Although selective or whole body cooling combined with optimal intensive care improves outcomes following neonatal encephalopathy in high-income countries, the safety and efficacy of cooling in low-and middle-income countries is not known.ObjectiveWe performed a systematic review and meta-analysis of all published randomised or quasi-randomised controlled trials of cooling therapy for neonatal encephalopathy in low-and middle-income countries.ResultsSeven trials, comprising a total of 567 infants were included in the meta-analysis. Most study infants had mild (15%) or moderate encephalopathy (48%) and did not receive invasive ventilation (88%). Cooling devices included water-circulating cooling caps, frozen gel packs, ice, water bottles, and phase-changing material. No statistically significant reduction in neonatal mortality was seen with cooling (risk ratio: 0.74, 95% confidence intervals: 0.44 to 1.25). Data on other neonatal morbidities and long-term neurological outcomes were insufficient.ConclusionCooling therapy was not associated with a statistically significant reduction in neonatal mortality in low-and middle-income countries although the confidence intervals were wide and not incompatible with results seen in high-income countries. The apparent lack of treatment effect may be due to the heterogeneity and poor quality of the included studies, inefficiency of the low technology cooling devices, lack of optimal neonatal intensive care, sedation and ventilatory support, overuse of oxygen, or may be due to the intrinsic difference in the population, for example higher rates of perinatal infection, obstructed labor, intrauterine growth retardation and maternal malnutrition. Evaluation of the safety and efficacy of cooling in adequately powered randomised controlled trials is required before cooling is offered in routine clinical practice in low-and middle-income countries.

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Although cooling therapy has been the standard of care for neonatal encephalopathy (NE) in high-income countries for more than half a decade, it is still not widely used in low- and middle-income countries (LMIC), which bear 99% of the encephalopathy burden; neither is it listed as a priority research area in global health. Here we explore the major roadblocks that prevent the use of cooling in LMIC, including differences in population comorbidities, suboptimal intensive care, and the lack of affordable servo-controlled cooling devices. The emerging data from LMIC suggest that the incidence of coexisting perinatal infections in NE is no different to that in high-income countries, and that cooling can be effectively provided without tertiary intensive care and ventilatory support; however, the data on safety and efficacy of cooling are limited. Without adequately powered clinical trials, the creeping and uncertain introduction of cooling therapy in LMIC will be plagued by residual safety concerns, and any therapeutic benefit will be even more difficult to translate into widespread clinical use.