CORD BLOOD ALBUMIN LEVEL AS A

CORD BLOOD ALBUMIN LEVEL AS A

PREDICTOR OF NEONATAL PHYSIOLOGICAL JAUNDICE

MADURAI

2016

THE TAMILNADU DR M.G.R MEDICAL UNIVERSITY CHENNAI,TAMILNADU

BONAFIDE CERTIFICATE

This is to certify that the dissertation entitled “ CORD BLOOD ALBUMIN LEVEL AS A PREDICTOR OF NEONATAL PHYSIOLOGICAL JAUNDICE” by Dr.K.SENTHILKUMAR to the Faculty of PAEDIATRICS, The Tamil Nadu DR. M.G.R.MEDICAL UNIVERSITY,CHENNAI in partial fulfillment of the requirement for the award of M.D.PAEDIATRICS is a bonafied research work carried out by her under our direct supervision and guidance.

PROF DR.K.MATHIARASAN, M.D., DCH.,

DIRECTOR AND PROFESSOR OF PAEDIATRICS,

INSTITUTE OF CHILD HEALTH & RESEARCH CENTRE, MADURAI MEDICAL COLLEGE,

MADURAI.

CERTIFICATE FROM GUIDE

This is to certify that the dissertation entitled “ CORD BLOOD ALBUMIN LEVEL AS A PREDICTOR OF NEONATAL PHYSIOLOGICAL JAUNDICE” by Dr.K.SENTHILKUMAR to the Faculty of PAEDIATRICS, The Tamil Nadu DR. M.G.R.MEDICAL UNIVERSITY,CHENNAI in partial fulfillment of the requirement for the award of M.D.PAEDIATRICS is a bonafied research work carried out by her under our direct supervision and guidance.

PROF DR.K.MATHIARASAN, M.D., DCH.,

DIRECTOR AND PROFESSOR OF PAEDIATRICS,

INSTITUTE OF CHILD HEALTH & RESEARCH CENTRE, MADURAI MEDICAL COLLEGE,

MADURAI.

CERTIFICATE FROM DEAN

This is to certify that the dissertation entitled “ CORD BLOOD ALBUMIN LEVEL AS A PREDICTOR OF NEONATAL PHYSIOLOGICAL JAUNDICE” by Dr.K.SENTHILKUMAR to the Faculty of PAEDIATRICS, The Tamil Nadu DR. M.G.R.MEDICAL UNIVERSITY,CHENNAI in partial fulfillment of the requirement for the award of M.D.PAEDIATRICS.

Dr. M.R.VAIRAMUTHU RAJU MD, DEAN, MADURAI MEDICAL COLLEGE,

GOVERNMENT RAJAJI HOSPITAL, MADURAI.

DECLARATION

I, Dr. K. SENTHILKUMAR solemnly declare that the Dissertation titled

has been

prepared by me. This is submitted to the Tamilnadu Dr. M. G .R.

Medical University, Chennai in partial fulfillment of the rules and

regulations for award of the M.D.PAEDIATRICS.

Place: Madurai

Date:

ACKNOWLEDGEMENT

I thank the DEAN, Madurai Medical College and Government Rajaji Hospital, Madurai for permitting me to perform this study.

It is with immense pleasure and privilege that I express my heartfelt gratitude, admiration and sincere thanks to my chief

Director, Institute of Child Health, Govt. Rajaji Hospital for his support, guidance, supervision and constant encouragement throughout this study.

I wish to express my sincere thanks to my guide and teacher, Assistant Professor Dr. E. SIVAKUMAR MD ,

Dr .D.RAJKUMAR MD and Dr. P.MURUGALATHA MD ,

for

their valuable suggestion, support and guidance at every stage of this

study.

I wish to express my sincere thanks to all my chiefs and assistant Professor for their valuable suggestion, support and guidance at every stage of this study.

I also express my gratitude to all my fellow post graduates forn their kind cooperation in carrying out this study and for their critical analysis. I thank the ethical committee for granting me permission to conduct the study.

I would like to pay high regards to my dear wife , my parents and my child for their sincere encouragement and their never ending support throughout my research work and lifting me uphill this phase of life. I owe everything to them.

