IndianJ. Pedlatr. 44 : 220, 1977

For General Praotioners

SOME PRACTICAL ASPECTS OF NEONATAL JAUNDICE* MEHARBAN SlNGH

New Delhi

Jaundice is the commonest abnormal physical finding during the first week of life. Clinical jaundice in the newborn manifests

itself at a serum bilirubin level cff 4 mg per 100 ml and is first evident over the skin of

the face, especially around the naso!abial

folds (Singh and Ghai 1976). The yellow

discoloration can be better visualised by

blanching the plethoric skin of the baby.

Scleral conjunctiva is difficult to inspect in

the neonate because of physiological photo-

phobia. I t is essential that a newborn baby be examined for the presence of jaundice at least twice a day during the first week of life. The jaundice must be

looked for in good daylight and there

should be no yellow clothes or curtains in

the background.

Clinical Asses sment of Severity of Jaundice

Jaundice is first seen over the skin of the face when the serum bilirubin level rises

to about 4-5 mg per 100 ml. Subsequently,

with further increase in serum bilirubin, the skin of the trunk becomes yellow stained

(serum bilirubin around 10 mg per I00 ml). Yellow staining of the palms and the soles

suggests that serum bilirubin is at least

15 mg per 100 ml or above. The clinical

observations, however, must be confirmed

by laboratory estimation of serum bilirubin

when jaundice is of moderate severity.

*From the All India Institute of Medical Sciences,

New Delhi-ll0016.

Received on July 30, 1977.

Causes of Jaundice The age at onset of jaundice gives an

impor tant clue to the possible aetiology (Table). The appearance of jaundice

during the first day of life is always sugges-

tive of a serious disease process and such a

baby should preferably be transferred to a

centre where adequate facilities for neo-

natal care are available. The common causes of jaundice in the newborn in our

country in order of their frequency include

physiologic jaundice, immatur i ty , blood group incompat ibi l i ty between the mother

and the foetus, G-6-PD deficiency, infections both intrauterine and post natal , cephal-

haematoma, drugs and breast milk jaun-

dice. A brief description of these condi-

tions follows.

Physiologic jaundice About 60 per cent of term and 70 per cent

of pre term babies develop physiologic jaundice. I t is basically due to hepatic immatur i ty though more than one factor is

operative (Thaler t972). In term babies

physiologic jaundice appears between

30-72 hours of age, max imum intensity is seen on the 4th day when serum bilirubin

level may approach 12 mg per 100 ml and

it disappears by 7-10 days of age. The age

of onset of physiologic jaundice in preterm

babies is identical to the term babies but

jaundice is likely to be more severe (maxi- mum serum bilirubin up to 15 mg per

100 ml), and lasts longer.

sINGH--SOME PRACTICAL ASPECTS OF NEONATAL AUNDICE

T a b l e . Causes of jaundice on the basis of age at onset.

22I

v

I.

II .

I I I .

Within 24 houts of birth (a) Haemolytic disease of the newborn due to foeto-maternal blood group incompatibi-

(c)

(d)

lity in the Rhesus and ABO group systems.

(b) Intra-uterine infections.

Deficiency of glucose-6-phosphate dehydrogenase (G-6-PD).

Administration of large amounts of certain drugs such as vitamin K, salicylates,

sulfisoxazole etc. to the mother.

Between 2g-72 hours of age Physiologic jaundice appears during this period but can be aggravated and prolonged

by immat , r i ty (gestation of less than 37 weeks), birth asphyxia, drugs, cephalhaema- toma or bruises, cretinism, infections and breast milk.

Alter 72 hours of age (a) Septicaemia

(b) Neonatal hepatitis (c) Extra hepatic biliary atresia

(d) Breast milk jaundice

Physiologic jaundice does not need any therapy but the baby must be watched

closely for the severity of jaundice and presence of any adverse factors which may

aggravate and prolong the jaundice

(Table). The infant must be given ade- quate fluids and feeds and the mother

should be reassured about the benign

nature of the condition. V~tamin K should neveT be administered because it may aggravate jaundzce and lead to kernicte~us.

Haemolytic disea ~e of the newborn ( HDN) Haemolytic disease of the newborn

due to Rhesus and ABO incompatibility is the commonest cause of hyperbilirubinae- mia in the newborn.

