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

Area of Science:

• Neonatal Medicine
• Pediatric Neurology
• Global Health

Background:

• Hypoxic-ischemic encephalopathy (HIE) is a major cause of neonatal mortality and long-term disability.
• Therapeutic hypothermia (TH) is a standard treatment for HIE in high-income countries.
• Limited data exist on TH effectiveness in low- and middle-income countries (LMICs).

Purpose of the Study:

• To evaluate the efficacy and safety of therapeutic hypothermia (TH) for moderate to severe HIE in infants in LMICs.
• To synthesize evidence from randomized controlled trials (RCTs) on TH for HIE in resource-limited settings.

Main Methods:

• A systematic review and meta-analysis of RCTs was conducted.
• Searches included Medline, Embase, and CENTRAL up to September 19, 2024.
• Data on death or neurodevelopmental impairment (NDI) and secondary outcomes were extracted and analyzed using GRADE methodology.

Main Results:

• Eighteen RCTs involving 804 records were included, with 12 focusing on term infants.
• TH did not show a statistically significant benefit or harm for the primary outcome of death or moderate-to-severe NDI (RR 0.63; 95% CI 0.38-1.04; moderate certainty).
• A possible reduction in NDI at 18-24 months was observed in infants treated with TH (RR 0.51; 95% CI 0.35-0.76; low certainty).

Conclusions:

• In LMICs, TH may offer benefits for secondary outcomes like NDI in infants born at or after 37 weeks gestational age.
• These findings apply to hospitals with established protocols, intensive care capacity, and follow-up capabilities.
• Further research may be needed to confirm benefits and optimize TH protocols in LMICs.