CONTROL OF JAUNDICE IN PRETERM NEWBORNS BY AN INHIBITOR OF BILIRUBIN PRODUCTION - STUDIES WITH TIN-MESOPORPHYRIN

Background. Studies invitro,in animal models, and in adult and newborn humans have demonstrated that certain tin(Sn)-porphyrins that competi tively inhibit the activity of heme oxygenase, the rate-limiting enzym e in heme catabolism, reduce production of bilirubin and can thereby s ubstantially diminish plasma levels of the bile pigment. Objectives. T o assess the effectiveness of increasing doses of the heme oxygenase i nhibitor, Sn-mesoporphyrin (SnMP), in moderating the development of si gnificant hyperbilirubinemia and thus the requirements for phototherap y in preterm newborns. Methods. In five randomized, blinded, placebo-c ontrolled trials, SnMP in increasing doses from 1 mu mol to 6 mu mol/k g body weight was administered intramuscularly in the first 24 hours o f life in preterm newborns of 210 to 251 days gestational age. ''Speci al blue'' lamps (Phillips F20T12/BB) were used for phototherapy in new borns exceeding a predetermined plasma bilirubin concentration, irresp ective of study group. Results. A total of 517 newborns were randomize d in the five trials carried out sequentially over a 4-year period. Sn MP in a dose-related manner significantly ameliorated the course of hy perbilirubinemia in the treated newborns of all gestational ages. With a SnMP dose of 6 mu mol/kg body weight, the mean peak incremental pla sma bilirubin concentration was reduced by 41% and the phototherapy re quirements were decreased by 76% compared to control subjects. Erythem a observed in a few SnMP-treated newborns who required phototherapy wa s mild, transient, and without sequelae. No other untoward effects wer e observed during hospitalization or at a follow-up at postterm age of 3 and 18 months. Conclusions. SnMP, by inhibiting the production of b ilirubin, substantially moderates the development of hyperbilirubinemi a in preterm newborns. This compound and similarly acting enzyme inhib itors merit further clinical study as agents for controlling neonatal hyperbilirubinemia, particularly in neonatal populations for whom othe r treatment modalities are not available.