Rhesu~ haemolytic disease of the newborn

In India about 5-7 per cent of the

population is Rh negative. There are no

inborn antibodies in the Rhesus blood

group system. During pregnancy, especial- ly after the first three months, when

placental circulation is well established,

foetal red blood cells may seep into the

maternal circulation. When an Rh negative mother is carrying an Rh positive foetus,

the antigen of the foetal red blood cells may invoke antibody response in the mater-

nal immunologic system. Enough anti-

bodies are not produced during the first

pregnancy but each subsequent pregnancy

with an Rh positive foetus leads to increas- ing antibody response.

There is a wide spectrum of clinical

manifestations and increasing severity of disease is encountered with each subse- quent pregnancy. The affected baby is

anaemic and has hepatosplenomegaly.

222 [NDIAN JOURNAL OF PEDIATRICS VOL. 44, No. 355

Jaundice appears within 24 hours of age

and rapidly increases in intensity. In severely affected infants, the clinical picture

is characterized by severe anaemia, gross hepatosplenomegaly and generalised ana-

sarca (hydrops fetalis). Diagnosis is suspected when an Rh

negative mother shows an increasing titre

of anti-D antibodies (Indirect Coombs test) during pregnancy. I t is supported by the findings of cord blood haemoglobin of less

than 12 G per 100 ml, bilirubin of more than 4 mg per 100 ml and confirmed by

positive direct Coombs test.

Prevention of Rhesus HDN The administration of anti-D globulin

to an unsensitized (Indirect Coombs test negative) mother soon after delivery is likely to destroy any Rh positive red blood

cells which might have seeped into the

maternal ciculation. The unsensitized Rh

negative mother should receive 250/~g of anti-D globulin within 72 hours of birth of each Rh positive baby or abortus. The protective efficacy of this prophylaxis is

up to 98 per cent though its universal appli- cability in our country is limited by its cost

and availability. I t is important that an Rh negative woman should never receive

Rh positive blood transfusion which can

cause 25 fold sensitization as compared to pregnancy with an Rh positive foetus.

ABO haemolytic disease of the newborn Foeto-maternal ABO incompatibility

exists in about 25 per cent of pregnancies but haemolytic disease develops in only

one in ten such offpsrings. The commonest foeto-maternal combinations are O group mother and A or B group foetus. Unlike Rh HDN, ABO haemolytic disease is

milder and a history of increasing severity

of the disease in subsequent pregnancies is generally not seen.

The diagnosis is suspected by early onset of jaundice in an A or B group infant of an O group mother. Anaemia and splenomegaly is seen in severely affected

cases. The diagnosis is confirmed by

demonstration of a high titre of IgG haemolysins in maternal blood against the baby's blood group. Reticulocytosis, micro-

spherocytosis and increased fragility of the red blood cells is often present. The Direct Coombs test is generally negative.

The disease cannot be predicted ante-

natally and is not preventable. The jaundice may reach critical levels especially in pre- term babies and may need exchange trans- fusion and other measures to reduce biliru- bin levels.

Glucose-6-phosphate dehydroget:ase deficiency The incidence of deficiency of G-6-PD

in blood ceils varies from 2-15 per cent in different ethnic groups in India (Das #t al. 1974). I t is inherited as a sex linked

recessive disorder though the female carrier may also manifest mild enzymatic defi- ciency. The haemolysis generally follows administration of certain oMdant drugs though it can follow infections or may occur spontaneously. The infant may receive the offending drug transplacentally,

through breast milk or directly. The jaun-

dice occurs any time during the neonatal period or subsequently and may be severe enough to require exchange transfusion.

Infections causing jaundice Intra-uterine infections such as toxo-

plasmosis, cytomegalic inclusion disease,

syphilis, herpes simplex and Au antigen

may cause giant cell hepatitis. Jaundice

S I N G H - - SOME P R A C T I C A L A S P E C T S OF N E O N A T A L J A U N D I C E 223

may occur any time during the neonatal period. Hepatosplenomegaly, petechiae and meningoencephalitis may be associated.

Bacterial septicaemia is an important cause of neonatal jaundice and should be consi-

dered when it appears after 3 days of age. The general inactivity, refusal of feeds, diarrhoea, abdominal distension, hypo- thermia and poor Moro response support the diagnosis of septicaemia. The direct reacting bilirubin is generally more than 2 mg per 100 ml in infants with hepatitis.

Drugs and neonatal jaundice Drugs may cause or aggravate neonatal

jaundice. Vitamin K in large doses, sali- cylates, sulfonamides, caffein and nitrofu- rantoin should be avoided during the first week of life. In addition to causing hyper-

bilirubinaemia, the drugs may predispose the baby to develop bitirubin brain damage

at Lower serum bilirubin IeveIs.

