Medicine was based on four humors – phlegm, yellow bile, blood and

black bile. Hippocrates (460-370 BC) “Father of Medicine” – made frequent

references to jaundice as a serious disease.8

Word “bile” is derived from latin bilis (“bile”).9

Word ‘Bilirubin’ and ‘Biliverdin’- means “red bile” and “green bile” in Latin.

Icterus derived from Greek “iketros”, meaning “yellow colored”, a word

applied to a yellow bird as well.

Word ‘Jaundice’- derived from Old French jaundice, a word rooted in the

Latin galbinus, meaning “greenish yellow”, from galbus (“yellow”).9

The first reference to jaundice in newborns is from a book published in the

mid 15th century by Mettlinger, Germany entitled “Ein Regiment Der Jungenlannder”

[Aurberg – 1473].13

In 1654, Panaroli reported apparent case of hemolytic disease of the

newborn.10

4
 Erythroblastosis fetalis may well have been described in 1609 in France, a

report by a midwife named Bourgeois described an hydropic infant girl died 15 min

after birth with severe jaundice of the placenta and blood.11

Juncker in 1724, speaks of true jaundice “the icteric tinge which may be

observed in infants, immediately after birth” The latter, he says, is of no account and

disappears spontaneously after the meconium is passed.12

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 infants.

The first case was Baumes’ own daughter, Justine. He believed that delayed

meconium passage was a primary cause of neonatal jaundice, and espoused breast

milk, particularly colostrum, from the infant’s own mother as the best remedy for this

problem.14

Dewees writes in his 1825 American text book “Jaundice in the newborn

infant is but too often fatal, with whatever property or energy we may attempt to

relieve it”.15

In 1847 Virchow isolated bilirubin crystals from hematomas and suggested

that bilirubin was derived from blood.16

The relationship between the clinical encephalopathy associated with elevated

serum bilirubin concentration and gross pathological changes seen as yellow staining

of specific areas of the CNS was observed and described by Orth in 1875. Orth is an

assistant to Virchow. His article, primarily focused on pigment crystals in various

organs.17

5
 In the first edition of Holt’s “The diseases of Infancy and Childhood”

published in 1897, the clinical description of physiologic jaundice is entirely

compatible with modern concepts.18

In 1903, Schmorl coined the term ‘Kernikterus (Jaundice of the nuclei)’ and

described the pathology of the jaundice in the brain.19

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).9

The first use of the term “Erythroblastosis fetalis” was by Rautmann in 1912

in reference to an hydropic still born.20 Halban in 1900 suggested that

isoimmunization of the mother could be basis of erythroblastosis.21 Ottenberg in 1923

proposed that feto-maternal transfusion was etiologically responsible.22 Later, Levine

and Colleagues in 1941, demonstrated the role of Rh antibodies in the etiology of

erythroblastosis fetalis.23

In 1913, Yllpo demonstrated that the newborn had an elevated serum bilirubin

concentration.24

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.9

6
 In 1932, Diamond and Colleagues found that generalized edema of the fetus,

icterus gravis and congenital anemia of the newborn were in fact all part of a single

condition, which they termed Erythroblastosis fetalis.25

In 1939, Landsteiner and Weiner, Levine and Stetson demonstrated the

serological basis of maternal fetal blood group incompatibility and the identification

of the Rh system of antigens.26

In 1944, Halbrecht coined the term “Icterus Precox” for jaundice developed

within 24 hours of birth.27

In 1952, Crigler and Najjar described Congenital familial nonhemolytic

jaundice with Kernicterus.28

The first exchange transfusion in a newborn was performed in 1925 by Hart

for treatment of erythroblastosis fetalis29 and in 1946, Wallerstein reported the

successful exchange transfusion of three infants with erythroblastosis fetalis.30

Cremer and Colleagues in 1958, observed the effect of sunlight on the serum

bilirubin level of premature infant nursed outdoors, prompted the first use of a ‘Cradle

illumination machine’.31

B. Fetal bilirubin metabolism

Most unconjugated bilirubin formed by the fetus is cleared by the placenta into

the maternal circulation. Formation of conjugated bilirubin is limited in the fetus

because of decreased fetal hepatic blood flow, decreased hepatic ligandin and

decreased UDPG-T activity. Uridine diphosphoglucuronyl transferase (UDPGT) is

detectable at 18 – 20 weeks. UDPGT levels in full term and preterm neonates are

7
usually less than 0.1% of adult values. Adult value of this enzyme activity is

demonstrable only by 6–14 weeks of postnatal life.32

Bilirubin is detected in normal amniotic fluid as early as 12 weeks of

gestation, but usually disappears by 36- 37 weeks.4

During the neonatal period, metabolism of bilirubin is in transition from the

fetal 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.33

C. Neonatal Bilirubin metabolism

Jaundice is the commonest abnormal physical finding during first week of life.

Sources of bilirubin4

Bilirubin is derived from the breakdown of heme containing protein in the

reticuloendothelial system.

1. The major heme containing protein is red blood cell hemoglobin. This is the

source of 75% of all bilirubin production.

2. The other 25% of bilirubin is called early labeled bilirubin. It is derived from

hemoglobin released by ineffective erythropoiesis in the bone marrow, from other

heme containing proteins in tissues (ex: myoglobin, cytochromes, catalase,

peroxidase) and from free heme.

8
 Stool-Stercobilinogen.

Fig 1: Bilirubin Metabolism40

9
Bilirubin Metabolism4

The conversion of heme to bilirubin requires two closely linked enzymatic

steps.

Bilirubin synthesis

1st step is conversion of heme to a linear tetrapyrrole biliverdin ,1 molecule of

ferrous ion and 1 mol of carbonmonoxide is released by enzyme Heme oxygenase. It

is the rate limiting step and upregulated during hemolysis.34

2nd step of bilirubin synthesis involves Biliverdin reductase found in cystosol

of most cells. Biliverdin is converted to Bilirubin.34

Bilirubin transport in the plasma

Bilirubin in plasma is tightly bound to serum albumin, usually does not enter

the central nervous system and is thought to be nontoxic.4

Bilirubin uptake4

Non polar, fat, soluble bilirubin (dissociated from albumin) crosses the

hepatocyte plasma membrane and is bound mainly to cytoplasmic ligandin (Y

protein) for transport to the smooth endoplasmic reticulum. Phenobarbital increases

the concentration of ligandin.

Bilirubin conjugation4

Unconjugated bilirubin (UCB) is converted to water soluble conjugated

(direct) bilirubin (CB) in the smooth endoplasmic reticulum by uridine diphosphate

glucuronyl transferase (UDPG-T). This enzyme is inducible by phenobarbital and

catalyzes the formation of bilirubin monoglucuronide. Both mono and diglucuronide

10
forms of conjugated bilirubin are able to be excreted into the bile canaliculi against a

concentration gradient.

Bilirubin excretion

Conjugated bilirubin in the biliary tree enters the gastrointestinal tract and is

thus eliminated from the body in the stool, which contains large amount of bilirubin.

Excretion is considered to be the rate limiting step of overall bilirubin clearance from

the plasma.4

Enterohepatic circulation of bilirubin

Conjugated bilirubin is not normally reabsorbed from the bowel unless it is

converted back to unconjugated bilirubin by the intestinal enzyme β-glucuronidase.

Intestinal bacteria can prevent the enterohepatic circulation by converting the

conjugated bilirubin to urobilinoids, which are not substrates of β-glucuronidase.4

Albumin Metabolism and its role in Neonatal Hyperbilirubinemia

Albumin (69 kDa) is the major protein of human plasma and makes up

approximately 60% of the total plasma protein. About 40% of albumin is present in

the plasma, and the other 60% is present in the extracellular space. Albumin is

initially synthesized as a preproprotein. Its signal peptide is removed as it passes

into the cisternae of the rough endoplasmic reticulum, and a hexapeptide at the

resulting amino terminal is subsequently cleaved off farther along the secretory

pathway.35

It has been long known that animal and human fetuses are capable of

endogenous albumin synthesis from early pregnancy onwards. All albumin in the

11
fetus is from fetal origin because albumin does not cross the hemochorial placenta as

shown in the rat, guinea pig, and the in vitro dually perfused human placenta.36

Synthesis of albumin appears at approximately the 7th-8th wk in the human

fetus and increases in inverse proportion to that of α-fetoprotein, which is the

dominant fetal protein. Albumin concentrations are low in a neonate (‫׽‬2.5 g/dL),

reaching adult levels (‫׽‬3.5 g/dL) after several months.33

Albumin constitutes 70 – 75% of Plasma oncotic pressure. Albumin has been

described as “the body’s tramp steamer, shuttling cargo of various kinds between

ports of call”. Its load includes bilirubin, cysteine, free fatty acids, calcium, and drugs.

Another important function of albumin is its antioxidant property.36

Serum albumin is frequently utilized as an index of the hepatocyte’s ability to

carry out synthetic function. Because the half-life of albumin is 19–21 days, serum

albumin may not reflect acute changes in liver synthetic ability.38

Little data is available regarding reference ranges for serum albumin

concentrations in preterm and term infants. Lower Normal limit for serum albumin in

12
term babies is 2.8gm/dl.37 And Mean serum albumin level at term is 3.1gm/dl.38

Hence the normal range of Serum albumin at term is 3.1±3g./dl.

In general, postnatal albumin concentrations follow the gestational trend and

increase with gestational age. Considering the functions of albumin, which include

acting as an antioxidant and transporting bilirubin and free fatty acids.38

During intrauterine life, oxygen tension in blood is low, thereby generating

only low amounts of radicals, which could damage albumin. The low oxygen tension

is compensated for by the increased oxygen affinity of fetal hemoglobin. After birth,

fetal hemoglobin is rapidly broken down, thereby releasing large amounts of bilirubin

that should be transported off by albumin. Also, during the beginning of the third

trimester, fatty acid concentrations are low and will be of no burden to albumin. The

surge in albumin synthesis would therefore be expected just before term birth, as a

preparation against an elevated radical exposure and for a higher transport load

consisting of hemoglobin breakdown products and fatty acids, the latter found in high

amounts in postnatal nutrition (breast milk).36

Bilirubin binds to albumin in an equimolar ratio. Free bilirubin is anticipated

when the molar bilirubin- to- albumin (B: A) ratio is > 0.8. Around 8.5mg of bilirubin

will bind tightly to 1 g of albumin.4

It is the free bilirubin which can cross the blood brain barrier. There are no

precise data to correlate a specific bilirubin value or albumin value with

neurotoxicity.4

D. Etiology of hyperbilirubinemia in newborn

13
 Any process that increases the production or impairs the elimination of

bilirubin can exacerbate the normally occurring physiologic jaundice in newborn.

Etiology

I. Physiologic jaundice4

a. Increased bilirubin production due to

• Increased RBC volume per kilogram and decreased RBC survival (90 days

versus 120 days) in infants.

• Increased ineffective erythropoiesis and increased turnover of non

hemoglobin heme proteins.

b. Increased enterohepatic circulation due to high levels of intestinal β-

glucuronidase enzyme, decreased intestinal bacteria, decreased gut motility.

c. Defective uptake of bilirubin from plasma due to decreased ligandin and binding

of ligandin by other anions.

d. Defective conjugation due to decreased UDPG-T activity.

e. Decreased hepatic excretion of bilirubin.

II. Non Physiologic Jaundice4

a. Over production

• Feto maternal blood group incompatibility.

• Hereditary Spherocytosis, Elliptocytosis, Stomatocytosis.

• Nonspherocytic hemolytic anemias.

• G6 PD deficiency and drugs.

• Pyruvate kinase deficiency.

• Other red cell enzyme deficiencies

• α - Thalassemia

14
 • δ - β-Thalassemia

• Acquired hemolysis due to vitamin K, Nitrofurantoin, Sulfonamides,

Antimalarials, Penicillin, Oxytocin, Bupivacaine or Infection.

• Extra vascular blood: Petechiae, hematomas, pulmonary, cerebral or occult

hemorrhage.

• Polycythemia: Fetomaternal or fetofetal transfusion. Delayed clamping of the

umbilical cord.

• Increased enterohepatic circulation

• Pyloric stenosis,

• Intestinal atresia or stenosis including annular pancreas,

• Hirschsprung disease,

• Meconium ileus or Meconium plug syndrome,

• Swallowed blood.

b. Undersecretion

• Metabolic or endocrine conditions

• Galactosemia

• Familial Nonhemolytic jaundice (crigler-Najjar syndrome and Gilbert

syndrome)

• Hypothyroidism

• Tyrosinosis

• Hypermethioninemia

• Drugs and Harmones – Novobiocin, Pregnanediol

• Lucy – Driscoll syndrome

• Infants of diabetic mothers

15
 • Prematurity, Hypopitutarism and Anencephaly.

• Obstructive disorders

• Biliary atresia

• Dubin Johnson and Rotor syndrome

• Choledochal cyst

• Cystic fibrosis (inspissated bile)

• Tumor or band (extrinsic compression)

• Parenteral nutrition

• α1 – antitrypsin deficiency

c. Mixed

• Sepsis

• Intrauterine infections

• Toxoplasmosis

• Rubella

• Herpes simplex

• Syphilis, Hepatitis

• Respiratory distress syndrome

• Asphyxia

• Infant of diabetic mothers

• Severe erythroblastosis fetalis

d. Uncertain mechanism

• Breast milk jaundice

• Chinese, Japanese, Korean and American indian infants.

CAUSES OF JAUNDICE ON THE BASIS OF AGE OF ONSET39

16
Within 24hours 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.

• Enhanced enterohepatic circulation.

• Extra vascular bleed.

• Neonatal hepatitis.

• Hypothyroidism.

• Hypopituitarism.

• Galactosemia..

• Criggler-Najjar syndrome type – II.