Besides this, several people have knowingly and unknowingly helped me in the successful completion of this project.

I thank all the neonates and parents who have congrudingly lent themselves to undergo this study without whom this study would have not seen the light of the day.

I am ever grateful to the ALMIGHTY GOD for always showering his blessings on me and my family. I pray ALMIGHTY GOD to give me strength to achieve all my endeavour.

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 210 healthy term newborns. Cord blood was collected from the healthy term newborns delivered either vaginally or caesarean 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 bperiod

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 92.8% (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.

TABLE OF CONTENTS

SI.NO TITLE PAGE No.

1 INTRODUCTION 1

2 AIMS AND OBJECTIVES 4

3 REVIEW OF LITERATURE 5

4 METHODOLOGY 49

5 SATISTICAL METHODS 54

6 RESULTS AND OBSERVATIONS 55

7 DISCUSSION 86

8 CONCLUSION 93

9 BIBLIOGRAPHY 95

10 ANNEXURE

 PROFORMA 104

 KEY TO MASTER CHART 105

 MASTER CHART 106

1

INTRODUCTION

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The commonest abnormal physical finding during the first week of life is Neonatal Hyperbilirubinemia (NH). Clinical jaundice present in two third of newborn babies. Accumulation of unconjugated bilirubin results in yellowish discoloration of the sclera and skin in newborns,but in most infants this is a normal physiological phenomenon^.1

During first week of life NH affects nearly 60% of term and 80% of preterm neonates.6.1% normal newborn have a serum bilirubin over 12.9 mg%. 3% of normal term newborn has Serum bilirubin over 15mg%.Neonatal Hyperbilirubinemia (NH) is a cause of concern for the pediatrician as well as for the parents.⁴

Because of various reasons like to prevent nosocomial infections,economic constrains and naming ceremony etc, early discharge has become a common practice after normal vaginal delivery as well as LSCS in the healthy term newborns.

The most common cause for readmission (6.5% babies) during the early neonatal period^.2 is neonatal hyperbilirubinemia. Upto 4% of newborns babies who are readmitted to the hospital in their first week of life, among that 85% are for jaundice.³

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So, AAP recommends follow up visit for all newborn after 48 to 72 hours, if they are discharged early within first 48 hours of life⁵.

Because of limited follow up facilities in our country the above recommendation is not possible resulting in delay in recognition of jaundice which might result in bilirubin induced brain damage resulting in sequele which is very serious resulting in cerebral palsy, sensorineural deafness and intellectual disability.^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.

In India like developing countries because of limitation in NICU care,the ultimate aim should be early recognition and to make sure newborns gets benefited by early 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.

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OBJECTIVE OF THE STUDY

The present study is conducted to find out critical value of cord blood albumin in predicting the subsequent development of significant neonatal jaundice which will require interventions like phototherapy or exchange transfusion later. This helps us to decide an early discharge of the newborn in a resource limited setting.

AIM OF THE PRESENT STUDY :

 To evaluate the usefulness of umbilical cord blood albumin levels in predicting development of Neonatal Hyperbilirubinemia in healthy term infants.

 To predict the proportion of new born requiring intervention for NH (phototherapy or exchange transfusion) based on cord serum albumin level at birth , and hence predicting the early discharge in a resource limited setting.

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REVIEW OF LITERATURE.

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

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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 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 blood¹¹

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

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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

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 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 1903,Schmrol,coined the term Kernikterus.¹⁹

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,

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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

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

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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

FETAL BILIRUBIN METABOLISM

Conjugated bilirubin formation in the fetus is limited because of decreased fetal hepatic blood flow, decreased hepatic ligandin and decreased UDPG-T activity,but unconjugated bilirubin in fetus is cleared by placenta into maternal-circulation.

