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 photophobia. It is essential that a newborn baby be examined for the presence of jaundice at least twice a day during the first week of life. T h e jaundice must be looked for in good daylight and there should be no yellow clothes or curtains in the background.
Clinical A s s e s s m e n t 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 i m p o r t a n t clue to the possible aetiology (Table). T h e appearance of jaundice during the first day of life is always suggestive of a serious disease process and such a baby should preferably be transferred to a centre where adequate facilities for neonatal care are available. The c o m m o n causes of jaundice in the newborn in our country in order of their frequency include physiologic jaundice, immaturity, blood group incompatibility between the mother and the foetus, G-6-PD deficiency, infections both intrauterine and post natal, cephalh a e m a t o m a , drugs and breast milk jaundice. A brief description of these conditions follows.
Physiologicjaundice About 60 per cent of term and 70 per cent of preterm babies develop physiologic jaundice. I t is basically due to hepatic i m m a t u r i t y though more than one factor is operative (Thaler t972). In term babies physiologic jaundice appears between 30-72 hours of age, m a x i m u m intensity is seen on the 4th day when serum bilirubin level m a y a p p r o a c h 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 (maxim u m serum bilirubin up to 15 mg per 100 ml), and lasts longer.
sINGH--SOME P R A C T I C A L
ASPECTS
Table.
OF NEONATAL
AUNDICE
22I
Causes of jaundice on the basis of age at onset.
v
I.
Within 24 houts of birth (a) Haemolytic disease of the newborn due to foeto-maternal blood group incompatibility in the Rhesus and ABO group systems. (b)
Intra-uterine infections.
(c) Deficiency of glucose-6-phosphate dehydrogenase (G-6-PD). (d) Administration of large amounts of certain drugs such as vitamin K, salicylates, sulfisoxazole etc. to the mother. II.
III.
Between 2g-72 hours of age Physiologic jaundice appears during this period but can be aggravated and prolonged by immat,rity (gestation of less than 37 weeks), birth asphyxia, drugs, cephalhaematoma 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 adequate 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 hyperbilirubinaemia 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, especially 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 maternal immunologic system. Enough antibodies are not produced during the first pregnancy but each subsequent pregnancy with an Rh positive foetus leads to increasing antibody response. There is a wide spectrum of clinical manifestations and increasing severity of disease is encountered with each subsequent pregnancy. The affected baby is anaemic and has hepatosplenomegaly.
222
[NDIAN
VOL. 44, No. 355
JOURNAL O F PEDIATRICS
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 anasarca (hydrops fetalis). Diagnosis is suspected when an Rh negative mother shows an increasing titre of anti-D antibodies (Indirect Coombs test) during pregnancy. It 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 H D N 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 applicability in our country is limited by its cost and availability. It 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, microspherocytosis and increased fragility of the red blood cells is often present. The Direct Coombs test is generally negative. The disease cannot be predicted antenatally and is not preventable. The jaundice may reach critical levels especially in preterm babies and may need exchange transfusion and other measures to reduce bilirubin 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). It is inherited as a sex linked recessive disorder though the female carrier may also manifest mild enzymatic deficiency. 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 jaundice 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 toxoplasmosis, cytomegalic inclusion disease, syphilis, herpes simplex and Au antigen may cause giant cell hepatitis. Jaundice
SINGH -- SOME PRACTICAL
ASPECTS
OF N E O N A T A L
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 considered when it appears after 3 days of age. The general inactivity, refusal of feeds, diarrhoea, abdominal distension, hypothermia 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.
JAUNDICE
223
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 Hyperbilirubinaemia
Cephalhaematoma, bruising under the skin and concealed internal haemorrhage in the body cavities may cause or aggravate jaundice by virtue of red blood cells breakdown and increased bilirubin load on the liver. I f serum bilirubln approaches critical levels, the h a e m a t o m a should be aspirated.
The main danger of hyperbilirublnaemia 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 compartment and. enters the cells, particularly the neurones located in the basal ganglia, hippocampus and auditory nuclei. An unconjugated 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, hypothermia, acidosis and immaturity predispose the infant to manifest bilirubin encephalopathy at lower serum bilirubin levels.
Breast milk jaundice
Early features of kernicterus
The jaundice may start like physiological jaundice or it may appear for the first time at the end of the first weak (Leading article 1970). It is m a x i m u m 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-
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 treatment is delayed. During infancy the sequelae of bilirubin brain damage include cerebral palsy, choreo-athetosis, brownish staining of teeth, deafness and
Drugs and neonataljaundice Drugs may cause or aggravate neonatal jaundice. Vitamin K in large doses, salicylates, sulfonamides, caffein and nitrofurantoin should be avoided during the first week of life. In addition to causing hyperbilirubinaemia, the drugs may predispose the baby to develop bitirubin brain damage at Lower serum bilirubin IeveIs.
Cephalhaematoma
224
INDIAN JOURNAL OF PEDIATRICS
various grades of intellectual retardation 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, ttowever, other supportive and therapeutic measures may prevent excessive rise of serum bilirubin and reduce the need for exchange transfflsion.
