• global health
• neonatology
• mortality
• neurology
• therapeutics

Perinatal hypoxia-ischaemia (HI) is the single most common trigger of perinatal brain injury, and contributes to over 2 million deaths worldwide each year, of which about 96% were from low/middle-income countries (LMICs).1 2 In high-income countries (HICs), there is compelling evidence that therapeutic hypothermia for infants with HI encephalopathy (HIE) reduces grey and white matter lesions3 4 and improves survival without disability.5–7 In view of the differing populations, risks and medical systems, it cannot be assumed that even such a simple and low-cost treatment would be suitable for LMICs.8 Supporting this concern, the HELIX Study, a large, well-designed and executed randomised controlled trial of therapeutic hypothermia for HIE in LMICs, found that treatment did not reduce the combined outcome of death or disability at 18 months of age and increased mortality.9 The authors concluded that therapeutic hypothermia should not be offered to infants with neonatal encephalopathy in LMICs, even when tertiary-level neonatal intensive care support is available. The study raises two important questions: (1) why therapeutic hypothermia was not beneficial in this setting despite a high level of neonatal care and (2) how to reduce the burden of injury for affected infants in the future. We propose that better targeting of treatment may enable benefit even in this setting.

It is important to appreciate that some findings of the CoolCap Study, carried out in multiple HICs, were surprisingly consistent with HELIX. Secondary analysis of CoolCap suggested that not all …