Uridine diphosphoglucuronyl transferase (UDPGT) is detectable at 18 – 20 weeks.At birth UDPGT levels are only 0.1% of adult value, by 6–14 weeks of postnatal life,adult level is reached.³²

Bilirubin is detected in normal amniotic fluid as early as 12 weeks of gestation, but usually disappears by 36- 37 weeks.⁴

During neonatal period there occurs a transition,in which unconjugated bilirubin which was mainly excreated by placenta becomes conjugated and hepatic cells play a major role in excreation via biliary system and gastrointestinal tract^.33

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NEONATAL BILIRUBIN METABOLISM

Source of bilirubin⁴

It is mainly derived from breakdown of heme containing protein in reticuloendothelial system.

1. 75% is produced from breakdown of RBCs.

2. 25% (called early labeled bilirubin) derived from ineffective erythropoiesis in the bone marrow, from other heme containing proteins in tissues

(ex : myoglobin, cytochromes, catalase,peroxidase) and from free heme.

Bilirubin synthesis

Step 1- Heme is converted to biliverdin by heme oxygenase,where ,1 molecule of ferrous ion and 1 mol of carbonmonoxide is released. It is the rate limiting step and upregulated during hemolysis.³⁴

Step 2-Biliverdin is converted to bilirubin.³⁴ by bilirubin reductase in cytosol.

Bilirubin uptake⁴ and conjugation:

Bilirubin released in plasma is bound to albumin,which does not enter central nervous system and is non toxic,non polar fat soluble bilirubin dissociated from albumin,croses hepatocyte plasma membrane and is bound mainly to cytoplasmic ligandin(Y-protein)for transport to smooth endoplasmic reticulum

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where unconjugated bilirubin is converted to conjugated bilirubin by URIDINE DIPHOSPHATE GLUCURONYL TRANSFERASE-T which catalyzes the formation of bilirubin monoglucuronide. Both mono and diglucuronide¹¹ forms of conjugated bilirubin are able to be excreted into the bile canaliculi against concentration gradient.

12

13

Fig : Bilirubin Metabolism⁴⁰

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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

Among the total plasma proteins albumin forms about 60%,which about 40% is seen in plasma and rest in extracellular space,it is a preproprotein³⁵

It has been long known that animal and human fetuses are capable of endogenous albumin synthesis from early pregnancy onwards. All albumin in the 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

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Albumin synthesis 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% plasma oncortic pressure,it has antioxidant³⁶ property,it carries bilirubin,free fatty acids,cysteine etc.

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

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

Albumin concentration increases as postnatal age increases, 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

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hemoglobin breakdown products and fatty acids, the latter found in high amounts in postnatal nutrition (breast milk).³⁶

An important fact is that only free bilirubin croses blood brain barrier and cause neurotoxicity so albumin level plays an important role in hyperbilirubinemia and neurotoxicity in neonates.

ETIOLOGY OF HYPERBILIRUBINEMIA IN NEWBORN:

Neonatal jaundice is broadly classified as, 1)PHYSIOLOGICAL JAUNDICE

.2)PATHOLOGICAL JAUNDICE.

I. Physiologic jaundice⁴:

1. Due to increased bilirubin production-increased RBC volume per kilogram and decreased RBC survival (90 days versus 120 days) in infants.

2. Increased ineffective erythropoiesis and increased turnover of non hemoglobin heme proteins.

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

4. Decreased hepatic excretion of bilirubin.

5. Increased enterohepatic circulation due to high levels of intestinal β- glucuronidase enzyme, decreased intestinal bacteria, decreased gut motility.

6. Defective uptake of bilirubin from plasma due to decreased ligandin and binding of ligandin by other anions.

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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

 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,

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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.

 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

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c. Mixed

 Sepsis

 Intrauterine infections

 Toxoplasmosis

 Rubella

 Herpes simplex

 Syphilis, Hepatitis

 Respiratory distress syndrome

 Asphyxia

d. Uncertain mechanism

 Breast milk jaundice

 Chinese, Japanese, Korean and American indian infants.

CAUSES OF JAUNDICE ON THE BASIS OF AGE OF ONSET³⁹: 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

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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

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HIGH RISK FACTORS OF JAUNDICE^4,39

i. Prematurity.

ii. Low birth weight.

iii. Blood group incompatibility.

iv. Perinatal asphyxia.

v. Infant of diabetic mother.

vi. Intrapartum use of oxytocin.

vii. Problem in breastfeeding.

viii.

