Antenatal Phenobarbital to Prevent Neonatal Intracranial Hemorrhage

The administration of phenobarbital to pregnant women before delivery has been thought to
decrease the frequency of intracranial hemorrhage in preterm infants. To evaluate this
potential neuroprotective therapy further, we determined the effect of antenatal
administration of phenobarbital on the frequency of neonatal intracranial hemorrhage and
early death. Women who were 24 to 33 weeks pregnant and who were expected to deliver their
infants within 24 hours were randomly assigned to receive either intravenous phenobarbital
(10 mg/kg body weight) or placebo, followed by maintenance doses until delivery or 34 wks
gestation. Infants less than 34 wks at birth underwent serial cranial ultrasonography to
detect the presence of intracranial hemorrhage. The sample size of 1038 pregnancies was based
on an intracranial hemorrhage rate of 20 percent in the placebo and less than 12 percent in
the phenobarbital group; 90 percent power; a 5 percent two-tailed type 1 error; and an 8
percent noncompliance rate. The twin with the highest grade of intracranial hemorrhage was
included.

Degree of maternal sedation was evaluated after administration of study drug. Neonatal
ultrasound exams were performed at 3-5 days, 10-14 days, and 38-42 wks postmenstrual age;
neonatal medications were recorded during the first week of life; treatments, and outcomes
were recorded through death, discharge, or 120 days, whichever occurred first.
Neurodevelopmental outcome was evaluated at 18-22 months corrected age by certified examiners
masked to treatment status.

Inclusion Criteria:

- Admission to a high risk perinatal unit or labor and delivery unit;

- 24 to 32 completed weeks gestation;

- Expected delivery within 24 hrs;

- Preterm labor or no labor with planned delivery for maternal-fetal indications;

Exclusion Criteria:

- Anticipated delivery within two hours

- Multiple congenital or chromosomal abnormalities in the fetus

- Multiple gestation with more than two fetuses

- Administration of phenobarbital during the pregnancy

- Administration of indomethacin within one week before admission

- Maternal platelet count of less than 100,000 per cubic millimeter