Effects of hypothermia for perinatal asphyxia on childhood outcomes

N Engl J Med. 2014 Jul 10;371(2):140-9. doi: 10.1056/NEJMoa1315788.

Abstract

Background: In the Total Body Hypothermia for Neonatal Encephalopathy Trial (TOBY), newborns with asphyxial encephalopathy who received hypothermic therapy had improved neurologic outcomes at 18 months of age, but it is uncertain whether such therapy results in longer-term neurocognitive benefits.

Methods: We randomly assigned 325 newborns with asphyxial encephalopathy who were born at a gestational age of 36 weeks or more to receive standard care alone (control) or standard care with hypothermia to a rectal temperature of 33 to 34°C for 72 hours within 6 hours after birth. We evaluated the neurocognitive function of these children at 6 to 7 years of age. The primary outcome of this analysis was the frequency of survival with an IQ score of 85 or higher.

Results: A total of 75 of 145 children (52%) in the hypothermia group versus 52 of 132 (39%) in the control group survived with an IQ score of 85 or more (relative risk, 1.31; P=0.04). The proportions of children who died were similar in the hypothermia group and the control group (29% and 30%, respectively). More children in the hypothermia group than in the control group survived without neurologic abnormalities (65 of 145 [45%] vs. 37 of 132 [28%]; relative risk, 1.60; 95% confidence interval, 1.15 to 2.22). Among survivors, children in the hypothermia group, as compared with those in the control group, had significant reductions in the risk of cerebral palsy (21% vs. 36%, P=0.03) and the risk of moderate or severe disability (22% vs. 37%, P=0.03); they also had significantly better motor-function scores. There was no significant between-group difference in parental assessments of children's health status and in results on 10 of 11 psychometric tests.

Conclusions: Moderate hypothermia after perinatal asphyxia resulted in improved neurocognitive outcomes in middle childhood. (Funded by the United Kingdom Medical Research Council and others; TOBY ClinicalTrials.gov number, NCT01092637.).

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Asphyxia Neonatorum / complications
  • Asphyxia Neonatorum / mortality
  • Asphyxia Neonatorum / therapy*
  • Cerebral Palsy / epidemiology
  • Cerebral Palsy / etiology
  • Child
  • Developmental Disabilities / epidemiology
  • Developmental Disabilities / etiology
  • Female
  • Follow-Up Studies
  • Gestational Age
  • Health Status
  • Humans
  • Hypothermia, Induced*
  • Infant, Newborn
  • Intelligence*
  • Male
  • Psychological Tests
  • Survivors

Associated data

  • ClinicalTrials.gov/NCT01092637