H/o Jaundice in previous siblings.

ix. Cephalhematoma or significant bruising.

CRITERIA FOR PHYSIOLOGICAL JAUNDICE:

 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.

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CRITERIA FOR PATHOLOGICAL JAUNDICE⁴

 Jaundice arising from pathologic process(es) which appears within first 24 hours after birth

 Characterized by rapidly rising serum bilirubin and or elevated direct bilirubin concentration (>34 micromols/L or >20% of total serum bilirubin)

 Combination of factors:

a) increased production (polycythemia, sepsis, bruising)

b)decreased excretion (bowel obstruction, poor feeding, acidosis)

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.

Late onset jaundice beginning after 5th day of life, more uncommon Peaks during second or third week and continues for several weeks Caused by increased reabsorption of unconjugated bilirubin, perhaps due to unidentified factor in human milk.

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APPROACH TO A CASE OF NEONATAL JAUNDICE:

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Identify “high risk³⁹” newborns at delivery likely to develop Jaundice.

 Ensure appropriate follow up for Jaundice.

 Emphasize need for early, exclusive breast feeds and ensure adequacy of breast feeding.

 Assess clinical condition (well or ill)

 Ascertain birth weight & gestation Evaluate Jaundice with post-natal age in hours

 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 orconvulsions)

 If Jaundice is pathological perform lab tests.

 Initiate appropriate measures to reduce elevated bilirubin

 Counsel parents.

COMPLICATIONS OF NEONATAL JAUNDICE

 Bilirubin encephalopathy refers to the clinical manifestations of the effects of bilirubin on the central nervous system,it is a multifocal process,where free bilirubin has access to blood brain barrier and cause neuropathological

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condition due to pigment deposition in in specific areas of the CNS such as basal ganglia, pons and cerebellum^.9 called kernicterus.

THEORIES ON HOW BILIRUBIN CROSSES BBB

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

I. Bilirubin is lipophilic and any condition causing increased free bilirubin or decreased 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

II. In this theory, the rate of tissue uptake of bilirubin depends on both the concentration of albumin-bound bilirubin and the pH. Low pH increases deposition and increased uptake of bilirubin.

III. Third theory suggests that bilirubin traverses only damaged blood brain barrier.⁹

IV. 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

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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

Bilirubin encephalopathy:

Normally, hyperbilirubinemia resolves on its own as the infant processes the bilirubin and excretes it.

However, in some infants, it can become harmful and will need treatment. If not detected or left untreated and levels rise too high, some of the bilirubin may cross the blood brain barrier and settle into brain tissue where it can cause acute bilirubin encephalopathy (ABE).

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This encephalopathy, if not detected early and treated, can develop into kernicterus. Kernicterus is a potentially fatal disease and results in permanent injury to specific parts of the brain.

To help quantify the degree of ABE, the Bilirubin-Induced Neurological Dysfunction (BIND) score was developed. It describes three phases of worsening encephalopathy and the clinical signs in each phase:

Clinical features⁴

Initial phase:

 lethargy, decrease in tone or activity

Intermediate phase:

 moderate stupor, irritability and variable activity

 increased tone, some retrocollis/opisthotonus

 minimal feeding, high-pitched cry

Advanced phase:

 deep stupor to coma, hypertonicity

 retrocollis/opisthotonus

 no feeding, shrill cry, seizures, death.

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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

Infant Cry Analysis

Nuclear Magnetic Resonance Techniques

These techniques are used for predicting acute brain cell injury in the face of hyperbilirubinemia

Evaluation and diagnosis of neonatal jaundice:

Kramer staging can be used as a clinical guide⁴⁵ in assessing level of jaundice:

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.

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Kramer’s Dermal staining for clinical assessment of jaundice⁴⁵

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. But Physical examination is not a suitable measure of serum bilirubin estimation.⁴

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LABORATORY INVESTIGATIONS

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.

 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 < 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,Salicylates)

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Management guidelines:

Management is mainly based on total serum bilirubin level,standard charts are used and either phototherapy or exchangetransfusion is planned based on guidelines to prevent brain damage due to hyperbilirubinemia.

