Hypothermia for neonatal encephalopathy - a refinement

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There have now been two large trials demonstrating that 72h of hypothermia may improve the neurodevelopment outcomes of infants with neonatal encephalopathy. Only infants with moderate encephalopathy after birth seem to benefit. Few infants with mild encephalopathy have long-term deficits and the severe cases appear to have no benefit. There are ongoing trials, which will better inform us about this therapy, but multiple questions will remain. For example, there is no information in humans about the interval from birth to initiation of cooling that can protect the brain, the optimal temperature, or the optional duration of cooling. Trials of cooling for neonatal encephalopathy are very difficult. Most of these infants are born outside level 3 units capable of providing hypothermia, and the clinical assessments for the hypothermia, consent, and initiation of therapy within 6h of birth limits enrollment in trials. Careful in-depth analysis of the limited available data can provide some information to guide clinical care. In this issue of The Journal, Gunn et al provide a secondary analysis of the Cool Cap Trial, which demonstrates that the degree of encephalopathy is not altered by hypothermia on day 4. This information indicates that a therapeutic response cannot be evaluated by the clinical exam. As previously reported, infants with moderate encephalopathy are most likely to benefit.