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Data from the whole-body hypothermia trial was analyzed to examine the effects of phenobarbital administration prior to cooling (+PB) on the esophageal temperature (T-e) profile, during the induction phase of hypothermia. A total of 98 infants were analyzed. At enrollment, +PB infants had a higher rate of severe hypoxic-ischemic encephalopathy and clinical seizures and lower T-e and cord pH than infants that have not received phenobarbital (-PB). There was a significant effect of phenobarbital itself and an interaction between phenobarbital and time in the T-e profile. Mean T-e in the +PB group was lower than in the -PB group, and the differences decreased over time. In +PB infants, the time to surpass target T-e of 33.5 degrees C and to reach the minimum T-e during overshoot were shorter. In conclusion, the administration of phenobarbital before cooling was associated with changes that may reflect a reduced thermogenic response associated with barbiturates