Cephalhaematoma Cephalhaematoma, bruising under the

skin and concealed internal haemorrhage

in the body cavities may cause or aggravate jaundice by virtue of red blood cells break- down and increased bilirubin load on the

liver. I f serum bilirubln approaches critical levels, the haematoma should be aspirated.

Breast milk jaundice The jaundice may start like physiologi-

cal jaundice or it may appear for the first

time at the end of the first weak (Leading

article 1970). I t is maximum in intensity

between 7-10 days and hyperbilirubinaemia is never severe enough to require exchange transfusion. The jaundice occurs either

due to inhibition of bilirubin conjugation

in the liver by 3 alpha, 20 beta pregnane-

diol excreted in the breast milk or as a result of high concentrations of unsaturated fatty

acids in the human breast milk. When the infant is taken off the breast, the

jaundice promptly clears.

Dangers of Neonatal Hyperbiliru- b inaemia

The main danger of hyperbilirubln-

aemia is its potentiality to cause brain damage in the newborn. Unconjugated bilirubin which is lipid soluble, is toxic to

the brain. The bilirubin in plasma exists mostly bound to albumin. The bilirubin albumin complex cannot permeate or leak

through blood vessels and hence is harmless. When the serum bilirubin level markedly

rises or if there is hypoalbuminaemia, free bilirubin accumulates which can diffuse readily into the interstitial fluid compart- ment and. enters the cells, particularly the

neurones located in the basal ganglia, hip- pocampus and auditory nuclei. An un-

conjugated serum bilirubin level of 20 mg

per 100 ml or bilirubin protein ratio of more than 3.5 is associated with bilirubin brain damage or kernicterus (Singh et al. 1974). Hypoxia, hypoglycaemia, hypother- mia, acidosis and immaturi ty predispose

the infant to manifest bilirubin encephalo- pathy at lower serum bilirubin levels.

Early features of kernicterus Lethargy, refusal of feeds, a shrill high

pitched cry and incomplete Moro response in a jaundiced neonate are suggestive of kernicterus. Subsequently convulsions, opisthotonus and the setting sun sign appear if t reatment is delayed. During infancy the sequelae of bilirubin brain damage

include cerebral palsy, choreo-athetosis,

brownish staining of teeth, deafness and

224 INDIAN JOURNAL OF PEDIATRICS VOL. 44, N o 355

various grades of intellectual retardat ion and learning disabilities.

Management of Hyperbilirublnaemla The aim of therapy is to ensure that

serum bilirubin is kept at a safe level and brain damage is prevented. Exchange

blood transfusion is the most effective and reliable method to reduce bilirubin when it approaches critical levels, t towever, other supportive and therapeutic measures may prevent excessive rise of serum bilirubin and reduce the need for exchange transffl-

sion.

Supportive measures 1. Adequate feeding

The hydrat ion should be maintained and hypoglycaemia prevented by early feeding when jaundice is anticipated or is

already present. Breast feeding should be

temporarily abandoned it breast milk jaun, dice is suspected.

2. Aspiration of cephalhaematoma The presence of critical hyperbilirubin-

aemia (serum bilirubin of 15 mg per 100 ml

or m o r e ) i n association with cephalhaema- toma is an indication for its aspiration.

3. Trea tment of sepsis and hepatitis

In case septicaemia is suspected, genta-

micin and penicillin should be administered. Corticosteroids are indicated when viral hepatitis is strongly suspected. Vitamin K should not be given.

/

Measures to reduce serum bilirubin levels

1, Phenobarbitone

It has been shown to induce the matu- ration of hepatic enzymes thus improving

uptake, conjugation and e.xcretion of biliru- bin by the liver (Singh and Narayanan 1974). I t can be administered to the

mother during 2 weeks prior to the expected date of delivery or given to the neonate

after birth. Its utility is prophylactic and is recommended in early onset (within

24 hours of age) of jaundice due to any

cause, ABO and Rh HDN, difficult delivery

with bruising and cephalhaematoma,

G-6.PD deficiency and the Crigler-Najjar syndrome. I t is administered orally in a

dose of 5.0 to 7.5 mg every 12 hours and

does not generally produce any sedation or

side effects.

2. Phototherapy Light causes photo oxidation of biliru-

bin to harmless substances. Blue light is

most effective but white or day light floures- cent tubes or sunlight can also be used.

