NEW YORK (Reuters Health) – The addition of prophylactic phenobarbital to whole-body cooling reduced seizures in newborns with hypoxic-ischemic encephalopathy (HIE) in a small observational study.

According to the report in the Journal of Pediatrics published online on May 31, the findings also showed a nonsignificant trend toward reduced rates of death or neurodevelopmental impairment at follow-up.

Previous research indicates that moderate hypothermia is beneficial for neonatal HIE (see meta-analysis in Reuters Health article of February 22, 2010). Animal studies suggest that whole-body cooling and anticonvulsants together are neuroprotective as well.

Researchers at the University of Alabama at Birmingham looked at outcomes for 42 infants treated with whole-body hypothermia (target temperature 33.5 degrees Celsius) at their tertiary referral center between 1999 and 2007. At the discretion of their physicians, 20 were given a single dose of phenobarbital 40 mg/kg. The other infants were treated with phenobarbital if seizures were observed.

Lead author Dr. Donald F. Meyn, Jr., and colleagues note that the median total phenobarbital dose given during hospitalization was 40 mg/kg in the prophylaxis group and 43 mg/kg in the control group.

Three infants in the prophylaxis group (15%) and 18 in the control group (82%) had seizures while they were in the NICU (p < 0.0001).

Follow-up data after 18 months of age were available for 17 patients and 21 patients in the two groups, respectively. At follow-up, there were no deaths among the patients treated prophylactically compared with three deaths (14%) in the control group (p = 0.3). Corresponding rates of death or moderate to severe neurodevelopmental impairment (defined as hemiparesis, quadriparesis, blindness, deafness, or need for tube feeding) were 23% (4 infants) and 42% (9 infants) (p = 0.3).

In multivariate analysis, however, prophylactic phenobarbital was associated with improved outcome (odds ratio 0.069, p = 0.03).

The small study size, lack of randomization and failure to routinely perform electroencephalograms are all limitations of this study.

Dr. Meyn