Therapeutic hypothermia for neonatal encephalopathy in developing countries: Current evidence

Problem considered: Birth asphyxia and resultant brain injury are an important cause of neonatal mortality and morbidity in resource-limited countries. Prevention of birth asphyxia needs effective coverage of evidence-based interventions during antenatal care, childbirth, and high-risk pregnancies, close intrapartum monitoring, access to emergency obstetric care, and neonatal resuscitation. Therapeutic hypothermia is the only specific therapy proven to reduce the incidence of death and disability in neonates with hypoxic-ischemic encephalopathy (HIE). While therapeutic hypothermia is the standard of care in high-income contours, its benefit in low- and middleincome countries remains unproven. Methods: This article analyzes the evidence from randomized controlled trials conducted in different settings. As systematic reviews of these trials have shown significant statistical heterogeneity in the efficacy of therapeutic hypothermia, this article examines the reasons behind heterogeneity in the outcome of death before discharge from the hospital. Results: The following factors were found to be associated with the loss of efficacy of therapeutic hypothermia - the absence of objective evidence of acute birth asphyxia, suboptimal care during transport of extramural neonates, uncontrolled hypothermia before admission to a neonatal unit, and the severity of HIE. Conclusion: A sufficiently powered randomized controlled trial that takes into account these effect modifiers needs to be conducted in rescue-limited settings.