Does Neonatal Phenobarbital Treatment Affect Testicular and Adrenal Functions and Steroid Binding in Plasma in Infancy?*

Abstract

Because of its enzyme-inducing properties, which presumably explain its lowering effect on neonatal hyperbilirubinemia, phenobarbital (PB) was widely used as prophylactic treatment in neonatal jaundice. Because PB might have various effects on endocrine metabolism or regulation whether PB had some adverse effects on testicular or adrenal function in human neonates was investigated. A group (I) of 12 prematures given a single i.m. injection of 10 mg/kg PB on the day of birth were studied longitudinally for 6 mo. and compared with untreated, premature (group II) and fullterm (group III) infants. Plasma testosterone (T), .DELTA.4-androstenedione (.DELTA.4), 17.alpha.-hydroxyprogesterone and cortisol (F) were similar in the 3 groups at birth and before PB therapy. A postnatal rise in T and 17.alpha.-hydroxyprogesterone levels occurred in the 3 groups. Study of the temporal patterns showed that peak T levels were lower, and their decline beyond 2 mo. of age was more rapid, in group I than in group II. Peak T levels were delayed in both groups compared with group III. Temporal patterns and mean levels of .DELTA.4 and F, their binding to plasma proteins and their unbound plasma concentrations were comparable in the 3 groups. The postnatal rise in T binding was markedly delayed in group I; it was identical in groups II and III. Unbound T levels were greatly elevated in group I in comparison to control groups. Apparently prophylactic PB treatment does not affect testicular or adrenal secretions in infancy. PB did not displace T, .DELTA.4 or F from their binding sites in plasma in vitro. PB may selectively inhibit the synthesis of T-estradiol-binding globulin, but a competition of the metabolites of the drug on T-estradiol-binding globulin-binding sites cannot be excluded. Increased unbound T levels may have an enhanced metabolic clearance rate of T, explaining the temporal patterns observed. The long term effect, if any, of the exposure to high levels of unbound T for the 1st 2 mo. of life in these infants treated by PB is unknown.