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Approach to the diagnosis of Neonatal jaundice

By

Gelaye Mandefro

Ambo Universit

y

Department of

Medicine

August 2015

outline Definitions

Clinical classification

Clinical Assessment

Principles of management

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Definition and Basic concept

Jaundice is the visible manifestation of increased level of

bilirubin in the body

It is not a disease rather a symptom of diseases

In adults sclera appears jaundiced when serum bilirubin

exceeds 2 mg/dl

However it is difficult to see sclera in newborn due to difficulty

in opening eye

But in new born it is very easy to see jaundice in skin.

Definition and Basic concept…

Burden:

Important problem in the 1st week of life

Almost all neonates (60% Term and 80% Preterm) will have bilirubin >

5 mg/dl in the 1st week of life and become visibly jaundiced, vast

majority being benign

Some of the term babies (8 to 9%) have levels exceeding 15 mg/dl in

1st 7 days of life

High bilirubin level is toxic to the developing CNS(KERNICTERUS;

Bilirubin≥25mg/dl)

Definition and Basic concept…

Bilirubin:

End product of hemoglobin metabolism that is excreted in bile

In neonates

-75% : from catabolism of circulating RBCs

-25% :*from ineffective erythropoiesis (bone marrow)

*from turnover of heme proteins & free heme(liver).

Normal Bilirubin Metabolism

Hemoglobin----Bilivervdin-----Bilirubin---Uptake in the liver---

Conjugation----Excretion

Unconjugated bilirubin bind albumin

Unconjugated and un bound bilirubin cross blood brain barrier

Conjugated bilirubin (direct bilirubin) is non toxic to the brain and

not cross blood brain barrier

Conjugated bilirubin is excreted via bile ducts to the gut and pass

through feces

Conjugated bilirubin damages liver if not excreted

Neonatal jaundice

Clinical classification

1. Physiologic Jaundice

Jaundice becomes evident as physiologic in neonates B/c :

Short life span of RBCs(70-90days)

RBC mass is increased

Immature ligandine

Less UDPGT

High activity β-glucuronidase (gut)

Decreased flora in the gutcommon neonatal problems

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05/03/23

Preterm Term

Peak time 4th -7th days 2nd – 4th day

Peak level 8 – 12 mg/dl 5 -6 mg/dl

Resolution time

Before 10th day

5th – 7th day

common neonatal problems

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Clinical classification…Physiologic jaundice ( Icterus neonatorum)

05/03/23

Clinical classification…

2. Pathologic jaundiceJaundice detected on the first day of life

Jaundice persisting more than two weeks

Jaundice rising at a rate more than 0.5mg/dl/hr

Direct bilirubin more than 2mg/dl

Underlying systemic illness

Clinical classification…Physiologic Vs pathologic

Signs PhysiologicJx Pathologic JxClinical Jx Visible in 2-3day With in 24hrs

TSB rise <5mg/dl/day >5mg/dl/day

TSB Term<12mg/dl Preterm<15mg/dl

Term>12g/dl Preterm>15mg/dl

Conj BBn <1.5mg/dl >1.5(2)mg/dl

Jaundicepersisting

Term <1 week Preterm <2weeks

Term >1week Preterm >2weeks

common neonatal problems

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Causes of pathologic jaundice

Increased production Hemolytic diseases (ABO and RH)

Enclosed hemorrhage

Polycythemia

Decreased clearance Sepsis

Prinatal asphyxia

Prematurity

Hypothyroidism

Crigler-Najjar syndrome

Causes of pathologic jaundice

Increased enterohepatic circulation

Breast milk jaundice

Gastro intestinal obstruction

Breast feeding jaundice

Obstructive lesions (Direct Bilirubin)

Choledochal cyst

Biliary atresia

Sepsis and congenital infections

Causes of pathologic jaundice…

Blood Group Incompatibilities

Rh negative mother & Rh positive infant

ABO incompatibilities

Strongly considered if there is jaundice in the first 24 hours of lifeNon-Immune Hemolytic Anemias:

G6PD Deficiency:

Deficiency-decreased NADPH- decreased reduced Glutathione –

decreased protection of RBCs from oxidants-hemolysis

Causes of pathologic jaundice…

Structurally Abnormal RBCs: Spherocytosis

Pyknocytes ( irregular borders)

Thyroxine Deficiency: Thyroxine increases the activity of Glucoronyl transferase which promotes

conjugation of bilirubin.

Inhibition of Conjugation: Sulfonamides and Vitamin K results in competitive conjugation inhibition of bilirubin. GALACTOSEMIA:

Absent or deficient Galactose 1-phosphoate uridyl transferase which is needed in

glucoronidaton of indirect bilirubin.

