Control of Jaundice in Preterm Newborns by an Inhibitor of Bilirubin Production: Studies With Tin-Mesoporphyrin

Abstract

Studies in vitro, in animal models, and in adult and newborn humans have demonstrated that certain tin(Sn)-porphyrins that competitively inhibit the activity of heme oxygenase, the rate-limiting enzyme in heme catabolism, reduce production of bilirubin and can thereby substantially diminish plasma levels of the bile pigment. To assess the effectiveness of increasing doses of the heme oxygenase inhibitor, Sn-mesoporphyrin (SnMP), in moderating the development of significant hyperbilirubinemia and thus the requirements for phototherapy in preterm newborns. In five randomized, blinded, placebo-controlled trials, SnMP in increasing doses from 1 mumol to 6 mumol/kg body weight was administered intramuscularly in the first 24 hours of life in preterm newborns of 210 to 251 days gestational age. "Special blue" lamps (Phillips F20T12/BB) were used for phototherapy in newborns exceeding a predetermined plasma bilirubin concentration, irrespective of study group. A total of 517 newborns were randomized in the five trials carried out sequentially over a 4-year period. SnMP in a dose-related manner significantly ameliorated the course of hyperbilirubinemia in the treated newborns of all gestational ages. With a SnMP dose of 6 mumol/kg body weight, the mean peak incremental plasma bilirubin concentration was reduced by 41% and the phototherapy requirements were decreased by 76% compared to control subjects. Erythema observed in a few SnMP-treated newborns who required phototherapy was mild, transient, and without sequelae. No other untoward effects were observed during hospitalization or at a follow-up at post-term age of 3 and 18 months. SnMP, by inhibiting the production of bilirubin, substantially moderates the development of hyperbilirubinemia in preterm newborns. This compound and similarly acting enzyme inhibitors merit further clinical study as agents for controlling neonatal hyperbilirubinemia, particularly in neonatal populations for whom other treatment modalities are not available.