Therapeutic Hypothermia for Hypoxic-Ischemic Encephalopathy in Low- and Middle-Income Countries: A Scoping Review

Abstract

Introduction: Therapeutic hypothermia (TH) is standard care for moderate-to-severe hypoxic-ischemic encephalopathy (HIE) in high-income settings. However, TH efficacy and safety in low- and middle-income countries (LMICs) is uncertain due to differences in baseline care, comorbidities, and etiologies of HIE.

Methods: This scoping review followed PRISMA-ScR guidelines. Databases: PubMed, Global Health, LILACS. Included original studies from LMICs (World Bank classification) evaluating TH for HIE (any cooling method) published 2010–2025. Outcomes: mortality, neurodevelopmental impairment at 18–24 months, adverse events. No meta-analysis due to heterogeneity.

Results: Twenty-three studies (n=2,109 infants) were included: 6 RCTs, 17 observational. Pooled mortality in cooled infants was 28% (range 15–45%) compared to 35% (20–52%) in controls. Neurodevelopmental impairment among survivors was 42% in cooled vs. 58% controls. However, serious adverse events (sepsis, coagulopathy, arrhythmia) occurred in 22% of cooled infants versus 12% controls. Studies using servo-controlled devices had better outcomes (mortality 24%) than those using low-tech methods (gel packs, fans) (mortality 38%).

Discussion: TH appears beneficial in LMICs but with attenuated effect size and higher complication rates compared to high-income trials. Lack of rigorous neurodevelopmental follow-up limits certainty. Implementation barriers include cost, monitoring equipment, and nurse-to-patient ratios.

Conclusions: TH reduces mortality and disability in LMIC settings but with increased adverse events. Servo-controlled devices are superior to low-tech cooling. Context-specific protocols and post-discharge support are essential before universal implementation.