Forty-two infants with hypoxic-ischemic encephalopathy (HIE) admitted to University of Alabama, Birmingham, from 1999 to 2007, received whole-body hypothermia and of these, 20 also received a single dose (40 mg/kg) of prophylactic phenobarbital. Infants in the phenobarbital group achieved a body temperature of 33.5C at 3 +/- 2 hrs after birth, and controls with cooling only achieved the same degree of hypothermia but at 5 +/- 2 hours (P=0.03). Follow-up data at 18 to 49 months found 23% infants in the phenobarbital group had moderate to severe neurodevelopmental impairment or death compared with 45% of controls (P=0.3). During NICU admission, only 15% of infants treated with cooling and prophylactic pnenobarbital had clinical seizures compared with 82% of control infants (P<0.0001). Patients who received phenobarbital at birth were less likely than controls to be discharged on phenobarbital (P=0.01). Higher birth weight, higher 5-min Apgar score, and prophylactic phenobarbital were associated with significantly improved outcome. [1]

COMMENT. Adverse cognitive effects of phenobarbital must be considered in weighing possible neuroprotective benefits of prophylactic phenobarbital in HIE.