Antenatal Phenobarbital to Prevent Neonatal Intracranial Hemorrhage

Study Overview
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Brief Summary
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This large randomized trial tested whether phenobarbital given to a pregnant woman about to deliver a premature infant would prevent brain injuries in their newborns. Women with 24 to 32 week fetuses who were in preterm labor and were expected to deliver within 24 hrs were randomized to phenobarbital or usual care. They were treated until they deliver or the fetus reaches 33 wks gestation. Babies were followed until discharge and evaluated at 18-22 mos corrected age for neurodevelopmental outcome.

Detailed Description
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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.

Official Title
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Randomized Clinical Trial of Antenatal Phenobarbital in the Prevention of Neonatal Intracranial Hemorrhage

Conditions
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Infant, Newborn, Infant, Low Birth Weight, Infant, Small for Gestational Age, Infant, Premature, Intracranial Hemorrhages

Intervention / Treatment
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* Drug: Phenobarbital
* Drug: Saline


Participation Criteria
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Eligibility Criteria
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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
Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Phenobarbital<br> | Drug: Phenobarbital<br>* 10 mg of phenobarbital per kilogram of body weight intravenously over a period of 20 to 40 minutes (maximal dose, 1000 mg)<br>|
| Placebo Comparator: Placebo<br> | Drug: Saline<br>* Infusion of normal sal<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Neonatal intracranial hemorrhage or death |  | 72 hours of life | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Intracranial hemorrhage (grade I, II, III, or IV) |  | 72 hours of life | 
| Periventricular leukomalacia |  | 72 hours of life | 
| Neurodevelopmental impairment |  | 18 to 22 months of corrected age | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Prematurity, NICHD Neonatal Research Network, Extremely Low Birth Weight (ELBW), Cerebral hemorrhage, Phenobarbital, Pregnancy, Prenatal care, Intraventricular hemorrhage, Periventricular leukomalacia, Brain injury, Brain hemorrhage