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