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Randomized clinical trials performed around the world have shown that therapeutic hypothermia reduces death and major neurodevelopmental disability for infants with moderate-to-severe hypoxic ischemic encephalopathy (HIE).1, 2, 3, 4, 5, 6, and 7

Hypothermia is initiated within 6 hours after birth and continued for 72 hours, with a target temperature of 33°C–34°C for whole-body hypothermia and 34°C–35°C for selective head cooling. Eligible infants were 35 weeks or greater gestational age in 2 trials and 36 weeks or greater or 37 weeks or greater in the remaining trials. A recent systemic review and meta-analysis that included 7 large randomized clinical ­trials and 1214 newborns showed a reduction in the risk of death or major neurodevelopmental disability (risk ratio [RR], 0.76; 95% confidence interval [CI], 0.69–0.84) and an increase in the rate of survival with normal neurological function (RR, 1.63; CI, 1.36–1.95) at age 18 months.8 The number needed to treat is 7 to prevent 1 case of neonatal death or major disability. Newborns with moderate HIE had a greater reduction in the risk of death or major neurodevelopmental disability at age 18 months (RR, 0.67; 95% CI, 0.56–0.81) when compared to those with severe HIE (RR, 0.83; CI, 0.74–0.92). There was no difference in head vs whole-body cooling. Follow-up at 6 to 7 years of age of the National Institute of Child Health and Human Development (NICHD) Neonatal Network trial participants found that death or an IQ score below 70 occurred in 47% of the hypothermia group compared to 62% of the control group (p = .06).9 This result was not statistically significant; however, hypothermia was associated with a lower death rate without an increase in the rate of severe disability in survivors.

Clinical Findings


The recognition of moderate or severe HIE requires a detailed obstetric history, including any acute perinatal event, such as a placental abruption, cord events such as prolapse or complete knot, maternal hemorrhage, uterine rupture, prolonged fetal bradycardia, or nonreassuring fetal heart tracings. Other essential criteria include Apgar score of 5 or less at 10 minutes or the continued need for ventilator support initiated at birth and continued for more than 10 minutes.


A modified Sarnat neurologic examination is performed to determine eligibility for therapeutic hypothermia unless seizures have been observed. Abnormalities must be identified in at least 3 of the following 6 categories: level of consciousness, spontaneous activity, posture, tone, primitive reflexes, and autonomic nervous system (Table 76-1).

Table 76-1Criteria for Defining Moderate and Severe Encephalopathy

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