Antenatal phenobarbital therapy and neonatal outcome. I: Effect on intracranial hemorrhage.

OBJECTIVE

To evaluate the effect of antenatal phenobarbital (PB) therapy on neonatal intracranial hemorrhage (ICH) in preterm infants.

DESIGN

Prospective, randomized, controlled trial.

SETTING

Single institution study.

SUBJECTS AND INTERVENTIONS

Women in preterm labor ( < 35 weeks' gestation) were assigned to control and treatment groups. The treatment group received 10 mg/kg (maximum, 1000 mg) PB intravenously, followed by 100 mg orally daily, until delivery. Neonates did not receive PB after birth. Head sonograms were performed on days 3, 7, and 14 and at discharge. Hemorrhage was classified as mild, moderate, or severe by a single reader.

OUTCOME MEASURES

Incidence of neonatal ICH in all infants, infants weighing less than 1250 g, and infants of multiple gestations.

RESULTS

The study population comprised 110 women, 60 in the control group and 50 in the PB group. Neonates in the control group (n = 74, including 10 pairs of twins and 2 sets of triplets) were comparable to those in the treatment group (n = 62, including 7 pairs of twins, 1 set of triplets, and 1 set of quadruplets) regarding birth weight, gestational age, and other clinical risk factors for ICH. There was a trend for the incidence of any grade of hemorrhage to be lower in the PB group (22% [14 of 62]) compared with the control group (35% [26 of 74]). Moderate and severe hemorrhages were significantly lower in the PB group (1.6% [1 of 62]) compared with the control group (9.4% [7 of 74]). Among infants weighing less than 1250 g, overall ICH was lower in the PB group (23% [6 of 26]) compared with the control group (51% [18 of 35]). Among multiple-gestation infants, overall ICH was 4.7% (1 of 21) in the PB group, compared with 31% (8 of 26) in the control group.

CONCLUSIONS

Antenatal PB therapy results in a significant decrease in moderate and severe ICH in infants born at less than 35 weeks' gestation. Antenatal PB therapy also resulted in a decrease in the incidence of all grades of ICH in infants weighing less than 1250 g and infants born of multiple gestations.