Antenatal phenobarbital for the prevention of periventricular and intraventricular hemorrhage: a double-blind, randomized, placebo-controlled, multihospital trial. To determine whether the neuroprotective properties of phenobarbital would alter the incidence and severity of intracranial hemorrhage in premature infants, we randomly assigned 110 women at less than 31 weeks of gestation to receive 10 mg/kg phenobarbital or placebo in a blinded fashion before delivery. Infants were examined postnatally with real-time ultrasonography for evidence of intracranial hemorrhage. Maternal demographics, pregnancy complications, antenatal management, and route of delivery did not differ between the phenobarbital group (n = 50) and the placebo group (n = 60). The total incidence of periventricular-intraventricular hemorrhage did not differ between the phenobarbital-treated (n = 54) and the placebo-treated (n = 67) infants. However, the frequency of grade 3 and grade 4 hemorrhages was 15% (10 infants) in the placebo group and 3.7% (2 infants) in the phenobarbital group (p less than 0.05). There were no differences in the severity of associated conditions in the babies to explain the difference in the incidence of severe hemorrhage between the study groups. We conclude that antenatal administration of phenobarbital appears to be effective in decreasing the severity of periventricular-intraventricular hemorrhage in infants delivered at less than 31 weeks of gestation. 