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Three large randomized controlled trials have demonstrated benefits from 3 days of cooling to 33–34°C after perinatal asphyxia. No serious adverse effects were documented. The trials excluded many infants for hypothermia (HT) therapy, including those of age >6 hours and those with prematurity of <36 weeks gestation, abnormal coagulation, persistent pulmonary hypertension, and congenital abnormalities. This article considers whether the foregoing trial exclusion criteria are feasible given current knowledge and evidence. HT affects the validity of some outcome predictors (eg, clinical examination, amplitude-integrated electroencephalography), but not of magnetic resonance imaging. HT is a time-critical emergency treatment after perinatal asphyxia that requires optimal collaboration among local hospitals, transport teams, and cooling centers.