Initiation of hypothermia within 6 to 24 hours after birth is associated with a greater reduction in death or disability compared with non-cooling among term infants with hypoxic-ischemic encephalopathy, according to a randomized trial published in JAMA.
The randomized clinical trial (Clinicaltrials.gov identifier: NCT00614744) included 83 infants who received therapeutic hypothermia at 33.5°C for 96 hours and 85 non-cooled infants who were kept at 37.0°C. Infant study participants had moderate encephalopathy and were randomly assigned at 15 and 16 hours to receive either non-cooling or hypothermia, respectively.
The primary end point was comprised of a composite of death or disability at 18 to 22 months. A total of 21 US Neonatal Research Network centers were involved in identifying and recruiting participants for this study.
Among the infants undergoing hypothermia, death or disability at 18 to 22 months occurred in 24.4%, compared with 27.9% of infants in the non-cooled group (absolute difference 3.5%; 95% CI, -1% — 17%).
An additional Bayesian analysis revealed that hypothermia was associated with a 76% posterior probability for reduced disability or death in relation to non-cooling (adjusted posterior risk ratio 0.86; 95% credible interval, 0.58-1.29).
Esophageal temperatures were elevated among the non-cooled infants, potentially contributing to the higher risk for disability or death in this study arm. Additionally, the investigators were unsure whether the results of this trial would have changed if the duration of the interventions had been shortened.
The investigators suggest that the “decision to use hypothermia at 6 to 24 hours will need to consider the probability of benefit, the frequency of adverse events, and the availability of evidence-based alternative treatments.”
Laptook AR, Shankaran S, Tyson JE, et al. Effect of therapeutic hypothermia initiated after 6 hours of age on death or disability among newborns with hypoxic-ischemic encephalopathy: a randomized clinical trial. JAMA. 2017;318(16):1550-1560.