Principles of treatment in Jaundiced neonates according to 2006 IAP NNF guidelines are.³⁹

i. Treatment decisions are based on total serum bilirubin.

ii. Gestation is more important than birth weight of the baby. A higher cut off can be used for a small for date baby.

iii. Post natal age in hours should be considered when deciding treatment

iv. Sick baby refers to presence of asphyxia, hypothermia, sepsis, acidosis, hypoxia, hypercapnia and evidence of haemolysis.

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GUIDELINES FOR PHOTOTHERAPY AND EXCHANGE TRANSFUSION Guidelines 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.

Guidelines for phototheraphy in hospitalized infants of 35 or more weeks’

gestation³³

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Guidelines for exchange transfusion in hospitalized infants of 35 or more weeks’ gestation³³

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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.

Effectiveness of phototherapy = Area of skin exposed + Radiant energy + Wavelength of light used.

Phototherapy acts on unconjugated bilirubin to a depth of 2 to 3 mm. Through photoisomerization, fat soluble molecules are reconfigured to water soluble molecules and are excreted by the liver without actual conjugation. 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.

35

Configurational photoisomerization:

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:

Blue ligh phototherapy is more effective than white light. Both units are also available in our country.Infants are placed in light source from distance of 45cm,it can be reduced to 15 to 20cm for more intense phototherapy.

Care for newborns receiving phototheraphy:

 The eyes and genitals should be covered during phototherapy.

 Continuous Breast feeding with 10-20% extra IV fluids are provided.

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 Continuous monitoring of 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.

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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

 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.

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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

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INDICATION

i. The newborn shows signs of acute bilirubin encephalopathy (hypertonia, arching, retrocollis, opisthotonos, fever, high pitched cry)

ii. TSB is ≥ 5 mg/dl (85 μmol/L) iii. Isoimmune hemolytic disease

iv. G6PD deficiency, asphyxia, significant lethargy, sepsis, acidosis

CHOICE OF BLOOD

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. [160ml/kg]. This replaces the 87% of infant’s blood volume with new blood.

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TECHNIQUE

a. Exchange transfusion is done by push pull technique through the umbilical vein inserted only as far as required to permit the free blood exchange.

b. 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.

c. 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

 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.

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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 factors³⁵ . 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

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PHARMACOLOGICAL MANAGEMENT

I. 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.

DOSAGE-10mg/kg i.m single dose 5mg/kg/day bid * 3 days

INDICATION: In cases of cord serum bilirubin level of >2.5mg/dl, early onset of jaundice due to any cause, difficult or instrumental delivery,Oxytocin induced delivery with bruising and cephalohematoma.

II. 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.

III. AGAR

It is a sea weed extensively used in processing of food. In dose of 250mg 6^th hourly orally it binds conjugated bilirubin in the gut and blocks the enterohepatic circulation. Its use is unpredictable and variable.

IV. CHOLESTYRAMINE

Enchances fecal excreation of bilirubin and prevents enterohepaic circulation.

DOSAGE-1.5mg/kg/day in 4 divided doses by mixing with milk SIDE EFFECTS

constipation,intestinal obstruction,hypercoleremic acidosis.

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V. OROTIC ACID:

It is a metabolic precursor of uridine diphosphate glucuronic acid and thus promotes the conjugation of bilirubin. Very costly.

VI. TIN MESOPORPHYRIN(SNMP)

Metalloporphyrins (Tin and Zinc) are structural analogs of heme. Inhibits heme oxygenase by decreasing bilirubin production.

DOSAGE: 6 μmol/kg/single dose IM

SIDE EFFECT-photo sensitive rash,renal toxicity.

VII. ALBUMIN INFUSION

Effective removal of bilirubin. and also improves the bilirubin binding capacity of the baby.

DOSAGE:1g/kg.

SIDE EFFECTS: over load ,viral infections.

VIII. IVIG AND IV HYDRATION Used mainly in hemolytic jaundice, DOSAGE: 500 -1 g /kg

SIDE EFFECTS: NEC, intestinal injury.

