Current drug treatment options in neonatal hyperbilirubinaemia and the prevention of kernicterus

Abstract

Neonatal jaundice is a frequent problem in neonatology, but the advent of phototherapy which has simplified its treatment, it no longer represents a major concern. Early hospital discharge of neonates has now resulted in a re-emergence of kernicterus. Neonatal jaundice is principally the result of a transient deficiency of bilirubin conjugation, of a partial deficiency of hepatic bilirubin uptake and intracellular transport and of an increased enterohepatic circulation of the pigment. The fact that bilirubin production in the neonate is 2 or more times greater than in the adult per kilogram of bodyweight represents the mainstay of this condition. Prevention of kernicterus in full term infants is based on the detection of neonates at risk for developing hyperbilirubinaemia, and can be accomplished with simple tests performed on umbilical cord blood such as blood type, Rh, Coombs' test and glucose-6-phosphate dehydrogenase, in order to detect haemolytic diseases. The daily evaluation of transcutaneous bilirubin measurement gives additional information on the rise of serum bilirubin level, and can help to distinguish physiological from nonphysiological hyperbilirubinaemia. A significant hyperbilirubinaemia is more frequent in infants born before term, and in neonates who do not feed well and lose more than 10% of bodyweight. In preterm infants the typical clinical feature of kernicterus is seen very rarely, and kernicterus is now a very infrequent postmortem observation. Since it is very difficult to distinguish the effects of bilirubin from other potentially toxic factors, it is difficult to give guidelines for the treatment of jaundice in very low birthweight infants other than to keep the serum bilirubin levels to a lower level than in full term infant (e.g. 10 mg/dl lower than in full term babies). The intramuscular administration of a single dose of Sn-mesoporphyrin (6 mumol/kg bodyweight) in healthy term or near-term infants seems to be a promising treatment modality for controlling hyperbilirubinaemia.