Therapeutic Hypothermia in Low- and Middle-Income Countries: A Systematic Review and Meta-Analysis

Abstract

Objective

To evaluate therapeutic hypothermia (TH) for moderate or severe hypoxic-ischemic encephalopathy in low- and middle-income countries.

Study design

Medline, Embase, and CENTRAL were searched until September 19, 2024. Screening, article selection, bias assessment using Cochrane RoB2, and data extraction were performed. Meta-analyses of randomized controlled trials were performed for the composite primary outcome of death or moderate to severe neurodevelopmental impairment (NDI) at 18-24 months, and secondary outcomes were followed by certainty of evidence evaluation using Grading of Recommendations, Assessment, Development and Evaluations.

Results

From 804 records retrieved, 18 randomized controlled trials were included. Twelve included only term infants. All used TH protocols and provided neonatal intensive care, but methods of TH varied. Comparing TH with no TH, for the primary outcome of death or NDI at 18-24 months, benefit or harm could not be excluded (relative risk [RR] 0.63; 95% CI 0.38-1.04; P = .07; I² 80%, 4 studies, 717 infants; moderate certainty). For death by 18 to 24 months, benefit or harm could not be excluded (RR 0.81, 95% CI 0.43-1.52; P = .51; I² 67%, 4 studies, 722 infants; moderate certainty). In TH-treated infants, NDI at 18-24 months was possibly lower (RR 0.51; 95% CI 0.35-0.76; P < .0001; I² 0%, 4 studies, 511 infants, low certainty).

Conclusions

In low- and middle-income countries, in hospitals using defined protocols and having capacity for intensive care and follow-up, TH has possible benefit for infants ≥37 weeks gestational age for important secondary outcomes, including NDI.