17
 • Gilbert disease.

E. Complications of neonatal jaundice

Bilirubin encephalopathy refers to the clinical manifestations of the effects of

bilirubin on the central nervous system, where as kernicterus refers to the

neuropathologic changes that are characterized by pigment deposition in specific

areas of the CNS such as basal ganglia, pons and cerebellum.9

Bilirubin encephalopathy is a multifactorial process that requires a critical

level of free bilirubin, access to the brain across the blood-brain barrier, and presence

of susceptible nerve cells. The severity and duration of hyperbilirubinemia, the

maturity of the structures involved, the binding capacity of albumin, the physiologic

environment, and the cell membrane composition and metabolic state probably all are

critical to the development of neurodysfunction.33

Entry of bilirubin into the brain

The mechanism by which uncojugated bilirubin enters the brain and damages

it is unclear. Several hypotheses regarding entrance of bilirubin into the brain have

been proposed.9

One hypothesis is the lipophilic nature of free bilirubin, in equilibrium with

bound bilirubin, has access to tissues. Thus, any increase in the amount of free

bilirubin or reduction in the amount or binding capacity of albumin could increase the

level of unbound bilirubin within the brain tissue, saturating membranes and causing

precipitation of bilirubin acid within the nerve cell membrane.9

Second hypothesis is based on close examination of the chemical nature of

bilirubin in solution and seeks to explain the increased risk in acidotic infants. In this

18
theory, the rate of tissue uptake of bilirubin depends on both the concentration of

albumin-bound bilirubin and the pH, with low pH enhancing precipitation and tissue

uptake.9

Third theory suggests that bound bilirubin enters the brain mainly through a

damaged blood-brain barrier.9

Recent studies suggest that unconjugated bilirubin is a substrate for

Pglycoprotein (P-gp) and that the blood-brain barrier P-gp may play a role in limiting

the passage of bilirubin into the CNS. P-gp is an ATP – dependent integral plasma

membrane transport protein that translocates a wide range of substrates across

biologic membranes.9

Factors that increase susceptibility to Neurotoxicity associated with

Hyperbilirubinemia

Asphyxia, Hyperthermia, Septicemia, Hypoalbuminemia, Acidosis, Calorie

deprivation, Prolonged Hyperbilirubinemia, Low birth weight, Young gestational age,

Excessive hemolysis.9

Bilirubin toxicity at cellular level9

Four possible mechanisms have been proposed:

• Interruption of normal neurotransmission

• Mitochondrial dysfunction

• Cellular and intracellular membrane impairment

• Interference with enzyme activity

Clinical features4

1. Early : Lethargy, poor feeding, high pitched cry, hypotonia.

19
2. Intermediate : Irritability, opisthonous, seizures, apnea, oculogyric crisis,

hypertonia, retrocollis.

• All infants who survive this phase develop chronic bilirubin encephalopathy

(clinical diagnosis of kernicterus)

3. Advanced phase : Pronounced opisthonous, shrill cry, apnea, seizures, coma and

death.

Chronic bilirubin encephalopathy (kernicterus)

It is marked by athetosis, athetoid cerebral palsy, partial or complete high

frequency sensorineural hearing loss, paralysis of upward gaze, dental dysplasia and

intellectual deficits.4

Predicting Encephalopathy and Reversibility of damage9

Brainstem Evoked Auditory Response- Because auditory pathway of the

newborn is particularly vulnerable to insult from the bilirubin, BEAR testing has been

suggested as a tool that could identify or predict early effects of hyperbilirubinemia.

Studies have shown increased bilirubin concentrations with changes in the amplitude

and latency of these responses. BEAR is accurate and non invasive and assesses the

functional status of the auditory nerve in the brainstem pathway. In a study of 50 full

term infants with moderate hyperbilirubinemia, the latency of BEAR waves lV and V

was longer than in those infants with lower TSB levels (Shapiro and Nakamura,

2001).41 BEAR testing could be used to screen hyperbilirubinemic full-term and

premature infants for sensorineural hearing loss and could be incorporated into the

assessment of need for exchange transfusions (Nwaesei et al, 1984;42 Wennberg et al,

198243).

20
 Infant Cry Analysis - It has been shown that with moderately elevated TSB

levels, there is interference with neural conduction, as demonstrated by the BEAR,

and changes in neural function in adjoining pathways, with resultant effects on the

vocal cords (increased tension on phonation).9

Nuclear Magnetic Resonance Techniques – Nuclear magnetic resonance

(NMR) techniques, both imaging and spectroscopy, have been proposed as a rapid,

noninvasive measure of impending or actual brain cell injury in the face of

hyperbilirubinemia9 (Palmer and Smith, 1990).44

F. Evaluation and diagnosis of neonatal jaundice

NH affects nearly 60% of term and 80% of preterm neonates during first week

of life. 6.1% of well term newborn have a serum bilirubin over 12.9 mg%. Serum

bilirubin over 15 mg% is found in 3% of normal term newborns.

Dermal staining of bilirubin may be used as a clinical guide to assess the level

of jaundice which was described by Kramer.45

The newborn should be examined in good daylight. The skin should be

blanched with digital pressure and the underlying color of skin and subcutaneous

tissue should be noted. A rough guide for level of dermal staining with level of

bilirubin is included in table 1.

Table 1: Kramer’s Dermal staining for clinical assessment of jaundice45

Area of body Level of bilirubin

Face 4-6 mg/ dl

Chest, upper abdomen 8-10 mg/dl

21
 Lower abdomen, thighs 12-14 mg/dl

Arms, lower legs 15-18 mg/dl

Palms, soles 15-20 mg/dl

Dermal staining in newborn progresses in a cephalo-caudal direction. The

Cephalo-caudal progression of jaundice is apparently related to the relative thickness

of skin at various parts, skin being thinnest on the face and extremely thick over the

palms and soles. The skin of premature babies is relatively thinner and therefore

jaundice shows through more readily even at lower serum bilirubin level.1

But Physical examination is not a suitable measure of serum bilirubin

estimation.4

HIGH RISK FACTORS OF JAUNDICE4,39

• 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.

G. APPROACH TO A JAUNDICED NEWBORN.39

• Identify “high risk” newborns at delivery likely to develop Jaundice.

• Ensure appropriate follow up for Jaundice.

22
• 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

• 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.

23
 Fig 2: Schematic approach to the diagnosis of neonatal jaundice33

Criterion for physiological jaundice39

• Type of bilirubin – Indirect bilirubin,

• Direct bilirubin never more than 2mg/dl or less than 15% of total bilirubin,

• Appearance - after 36 hours of age,

• Rate of rise of bilirubin – less than 5mg / dl/day,

• Severity of jaundice – Usually does not exceed 15 mg/dl,

• Natural course – Peak TSB levels seen between 3rd – 5th days of life in term

neonates and 3rd – 7th day in preterm and disappears by 2 weeks.

24
 • Clinical condition – Healthy newborn.

Pathological jaundice is suspected in the newborn with39

• Clinical jaundice in the first 24 hours of life.

• TSB > 15 mg/dl

• Rate of TSB increase > 0.2 mg/dl/hr or 5mg/dl/day.

• Direct serum bilirubin > 2mg/dl or > 15% of total bilirubin

• Clinical jaundice persisting for > 2 weeks.

Guidelines for Phototherapy and Exchange transfusion in hospitalized infants

of 35 or more weeks’ gestation are depicted in Fig. 4 and Fig. 5 respectively. (From

American Academy of Pediatrics Subcommittee on Hyperbilirubinemia: Management

of hyperbilibubinemia in the newborn infant 35 or more weeks of gestation. Pediatrics

2004; 114:297-316).

Fig. 3 : Guidelines for phototherapy in hospitalized infants of 35 or more weeks’

gestation33

• Use total bilirubin. Do not subtract direct reacting or conjugated bilirubin.

25
• Risk factors = isoimmune hemolytic disease, G6PD deficiency, asphyxia,

significant lethargy, temperature instability, sepsis, acidosis, or albumin <3.0 g/dL

(if measured).

• For well infants 35-37 6/7 wk can adjust TSB levels for intervention around the

medium risk line. It is an option to intervene at lower TSB levels for infants closer

to 35 wks and at higher TSB levels for those closer to 37 6/7 wk.

• It is an option to provide conventional phototherapy in hospital or at home at TSB

levels 2-3 mg/dl (35-50mmol/L) below those shown but home phototherapy

should not be used in any infant with risk factors.

Fig. 4: Guidelines for exchange transfusion in hospitalized infants of 35 or more

weeks’ gestation33

• The dashed lines for the first 24 hours indicate uncertainty due to a wide range of

clinical circumstances and a range of responses to phototherapy.

• Immediate exchange transfusion is recommended if infant shows signs of acute

bilirubin encephalopathy (hypertonia, arching, retrocollis, opisthotonos, fever,

high pitched cry) or if TSB is ≥ 5 mg/dl (85 μmol/L) above these lines.

26
• Risk factors – isoimmune hemolytic disease, G6PD deficiency, asphyxia,

significant lethargy, temperature instability, sepsis, acidosis.

• Measure serum albumin and calculate B/A ratio.

• Use total bilirubin. Do not subtract direct reacting or conjugated bilirubin.

• If infant is well and 35-37 6/7 wk (median risk) can individualize TSB levels for

exchange based on actual gestational age.

H. Laboratory Evaluation Of Jaundiced Newborn9

These tests are individualized to a newborn to know the cause for NH. Even

after detailed investigations, the cause of NH remains uncertain in about one-third of

cases. Investigation list as follows:

I. Maternal: Blood grouping and Indirect Coombs Test (ICT) to test for Isoimmune

hemolytic disease, Serology to rule out syphilis.

II. Infant:

• Total serum bilirubin (TSB) and or Transcutaneous bilirubin.

• Blood grouping, Rh typing and Direct coomb test to test for isoimmune hemolytic

disease.

• Hemoglobin and Hematocrit. Anemia suggests hemolytic disease and large

entrapped hemorrhage.

• Polycythemia cause jaundice.

• Reticulocyte count is elevated in hemolytic anemia.

27
• Red cell morphology – By peripheral blood smear

• Red cell fragmentation seen in disseminated intravascular coagulation (DIC)

• Spherocytes suggests ABO incompatibility or Hereditery Spherocytosis.

• Platelet count is decreased in infections.

• White blood cell count less than 50,000 cells/cumm or BNR> 0.2 suggest

infection.

• Urine analysis for reducing substance to diagnose Galactosemia.

• Screening of G6 PD deficiency.

• Serum protein and albumin to estimate albumin binding capacity and reserve

albumin binding site.

• pH

• Protein binding (2,4 hydroxybenzene azobenzoic acid (HABA), Salicylates)

These tests help to measure the quantity of binding of bilirubin in the serum of

jaundice infants.

I. Treatment of Neonatal Hyperbilirubinemia1

The aim of the therapy is to ensure that serum bilirubin is kept at a safe level

and brain damage is prevented. Neonatal Hyperbilirubinemia is a medical emergency

and delay in its management can lead to irreversible brain damage and death.

Reduction of serum bilirubin levels and prevention of neurotoxicity can be

achieved by phototherapy, exchange transfusion and Pharmacotherapy.

Exchange blood transfusion remains the single most effective and reliable

method to lower the bilirubin when it approaches critical levels.

28
 Principles of treatment in Jaundiced neonates according to 2006 IAP NNF

guidelines are:39.

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 (PT) was first introduced in the treatment of neonatal

hyperbilirubinemia in the late 1950s.31

The goal of therapy is to lower the concentration of circulating bilirubin or

keep it from increasing.

PT is widely accepted, relatively safe and effective method for treatment of

neonatal hyperbilirubinemia. Bilirubin absorbs light maximally at 450-460 nm and

light sources with peak emissions in this range lower serum bilirubin levels by several

mechanisms.

Photo oxidation

Photo oxidation of bilirubin into water soluble colorless form of bilirubin is

very slow, ineffective.

Configurational photoisomerization

29
 Here E-isomers (4Z 15E, 4E 15E, 4E 15Z) which are more polar water soluble

diazo negative compounds are produced. E isomers are nontoxic and after 8-12 hours

of phototherapy they constitute about 25% of total serum bilirubin.

Structural isomerization

It is the production of stable water soluble structural isomers of bilirubin like

lumirubin. These photocatabolites are readily excreted in bile, feces and to a lesser

extent in urine. The conversion of bilirubin to lumirubin is irreversible and it cannot

be reabsorbed. It is most important pathway for the lowering of serum bilirubin levels

and strongly related to the dose of phototherapy used in the range of 6 to 12

μw/cm2/nm.

Procedure of phototherapy

The narrow spectral blue light is most effective for phototherapy but it

interferes with proper observation of the infant. White day light fluorescent lamps are

quite effective and commonly used in our country. Blue and white tubes phototherapy

unit are also available.

Nude infant is exposed to a portable or fixed light source kept at 45cm from

the skin. Distance between the baby and phototherapy unit can be reduced to 15-20

cms to provide effective and more intensive phototherapy.

During phototherapy eyes must be shielded to prevent retinal damage and a

diaper should be kept on to cover the genitals. For effective phototherapy, the

30
minimal spectral irradiance or ‘flux’ of 4 to 6 μw/cm2/nm is available and maintained

at the level of the infant’s skin.

CARE OF A NEWBORN RECEIVING PHOTOTHERAPY39

• 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.

31
 Fig 5: Important factors in efficacy of phototherapy.46

Side effects

• Passage of loose green stools because of transient lactose intolerance and irritant

effect of photocatabolites causes increased colonic secretory losses.

• Hyperthermia

• Irritability

• Dehydration

• Flea bite rash on the trunk or extremities

• Risk of opening up to PDA in preterm babies.