VOL.
44,
No
355
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. It 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.
Supportive measures 1. Adequate feeding The hydration 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 hyperbilirubinaemia (serum bilirubin of 15 mg per 100 ml or m o r e ) i n association with cephalhaematoma is an indication for its aspiration. 3.
T r e a t m e n t of sepsis and hepatitis In case septicaemia is suspected, gentamicin 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 maturation of hepatic enzymes thus improving uptake, conjugation and e.xcretion of bilirubin by the liver (Singh and Narayanan 1974). It can be administered to the
Phototherapy Light causes photo oxidation of bilirubin to harmless substances. Blue light is most effective but white or day light flourescent tubes or sunlight can also be used. The naked baby is exposed to light and his position is changed frequently for maximum benefit. It is indicated whenever serum bilirubin approaches 10-12 mg per 100 ml in preterm and 14-15 mg per 100 ml in term babies. It is instituted only when the baby is jaundiced and not prophylactically unlike phenobarbitone. During exposure to light, the eyes must be protected 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.
225
s I N G I t - - S O M E P R A C T I C A L ASPECTS OF N E O N A T A L J A U N D I C E
4.
Albumin inflMon
Albumin infusion improves the bilirubin binding capacity of the infant thus protecting 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.
(b)
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 d o n e . However, a lusty term baby u i t h 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.
10 G per
Role of General Practitioner Obstetrician
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. It is indicated in the tollowing situations:
Cord haemoglobin of
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 1 5 r a g per 1 0 0 m l 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. and
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 midwives must be trained in this art. Unnecessaly 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 regression. Mothers andlor newborn babies should be referred to a centre with adequate facilities for neonatal care, exchange blood transfusion and bilirubin estimation if the following conditions obtain: 1. 2. 3. 4.
History of severe neonatal jaundice in previous sibling. Rhesus negative mother especially if indirect Coombs test is positive. Neonate with early onset of jaundice (within 24 hours of age). Moderately severe or prolonged neonatal jaundice. It is important to remember that neonatal hyperbilirubinaemia is a medical ernergen0 and delay in referral could result in irreversible brain damage or death.
226
VOL. 44, No. 355
INDIANJOURNAL OF PEDIATRICS References
Breast milk jaundice (1970). Leading article. Brit. Med. o7. 3, 178.
Das, B.N., Bhakoo, O.N. and Jolly, J.G. (1974). Neonatal hyperbilirubinaemiaassociated 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 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 hyperbillrubinaemia. Seminars in Hemat. 9, 107. Pediatr.
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 photophobia. It is essential that a newborn baby be examined for the presence of jaundice at least twice a day during the first week of life. T h e jaundice must be looked for in good daylight and there should be no yellow clothes or curtains in the background.
Clinical A s s e s s m e n t 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 i m p o r t a n t clue to the possible aetiology (Table). T h e appearance of jaundice during the first day of life is always suggestive of a serious disease process and such a baby should preferably be transferred to a centre where adequate facilities for neonatal care are available. The c o m m o n causes of jaundice in the newborn in our country in order of their frequency include physiologic jaundice, immaturity, blood group incompatibility between the mother and the foetus, G-6-PD deficiency, infections both intrauterine and post natal, cephalh a e m a t o m a , drugs and breast milk jaundice. A brief description of these conditions follows.
Physiologicjaundice About 60 per cent of term and 70 per cent of preterm babies develop physiologic jaundice. I t is basically due to hepatic i m m a t u r i t y though more than one factor is operative (Thaler t972). In term babies physiologic jaundice appears between 30-72 hours of age, m a x i m u m intensity is seen on the 4th day when serum bilirubin level m a y a p p r o a c h 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 (maxim u m serum bilirubin up to 15 mg per 100 ml), and lasts longer.
sINGH--SOME P R A C T I C A L
ASPECTS
Table.
OF NEONATAL
AUNDICE
22I
Causes of jaundice on the basis of age at onset.
v
I.
Within 24 houts of birth (a) Haemolytic disease of the newborn due to foeto-maternal blood group incompatibility in the Rhesus and ABO group systems. (b)
Intra-uterine infections.
(c) Deficiency of glucose-6-phosphate dehydrogenase (G-6-PD). (d) Administration of large amounts of certain drugs such as vitamin K, salicylates, sulfisoxazole etc. to the mother. II.
III.
Between 2g-72 hours of age Physiologic jaundice appears during this period but can be aggravated and prolonged by immat,rity (gestation of less than 37 weeks), birth asphyxia, drugs, cephalhaematoma 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 adequate 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 hyperbilirubinaemia 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, especially 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 maternal immunologic system. Enough antibodies are not produced during the first pregnancy but each subsequent pregnancy with an Rh positive foetus leads to increasing antibody response. There is a wide spectrum of clinical manifestations and increasing severity of disease is encountered with each subsequent pregnancy. The affected baby is anaemic and has hepatosplenomegaly.
