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BACKGROUND:: Decreases below the target temperature were noted among neonates undergoing cooling in the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network Trial of whole body hypothermia for neonatal hypoxic-ischemic encephalopathy. OBJECTIVE:: To examine the temperature profile and impact on outcome among >/=36 wk gestation neonates randomized at </=6 hrs of age targeting an esophageal temperature of 33.5 degrees C for 72 hrs. DESIGN, SETTING, PATIENTS:: Infants with intermittent temperatures recorded of <32.0 degrees C during induction and maintenance of cooling were compared to all other cooled infants, and the relationship with outcome at 18 months was evaluated. INTERVENTIONS:: None. MEASUREMENTS AND MAIN RESULTS:: There were no differences in the stage of encephalopathy, acidosis, or 10 min Apgar scores between infants with temperatures of <32.0 degrees C during induction (n = 33) or maintenance (n = 10) and all other infants who were cooled (n = 58); however, birth weight was lower and the need for blood pressure support higher among infants with temperatures of <32.0 degrees C compared to all other cooled infants. No increase in acute adverse events was noted among infants with temperatures of <32.0 degrees C, and hours spent at <32 degrees C was not associated with the primary outcome of death or moderate/severe disability or the Bayley II Mental Developmental Index at 18 months. CONCLUSIONS:: Term infants with a lower birth weight are at risk for decreasing temperatures of <32.0 degrees C while undergoing body cooling using a servo-controlled system. This information suggests extra caution during the application of hypothermia as these lower birth weight infants are at risk for overcooling. Our findings may assist in planning additional trials of lower target temperature for neonatal hypoxic-ischemic encephalopathy