Neonatal jaundice and bilirubin encephalopathy: a clinical and experimental reappraisal.

Hyperbilirubinemia and bilirubin encephalopathy are well-known occurrences in the neonatal period. The fact that bilirubin might be toxic to neural cells stems from the neurological picture that has emerged and the associated hyperbilirubinemia. Studies of the relationship between hyperbilirubinemia in healthy full-term infants and the long-term consequences showed little or no effect of bilirubin. Nevertheless, bilirubin is still considered toxic to premature infants and infants with hemolysis. In addition, in spite of a fairly detailed understanding of the chemistry of bilirubin and the biochemistry of bilirubin metabolism, the primary target of its toxic effect is still not known. The difficulties in analyzing the results are due to the variation in experimental designs, the use of different animal models and cell systems and the use of unstable bilirubin solutions. We review some of the problems related to clinical and experimental studies of bilirubin toxicity.