SUPPORTIVE MEASURES

 Drugs known to aggravate jaundice or block the bilirubin binding sites on albumin should be withheld.

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 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.

PREDICTION OF NEONATAL HYPERBILIRUBINEMIA

In the first week of life Jaundice will occur in 60% of term & 80% of preterm infants.Up to 4% of term newborns who are readmitted to the hospital during their first week of life, among that 85% are readmitted for Jaundice.

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.

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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 this study shows the umbilical cord blood bilirubin was predicting the development of significant hyperbilirubinemia in healthy newborn.

84 healthy newborn infants were enrolled and followed up for first 5 days of life.

Newborn babies were divided into two groups.

 Group-I consisted of 71 babies, who did not develop significant hyperbilirubinemia (TSB <17mg/dl);

 Group-II consisted of 13 babies, who developed significant hyperbilirubinemia (TSB >17mg/dl) during the follow up.

 Male-46 (55%), female38 (45%).

 Term babies 64 (76%), pre-term babies 20 (24%).

pre-term babies developed hyperbilirubinemia.in the significant persantage. 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

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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

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 :

Risk designation of term and near-term well newborns based on their hour specific serum bilirubin values

.

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There are limited studies done using either total protein or cord serum albumin measurement as a risk indicator for predicting significant neonatal hyperbilirubinemia.

Suchanda Sahu et al. / Int J Biol Med Res. 2011; 2(1): 436-438 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 BLOOD ALBUMIN LEVELS

<2.8 gm/dl 2.8 – 3.3 gm/dl

>3.3 gm/dl

Number of neonates (n) 17 15 8

Neonates developing hyperbilirubinemia

14 (82.5%) 6 (40%) 0

Number of newborns requiring phototherapy

14 (82.35%) 6 (40%) 0

Number of newborns requiring exchange transfusion

2 (11.8%) 0 0

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Group1 – 82% newborns developed significant Neonatal Hyperbilirubinemia, Group2 – 40% 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. Among the total number of babies 205(33.88%) babies developed significant NH.

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

 12.68% babies had cord serum albumin level >3.5g/dl.

This study concluded that cord serum albumin gives additional clue in visualizing future significant NH.⁵⁷

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METHOD AND MATERIAL

The present study was conducted in Institute of Child Health & Research Centre, Govt Rajaji Hospital, Madurai Medical College, Madurai. The study cohort consists of 210 randomly selected eligible term neonates delivered at Department of obstetrics and Gynaecology, Govt. Rajaji Hospital

Madurai., from OCTOBER 2015 – MARCH 2016.

This study was approved by the Research Ethics Committee of Madurai medical college, Madurai.

INCLUSION CRITERIA

Term babies

Both genders

Mode of delivery ( normal and LSCS)

Birth weight >2.5kg

APGAR > 7/10 at 1st and 5th min of life

EXCLUSION CRITERIA

 Preterm

 Rh incompatibility.

 Neonatal sepsis.

 Instrumental delivery (forceps and vacuum)

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 Birth asphyxia.

 Respiratory distress Syndrome

 Meconium stained amniotic fluid.

 Neonatal jaundice within 24 Hours of life.

METHOD OF COLLECTION OF DATA

1. Newborn were enrolled in the study after getting an informed consent from the parents of the newborn.

2. A structured proforma was used t collect data on Demographic profile and relevant information by interviewing the mother and from mother’s case sheet.

3. New Ballard score (if LMP not sure) was used to assess the gestational age.

4. Cord Serum Albumin level estimation was done 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.

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LABORATORY INVESTIGATION:

Cord blood (2ml) was collected from placental side after its separation and was investigated for:

 Cord Serum Albumin level

At 72 to 96 hours of life, Venous blood samples were collected from the baby.

These samples were collected and investigated for

 Total and Direct Serum Bilirubin.

 Blood group analysis.

Laboratory Procedures:

a) Cord blood collected at birth was analyzed by auto analyzer method for Cord Serum Albumin estimation.

Fig : Autoanalyser Machine used for cord serum albumin estimation.

