Indian J. Pedlar. 36 : 161, 1969

EXCHANGE TRANSFUSION IN THE NEWBORN*

A Four-year Experience

MEHARBAN S1NGH AND S. K. MITTAL

New Delhi

Exchange transfusions have saved a large number of infants from cerebral palsy and or death due to erythro- blastosis foetalis since their use was first reported in 1946. There have been conflicting reports as to the bilirubin level at which the exchange transfusion is indicated (Mollison and Cutbush 1954, Shiller and Silverman 1961, Jablonski 1962). Since the decision to perform an exchange trans- fusion is based essentially on the risks inherent in the procedure itself versus those associated with the concentration of serum bilirubin, more precise knowledge of these hazards would enable the operator to make his decision on a more rational basis. In our country the procedure of exchange transfusion in the newborn is limited to a few specialized centres. In this communication, we place on record our observations on 27 exchange-trans- fusions conducted in the neonatal unit of All India Institute of Medical Sciences, New Delhi.

Material and Methods

The neonates born at the All-India Institute of Medical Sciences Hospital

*From the Department of Pediatrics, All India Institute of Medical Sciences, New Delhi-16.

and requiring exchange transfusion during the period from July 1964 through August 1968 have been analysed. The indications for ex- chang,z transfusion were either one or both of the following criteria :

1. Cord haemoglobin of less than 10 G.%, cord bilirubin of more than 4 mg.~o, serum bilirubin of over i0 mg.% at 12 hours, serum bilirubin of over 20 rag. % at any time during the first 5 days of life, hourly increase in serum bilirubin of more than 0.5 rag./100 ml.

2. Rh incompatibility (if present). positive direct Coomb's test, anti-Rh (D) antibody titre of over 1 : 64 in the maternal serum.

In anticipated severe Rh incompati- bility disease, group O/Rh-negative blood cross-matched with the maternal serum was kept ready before the b~.rth of the baby. In other cases, the blood was cross-mtached with the baby's serum. Fresh (not older than 3 days in any case) citrated whole blood was used in the amount~ of 120-160 ml./Kg. The procedure was performed in the maternity operation theatre through the umbilical vein in most of the cases. To counteract the citrate

162 INDIAN JOURNAL OF PEDIATRICS VOL. 36 No. 2~6

toxicity, 1 ml. of 10 % calcium gluconate wa given I . V . slowly after each 100 ml. exchange. After the procedure penicillin and streptomycin were rou- tinelyadministered as a prophylactic measure.

Observations

The maternity unit at the All India Institute of Medical Sciences, New Delhi, conducts an average of 600 deliveries every year. During the period from July 1964 through August, 1968, 14 children needed an exchange transfusion and a total of 27 trons- fusions were performed. The details of all the cases are mentioned in the table. Out of the 14 children who required exchange transfusion, the hyperbilirubinaemia was due to Rh incompatibility in 11 cases and ABO incompatibility, septicaemia and the Criggler-Najjar syndrome in one ease each. The mean time taken to com- plete the procedure was two hours 20 minutes and the average amount of blood exchanged in each procedure was 115 ml./Kg. Three children died during the procedure giving the mortality rate of 11 per 100 procedures, and of 21.4% for the number of infants. AIlthose children who died were severely affected and moribund before the pro- eedure. Two children developed late complications of exchange transfusion in the form of fatal staphylococcal septicaemia in Case 6 and induced malaria in Case 14. The overall mortality rate was 28.6 per cent.

Out of the nine eases .which survived the initial neonatal period, seven have been recently assessed for their develop- ment. All except case 3, showed nor-. real physical and mental develop- ment. Two children (case 1 and 2)

showed brownish discoloration and brittleness of the teeth. They had also received tetracycline hydrochloride therapy during the first two weeks of life. None of the children, on follow- up, showed any evidence of portal hypertension.