The naked baby is exposed to light and his

position is changed frequently for maximum benefit. I t is indicated whenever serum

bilirubin approaches 10-12 mg per 100 ml

in preterm and 14-15 mg per 100 ml in term babies. I t is instituted only when the baby is jaundiced and not prophylacti-

cally unlike phenobarbitone. During exposure to light, the eyes must be pro-

tected effectively to prevent retinal damage

(Fig. 4, Plate I). The other side effects

include passage of greenish loose stools,

skin rash, hyperthermia and sometimes slow weight gain. Phototherapy should be instituted solely at cerztres where facilities for round the

clock eJtimation of serum bilirubin and exchange transfusion exist.

3. Agar

When given orally, agar (250 mg every 6 hours)interferes with the entero-hepatic

circulation of bilirubin and promotes its excretion in the stools.

s I N G I t - - S O M E PR A C TICAL ASPECTS OF NEONATAL J A U N D I C E 225

4. Albumin inflMon

Albumin infusion improves the bilirubin

binding capacity of the infant thus protect- ing him from its toxic effects. When administered (I G per kg as 25 per cent

salt free albumin), half to one hour before exchange transfusion, it facilitates more

effective rcmoval of bitirubin. It should

not be given to infants ,aith severe anaemia

and congestive heart lailure.

Exchange blood tran,*fiLsion This should be carried out in neonatal

centres with adequate special care facilities

and round the clock services for serum

bilirubin estimation. I t is indicated in the

tollowing situations:

I. Jaundice of any aetiology

Exchange transfusion is indicated when

serum unconjugated bilirubin approaches

20 mg per 100 ml or bilirubin protein ratio

exceeds 3.5. In preterm and sick babies,

it may be required even at lower serum

bilirubin levels. I f at any stage early signs

suggestive of kernicterus are manifested,

immediate exchange transfusion should be

done . However, a lusty term baby ui th a

serum bilirubin of around 20 mg per

I00 ml on the 5th or 6th day should not be

hurriedly exchanged because improving

hepatic maturity at this age is likely to

clear off the bilirubin spontaneously.

2. Rhesus haemolytic disease of the newborn

Exchange transfitsion is required

u,'gently soon after birth in the following situations.

(a) Maternal anti-D antibody titre

of 1:64 or more in a baby with positive

direct Coombs test and a history of a

severely affected previous sibling.

(b) Cord haemoglobin of 10 G per

100ml or less and bilirubin of 5 mg per

100 ml or more.

(c) Serum unconjugated bilirubin of

more than 10 mg per 100 ml within 24hours or a level of 15rag per 100ml

within 48 hours of age or if serum bilirubin

is rising at a r a t e o f 0.5rag per 1 0 0 m l p e r

hour or more.

R o l e o f Genera l P r a c t i t i o n e r and O b s t e t r i c i a n

All newborn babies must be examined

in good daylight at least twice a day

during the first week of life for detection of

onset of jaundice. The nurses and mid- wives must be trained in this art. Un-

necessaly medications should be avoided

to all neonates and vitamin K when needed

should never be administered in a dose

exceeding 1.0 rag. Physiological jaundice

should be recognized by its characteristic time table and the mother reassured about

its benign nature and spontaneous regres-

sion. Mothers andlor newborn babies

should be referred to a centre with ade- quate facilities for neonatal care, exchange

blood transfusion and bilirubin estimation

if the following conditions obtain:

1. History of severe neonatal jaundice in

previous sibling. 2. Rhesus negative mother especially if

indirect Coombs test is positive.

3. Neonate with early onset of jaundice (within 24 hours of age).

4. Moderately severe or prolonged neo-

natal jaundice.

It is important to remember that neo-

natal hyperbilirubinaemia is a medical ernergen 0 and delay in referral could

result in irreversible brain damage or

death.

226 INDIAN JOURNAL OF PEDIATRICS VOL. 44, No. 355

R e f e r e n c e s

Breast milk jaundice (1970). Leading article. Brit. Med. o7. 3, 178.

Das, B.N., Bhakoo, O.N. and Jolly, J.G. (1974). Neonatal hyperbilirubinaemia associated with G-6-PD deficiency. Indian Pediatr. 2, 645.

Singh i , , Patra, D.P., Seth. V., Vasuki, K. and Ghai, O.P. (1974). Evaluation of additional criteria

for exchange transfusion in the newborn. Indian

Pediatr. 2, 261. Singh, M. and Narayanan, P. (1974). Effect of

phenobarbitone on physiological jaundice. Indian

Pediatr, 2, 43. Singh, M. and Ghai, O.P (1976). Care of the

newborn. Sagar Publications, Delhi. Thaler, M.M. (1972). Neonatal hyperbillrubin-

aemia. Seminars in Hemat. 9, 107.