• Hypocalcemia due to secretion of melatonin from pineal gland

32
• Bronze baby syndrome – Infants with parenchymal liver disease with biliary

obstruction, due to excessive accumulation of bilifucin (Polymerized form of

lumirubin) imparting brownish discoloration to the skin.

• Theoretically increased risk of skin malignancy later in life.

• Exposure to light may disturb the Circadian rhythm of the sex hormones thus

having potential implications on onset of puberty and disturbances in future sex

behavior.

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

sensitizing antigen.47

Need for exchange transfusion is based on level of unconjugated serum

bilirubin, gestational maturity, postnatal age, existence of or otherwise perinatal

distress factors and the cause of jaundice.4

Choice of blood4

• O Rh negative blood in emergency situations.

• Fresh (<7 days old) type O cells with AB plasma to ensure that no anti A and anti

B antibodies are present.

• In non immune hyperbilirubinemia, blood is typed and cross matched against the

plasma and red cells of the infant. Exchange transfusion usually involve double

the volume of the infant’s blood and is known as a Two volume exchange. [160

ml/kg]. This replaces the 87% of infant’s blood volume with new blood.

33
Technique

b. Exchange transfusion is done by push pull technique through the umbilical vein

inserted only as far as required to permit the free blood exchange.

c. Isovolumetric exchange transfusion –Simultaneously pulling blood out of the

umbilical artery and pushing new blood in the umbilical vein may be better

tolerated in small sick or hydropic infants.

d. Exchange transfusion can be accomplished through central venous pressure line

placed through the anticubital fossa or into the femoral vein through the

saphenous vein and radial artery.

• In push pull method, blood is removed in aliquots that are tolerated by the

infant. Usually 5ml for <1500gms, 10ml for infants 1500-2500gms, 15ml for

2500- 3500gms and 20ml for >3.5kgs.

• The recommended time for the exchange transfusion is 1 hour.

Complications of Exchange transfusion

1. Hypocalcaemia and Hypomagnesemia : The citrated blood used binds ionic

calcium and magnesium.

2. Hypoglycemia : High glucose content of CPD (300mg/dl) stimulates insulin

secretion and causes hypoglycemia 1-2 hours after exchange.

3. Acid base balance : Citrate in CPD blood is metabolized to alkali resulting in late

metabolic alkalosis.

4. Hyperkalemia : Potassium levels may be greatly elevated in stored PRBC’s.

5. Cardiovascular : Perforation of vessels, embolisation, vasospasm, thrombosis,

infarction, arrhythmia, volume overload, arrest.

6. Bleeding : Thrombocytopenia, deficient clotting factors.

34
7. Infections : Bacteremia, hepatitis, CMV, HIV, West Nile virus and malaria.

8. Hemolysis : Hemoglobinemia, hemoglobinuria, and hyperkalemia caused by over

heating of the blood have been reported.

9. Graft-versus-host disease : This is prevented by using irradiated blood.

10. Miscellaneous: Hypothermia, hyperthermia and possibly necrotizing enterocolitis.

Pharmacological management

Phenobarbitone

Barbiturates have been shown to induce the maturation of microsomal

enzymes, ligandin (Y-acceptor protein) and glucuronyl transferase (UDPG-T), thus

improving the uptake, conjugation and excretion of bilirubin by the liver.

Phenobarbitone in a single dose of 10 mg/kg im or 5mg/kg/day in two divided

doses orally for 3 days is indicated in cases of cord serum bilirubin level of > 2.5

mg/dl, early onset of jaundice due to any cause, difficult or instrumental delivery,

Oxytocin induced delivery with bruising and cephalohematoma.

Clofibrate

It is a potent enhancer of glucuronyl transferase. It is more efficacious but it is

slow in its action and takes several days to show the beneficial effect.

Agar

It is a sea weed extensively used in processing of food. In dose of 250mg 6th

hourly orally it binds conjugated bilirubin in the gut and blocks the enterohepatic

circulation. Its use is unpredictable and variable.

Cholestyramine

35
 In dose of 1.5 mg/kg/day in 4 divided doses mixing in milk feeds has been

shown to enhance fecal exertion of bilirubin and thus blocking enterohepatic

circulation. Infant should be watched for constipation – intestinal obstruction and

hypercholeremic acidosis.

Orotic acid

It is a metabolic precursor of uridine diphosphate glucuronic acid and thus

promotes the conjugation of bilirubin. Its ability is limited and cost is prohibitive.

Tin-mesoporphyrin (SnMP)

Metalloporphyrins (Tin and Zinc) are structural analogs of heme and they

inhibit heme oxygenase. It diminishes the production of bile pigments by competitive

inhibition. Heme oxygenase is a rate limiting enzyme in heme metabolism. Tin

mesoporphyrin (6 μmol/kg/single dose IM) has been shown to significantly reduce

bilirubin production. It is associated with high incidence of photosensitive skin

reactions and potential risk of hepatic and renal toxicity.

Albumin infusion

When administered (1 gm/kg), half an hour before exchange transfusion it

facilitates more effective removal of bilirubin and also improves the bilirubin binding

capacity of the baby. Use is avoided in babies with congestive cardiac failure because

of risk of overloading the circulation. Rarely used due to exorbitant cost and risk of

transmission of viral infections.

Inhibiting hemolysis4

IvIg (500-1gm/kg) used to reduce bilirubin levels in infants with Isoimmune

Hemolytic disease. The immunoglobulins act by occupying the Fc receptors of

36
reticuloendothelial cells, there by preventing them from taking up and lysing antibody

coated Red Blood Cells.

Preventive and suggestive measures

• Drugs known to aggravate jaundice or block the bilirubin binding sites on albumin

should be withheld.

• Vitamin K in large doses should be avoided.

• Perinatal distress factors such as hypoxia, acidosis, hypothermia, hypoglycemia

should be prevented or adequately managed.

• Uses of phenolic detergents are avoided in nursery as they may enhance the

jaundice in the babies.

Adequate feeding

Early feeding augments colonization of the gut and reduces the enterohepatic

circulation. Effective evacuation of meconium is associated with elimination of

conjugated bilirubin and stercobilin.

J. Prediction of Neonatal Hyperbilirubinemia.

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.

Of all conditions found to account for readmission to the hospital within first

14 days, hyperbilirubinemia and others like dehydration / failure to thrive are

susceptible to some kind of intervention that might prevent readmission.

37
 In order to reduce hospital cost, most healthy term babies delivered by vaginal

route without any complication are discharged from hospital within 48 hours or less.

These babies may develop neonatal jaundice which may be missed or delay in

recognition if the follow up is not done.

Concern of pediatrician regarding the early discharge are reports of bilirubin

induced brain damage occurred in healthy term infants even without hemolysis. This

is addressed by predicting the newborns developing significant neonatal jaundice

early at birth.

Zakia Nahar et al 2009 carried a study on the value of umbilical cord blood

bilirubin measurement in predicting the development of significant

hyperbilirubinemia in healthy newborn. For this purpose 84 healthy newborn infants

were enrolled and followed up for first 5 days of life. Study subjects were divided into

two groups. Group-I consisted of 71 subjects, who did not develop significant

hyperbilirubinemia (bilirubin <17mg/dl); Group-II consisted of 13 newborns, who

developed significant hyperbilirubinemia (bilirubin >17mg/dl) during the follow up.

Of the enrolled subjects, 46 (55%) were male and rest 38 (45%) were female; 64

(76%) were term babies and 20 (24%) were pre-term babies. Significantly higher

percentage of pre-term babies developed hyperbilirubinemia. ROC (receiver operating

characteristic) analysis demonstrates that the critical value of cord blood bilirubin

>2.5mg/dl had the high sensitivity (77%) and specificity (98.6%) to predict the

newborn who would develop significant hyperbilirubinemia. At this level the negative

predictive value was 96% and positive predictive value 91%.49

In 1977, Risemberg et al. established a correlation between bilirubin levels in

the umbilical cord blood and hyperbilirubinemia in newborns with ABO

38
incompatibility. These researchers concluded that newborns presenting levels higher

than 4 mg/100ml were a group at risk of developing severe hyperbilirubinemia and

should be followed up and reassessed, since all of them presented serum bilirubin

levels that were higher than 16 mg/100ml between 12 and 36 hours of life.50

In 1986, Rosenfeld analyzed a group of 108 full-term newborns according to

their risk of developing severe hyperbilirubinemia and concluded that babies with an

umbilical cord blood bilirubin level of lower than 2 mg/100 ml had a 4% chance of

developing significant jaundice, in comparison with a 25% chance presented by the

ones with levels higher than 2 mg/100ml. In addition, the latter group also presented a

higher chance of needing to undergo phototherapy.51

Similar study done by Sao Paulo et al, showed cord blood bilirubin level of 2.0

mg/dl indicates there is 53% probability of phototherapy required in that baby and as

the cord blood bilirubin level increased the probability of phototherapy requirement in

baby increased.52

Bhutani and colleagues (1999) generated a percentile based bilirubin

nomogram using hour specific pre discharge TSB levels from a racially diverse group

of term healthy newborns with no ABO or Rh incompatibility who did not need

phototherapy before 60 hours of age and of whom 60% were breastfed. Post discharge

TSB levels were measured by a hospital based bilirubin assay within 3 days after

discharge. The risk for significant hyperbilirubinemia (TSB greater than 17 mg/dl) for

infants with a pre-discharge TSB above the 95th percentile (high risk zone) was 57%,

for infants with TSB between the 75th and 95th percentiles (high intermediate risk) it

was 13%, for infants with TSB between the 40th and 75th percentiles (low

39
intermediate risk zone) it was 2.1%, and for infants below 40th percentiles (low risk)

it was 0.

This study showed that universal policy of measuring pre-discharge serum

bilirubin would facilitates targeted intervention, follow-up and also helps to reduce

the potential risk for kernicterus development.53

Fig no 6: Risk designation of term and near-term well newborns based

on their hour-specific serum bilirubin values.
The intermediate at risk zone is subdivided into upper and lower
risk zones by the 75th percentile track. The low-risk zone has
been electively and statistically defined by the 40th percentile.

A similar study done by measuring predischage bilirubin, but by

transcutaneous bilirubinometer (bilicheck) and plotting its value on hour-specific

bilirubin normogram. Transcutaneous bilimeter works on the principle of

computerized spectro-photometery to provide digital display of total bilirubin. During

first week of life, total bilirubin is by and large equivalent to unconjugated bilirubin

for practical purposes. However, transcutaneous bilirubin estimation is not reliable

when serum bilirubin goes above 15mg/dl. Bilicheck values above 75th percentile on

40
hour-specific bilirubin normogram may be considered to be at high risk for

subsequent excessive hyperbilirubinemia.54

A study done by Thomas B Newman et al, combing clinical risk factors with

serum bilirubin levels to predict neonatal jaundice course in new born, showed

significant improved prediction of neonatal jaundice when clinical risk factors are

combined with early total serum bilirubin compared with early total serum bilirubin

alone.48

A study done by David K Stevenson, et al, to predict hyerbilirubinemia, by

measuring End Tidal Carbon monoxide (ETCO), failed to improve the predictive

ability of an hour-specific bilirubin normogram. But the combination of measuring

serum total bilirubin with ETCO as early as around 30 hours of life, helps in

identifying increase bilirubin production (eg: hemolysis) or decrease elimination of

bilirubin (eg: conjugation defect) hence helps in determining early follow-up for

problems like pathological jaundice or late anemia.55

There are limited studies done using either total protein or cord serum albumin

measurement as a risk indicator for predicting significant neonatal

hyperbilirubinemia.

In 2011, Suchanda Sahu, measured cord serum albumin to predict significant

neonatal jaundice. 40 healthy term new borns were included in the study and divided

it into 3 groups based on cord serum albumin level.

Cord Serum albumin level

Group Number of neonates
(g/dl)
Group 1 17 < 2.8

41
 Group 2 15 2.9-3.3

Group 3 8 > 3.4

82% of the newborn in Group 1 developed significant Neonatal

Hyperbilirubinemia, 40% in Group 2, whereas none in Group 3 developed significant

neonatal hyperbilirubinemia. This study concluded that umbilical cord serum albumin

is useful in predicting low or high risk for significant hyperbilirubinemia.56

In 2013, Trivedi et al, studied correlation of cord serum albumin level with

cord serum bilirubin to predict the risk for hyperbilirubinemia in term newborns.

Total of 605 healthy term babies included and were followed up for first 7 days of life

for any development of significant neonatal hyperbilirubinemia. 205(33.88%) babies

developed significant NH. Babies with cord serum bilirubin >2.0mg/dl, 76.3%

developed significant NH in first seven day of the life. Among 205 babies who

developed significant NH, 53.53% babies had cord serum albumin < 2.8g/dl , 28.78%

babies having cord serum albumin in range 2.8-3.5g/dl also developed significant NH.

Whereas 12.68% babies who developed significant NH had cord serum albumin level

>3.5g/dl. This study concluded that cord serum albumin gives additional clue in

visualizing future significant NH.57

42
 METHOD AND MATERIAL

The present study was conducted in Adichunchanagiri Institute of Medical

sciences. The study cohort consists of 174 randomly selected eligible term neonates

delivered at Adichunchanagiri Hospital and Research Center from December 1st 2011

to May 31st 2013.

The study was approved by the Research Ethics Committee of AIMS,

Mandya.

INCLUSION CRITERIA

• Term babies both genders

• Mode of delivery ( normal and c-section)

• Birth weight ≥2.5kg.

• APGAR ≥7/10 at 1 min.

EXCLUSION CRITERIA

• Preterm

• Rh incompatibility.

• Neonatal sepsis.

• Instrumental delivery (forceps and vacuum)

• Birth asphyxia.

• Respiratory distress.

• Meconium stained amniotic fluid.

• Neonatal jaundice within 24 Hours of life.