Discussion

The management of hyperbilirubine- mia in the newborn has not received sufficient attention in India, as reflected in the paucity of published reports (Mammen et al. 1963, Mammen 1967). The mortality of 11% for the procedure and of 21.4% and 28.6 % for immediate and overall deaths respectively, iL~ our series, is alarmingly high and is cause for serious concern. A morta- lity of 12.5 per cent was reported by Mammen et al. (1963), which is also much higher than the average mortality rate of 1.5-4.4% as reported by Western workers (Forfar et al. 1958, Crosse et al. 1958, Boggs and Westphal 1960, Jablonski 1962). Since there are definite inherent risks associated with the procedure of exchange transfusion, there is a need to define the absolute indications for exchange transfusion. The risk of procedure versus the possible neuro-toxic hazards of indirect hyperbilirubinaemia in an individual case should determine the decision to employ or withhold transfusion. It is generally believed that a serum bilirubin level of upto 20 rag% is not associated with the risk of kernicterus (Hsia et al. 1952, Mollison et al. 1954, Rapmund et al. 1960), while lately, the more permissive serum bilirubin level of 25 rag% is considered as safe for a full-term neonate (Zeulzer and Brown 1961, Jablonski 1962, Johnston

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166 INDIAN JOURNAL OF PEDIATRICS VOL. 36 NO. 256

et al. 1967, Ose Toru et al. 1967). In addition to the absolute level of indirect bilirubin, a large number of associated factors determine the ability of the bilirubin to cross the blood-brain barrier, e.g. anoxia at birth, birth injury, maturity and weight of the neo- nate, sex, cause of jaundice--whether hemolytic disease or otherwise, age of the newborn in relation to the highest level of bilirubin, administration of certain drugs like vitamin K, long- acting sulfonamides~ pheno-thiazines, salicylates, serum albumin levels, ex- posure to ultraviolet rays, etc. In fact, the better criteria for a given bili- rubin level to be safe or otherwise would be to estimate the tissue fluid bilirt~bin or better still cerebral inter- cellular bilirubin level.

In the West, where the l~h-negative blood group is present in 15~o of the population, erythroblastosis due to Rh-hemolytic disease occurs in 1 " 200 pregnancies while in Delhi with an incidence of Rh-negativity at about 5 ~ , the probability for Rh-disease is about 1" 1000. The maximum theoretical incidence of ABO hemolytic disease is 1 : 5 of all infants born to 0 group mothers (Mollison 1961). Allen and Diamond (1957), have stated that ABO hemolytic disease occurs twice as often as Rh-hemolytic disease. The presence of only one case due to ABO incom- patibility in our series suggests that hemolytic disease due to ABO incom- patibility is generally a mild disease and even in India the commonest cause of severe hyper-bilirubinaemia de- manding exchange transfusion is Rh- incompatibility. The ante-natal prediction of hemolytic disease due to Rh-incon-~pafibility by assessment of the previous obstetrical history, indirect Coomb's test titre on the maternal

serum and amniocentesis followed by spectrophotometry of the fluid, often alerts the pediatrician to art anticipated neonatal emergency. In 6 out of 11 cases o f Rh-erythroblastosis in our study, the condition was strongly suspected ante-natally by the raised titres of indirect Coombs' at,tibodies in the maternal serum. On the other hand, ABO disease is unpredictable in its occurrence and severity. Recently, Tovey et al. (1962) have suggested the estimation of maternal antibodies against Ap (Group A pig cells) antigen as a possible ndex for the antenatal diagnosis of ABO incompatibility. Even tl/e postnatal diagnosis of ABO disease is generally made by exclusion of Rh-incompatibility and occasionally confirmed by the presence of free homo- logous antibodies (anti-A and anti-B) in the infant's serum in the first 3-4 days of birth (Gunson 1963). There was only oae case due to AB incom- patibility in the present series and this was diagnosed by exclusion of other blood group incompatibilities.

In two out of our fourteen cases, there was early evidence of kernicterus but exchange transfusion was still done. One of these children, on folloW-up, did not show any evidence of brain damage. In 11 cases of Johnston et al. (1967), though kernicterus was suspected on clinical grounds in the neonatal period (lethargy, vomiting, poor feeding, wep.k cry, mi ld jhead retraction), only two developed sequelae like athetoid movements. This~em- phasizes the non-specificity of early signs of kernicterus and indicates that kernicterus is not an all~or2none~pheno- menon. The exchange transfusion should be performed whenever there is pending or even suspected early bilirubin encepb_alopathy so that ulti-

SINGH AND MITTAL--EXCHANGE TRANSFUSION IN THE NEWBORN 167

mate toxic damage is reduced to the minimum.

