Hypothermia to treat neonatal hypoxic ischemic encephalopathy: systematic review

Arch Pediatr Adolesc Med. 2007 Oct;161(10):951-8. doi: 10.1001/archpedi.161.10.951.


Objectives: To systematically review the effectiveness, as determined by survival without moderate to severe neurodevelopmental disability in infancy and childhood, and the safety of hypothermia vs normothermia in neonates with postintrapartum hypoxic-ischemic encephalopathy and to perform subgroup analyses based on severity of encephalopathy (moderate or severe), type of hypothermia (systemic or selective head cooling), and degree of hypothermia (moderate [<or=32.0-33.5 degrees C] or mild [>or=33.6 degrees C]).

Data sources: MEDLINE, EMBASE, CINAHL (Cumulative Index for Nursing and Allied Health Literature), the Cochrane Library, abstracts of annual meetings of the Pediatric Academic Societies, and bibliographies of identified articles.

Study selection: Randomized and quasi-randomized controlled trials without language restriction were assessed by 2 reviewers independently and discrepancies were resolved by involving a third reviewer. Quality of the trials was assessed on the basis of concealment of allocation, method of randomization, masking of outcome assessment, and completeness of follow-up.

Intervention: Systemic or selective head hypothermia compared with normothermia.

Main outcome measure: Death or moderate to severe neurodevelopmental disability.

Results: Eight studies of acceptable quality were included. The combined outcome of death or neurodevelopmental disability in childhood was reduced in infants receiving hypothermia compared with control infants (4 studies including 497 infants; relative risk, 0.76, 95% confidence interval, 0.65-0.88; number needed to treat, 6; 95% confidence interval, 4-14), as were death and moderate to severe neurodevelopmental disability when analyzed separately. Cardiac arrhythmias and thrombocytopenia were more common with hypothermia; however, they were clinically benign.

Conclusions: In neonates with postintrapartum asphyxial hypoxic-ischemic encephalopathy, hypothermia is effective in reducing death and moderate to severe neurodevelopmental disability either in combination or separately and is a safe intervention.

Publication types

  • Meta-Analysis
  • Review
  • Systematic Review

MeSH terms

  • Humans
  • Hypothermia, Induced / adverse effects
  • Hypothermia, Induced / methods*
  • Hypoxia-Ischemia, Brain / physiopathology
  • Hypoxia-Ischemia, Brain / therapy*
  • Infant
  • Infant, Newborn
  • Outcome Assessment, Health Care*
  • Postpartum Period*
  • Severity of Illness Index
  • Sickness Impact Profile
  • Time Factors