43
METHOD OF COLLECTION OF DATA

1. An informed consent was obtained from the parents of the newborn before

enrolling them in the study.

2. Demographic profile and relevant information was collected by using structured

Proforma by interviewing the mother and from mother’s case sheet.

3. Gestational age was assessed by New Ballard score (if LMP not sure).

4. Cord Serum Albumin level was estimated at birth.

5. Total Serum Bilirubin (TSB) estimation was done at 72-96 hours of age.

6. All the babies were followed up daily for first 4 postnatal days and babies were

daily assessed for NH and its severity.

LABORATORY INVESTIGATION:

1. Cord blood (2ml) was collected from placental side after its separation and

subjected to investigation:

• Cord Serum Albumin level

2. Venous blood samples were collected from the baby at 72 to 96 hours of life.

These samples were subjected to following investigation

• Total and Direct Serum Bilirubin.

• Blood group analysis.

Laboratory Procedures:

1. Cord blood collected at birth will be analyzed by auto analyzer method (Erba EM

200) for Cord Serum Albumin estimation.

2. Venous blood sample collected was stored away from light. The sample was

refrigerated between 2 -8 degree C till serum bilirubin estimation is done. Serum

44
 bilirubin estimation was done within 12 hours of collection of sample by

Diazotized sulfanilic test.

Principle - Bilirubin reacts with diazotized sulfanilic acid to produce

azobilirubin which is quantified by spectrometry. Both direct and indirect bilirubin

couple with diazo in the presence of cetremide. The terms ‘direct’ and ‘indirect’ are

approximately equivalent to conjugated and unconjugated fractions.

3. Blood group of newborn analyzed by antisera method.

Principle: The red cells contain different types of agglutinogens (antigens) and

plasma contains agglutinins(antibodies). The red cells of the subject are allowed to

react with commercially made agglutinins (anti sera). The presence or absence of

clumping of red cells in different agglutinins determines the blood groups.

Fig 7: Autoanalyser Erba EM 200 Machine used for cord serum albumin estimation.

45
 Fig 8: Antisera bottles with slides showing A+ Blood group of neonate.

Inference:

The main outcome of the study was inferred in terms of neonatal

hyperbilirubinemia.

Serum bilirubin ≥17 mg/dl after 72 hours of life was taken as

hyperbilirubinemia and treatment is advised, as per the American academy of

pediatrics practice parameter, 2004.

IAP-NNF also recommends considering Phototherapy with neonatal serum

bilirubin levels of ≥17mg/dl after 72 hours of life.

So in the present study newborn with Total serum bilirubin level of ≥17mg/dl

are considered hyperbilirubinemia and needs intervention (like Phototherapy or

Exchange Transfusion) after 72 hours of postnatal life.

46
 RESULTS
The study was conducted on total of 174 newborns after obtaining a written

consent from the parents. Proforma was filled for each newborn. And the data were

analyzed using appropriate statistical software like namely SAS 9.2, SPSS 15.0, Stata

10.1, MedCalc 9.0.1 ,Systat 12.0 and R environment ver.2.11.1.

Table 2: Gender distribution of newborns

Gender No. of patients %

Male 98 56.3

Female 76 43.7

Total 174 100.0

Graph 1: Gender distribution of newborns

This table shows the gender distribution of newborn in the study group; 98

(56.3%) were male and 76(43.7%) were female newborns.

47
Table 3: Mode of delivery

Mode of delivery No. of patients %

Ceserian Section 51 29.3

Vaginal route 123 70.7

Total 174 100.0

Graph 2: Distribution of Mode of delivery in Study cohort

Above table shows the mode of delivery in the study group. Majority of the

newborn in the study group were delivered by vaginal route which constitutes 123 out

of 174, i.e 70.7%.

48
Table 4: Maternal weight

Maternal
No. of patients %
weight
50-60 kg 27 15.5

60-70 kg 76 43.7

70-80 kg 57 32.8

>80 kg 14 8.0

Total 174 100.0

Graph 3: Distribution of Maternal Weight in the present Study.

Maternal weight document in last trimester or just before delivery was

collected from case sheet. Maternal weight in the study group is concentrated between

60-70kg (43.7%) and 70-80kg (32.8%).

49
Table 5: Oxytocin administration in mother.

Oxytocin
No. of patients %
administration
No 69 39.7

Yes 105 60.3

Total 174 100.0

Graph 4: Oxytocin administered to Mothers in the study cohort.

Oxytocin drug were administered in 105 out of 174 deliveries. Oxytocin drug

usage in this study constitutes to 60.3%.

50
Table 6: Maternal blood group

Maternal
No. of patients %
blood group
A 33 19.0

B 34 19.5

AB 8 4.6

O 99 56.9

Total 174 100.0

Graph 5: Distribution of Maternal Blood Group in Study Cohort.

This table shows the distribution of maternal blood group. Majority (56.9%) of

Mother belonged to O positive blood group.

51
Table 7: Birth weight (kg) distribution in study group

Birth weight
No. of patients %
(kg)
2.5-3.0 120 68.9

3.0-3.5 47 27.1

>3.5 7 4.0

Total 174 100.0

Graph 6: Distribution of Birth weight of Newborn in the Study cohort.

This table shows distribution of birth weight among the studied newborns.

<2.5kg birth weight babies were excluded. And among the study group 68.9%

(n=120) newborns had birth weight between 2.5-3.0 kg. Mean birth weight among the

study cohort is 2.916 kg.

52
Table 8: Grouped based on Cord Serum Albumin (g/dl) level.

Cord Serum
No. of patients %
Albumin (g/dl)
≤ 2.8
81 46.6
(Group 1)
2.9-3.3
53 30.5
(Group 2)
≥ 3.4
40 23.0
(Group 3)
Total 174 100.0

Graph 7: Cord Serum Albumin levels in the Study Groups.

This table shows the distribution of study cohort into groups based on cord

albumin level measured at birth.

Group 1 consists of 81 newborns constituting to 46.6% of the study cohort. Whereas

Group 2 consists of 53 newborns (30.5%) and Group 3 consists of 40 newborns (23%)

of study cohort.

53
Table 9: Distribution of Newborn Blood Group in the study.

Baby Blood
No. of patients %
Group
A+ 28 16.1

B+ 35 20.1

AB+ 5 2.9

O+ 105 60.3

O- 1 0.6

Total 174 100.0

Graph 8: Distribution of Newborn Blood Group in Study Cohort.

This table shows the distribution of the newborn blood group. Most of the

newborn belong to O positive, which results to 60.3% of study cohort. Second most

common blood group in this study cohort was B positive (20.1%). ABO

incompatibility was seen in 4 newborns of the study group.

54
Table 10: Distribution of Total Serum Bilirubin (mg/dl) of neonate studied

Total Serum
Bilirubin No. of patients %
(mg/dl)
≤10 7 4.0

10-14 133 76.4

15-17 14 8.0

≥17 20 11.5

Total 174 100.0

Graph 9: Distribution of TSB estimated in postnatal life.

This table shows the distribution of Total Serum Bilirubin level estimated at

72-96 hours of postnatal life in the study cohort. 20 out of 174 newborn developed

NH.

55
Table 11: Distribution of Phototherapy requirement for Neonatal

Hyperbilirubinemia in the study.

Phototherapy No. of patients %

No 154 88.5

Yes 20 11.5

Total 174 100.0

Graph 10: Neonatal Hyperbilirubinemia Treated with Phototherapy.

This table shows the newborn in the study cohort those developed significant

NH requiring phototherapy treatment. 20 out of 174 (11.5%) newborn required

phototherapy.

56
Table 12: Need for Exchange Transfusion in the study

Exchange
No. of patients %
transfusion
No 174 100.0

Yes 0 0.0

Total 174 100.0

Graph11: Need for Exchange Transfusion in Study Cohort.

This table shows that none of the newborns in the study group developed NH

requiring exchange transfusion.

57
Table 13: Comparison table of Gender distribution and Cord Serum Albumin

level.

Cord Albumin levels (g/dl)

Gender Total
≤ 2.8 2.9-3.3 ≥ 3.4

Male 45(58.4%) 28(49.1%) 25(62.5%) 98(56.3%)

Female 32(41.6%) 29(50.9%) 15(37.5%) 76(43.7%)

Total 77(100%) 57(100%) 40(100%) 174(100%)

χ2=1.96; P=0.375

Graph 12: Comparison of Gender distribution and CSA level in Study cohort.

This table shows the comparison of cord albumin groups with gender. No

statistical significance is seen.

58
Table 14: Comparison of birth weight with cord serum albumin level.

Birth Weight Cord Albumin levels

Total
(kg) ≤ 2.8 2.9-3.3 ≥ 3.4

2.5-3 57(70.3%) 43(81.1%) 20(50%) 120(68.9%)

3-3.5 22(27.1%) 7(13.2%) 18(45%) 47(27.1%)

>3.5 2(2.6%) 3(5.6%) 2(5%) 7(4%)

Total 81(100%) 53(100%) 40(100%) 174(100%)

2
χ =2.82; P=0.588

Graph 13: Comparison of Birth weight of newborn with CSA level.

This comparison table shows no statistical significance between cord albumin

with birth weight. P value is >0.05.

59
Table 15: Comparison of Maternal weight with Cord serum albumin level.

Cord Albumin levels

Maternal weight Total
≤ 2.8 2.9-3.3 ≥ 3.4

50-60 kg 14(18.2%) 9(15.8%) 4(10%) 27(15.5%)

60-70 kg 39(50.6%) 22(38.6%) 15(37.5%) 76(43.7%)

70-80 kg 19(24.7%) 23(40.4%) 15(37.5%) 57(32.8%)

>80 kg 5(6.5%) 3(5.3%) 6(15%) 14(8%)

Total 77(100%) 57(100%) 40(100%) 174(100%)

χ2=8.43; P=0.208

Graph 14: Correlation of Maternal weight with CSA levels in Neonates.

This is a comparison table showing maternal weight with cord albumin

groups. There is no statistical significance noted in the present study.

60
Table 16: Comparison of oxytocin administration in mothers with cord serum

albumin level

Oxytocin Cord Albumin levels

Total
administration ≤ 2.8 2.9-3.3 ≥ 3.4

No 34(44.2%) 20(35.1%) 15(37.5%) 69(39.7%)

Yes 43(55.8%) 37(64.9%) 25(62.5%) 105(60.3%)

Total 77(100%) 57(100%) 40(100%) 174(100%)

χ2=1.23; P=0.542

Graph 15: Correlation of oxytocin administration in mother with cord serum

albumin level in neonates.

This comparison table shows oxytocin administration and cord albumin levels.

The p value is >0.05, which suggest no statistical significance between the two

variables.

61
Table 17: Comparison of Need for Phototherapy with Cord Serum Albumin level

Cord Albumin levels

Phototherapy Total
≤ 2.8 2.9-3.3 ≥ 3.4

No 58(75.3%) 56(98.2%) 40(100%) 154(88.5%)

Yes 19(24.7%) 1(1.8%) 0(0%) 20(11.5%)

Total 77(100%) 57(100%) 40(100%) 174(100%)

χ2=23.70; P<0.001**

Graph 16: Correlation of CSA level with NH requiring PT.

This table 17 shows the comparison between the newborns who developed

significant NH requiring phototherapy and cord albumin groups. Statistical significant

is seen with p value <0.001.

62
Table 18: Comparison of Need for Exchange Transfusion with Cord Serum

Albumin level.

Exchange Cord Albumin levels

Total
transfusion ≤ 2.8 2.9-3.3 ≥ 3.4

No 77(100%) 57(100%) 40(100%) 174(100%)

Yes 0(0%) 0(0%) 0(0%) 0(0%)

Total 77(100%) 57(100%) 40(100%) 174(100%)

χ2=0.000; P=1.000

Graph 17: Correlation of CSA level and NH requiring ExT.

There is no statistical significance observed in the study cohort on comparing

exchange transfusion with cord albumin levels.

63
Table 19: Correlation of Clinical Variable with Need for Phototherapy.

Phototherapy
Variables No Yes P value
(n=154) (n=20)
Gender

• Male 87(56.5%) 11(55%)

0.899
• Female 67(43.5%) 9(45%)
Mode of delivery

• Ceserian Section 45(29.2%) 6(30%)

0.943
• Vaginal route 109(70.8%) 14(70%)
Oxytocin drug use

• No 60(39%) 9(45%)
0.603
• Yes 94(61%) 11(55%)
Card blood Albumin
(mg/dl)
• ≤ 2.8 58(37.7%) 19(95%)
• 2.9-3.3 56(36.4%) 1(5%) <0.001**

• ≥ 3.4 40(26%) 0(0%)

ABO Incompatibility

• No 151(98.1%) 19(95.0%)
0.389
• Yes 3(1.9%) 1(5.0%)

This table shows the correlation of variables like gender, mode of delivery,

oxytocin, cord albumin level and ABO incompatability with newborns who developed

significant NH requiring phototherapy. Statistical significance is seen in cord albumin

levels only (p<0.001) and there was no statistical significance with other variables.

64
Graph 18: Correlation of NH requiring PT with Gender Predilection.
100
90
80
70

Percentage.
60
50 Phototherapy
40 No
30 Yes
20
10
0
Male Female
Gender

Graph 19: Correlation of NH requiring PT with Mode of Delivery in this Study

100

90

80

70
Phototherapy
60
Percentage.

50
No
40
Yes
30

20

10

0
ceserian section vaginal route
Mode of Delivery

65
Graph 20: Correlation of NH requiring PT with oxytocin use for induction of
labour.
100
90
80
70
Percentage. Phototherapy
60
No
50
40 Yes

30
20
10
0
No Yes

Oxytocin Administration

Graph 21: Correlation of NH requiring PT with CSA level estimated at birth.