RH hemolytic disease

RH negative woman conceiving RH positive fetus

IgG crosses the placenta and results in fetal red blood cell hemolysis

Anemia, jaundice, heart failure and generalized edema (hydrops fetalis) develop in utero

Affected new borns are delivered prematurely and may be still birth

Moderately affected new borns may show anemia, hepatosplenomegaly and signs of congestive heart failure

Early exchange transfusion is life saving

Unsensitized woman should take anti –D every delivery of RH positive neonate

Jaundice Risk Factors for Neonatal Hyperbilirubinemia

Jaundice visible on the 1st day of life

A sibling with neonatal jaundice or anemia

Unrecognized hemolysis (ABO, Rh, other blood group, incompatibility); UDP-

glucuronyl transferase deficiency (Crigler-Najjar, Gilbert disease)

Non-optimal feeding (formula or breast-feeding)

Deficiency of glucose-6-phosphate dehydrogenase

Infection (viral, bacterial). Infant of diabetic mother. Immaturity (prematurity)

Cephalohematoma or bruising. Central hematocrit >65% (polycythemia)

East Asian, Mediterranean, Native American heritage

Clinical assessment of jaundice

Jaundice in the newborn progresses in cephalocaudal direction Face =5-7mg/dlChest =10mg/dllower abdomen /thigh= 12mg/dlSole/palms≥15mg/dl

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Work up neonates with JxHistory

Age of onset

Family history of Jaundice,pallor,splenectomy

Previous sibling with Jaundice

Maternal illness during pregnancy

Maternal drug intake

Delivery history e.g. PROM ,sepsis, prolonged labor

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Cont’d

P/EProper classification of the newborn according to GA, & wgt.

Pallor, petechea

Bruises and cephalhematoma

Dark urine and clay colored stool

Examination geared to specific cause

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Schematic approach to the diagnosis of neonatal jaundice

Investigations

TSB with conjugated fraction

Hct with RBC morphology and reticulocyte count

Bg of the baby with direct coomb’s test

Bg of the mother with indirect coomb’s test.

Specific investigations for suspected specific problems

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Management

Aim lower serum billirubin decrease neurtoxicity

Principles of treatment Avoid drugs w/c interfere with BBn metabolism Treat factors w/c↑ neurotoxicity Give adequate feeding Specific therapy Decrease serum billirubin

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Management…

Physiological jaundice Explain about benign nature of the disease

Encourage to breastfeed frequently & exclusively

Ask Mother to bring baby back if baby looks deep yellow or palms &

soles have yellow staining.

Pathological jaundice

Mainly 2 modalities of treatment:

Phototherapy

Exchange transfusion

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Management…

Lower serum Billirubin Phototherapy Exchange transfusion

1. Phototherapy Mainstay of treatment

Under blue-green light(460-490nm), insoluble bilirubin is converted into

soluble isomers that can be excreted in urine & feces. Indicated when TSB rises more than normal but not exchange

transfusion level May be therapeutic or prophylactic

To be effective, bilirubin must be present in skin; hence nor role for

prophylactic phototherapy

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Prophylactic phototherapyINDICATIONS

RH isoimmunization with sever hemolysisBirth weight<1000gm(EVLBW)Sever multiple bruises

SIDE EFFECTSErythematous skin rashRetinal damageIncreased insensible water lossBronze baby syndromeLoose stoolLow calcium

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Exchange transfusion( ET)Most effective way of treating Jaundice and anemiaCould be partial or double exchange transfusion

INDICATIONSRh isoimmunization with hydrops fetalisCord blood Billirubin >5mg/dlRise in Billirubin >0.5mg/dl/hr despite phototherapyHemoglobin <11gm/dlTSB >20mg/dlVLBW, preterm, sepsis

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Choice of blood for exchange BT

ABO incompatibility Use O blood of same Rh type

Rh isoimmunization Emergency 0 -ve blood Ideal 0 -ve suspended in AB plasma or baby's blood group but Rh –ve

Other situations Baby's blood group

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Exchange transfusionCOMPLICATIONS

Portal vein thrombosis Umbilical vein perforation/bleeding Necrotizing enterocolitis Cardiac arrest/arrhythmia Hypoglycemia, hypocalcemia,

hypomagnisemia, hyperkalemia Increased risk of infection Respiratory and metabolic acidosis

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KERNICTERS (Billirubin encephalopathy)

Definition: neurologic syndrome resulting from deposition of unconjugated billirubin in brain cells .

Sites of billirubin staining and necrosis include -Basal ganglia , Hippocampal cortex, Sub

thalamic nucleus & cerebellum Cerebral cortex is spared

Half of the neonates with kernicters at autopsy have extra neuronal lesions

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Pathophysiologic mechanism

Unconjugated BBn is nonpolar ,lipid soluble and can traverse BBB.

Factors that ↑ billirubin toxicity Hypoxia (asphyxia) Hypothermia & hypoglycemia sepsis Prematurity Acidosis Hypoalbuminemia

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Clinical progression of encephalopathy34

Thank you!35