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b. Venous blood sample was collected and stored away from light. The sample was refrigerated between 2 -8 degree C till serum bilirubin estimation is done. Serum bilirubin estimation was done within 12 hours of collection of sample. 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

c. 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.

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Fig : Antisera bottles with slides showing 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⁽⁷¹⁾.

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STATISTICAL METHODS^{69 ,70}

Descriptive and inferential statistical analysis has been carried out in our 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:

i. Dependent variables should be normally distributed,

ii. 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.

Diagnostic statistics such as Sensitivity, Specificity, PPV, NPV, were obtained to prediction potential of Cord Serum albumin Albumin level as a risk indicator for neonatal hyperbilirubinemia.

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RESULTS

In our study, we enrolled a total of 210 term healthy newborns. Out of which 28 developed hyperbilirubinemia. The incidence from our study was 13.3%.

GENDER

Table 6: Gender distribution of newborns Graph 6: Gender distribution of newborn

This table shows the gender distribution of newborn in the study group.

116(55%) were male and 94(45%) were female newborns

Gender

116 55.2 55.2 55.2

94 44.8 44.8 100.0

210 100.0 100.0

Male Female Total Valid

Frequency Percent Valid Percent

Cumulativ e Percent

male female

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Table : Comparison of Gender with CSA Graph : Correlation of Gender with CSA

This table showing Gender with cord albumin level.

There is no statistical significance noted in the present study

Crosstab

19 58 39 116

40.4% 65.2% 52.7% 55.2%

28 31 35 94

59.6% 34.8% 47.3% 44.8%

47 89 74 210

100.0% 100.0% 100.0% 100.0%

Count

% wit hin Cord Serum Albumin Count

% wit hin Cord Serum Albumin Count

% wit hin Cord Serum Albumin Male

Female Gender

Total

< = 2.8 2.9 - 3. 3 >= 3.4 Cord Serum Albumin

Total

0 10 20 30 40 50 60 70

<=2.8 2.9 - 3.3 >=3.4

Percentage

cord serum albumin (g/dl)

Male female

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Table : Comparison of Gender with PT.

Graph : Correlation of Gender with PT

This table showing Gender with PT.

There is no statistical significance noted in the present study Crosstab

13 103 116

46.4% 56.6% 55.2%

15 79 94

53.6% 43.4% 44.8%

28 182 210

100.0% 100.0% 100.0%

Count

% wit hin PT Count

% wit hin PT Count

% wit hin PT Male

Female Gender

Total

Y es No

PT

Total

0 10 20 30 40 50 60

male female

Percentage

gender

yes no PT

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MODE OF DELIVERY

Table : Mode of delivery

Graph : Distribution of Mode of delivery

This table shows the mode of delivery in the study group. Majority of thenewborn in the study group were delivered by labour natural which constitutes 134 out of 210 (64%)

Mode of delivery

76 36.2 36.2 36.2

134 63.8 63.8 100.0

210 100.0 100.0

LSCS LN Total Valid

Frequency Percent Valid Percent

Cumulat iv e Percent

LSCS LN

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Table : Comparison table of mode of delivery and CSA

Graph : Comparison of mode of delivery and CSA level in Study cohort.

This table shows the comparison of cord albumin groups with mode of delivery.

No statistical significance is seen.

Crosstab

17 29 30 76

36.2% 32.6% 40.5% 36.2%

30 60 44 134

63.8% 67.4% 59.5% 63.8%

47 89 74 210

100.0% 100.0% 100.0% 100.0%

Count

% wit hin Cord Serum Albumin Count

% wit hin Cord Serum Albumin Count

% wit hin Cord Serum Albumin LSCS

LN Mode of deliv ery

Total

< = 2.8 2.9 - 3.3 >= 3.4 Cord Serum Albumin

Total

0.00%

50.00%

100.00%

LSCS LN TOTAL

36.20%

63.80%

100%

32.60%

67.40%

100%

40.50%

59.50%

100%

Mode of Delivery vs Cord Serum Albumin

<=2.8 mg/dl 2.9-3.3 mg/dl >=3.4 mg/dl