100

90

80

70
Phototherapy
60
Percentage.

50 No

40 Yes
30

20

10

0
<=2.8 2.9‐3.3 >=3.4
Cord Serum Albumin(g/dl)

66
Graph 22: Correlation of NH requiring PT with ABO incompatibility in the
Study Cohort.

67
Table 20: Diagnostic Predictability of Cord Serum Albumin levels for Neonatal

Hyperbilirubinemia.

Variables Sensitivity Specificity PPV NPV Accuracy Kappa

Cord Albumin
95.00 62.44 24.68 98.97 66.09 0.256
level ≤ 2.8
Cord Albumin
5.00 63.16 1.75 83.40 56.40 Negative
level 2.9-3.3
Cord Albumin
0.00 73.33 0.00 84.62 64.71 Negative
level ≥ 3.4

Graph 23: CSA level as a Risk factor to Predict NH

The above table shows that the neonates who developed NH, 95% of these

cases had cord serum albumin level ≤ 2.8g/dl (19/20). If cord serum albumin level

≤ 2.8g/dl, 24.68% probability of developing NH and if CSA >2.9g/dl, then 98.97%

chance of not developing NH.

Similarly if CSA level ≥3.4g/dl, nil or 0% chance of developing NH. Hence

CSA level ≤ 2.8g/dl can be considered as critical value or risk factor for development

of NH. Whereas newborn with CSA level ≥3.4g/dl is safe for early discharge.

68
 DISCUSSION

There is concern regarding early discharge of healthy term newborns due to

reports of bilirubin induced brain damage resulting in sequalae like kernicterus.

Kernicteus is the chronic sequelae of acute bilirubin encephalopathy. Incidence of

kernicterus is unknown. Hence defining a certain bilirubin level as physiological can

be misleading and potentially dangerous. Neonatal hyperbilirubinemia is a potentially

correctable and kerniterus is preventable.

Neonatal hyperbilirubinemia is one of the most common causes for

readmission of the newborns. The need for early detection of hyperbilirubinemia in

the early discharged newborns from the hospital is therefore important.

Knowledge of the neonates at risk for developing jaundice allows simple

bilirubin reducing methods to be implemented before bilirubin reaches critical levels.

There are a few references which predict Neonatal hyperbilirubinemia by

estimating cord blood bilirubin levels but vary in opinions.

In this present study, we assessed the Cord Serum Albumin level as a tool for

screening for the risk of subsequent NH.

69
1. Sex of newborns

Table 21: Comparison of Gender Predilection for Neonatal Hyperbilirubinemia

outcome in other studies.

Studies Male Female p Value

Present study 98 76 0.899

Amar Taksande et 118 82 0.323

al58(2005)

Rostami et al61 300 343 >0.05

(2005)

In the present study, study group is uniformly distributed with 98 male and 76

female babies. There is no significant correlation (p 0.89) in the TSB levels and the

sex of the newborn. Hence the present study infers that the neonatal

hyperbilirubinemia (≥ 17mg/dl) is independent of the sex of the newborn.

Maisal et al60 1998, showed in a study consisting of 29934 infants, factors

associated with readmission for jaundice. Male sex in the study group is 74.8%

compared to control with 49.6%, with p value 0.007, showing that male sex has more

risk of readmission for neonatal hyperbilirubinemia.

Amar Taksande et al58 2005, in a study on 200 neonates with 82 males and

118 females, 8 males and 11 females have serum bilirubin level of (≥17mg/dl) with p

value of 0.323. So they found no correlation between the sex of the newborn and the

neonatal hyperbilirubinemia (≥17mg/dl).

Rudy Satrya et al59 2009, showed significant correlation between the sex of

the newborn and neonatal hyperbilirubinemia with p <0.05. Off 88 newborns 21

develop hyperbilirubinemia, 16 were males and 5 females.

70
 Rostami et al61 in 2005, in Iran in a study showed that there is no correlation

between the neonatal hyperbilirubinemia and the sex of the newborn.

Trivedi et al57 2013 showed, gender wise male babies have shown higher

incidence of developing hyperbilirubinemia than female babies. Study group

consisted of 605 newborn, 305 male and 300 female. Neonatal hyperbilirubinemia

developed in 115 male and 90 female.

The present study is in correlation with the study done by Amar Taksande et al

(2005) and Rostami et al (2005).

2. Mode of delivery.

Table 22: Comparison of Mode of delivery with Neonatal Hyperbilirubinemia

outcome in other studies.

Studies Total Cut-off Vaginal Ceserain P value

cases NH section
delivery

Present study 174 ≥17mg/dl 14/123 6/51 0.943

Amar taksande et 200 ≥17mg/dl 11/103 8/103 0.527

al58 (2005)

Rudy Satrya et 88 ≥14.9mg/dl 16/50 5/17 0.885

al59 (2009)

In the present study association between the neonatal hyperbilirubinemia and

the mode of delivery was studied. 123 cases with vaginal delivery 14 developed

serum bilirubin ≥17mg/dl and off 51 cases with caesarean section 6 developed

significant hyperbilirubinemia (≥17mg/dl). With p value of 0.943, there is no

significant association between the neonatal hyperbilirubinemia (≥17mg/dl) and the

mode of the delivery.

71
 Amar Taksande et al58 (2005), in their study on 200 newborns,11 cases of 114

vaginal delivery and 8 cases of 66 caesarean section developed significant

hyperbilirubinemia. With p value of 0.527, showed no correlation between the mode

of delivery and neonatal hyperbilirubinemia.

Rostami et al61 2005, in their study found that there is no significant

association between neonatal hyperbilirubinemia and the mode of delivery.

Rudy Satrya et al59 2009, in a study on 88 newborns, with cut off neonatal

hyperbilirubinemia of ≥14.9mg/dl, showed that there is no association (p 0.885)

between the mode of delivery and neonatal hyperbilirubinemia.

The present study is in correlation with the other studies.

3. Association between the neonatal hyperbilirubinemia (≥17mg/dl) and the

Oxytocin induction of labour

In the present study, there is no significant association (p >0.05) between the

newborn born to mother who received oxytocin and those who didn’t. Out of 174 ,

only 105 received oxytocin for induction of labour. NH developed in 11/105 neonates

whose mothers received oxytocin and in 9/69 neonates who didn’t.

Rostami et al61 2005, in his study on 643 full term infants, bilirubin level

>14mg/dl were observed in 16.9% of infants whose mother had received Oxytocin

during delivery and in 10.6% of infants whose mother had not received it.

Oral E et al62 2003, in their study, a total of 80 patients managed with oxytocin

during labour, patients randomly divided into isotonic 0.9% saline (Group 1) and 5%

glucose solutions (Group 2) by a consecutive order using a balanced block

72
randomization scheme. Forty multiparous patients delivering without oxytocin

infusion formed the control group (Group 3). Sodium and initial bilirubin levels were

measured in the cord blood. Later on, capillary blood bilirubin and hematocrit

concentrations were measured on day 1 and 2 in the newborn nursery. The results

showed the cord plasma bilirubin levels and day 2 plasma bilirubin levels were

significantly higher in the accelerated group. So they concluded that there is no

significant effect of Oxytocin infusion on neonatal hyperbilirubinemia unless it was

for the augmentation of labour.

Amar Taksande et al58 (2005) in his study showed no significant association (p

0.245) between the Oxytocin induction of labour and neonatal hyperbilirubinemia.

The present study is correlation with the studies of Amar Taksande et al

(2005) and Oral E et al (2003).

4. Incidence of Neonatal Hyperbilirubinemia.

Table 23: Comparison of Incidence of NH with other Studies.

No. Of Cases Incidence of

Studies Year
Hyperbilirubinemia(%)

Palmer et al63 1983 41057 10.70

Phurpradit et al64 1993 7644 8.35

Awasthi et al58 1998 274 12.80

Alpay et al65 2000 498 12.05

Agarwal et al66 2002 213 10.30

Knuffer M et al67 2005 1100 10.60

Randev S et al68 2010 200 12.00

Present study 2013 174 11.5

73
 Incidence of hyperbilirubinemia varies from 8.3% to 12.8% in above

mentioned studies.

Incidence of hyperbilirubinemia in the present study is 11.5% which correlates

with most of the above studies mentioned.

5. Association between the cord blood albumin level with neonatal

hyperbilirubinemia (≥17mg/dl).

Table 24: Comparison of CSA level as risk indicator for NH in other studies.

Cord albumin level correlation with NH

P value
No of
Total
case
Studies Year no of
with Group 1 Group 2 Group 3
cases
NH (CSA level in (CSA level in (CSA level in
g/dl) g/dl) g/dl)

Sahu
2011 40 20 14(<2.8 g/dl) 6 (2.9-3.3 g/dl) 0 (>3.4 g/dl) < 0.001
et al

Trivedi
2013 605 205 120 (< 2.8g/dl ) 59 (2.9-3.5 g/dl) 26 (>3.5 g/dl) <0.05
et al

Present
2013 174 20 19(≤ 2.8g/dl ) 1 (2.9-3.3g/dl) 0 (≥3.4g/dl ) <0.001
study
CSA=Cord Serum Albumin.

P value <0.05 is significant.

Sahu et al56 study, 2011, showed that 70% {14/20} newborn who developed

significant NH had cord serum albumin level < 2.8 g/dl, 30% {6/20} newborn had

CSA level 2.9-3.3 g/dl and none of newborns with CSA level > 3.4g/dl developed

NH. There is Statistical significance noted between CSA with development of NH (p

value <0.001).

74
 Trivedi et al57, 2013, studied total of 605 newborn and 205 newborn developed

significant NH in study group. Study group were divided into 3 groups based on CSA

levels <2.8 g/dl, 2.9-3.5g/dl, and >3.5g/dl. In group 1, 58.35% (120/205); group 2,

28.78% (59/205) and group 3, 12.68 % (26/205) developed NH. There is statistical

significance with CSA level and NH, with p value of <0.05.

In the present study, 174 newborn included and 20 newborn developed NH.

The study cohort are grouped into Group 1, Group 2, Group 3, based on cord Serum

Albumin level ≤ 2.8g/dl, 2.9-3.3g/dl and ≥ 3.4g/dl respectively. In group 1, 95%

(19/20); Group 2, 5% (1/20) and Group 3, % developed NH requiring PT.

The present study results correlated well with Shau et al and Trivedi et al

study.

Thus CSA level appears risk indicator in predicting neonatal

hyperbilirubinemia. Hence this study indicates that CSA level ≤ 2.8g/dl is high risk

factor for future development of NH and CSA level ≥ 3.4g/dl is probably safe for

early discharge.

75
 CONCLUSION

Neonatal hyperbilirubinemia occurs in 5-10% of healthy term neonates. Up to

4% of term neonates who are readmitted to the hospital during their first week of life,

approximately 85% for jaundice.

Sex, mode of delivery and oxytocin administration in mother, are not

associated with neonatal hyperbilirubinemia in the present study.

In the present study neonates with hyperbilirubinemia (≥17mg/dl) had

significantly lower levels of cord serum albumin (≤ 2.8g/dl). So it is possible to define

a group of neonates at risk of developing jaundice needing phototherapy at birth.

Knowledge of risk factors of NH in neonates could influence decision of early

discharge vs. prolonged observation.

From the present study, cord serum albumin level of ≤ 2.8g/dl has a

correlation with incidence of significant hyperbilirubinemia in term newborns. So this

≤ 2.8g/dl of cord serum albumin level can be used as risk indicator to predict the

development of significant hyperbilirubinemia. Whereas cord serum albumin level

≥3.4g/dl is considered safe, as none of neonates developed in this group had

significant hyperbilirubinemia.

76
 LIMITATIONS OF THE PRESENT STUDY

Present study was conducted to assess the usefulness of cord serum albumin as

a risk indicator in predicting neonatal hyperbilirubinemia requiring phototherapy.

Limitations of the study

1. In the present study only full term healthy neonates were taken for the study.

2. Since the peak bilirubin level reaches on 3rd and 5th postnatal days, babies are

followed till 5 days of delivery.

77
 RECOMMENDATIONS

The present study was done to assess the usefulness of the cord serum albumin

estimation as a risk indicator to predict significant neonatal hyperbilirubinemia in a

healthy term newborn who requires phototherapy subsequently.

Since the cord serum albumin level of ≤ 2.8g/dl has a sensitivity of 95%,

specificity of 74% and NPV of 98.97%. Newborn having cord serum albumin level of

≤ 2.8g/dl can be followed up in the hospital for 3-5 days (peak time for neonatal

hyperbilirubinemia) to prevent later readmission for neonatal hyperbilirubinemia and

the dangerous consequences of neonatal hyperbilirubinemia like Kernicterus.

A 84.62% Negative Predictive Value (NPV) in the present study suggests that

in Healthy Term newborn, cord serum albumin (≥3.4 g/dl) can help to identify those

newborns who are unlikely to require further evaluation and intervention.

78
 SUMMARY

• The study group consisted of 174 full term neonates delivered at

Adichunchanagiri Hospital and Research Center from December 1st 2011 to May

31st 2013.

• Informed written consent was taken from the parents.

• Neonates were followed from birth to 72-96 hours of postnatal life.

• Cord blood was collected at birth and cord serum albumin estimation was done

within 4-6 hours of collection of the blood.

• All the babies were followed up daily for the development of jaundice during

postnatal visits.

• Peripheral venous blood was collected for estimation of total serum bilirubin and

newborn blood group between 72-96 hours of life

• The outcome of the study was inferred in terms of neonatal hyperbilirubinemia

with TSB ≥17mg/dl at 72-96 hours of postnatal life, as per the American academy

of pediatrics practice guidelines 2004 and IAP-NNF recommendations.