222
[NDIAN
VOL. 44, No. 355
JOURNAL O F PEDIATRICS
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 anasarca (hydrops fetalis). Diagnosis is suspected when an Rh negative mother shows an increasing titre of anti-D antibodies (Indirect Coombs test) during pregnancy. It 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 H D N 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 applicability in our country is limited by its cost and availability. It 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, microspherocytosis and increased fragility of the red blood cells is often present. The Direct Coombs test is generally negative. The disease cannot be predicted antenatally and is not preventable. The jaundice may reach critical levels especially in preterm babies and may need exchange transfusion and other measures to reduce bilirubin 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). It is inherited as a sex linked recessive disorder though the female carrier may also manifest mild enzymatic deficiency. 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 jaundice 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 toxoplasmosis, cytomegalic inclusion disease, syphilis, herpes simplex and Au antigen may cause giant cell hepatitis. Jaundice
SINGH -- SOME PRACTICAL
ASPECTS
OF N E O N A T A L
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 considered when it appears after 3 days of age. The general inactivity, refusal of feeds, diarrhoea, abdominal distension, hypothermia 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.
JAUNDICE
223
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 Hyperbilirubinaemia
Cephalhaematoma, bruising under the skin and concealed internal haemorrhage in the body cavities may cause or aggravate jaundice by virtue of red blood cells breakdown and increased bilirubin load on the liver. I f serum bilirubln approaches critical levels, the h a e m a t o m a should be aspirated.
The main danger of hyperbilirublnaemia 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 compartment and. enters the cells, particularly the neurones located in the basal ganglia, hippocampus and auditory nuclei. An unconjugated 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, hypothermia, acidosis and immaturity predispose the infant to manifest bilirubin encephalopathy at lower serum bilirubin levels.
Breast milk jaundice
Early features of kernicterus
The jaundice may start like physiological jaundice or it may appear for the first time at the end of the first weak (Leading article 1970). It is m a x i m u m 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-
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 treatment is delayed. During infancy the sequelae of bilirubin brain damage include cerebral palsy, choreo-athetosis, brownish staining of teeth, deafness and
Drugs and neonataljaundice Drugs may cause or aggravate neonatal jaundice. Vitamin K in large doses, salicylates, sulfonamides, caffein and nitrofurantoin should be avoided during the first week of life. In addition to causing hyperbilirubinaemia, the drugs may predispose the baby to develop bitirubin brain damage at Lower serum bilirubin IeveIs.
Cephalhaematoma
224
INDIAN JOURNAL OF PEDIATRICS
various grades of intellectual retardation 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, ttowever, other supportive and therapeutic measures may prevent excessive rise of serum bilirubin and reduce the need for exchange transfflsion.
VOL.
44,
No
355
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. It 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.
Supportive measures 1. Adequate feeding The hydration 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 hyperbilirubinaemia (serum bilirubin of 15 mg per 100 ml or m o r e ) i n association with cephalhaematoma is an indication for its aspiration. 3.
T r e a t m e n t of sepsis and hepatitis In case septicaemia is suspected, gentamicin 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 maturation of hepatic enzymes thus improving uptake, conjugation and e.xcretion of bilirubin by the liver (Singh and Narayanan 1974). It can be administered to the
Phototherapy Light causes photo oxidation of bilirubin to harmless substances. Blue light is most effective but white or day light flourescent tubes or sunlight can also be used. The naked baby is exposed to light and his position is changed frequently for maximum benefit. It is indicated whenever serum bilirubin approaches 10-12 mg per 100 ml in preterm and 14-15 mg per 100 ml in term babies. It is instituted only when the baby is jaundiced and not prophylactically unlike phenobarbitone. During exposure to light, the eyes must be protected 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.
225
s I N G I t - - S O M E P R A C T I C A L ASPECTS OF N E O N A T A L J A U N D I C E
4.
Albumin inflMon
Albumin infusion improves the bilirubin binding capacity of the infant thus protecting 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.
(b)
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 d o n e . However, a lusty term baby u i t h 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.
10 G per
Role of General Practitioner Obstetrician
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. It is indicated in the tollowing situations:
Cord haemoglobin of
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 1 5 r a g per 1 0 0 m l 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. and
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 midwives must be trained in this art. Unnecessaly 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 regression. Mothers andlor newborn babies should be referred to a centre with adequate facilities for neonatal care, exchange blood transfusion and bilirubin estimation if the following conditions obtain: 1. 2. 3. 4.
History of severe neonatal jaundice in previous sibling. Rhesus negative mother especially if indirect Coombs test is positive. Neonate with early onset of jaundice (within 24 hours of age). Moderately severe or prolonged neonatal jaundice. It is important to remember that neonatal hyperbilirubinaemia is a medical ernergen0 and delay in referral could result in irreversible brain damage or death.
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VOL. 44, No. 355
INDIANJOURNAL OF PEDIATRICS References
Breast milk jaundice (1970). Leading article. Brit. Med. o7. 3, 178.
Das, B.N., Bhakoo, O.N. and Jolly, J.G. (1974). Neonatal hyperbilirubinaemiaassociated 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 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 hyperbillrubinaemia. Seminars in Hemat. 9, 107. Pediatr.