The long-term prognosis of neonatal hyperbilirubinaemia has been assessed by a number of workers (Shiller and Silverman 1961), Jablonski 1962, Koch 1964, Ose Toru et al. 1967, Johnston et al. 1967). Johnston et al. 1967 re-examined 129 children at 5 years of age who had indirect serum bilirubin levels of over 20 mg/100 ml. during the neonatal period. Seven children had bilateral sensorineural hearing impairment involving higher fre- quencies especially over 1000 cps. Three children had hearing defects alone while 3 had mild- athetosis, 3 had aphaqa and one was mentaUy retarded. The average I. Q. of children with neonatal hyperbilirubinaemia was the same as that of their sibling controls and the general population on subsequent follow up. (Gerrard 1962, Perlstein 1960, Johnston et. al. 1967).

The follow up studies by Jablonski (1962) showed no increase in the frequency of neurologic defects in babies with serum bilirubin levels of 20-25 mg/100 ml. over those whose bilirubin levels never appeared to exceed 20 mgTo. Koch (1964) showed that no infant with a bilirubin level of less than 20 mgTo qleveloped any significant neurological abnormality. In the present study 7 out of 9 survivals were re-examined recently. One child (case 3) showed evidence of athetoid cereberal palsy and mental retardation. None Of the children showed any evidence of portal hypertension on follow up. O'Donnel and Maloney (1968) have emphasized the rarity of portal hypertension as a late sequela of exchange tranfusion through the umbilical vein.

Summary

Fourteen neonates who were given a total of 27 exchange transfusions during the period from July 1964 up to August, 1968, have been analysed. The hyper- bilirubinaemia was due to Rh-incompa- tibility in 11 cases and in one case each was due to ABO incompatibility, septi- caemia and the Criggler-Najjar syndrome. One case out of nine survivors showed evidence of kernic- terus on subsequent follow up. The transfusion mortality rate was 11 ~o, and the immediate and overall patient mortality rates were 21.4 and 28.6 per cent respectively. A critical evalua- tion of different factors must be made in every new born with severe jaurtdice, weighing the dangers ot kernicterus against the possible hazards of the exchange transfusion procedure itself.

The authors are thankful to Dr. O. P. Ghai, Professor of Pediatrics for his guidance and permission to publish this article. Our thanks are also due to Dr. P .K. Malkani, Professor of Obstetrics & Gynaecology, and her staff, for tho helpful co-operation.

References.

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Boggs, T .R. , Westphal, M.C. Jr. 0960). Mortality of exchange transfusion. Pediatrics, 26, 745.

Crosse, V. M., Walls, P. G-., Walsh, A. M. (1958). Replacement transfusion as means of preventing kernicterus of prematurity. Arch. Dis. Childh. 33, 403.

Forfar, J. O., Keay, A. J., Elliot, W. D. and Cumming, R. A. (1958). Exchange transfusion in neonatal hyperbilirubinaemia. Lancet, 2, 1131.

Gerrard, J. (1952). Kernicterus. Brain, 75, 526.

Gunson, H. H., (1963). Symposium on hemo- lytic disease of the newborn with special referenco to ABO incompatibility. Roy. Soc. Med. 56, 154.

108 INDIAN JOURNAL OF PEDIATRICS VOL. 36 NO. 256

Jablonski, W. H. (1962). Risks associated with exchange transfusion. New Engl. J. Med. 266, 155.

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Mollison, P. L. (1961). Blood Transfusion in Clinical Medicine. Blackwell Scientific Publica- tions, Oxford, page 657.

O'Donnel, B. and Maloney, M. A. (1968). Development and cause of extrahepatic portal obstruction in children. Lancet, 1, 789.

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Tovey, G. H., Lockyer, J. W. Blades, A. N. and Flavcll, H. C. G. (1962). Antenatal prediction of ABe hemolytic disease. Brit. J. Haemat. 8, 251.

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