• Study cohort was grouped into Group 1, Group 2 and Group 3 based on CSA level

≤ 2.8g/dl, 2.9-3.3g/dl and ≥ 3.4 g/dl respectively.

• Maternal variables and the development of neonatal hyperbilirubinemia were

compared in these study groups using appropriate statistical methods.

• Incidence of significant hyperbilirubinemia in our study population is 11.5%.

• There was uniform sex distribution in the study group.

• There is no association between the development of neonatal hyperbilirubinemia

and the mode of delivery either the normal vaginal delivery or the caesarean

section.

79
• There is no statistical significant association between the neonatal

hyperbilirubinemia and Oxytocin administration in mother for induction of labour.

• Cord serum albumin level of ≤ 2.8g/dl has a sensitivity of 95% and specificity of

64.44%, positive predictive value 24.68% and negative predictive value of

98.97% in predicting the risk of neonatal hyperbilirubinemia.

80
 BIBLIOGRAPHY

1. Meharban Singh. Care of the Newborn. 7th ed. New Delhi: Sagar Publications;

2010. Chapter 18, Neonatal Jaundice, p 254-74.

2. Radmacher P, Massey C, Adamkin D. Hidden Morbidity With ‘‘Successful’’

Early Discharge. J Perinatol. 2002;22:15-20.

3. Kiely M, Drum MA, Kessel W. Early discharge, risks, benefits and who decides.

Clin perinatol. 1998 Sep;25(3):539–53.

4. Cloharty JP, Stork AR, Eichenwald EC, Hansen AR. Manual of neonatal care. 7th

edn, Philadelphia: Lippincott Willams and Wilkins; 2012. Chapter 26, Neonatal

Hyperbilirubinemia; p. 304 -339.

5. American Academy Of Pediatrics, Clinical Practice Guideline; Management of

Hyperbilirubinemia in the Newborn Infant 35 or More Weeks of Gestation,

Pediatrics 2004;114(1):297-316

6. Penn AA, et al. Kernicterus in a full term infant. Pediatrics 1994;93:1003-1006.

7. Maisels MJ, et al. Kernicterus in otherwise healthy breast-fed term newborns,

Pediatrics 1995;96:730-733.

8. Niki Papavramidou, Elizabeth Fee and Helen Christopoulou-Aletra. Jaundice in

the Hippocratic Corpus. Springer New York, Journal of Gastrointestinal Surgery

2007; 11(12): 1728-1731.

9. Ashima Madan, James R.Macmohan, and David K. Stevenson. Avery’s

Neonatology.8th edn. Philadelphia:Lippincott Williams & Wilkins;2010. Neonatal

Hyperbilirubinemia in the Newborn.p1226-1257.

10. Panaroli D. Iatrologismorum sive observationum medicinalium. Pentacostae

quarta. Obs 1654; 44 : 137.

81
11. Bourgeois L. Observations Diverse sur la Sterilite Perte de Fruiot, Foecondite,

Accouchments, et Maladies de Femmes, et Enfants Nouveaux-naiz, Paris 1609.

12. Juncker DL. Conspectus Medicinae Theoreticopracticae. Halae Magdeburgeicae

1724; 717.

13. Brown AK. Kernicterus past, present and future. Neoreviews. 2003;4:e33.

14. Hansen TW. Pioneers in the Scientific Study of Neonatal Jaundice and

Kernicterus. Pediatrics 2000;106(2):e15.

15. Dewees WP. Treatise on the Physical and Medical Treatment of Children. First

Edition. Philadelphia. Carey and Lea 1825.

16. Virchow R. Die Pathologischen pigmente. Arch Pathol Anat 1847; 1:379.

17. Orth J. Uber das vorkommen von bilirubinkrystallen bei neugebornen kinder.

Arch Path Anat Phys u f Klin Med (virchows Arch) 1875; 63: 477.

18. Holt LE. Diseases of Infancy and Childhood. First Edition, D Appleton Co. New

York 1897.

19. Schmorl CG. Zur kenntnis des ikterus neonatorum, insbesondere der dabei

auftretenden gehirnveranderungen. Vehandl d Dent Path Gesell 1904; 6: 109.

20. Rautmann H. Ueber blutbildung bei fotaler allgemeiner wassersuch. Beit Z Path

Anat u z alleg Path 1912; 54 : 332.

21. Halban J. Agglutinationsversuche mit muuterlichen and kinderlichen blute. Wien

Klin Woch 1900; 13 : 545.

22. Ottenberg R. The etiology of eclampsia : historical and critical notes. J Amer Med

Ass 1923 ; 81 : 295.

23. Levine P, Burnham L, Katzin EM et al. The role of isoimmunisation in the

pathogenesis of erythroblastosis fetalis. Amer J Obstet and Gynec 1942; 42 :925.

82
24. Ylppo A. Icterus neonatorum and Gallenfarbstoffsekretion beim foetus and

neugenborenen. Z f Kinderh 1913; 9 : 208.

25. Diamond LK, Blackfan KD, Baty JM. Erythrobalstosis fetalis and its association

with universal edema of fetus, icterus gravis neonatorum andanemia of the

newborn. J Pediatr 1932; 1 : 269.

26. Landsteiner K. Wiener AJ. An agglutinable factor in human blood recognized by

immune sera for rhesus blood. Proc Soc Exp Biol and Med 1940 ; 74 :309.

27. Halbrecht L. Role of hemagglutinins anti-A and anti-B in pathogenesis of jaundice

of newborn (icterus neonatorum precox). Amer J Dis Child 1944 ; 68 : 248.

28. Crigler JF, Najjar VA. Congenital familial nonhemolytic jaundice with

kernicterus. Pediatrics 1952 ; 10 : 169.

29. Hart AP. Familial icterus gravis of the newborn and its treatment. Canad Med

Assn J 1925 ; 15 : 1008.

30. Wallerstein H. Treatment of severe erythroblastosis fetalis by simultaneous

removal and replacement of the blood of the newborn infant. Science 1946 ; 103:

583.

31. Cremer RJ, Perryman PW, Richards DH. Influence of light on the

hyperbilirubinemia of infants. Lancet 1958 ; 1 : 1094.

32. Guruprasad G. Bilirubin Metabolism- what we should know?. J Neonatol.

2001;1:4-7.

33. Kliegman RM, Behrman RE, Stanton BF, Schor.NF. Nelson text book of

Pediatrics. 19 th ed. New Delhi: Saunders Elsevier; 2012. Chapter 96.3, Jaundice

and Hyperbilirubinemia in the Newborn; p 603–08.

83
34. David G.Nathan, Staurt H.Orkin, David Ginsberg, Thomas LA .Hematology of

Infancy and Childhood. 6th edn. Philadelphia: Saunders Company; 2003. Disorder

of Bilirubin Metabolism; p. 86-120.

35. Robert K. Murray, Daryl K. Granner, Victor W. Rodwell. Harper’s Illustrated

Biochemistry.29th ed. USA: The McGraw-Hill Companies, Inc; 2006. Chapter 50,

Plasma Proteins and Immunoglobulins; p629-45

36. Chris HP, Van DA, Henk Schierbeek, et al, Human fetal albumin synthesis rates

during different periods of gestation. Am J Clin Nutr. 2008;88:997-1003

37. Burtis CA, Ashwood AR, Bruns DE, Tietz. Text book of clinical chemistry and

molecular diagnosis. 4th ed. Philadelphia: Elsevier; 2008, p2254.

38. Philip Rosenthal et al, Assessing liver function and hyperbilirubinemia in the

newborn. NACB Symposium. Clinical Chemisty 1997;43(1):228-234

39. Guruprasad.G, Deepak C, Sunil A. NNF Clinical Practice Guidelines[internet].

India: NNF;2010. Management of Neonatal Hyperbilirubinemia.[cited 2010].

Available from: http://www.nnfpublication.org.

40. Kumar V, Abbas AK, Fausto N. Robbins and Cotran: Pathologic basis of disease

8th edn. Kundli, Haryana: Saunders Elsevier; 2004. Chapter 18, Liver and biliary

tract; p 833- 890.

41. Shapiro S, Nakamura H. Bilirubin and the auditory system. J Perinatol

2001;21:52-55.

42. Nwaesei CG, Van Aerde J, Boyden M et al. Changes in auditory brainstem

responses in hyperbilirubinemic infants before and after exchange transfusion.

Pediatrics 1984 ; 74 : 800-803.

84
43. Wennberg RP, Ahlfors CE, Bickers R et al. Abnormal auditory brainstem

response in a newborn infant with hyperbilirubinemia: improvement with

exchange transfusion. J Pediatr 1982 ; 100 : 624-626.

44. Palmer C, Smith MB. Assessing the risk of kernicterus using nuclear magnetic

resonance. Clin Perinatol 1990 ; 17 : 307-329.

45. Kramer LI. Advancement of dermal icterus in the jaundiced newborn. Am J Dis

Child 1969 ; 118 : 454-458.

46. Maisles MJ, Mcdonag AF. Phototheraphy for Neonatal Jaundice. N Engl J Med.

2008 Feb 28;358:920-8.

47. Saluja S, Kleer N, Soni A, Garg P, Saxena U. Exchange Transfusion Through

Peripheral Vessels. J Neonatol. 2001;1:52-5.

48. Thomas B.Newman et al,. Combining Clinical Risk Factors With Serum Bilirubin

Levels to Predict Hyperbilirubinemia in Newborns . Archpediatrics,

2005;159:113-119.

49. Zakia Nahar et al, The Value of Umbilical Cord Blood Bilirubin Measurement in

Predicting the Development of Significant Hyperbilirubinemia in Healthy

Newborn, Bangladesh J Child health 2009;33(1):50-54.

50. Risemberg HM, Mazzi E, Macdonald MG, Peralta M, Heldrich F. Correlation

cord bilirubin levels with hyperbilirubinemia in ABO incompatibility. Arch Dis

Child 1977; 57 : 219-222.

51. Rosenfeld J. Umbilical cord bilirubin levels as predict-or of subsequent

hyperbilirubinemia. J Fam Pract 1986 ; 23 : 556-58.

52. Sao Paulo et al,. Bilirubin dosage in cord blood: could it predict neonatal

hyperbilirubinemia? Sao Paulo medical journal. 2004;122(3):99-103.

85
53. Bhutani V.K, Johson L, Sivieri E M. Predictive ability of a predischarge hour

specific serum bilirubin for subsequent significant hyperbilirubinemia in healthy

term and near term newborns. Pediatrics. 1999 Jan;103:6–14.

54. Vinod K Bhutani et al, Noninvasive Measurement of Total Serum Bilirubin in a

Multiracial Predischarge Newborn Population to Assess the Risk of Severe

Hyperbilirubinemia, Pediatrics 2000;104(2):1-9

55. David K.Stevenson et al, Prediction of Hyperbilirubinemia in Near-Term and

Term Infants, Pediatrics 2001;108(1):31-39.

56. Suchanda Sahu et al, Cord blood albumin as a predictor of neonatal jaundice,

International J.Biological and medical research 2011;2(1):436-438.

57. Treivedi et al, Cord Serum bilirubin and Albumin in Neonatal

Hyperbilirubinemia, International Journal of Integrative sciences, Innovation and

technology. 2013;2(2):39-42.

58. Amar Taksande, Krishna Vilhekar, Manish Jain, Preeti Zade, Suchita Atkari,

Sherin Verkey. Prediction of the development of neonatal hyperbilirubinemia by

increased umbilical cord blood bilirubin. Ind Medica 2005 ; 9(1) : 5-9.

59. Rudy Satrya, Sjarif Hidayat Effendi, Dida Akhmad Gurnida. Correlation between

cord blood bilirubin level and incidence of hyperbilirubinemia in term newborns.

Paediatrica Indonesiana 2009 ; 49(6) : 349-354.

60. Maisels MJ, Kring E Length of stay, Jaundice and hospital readmission. Pediatrics

1998; 101 : 995-998.

61. Rostami N, Mehrabi Y. Identifying the newborns at risk for developing significant

hyperbilirubinemia by measuring cord bilirubin levels. J Arab Neonatal Forum

2005 ; 2 : 81-5.

86
62. Oral E, Gezer A, Cagdas A, Pakkal N. Oxytocin infusion in labor: the effect

different indications and the use of different diluents on neonatal bilirubin levels.

Archgynecol Obstet 2003 Jan:267(3):117-20.

63. Palmer DC, Drew JH. Jaundice a 10 year review of 41000 live born infants. Aust

Pediatr. 1983 Jun;19(2):86-89.

64. Phupradit W, Chaturachinda K, Anutlamai S. Risk Factors for Neonatal

Hyperbilirubinemia. J Med Assoc Thai. 1993 Aug;76(8):424-8.

65. Alpay F , Sarici SU, Tosuncuk HD, Serdar MA, Inanç N, Gokcay E. The Value of

First Day Bilirubin Measurement in Predicting the Development of Significant

Hyperbilirubinemia in Healthy Term Newborns. Pediatrics. 2000

Aug;106(2):p.e16.

66. Agarwal R, Deorari AK. Unconjucated Hyperbilirubinemia in Newborn. Indian

Pediatr. 2002 Aug 17;39:30-42.

67. Knupfer M, Pulzer F, Gebauer C, Robel-Tillig E, Vogtmann C. Predictive value

of umbilical cord blood bilirubin for postnatal hyperbilirubinaemia. Acta Paediatr.

2005 May;94(5):581-7.

68. Randew S, Grower N. Predicting neonatal hyperbilirubinemia using first day

serum bilirubin levels. Indian J Pediatr. 2010 Feb;77:147-50.

69. Robert H Riffenburg (2005), Statistics in Medicine , second edition, Academic

press. 85-125.

