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Neonatal encephalopathy is the most common condition in neonates encountered by child neurologists. The etiology is most often global hypoxia-ischemia due to failure of cerebral perfusion to the fetus caused by uterine, placental, or umbilical cord compromise prior to or during delivery. Other etiologies of neonatal encephalopathy include ischemic stroke and intracranial hemorrhage, infection, developmental anomalies, and inborn errors of metabolism.Therapeutic hypothermia is standard of care for the treatment of neonatal encephalopathy presumed to be caused by hypoxia-ischemia. The number needed to treat is approximately 6 to 7 to prevent one child from either death or disability at age 18 to 22 months. EEG monitoring and MRI are important tools in determining the etiology of encephalopathy and prognosis of the infant.Neonatal encephalopathy is a heterogeneous disorder that is characterized by alterations in mental status, hypotonia, seizures, and abnormalities in feeding and respiration. The most common cause of neonatal encephalopathy is hypoxic-ischemic encephalopathy, for which treatment with 72 hours of therapeutic hypothermia is associated with reduced death or disability.