70. Sunder Rao P S S , Richard J(2006) : An Introduction to Biostatistics, A manual

for students in health sciences , New Delhi: Prentice hall of India. 4th edition, 86-

160

87
 ANNEXURE

PROFORMA

1. Serial No:

2. I.P.No.:

3. Mother’s Name and age:

4. Father’s Name:

5. Address:

6. Mothers blood group:

7. Maternal weight:

8. Family Income:

9. Date & Time of birth:

10. Sex of delivered newborn:

11. Birth Order:

12. Previous sibling neonatal Jaundice history:

13. Oxytocin Administration: Yes/No.

14. Delivery Type:

15. Normal Vaginal:

16. Caesarian Section:

17. Amniotic fluid:

18. Period of Gestational age: LMP: EDD:

19. APGAR @ 1 min:

20. APGAR @ 5 min:

21. Birth weight:

88
 22. Baby’s blood group:

23. Cord blood albumin level:

24. Clinical examination of newborn:

Day of life <24 hours 24-48 hours 48-72 hours 72-96 hours
Neonatal
Hyperbilirubinemia
Other significant
findings

25. Serum Total bilirubin level before 72 hours, if any:

26. Serum Total bilirubin level 72-96 hours:

27. Phototherapy given: Yes/ No.

28. Exchange transfusion: Yes/No.

89
 STATISTICAL METHODS69, 70

Descriptive and inferential statistical analysis has been carried out in the

present study. Results on continuous measurements are presented on Mean ± SD

(Min-Max) and results on categorical measurements are presented in Number (%).

Significance is assessed at 5 % level of significance. The following assumptions on

data is made, Assumptions: 1.Dependent variables should be normally distributed,

2.Samples drawn from the population should be random, Cases of the samples should

be independent.

Chi-square/ Fisher Exact test has been used to find the significance of study

parameters on categorical scale between two or more groups. Kappa Coefficeint of

agreement between Cord Serum Albumin at birth and Total Serum Bilirubin levels is

estimated at 72-96 hours of postnatal life to predict the Significant Neonatal

Hyperbilirubinemia based on phototherapy.

Diagnostic statistics such as Sensitivity, Specificity, PPV, NPV, Accuracy

were obtained to prediction potential of Cord Serum albumin Albumin level as a risk

indicator for neonatal hyperbilirubinemia.

1.Chi-Square Test: The chi-square test for independence is used to determine the

relationship between two variables of a sample. In this context independence means

that the two factors are not related. In the chi-square test for independence the degree

of freedom is equal to the number of columns in the table minus one multiplied by the

number of rows in the table minus one

χ 2
=
∑ (Oi − Ei) 2

,
Ei

90
Where Oi is Observed frequency and Ei is Expected frequency With (n-1) df

The Assumptions of Chi-square test

The chi square test, when used with the standard approximation that a chi-

square distribution is applicable, has the following assumptions:

• Random sample – A random sampling of the data from a fixed distribution or

population.

• Sample size (whole table) – A sample with a sufficiently large size is assumed.

If a chi square test is conducted on a sample with a smaller size, then the chi

square test will yield an inaccurate inference. The researcher, by using chi

square test on small samples, might end up committing a Type II error.

• Expected Cell Count – Adequate expected cell counts. Some require 5 or

more, and others require 10 or more. A common rule is 5 or more in all cells

of a 2-by-2 table, and 5 or more in 80% of cells in larger tables, but no cells

with zero expected count. When this assumption is not met, Fisher Exact test

or Yates' correction is applied.

2.Fisher Exact Test: The Fisher Exact Test looks at a contingency table which

displays how different treatments have produced different outcomes. Its null

hypothesis is that treatments do not affect outcomes-- that the two are independent.

Reject the null hypothesis (i.e., conclude treatment affects outcome) if p is "small".

The usual approach to contingency tables is to apply the χ2 statistic to each

cell of the table. One should probably use the χ2 approach, unless you have a special

reason. The most common reason to avoid χ2 is because you have small expectation

values

91
 Class1 Class2 Total

Sample1 a b a+b

Sample2 c d c+d

Total a+c b+d N

(a + b)!(c + d )!(a + c)!(b + d )! 1

2x2 Fisher Exact Test statistic= ∑p= n! ∑ a!b!c!d!

1: Fisher Exact test (rxc tables)

Let there exist two such variables and , with and observed states, respectively.

Now form an matrix in which the entries represent the number of observations

in which and . Calculate the row and column sums and , respectively,

and the total sum

of the matrix. Then calculate the conditional probability of getting the actual matrix

given the particular row and column sums, given by

which is a multivariate generalization of the hypergeometric probability function.

3. Diagnostic statistics
Disease

Test Present n Absent n Total

Positive True Positive a False Positive C a+c

Negative False Negative b True Negative d b+d

Total a+b c+d

The following statistics can be defined:

92
 • Sensitivity: probability that a test result will be positive when the disease is

present (true positive rate, expressed as a percentage).

= a / (a+b)

• Specificity: probability that a test result will be negative when the disease is

not present (true negative rate, expressed as a percentage).

= d / (c+d)

• Positive predictive value: probability that the disease is present when the test

is positive (expressed as a percentage).

= a / (a+c)

• Negative predictive value: probability that the disease is not present when the

test is negative (expressed as a percentage).

= d / (b+d)

• Accuracy is the sum of true positive and True negative divided by number of

cases

4. Diagnostic values based on Area under curve

0.9-1.0 Excellent test

0.8-0.9 Good test

0.7-0.8 Fair test

0.6-0.7 Poor test

0.5-0.6 Fail

5. Kappa Statistic for agreement: inter-rater agreement statistic (Kappa) to evaluate

the agreement between two classifications on ordinal or nominal scales (Cohen,

1960). Agreement is quantified by the Kappa (K) or Weighted Kappa (Kw) statistic:

• K is 1 when there is perfect agreement between the classification system;

• K is 0 when there is no agreement better than chance;

93
• K is negative when agreement is worse than chance.

Value of K Strength of agreement

< 0.20 Poor
0.21 - 0.40 Fair
0.41 - 0.60 Moderate
0.61 - 0.80 Good
0.81 - 1.00 Very good

94
 KEY TO THE MASTER CHART

Sl No. - Serial Number

M Wt. - Maternal weight

< 50 Kg - 0

51-60 Kg - 1

61-70Kg - 2

71-80 Kg - 3

>81 Kg - 4

MOD - Mode of Delivery

V - Vaginal route

CS - Ceserian Section

MBG - Maternal Blood Group

BBG - Baby Blood Group

B. wt. - Birth weight (Kg)

TB - Total Bilirubin in mg/dl

DB - Direct Bilirubin in mg/dl.

PT - Phototherapy

ET - Exchange Transfusion

Y - Yes

N - No

95
 MASTER CHART

Sl. MR/IP Oxytocin

Name MOD M Wt. MBG Sex B. Wt. Albumin TB DB BBG PT ET
No. No. Administration
1 B/O Chithra 403953 V 2 Y A+ F 2.60 2.36 17.13 1.15 O+ yes No
2 B/o Bhavitha 404288 V 2 Y O+ M 2.70 1.83 16.93 1.48 O+ yes No
3 B/O Radha 400751 V 3 Y O+ M 2.80 3.20 12.68 1.12 O+ No No
4 B/O Roopa 400634 V 2 Y O+ M 2.75 2.86 10.56 1.04 O+ No No
5 B/o Chandrakala 401859 CS 4 N O+ F 2.60 2.54 11.68 1.54 O+ No No
6 B/O Thejaswini 454644 V 3 Y O+ F 2.55 2.08 17.04 1.54 O+ yes No
7 B/oHema 417914 V 2 Y O+ F 3.90 2.13 17.10 1.61 O+ yes No
8 B/o Savitha 410516 V 1 Y A+ M 2.50 2.60 11.65 1.23 A+ No No
9 B/o Shruthi 412287 V 4 Y O+ M 3.20 3.10 13.60 1.12 B+ No No
10 B/O Sharadha 411958 V 2 Y O+ M 2.90 2.60 11.56 1.25 O+ No No
11 B/O padma 412287 CS 3 N O+ M 2.80 2.40 14.12 1.21 A+ No No
12 B/o Manjula 410964 CS 3 N A+ M 3.25 2.20 12.65 1.11 A+ No No
13 B/O Thejaswini 409807 V 2 Y O+ F 3.20 3.10 12.60 0.86 O+ No No
14 B/o Hema 409325 CS 2 N O+ M 3.40 2.60 12.25 0.75 O+ No No
15 B/O Roopa 409290 V 2 Y O+ M 3.10 2.80 11.25 0.85 O+ No No
16 B/o Kavitha 417767 V 3 Y O+ M 2.75 3.20 13.86 1.36 O+ No No
17 B/o Sufiya 429561 V 3 N A+ M 3.25 2.90 12.13 1.10 A+ No No
18 B/O Shantha 424320 V 2 Y AB+ M 3.00 1.79 16.31 1.54 A+ No No
19 B/O Umadevi 424163 V 2 Y O+ M 3.20 2.20 16.84 1.46 O+ No No
20 B/o Dayamani 429513 CS 2 N AB+ M 2.75 2.76 5.70 0.76 AB+ No No
21 B/O Suma 429644 V 2 Y B+ M 2.80 2.90 9.44 0.71 O+ No No
22 B/o Ashwini 423294 V 3 Y O+ M 3.20 3.21 14.07 1.00 O+ No No
23 B/o Shwetha 420691 V 1 N B+ F 2.50 4.20 11.72 1.20 B+ No No
24 B/o Poornima 422895 V 2 N A+ F 2.50 4.50 10.80 1.11 O+ No No
25 B/O Pallavi 422893 CS 2 N A+ M 2.95 3.20 11.45 0.98 O+ No No
26 B/o Shwetha 425016 V 2 Y B+ F 2.50 3.20 12.50 1.00 B+ No No
27 B/o Girija 418948 CS 2 N A+ F 2.80 5.30 12.45 0.98 A+ No No
28 B/o Savitha 418945 CS 3 N A+ M 3.25 3.30 12.00 1.00 A+ No No

96
Sl. MR/IP Oxytocin
Name MOD M Wt. MBG Sex B. Wt. Albumin TB DB BBG PT ET
No. No. Administration
29 B/O Dhanalakshmi 420688 V 1 Y O+ F 2.50 2.90 13.54 1.10 O+ No No
30 B/O Pavithra 423817 CS 4 N A+ M 3.20 3.89 13.00 0.90 AB+ No No
31 B/O Surekha 425003 V 3 N O+ F 3.25 3.84 13.00 1.00 O+ No No
32 B/O Yammuna 425010 V 4 Y O+ M 3.25 3.60 13.21 0.95 O+ No No
33 B/o Kavitha 426884 V 2 Y O+ M 3.00 3.40 12.00 0.92 O+ No No
34 B/o Savithri 421921 V 2 Y O+ M 2.90 2.80 14.70 1.10 A+ No No
35 B/o Vanitha 426885 V 3 Y O+ M 2.90 3.50 12.80 1.10 O+ No No
36 B/o Veena 423266 V 3 N O+ F 2.80 3.53 12.37 0.91 O+ No No
37 B/O Savitha 58444 V 3 Y O+ M 3.20 1.82 17.08 1.32 O+ yes No
38 B/O Komala 437680 V 1 N O+ F 2.50 2.80 12.30 1.20 O+ No No
39 B/o asha 435987 CS 2 N O+ F 2.80 2.50 13.85 1.11 O+ No No
40 B/o Girija 434312 V 2 Y O+ M 3.10 3.30 11.85 1.10 O+ No No
41 B/O Nandini 437139 V 1 Y O+ F 2.60 2.60 11.30 1.20 O+ No No
42 B/o Manjula 442845 CS 2 N AB+ M 3.25 2.00 12.84 1.00 AB+ No No
43 B/O Geetha 429621 V 1 N A+ F 2.50 3.00 11.80 1.10 A+ No No
44 B/O Uma 449711 V 2 Y A+ M 2.60 3.40 12.90 2.40 A+ No No
45 B/O Ningamma 448078 V 3 Y B+ F 3.00 3.10 13.87 0.82 B+ No No
46 B/O Ramya 446688 CS 2 Y O+ F 3.25 2.80 15.20 1.00 O+ No No
47 B/O Yashodha 448060 CS 1 N O+ F 2.50 2.10 10.56 0.90 O+ No No
48 B/O Kumari 444944 V 4 Y B+ M 3.50 1.58 17.18 1.52 B+ yes No
49 B/O Ambiika 448067 CS 1 N O+ F 2.50 2.40 9.25 0.87 O+ No No
50 B/O Sowmya 449700 V 2 N O+ F 3.00 2.50 13.45 1.12 O+ No No
51 B/O Padma 466848 V 1 N O+ M 2.50 1.94 17.40 1.22 O+ Yes No
52 B/o Shwetha 463737 V 2 N AB+ M 2.80 1.69 17.05 1.38 B+ yes No
53 B/O Pankaja 456069 V 3 Y B+ M 3.00 3.20 13.25 1.11 B+ No No
54 B/O Shobha 456572 V 2 Y A+ F 2.75 3.10 10.84 1.10 A+ No No
55 B/o Girija 458231 CS 3 N A+ F 3.25 3.30 13.84 1.15 A+ No No
56 B/O Mahalakshmi 458444 V 2 Y O+ F 3.25 3.00 10.90 1.00 O+ No No
57 B/O Roopa 474491 CS 2 N A+ M 2.75 1.78 17.03 1.48 A+ yes no
58 B/O Radha 470806 CS 4 Y O+ F 3.80 3.20 11.56 1.54 O+ No No
59 B/O Jestadevi 470814 V 2 Y O+ M 2.60 2.80 12.36 1.25 O+ No No
60 B/O Archana 470461 V 2 Y A+ M 2.70 2.70 10.86 1.05 A+ No No

97
Sl. MR/IP Oxytocin
Name MOD M Wt. MBG Sex B. Wt. Albumin TB DB BBG PT ET
No. No. Administration
61 B/O Geetha 470468 V 3 Y O+ M 2.70 2.50 10.65 1.03 O+ No No
62 B/o Poornima 469261 V 2 Y O+ F 2.50 3.10 11.20 1.11 O+ No No
63 B/O Nandini 468577 CS 1 N A+ F 2.50 2.91 12.30 1.22 A+ No No
64 B/O Shobha 472047 CS 2 N O+ F 2.80 2.50 12.98 1.26 O+ No No
65 B/O Mahalakshmi 472903 V 2 Y B+ M 2.70 2.70 12.32 1.03 B+ No No
66 B/O Asha 472953 V 3 Y A+ M 3.50 3.60 12.98 1.27 A+ No No
67 B/O Suma 472402 CS 2 Y B+ F 3.10 2.60 11.23 1.32 B+ No No
68 B/O Dhanalakshmi 473297 V 3 Y O+ M 2.80 2.40 9.88 1.00 O+ No No
69 B/O Sowmya 470482 CS 1 N B+ M 2.50 2.40 10.25 1.27 B+ No No
70 B/O Rekha 68709 CS 2 N O+ F 3.00 1.64 17.06 1.37 O- yes No
71 B/o Shruthi 483741 V 1 Y O+ M 2.50 2.50 12.86 1.25 O+ No No
72 B/O Parvathi 483742 V 3 N O+ M 2.90 3.60 10.62 1.26 O+ No No
73 B/O Nethravathi 482549 CS 4 Y O+ F 3.40 2.59 14.00 1.20 O+ No No
74 B/O Savitha 483168 V 3 Y O+ M 3.25 3.40 10.67 1.12 O+ No No
75 B/O Noorkhasheefa 484965 V 2 N A+ F 2.90 2.90 13.10 1.20 O+ No No
76 B/O Ushadevi 72739 CS 2 N O+ F 2.70 1.93 17.35 1.22 O+ yes No
77 B/O Sunitha 511638 V 3 Y O+ F 2.60 3.40 11.20 1.10 O+ No No
78 B/O Lakshmamma 511761 V 1 N B+ M 2.60 2.40 14.80 1.00 B+ No No
79 B/O Nandini 512109 V 1 Y B+ M 2.60 3.10 13.90 1.20 B+ No No
80 B/O Rajini 512062 V 2 Y A+ F 2.80 2.60 12.50 1.20 A+ No No
81 B/O Reshma Banu 512113 V 4 Y B+ F 3.70 2.80 13.50 1.10 B+ No No
82 B/O Joythi 516049 V 2 N O+ F 2.60 2.60 15.10 1.13 O+ No No
83 B/O Brunda 514925 V 3 Y O+ F 3.40 3.00 14.20 1.20 O+ No No
84 B/O Divya 514100 CS 3 N O+ F 2.70 2.80 13.21 1.25 O+ No No
85 B/O Sabana 513675 V 1 Y O+ M 2.50 3.40 12.92 1.07 O+ No No
86 B/O Latha 513693 V 2 Y B+ F 3.00 2.50 14.20 1.61 B+ No No
87 B/O Sowmya 513028 V 3 Y O+ M 2.80 3.50 11.65 1.36 O+ No No
88 B/o Veena 510645 CS 2 Y O+ F 2.50 3.20 13.19 1.25 O+ No No
89 B/O Harshitha 513087 V 3 N O+ M 2.80 2.80 12.54 1.21 O+ No No
90 B/O Savitha 511733 V 3 Y A+ M 2.75 2.30 11.80 1.10 O+ No No
91 B/o Chandrakala 475381 V 3 Y O+ M 3.00 2.59 11.83 1.32 O+ No No
92 B/O Geetha 528678 V 2 Y A+ F 2.75 3.47 13.63 1.43 A+ No No

98
Sl. MR/IP Oxytocin
Name MOD M Wt. MBG Sex B. Wt. Albumin TB DB BBG PT ET
No. No. Administration
93 B/O Ishra Thunisa 527191 CS 3 Y A+ F 3.20 2.91 13.63 1.25 A+ No No
94 B/O Nagarathana 535020 V 1 Y A+ M 2.60 2.74 12.80 1.23 A+ No No
95 B/O Nethravathi 531192 V 3 Y O+ M 3.40 2.52 14.02 1.36 O+ No No
96 B/O Sakamma 534672 V 1 Y O+ F 2.50 2.91 13.18 1.23 O+ No No
97 B/O Shobha 511521 CS 3 N B+ M 3.25 2.89 11.28 1.21 B+ No No
98 B/o Shwetha 528095 CS 3 N A+ M 2.90 2.86 13.26 1.26 A+ No No
99 B/O Varalakshmi 524374 V 2 N O+ M 2.80 2.28 13.21 1.27 O+ No No
100 B/o Veena 446773 V 2 Y O+ F 2.60 2.47 13.42 1.13 O+ No No
101 B/O Anitha 73757 CS 1 Y O+ F 2.50 1.88 17.20 1.17 O+ yes No
102 B/O Joythi 75087 CS 1 Y B+ F 2.60 1.63 17.60 1.20 B+ yes No
103 B/O Pushpalatha 533072 CS 4 Y O+ M 3.50 3.42 10.82 1.08 O+ No No
104 B/O Ambuja 542219 V 2 Y O+ F 2.80 3.83 13.05 1.40 O+ No No
105 B/O Rekha 545171 V 3 Y O+ F 3.00 2.73 12.00 1.10 O+ No No
106 B/O Indramma 546327 CS 3 N B+ M 3.25 2.07 13.81 1.04 B+ No No
107 B/O Ranjitha 546767 V 1 Y B+ M 2.50 3.69 12.52 1.17 B+ No No
108 B/O Usha 548966 CS 2 Y A+ F 3.00 2.83 13.60 1.21 A+ No No
109 B/O Harshitha 550670 V 2 Y O+ F 2.60 2.63 10.68 1.20 O+ No No
110 B/O Anitha 551377 CS 3 N O+ F 3.00 2.28 12.79 1.71 O+ No No
111 B/O Meenakshi 552643 V 2 N A+ M 2.80 3.80 10.35 1.02 A+ No No
112 B/O Ashwini 552708 V 3 Y B+ F 2.90 2.60 14.40 1.50 O+ No No
113 B/O Jayasheela 553825 CS 3 N A+ M 3.00 3.60 10.35 1.03 A+ No No
114 B/O Shobha 553831 V 2 Y AB+ M 2.70 2.79 12.56 1.20 AB+ No No
115 B/O Shanthamma 76524 V 2 N O+ M 2.80 1.73 17.08 1.39 O+ Yes No
116 B/O Geetha 554632 V 4 Y AB+ M 3.50 3.43 13.54 1.32 A+ No No
117 B/O Padma 555452 V 2 N O+ F 2.80 3.07 12.79 1.02 O+ No No
118 B/O Geetha 562235 V 1 Y O+ M 2.50 2.96 11.94 1.01 O+ No No
119 B/O Bhagya 563062 V 2 Y A+ M 3.25 2.92 14.12 1.20 A+ No No
120 B/o Shwetha 563880 V 3 Y B+ F 2.60 3.09 12.81 1.15 B+ No No
121 B/O Manu 566098 V 2 N B+ M 3.10 3.20 11.80 1.21 B+ No No
122 B/O Bhagya 569797 V 2 Y O+ M 3.00 3.69 10.12 1.03 O+ No No
123 B/O Nayanashri 555942 V 2 Y A+ M 2.60 3.26 11.93 1.14 A+ No No
124 B/O Kusuma Kumari 79801 V 3 Y O+ M 2.80 1.69 17.50 1.37 O+ yes No

99
Sl. MR/IP Oxytocin
Name MOD M Wt. MBG Sex B. Wt. Albumin TB DB BBG PT ET
No. No. Administration
125 B/O Vinoda.B.K 5774620 V 1 Y O+ M 2.50 3.40 10.70 1.09 O+ No No
126 B/O Asha 574808 V 2 Y O+ M 3.10 3.20 13.90 1.13 O+ No No
127 B/O Nagamma 578751 CS 2 N B+ F 2.80 3.70 11.10 1.21 B+ No No
128 B/O Radha 581562 V 3 Y O+ M 2.80 3.90 9.80 1.10 O+ No No
129 B/O Kalavathi 581785 V 2 N O+ F 2.70 2.90 11.30 0.92 O+ No No
130 B/O Kumari 582673 V 2 N B+ F 2.75 2.90 11.50 1.10 B+ No No
131 B/O Lakshmi 585312 V 3 Y O+ M 2.75 3.20 11.60 1.20 O+ No No
132 B/o Shruthi 587136 V 2 Y B+ F 3.00 3.40 12.30 1.20 B+ No No
133 B/O Vedavathi 589456 V 4 Y AB+ F 3.75 3.10 11.30 1.30 AB+ No No
134 B/O Sunitha 589463 V 3 Y O+ M 3.10 3.00 12.30 1.20 O+ No No
135 B/O Lakshmi 590925 CS 2 N O+ M 2.60 2.80 9.70 1.10 O+ No No
136 B/O Savitha 591016 V 3 N B+ M 3.20 2.80 13.00 1.30 B+ No No
137 B/O Shilaja 591713 CS 3 N B+ F 3.20 3.00 13.70 1.20 B+ No No
138 B/O Sheela 81062 V 3 N O+ F 2.50 3.10 17.20 1.60 O+ yes No
139 B/O Susheela. H.P 594096 CS 3 N B+ F 3.20 2.90 12.40 1.10 B+ No No
140 B/O Sumalatha 594945 CS 2 N O+ M 3.00 3.40 9.70 1.00 O+ No No
141 B/O Jayalakshmi 597345 V 1 N O+ F 2.60 2.70 12.70 1.20 O+ No No
142 B/O Asha 599468 V 2 N B+ M 3.20 3.20 13.90 1.10 B+ No No
143 B/O Vidyashree 601329 CS 2 Y B+ F 2.75 3.30 13.70 1.20 B+ No No
144 B/O Nagamma 602144 V 2 N O+ M 2.75 3.60 13.40 1.20 O+ No No
145 B/O Noorayesha 602825 V 3 Y O+ M 3.25 3.90 10.10 1.10 O+ No No
146 B/O Lalitha 606305 V 3 Y B+ M 3.20 3.60 11.50 1.30 B+ No No
147 B/o Manjula 606385 V 4 Y O+ F 3.75 3.80 12.50 1.10 O+ No No
148 B/O mamatha 609919 CS 3 N O+ F 3.20 3.40 13.60 1.20 O+ No No
149 B/O Abiliasha 84122 CS 2 N O+ M 2.70 2.30 17.04 1.40 O+ Yes No
150 B/O Rizyothi 85123 V 3 Y O+ M 2.80 2.00 17.38 1.50 O+ Yes No
151 B/O Bhargavi 628223 V 1 Y O+ F 2.50 3.10 11.80 1.10 O+ No No
152 B/o Manjula 624936 CS 2 N O+ M 3.30 2.80 12.30 0.90 O+ No No
153 B/O Uma 611266 CS 3 N AB+ M 3.30 3.40 10.70 1.20 B+ No No
154 B/O Hemalatha 612015 CS 3 Y O+ F 3.70 3.10 13.40 1.20 O+ No No
155 B/O Shruthi 616915 V 2 N O+ F 2.70 3.50 12.20 1.20 O+ No No
156 B/O Kumari 88916 V 1 Y O+ M 2.60 2.60 12.30 1.10 O+ No No

100
Sl. MR/IP Oxytocin
Name MOD M Wt. MBG Sex B. Wt. Albumin TB DB BBG PT ET
No. No. Administration
157 B/O Usha 89496 V 2 N O+ M 3.00 2.70 13.40 1.30 O+ No No
158 B/O mamatha 89699 CS 4 Y A+ F 3.50 2.80 10.90 1.10 O+ No No
159 B/O Gowramma 90201 V 2 Y O+ M 3.00 2.10 12.10 1.20 O+ No No
160 B/O Bhavya 91143 V 1 N O+ F 2.50 2.90 13.20 1.20 O+ No No
161 B/o Girija 90488 V 4 Y O+ M 4.00 3.50 11.50 1.00 O+ No No
162 B/O Anitha 91489 V 3 Y B+ M 3.20 3.40 11.60 1.10 B+ No No
163 B/O Drakshyani 90710 V 2 Y O+ M 2.50 2.40 17.05 1.40 B+ yes No
164 B/O Geetha 652428 CS 1 Y B+ M 2.50 3.00 13.40 1.20 O+ No No
165 B/O Susheela. 656554 CS 2 N O+ F 3.50 2.70 14.20 1.20 O+ No No
166 B/O Dhanalakshmi 659697 V 3 Y B+ M 3.50 3.30 13.70 1.20 B+ No No
167 B/O Bhagya 666315 V 2 N B+ F 2.50 2.80 17.24 1.40 B+ yes No
168 B/O Shobha 664776 V 3 Y O+ M 2.90 3.00 11.50 1.30 O+ No No
169 B/O Bhagya 668069 V 3 Y O+ M 2.90 2.80 13.50 1.10 O+ No No
170 B/O Ramya 666309 CS 3 N A+ M 2.90 3.30 13.90 1.30 A+ No No
171 B/O Joythi 668961 V 2 Y A+ F 2.70 3.50 13.70 1.30 O+ No No
172 B/o Shruthi 662436 V 3 Y B+ M 2.90 3.10 13.00 1.10 B+ No No
173 B/O Rukumini 654860 V 2 Y A+ F 2.70 3.70 11.30 1.10 O+ N No
174 B/O Vijaya 654905 V 2 N O+ M 2.50 2.90 13.30 1.20 O+ N No

101