Therapeutic Hypothermia for Neonatal Encephalopathy in Low- and Middle-Income Countries: A Meta-Analysis

Background: Perinatal asphyxia and hypoxic-ischemic encephalopathy (HIE) represent substantial sources of neonatal morbidity and mortality in low- and middle-income countries (LMICs), leading to high rates of adverse long-term neurological outcomes. Methods: A systematic review with meta-analysis of randomized controlled trials in LMICs was conducted. PubMed, Scopus, Web of Science, CENTRAL, ClinicalTrials.gov, and Google Scholar were searched from inception to August 20, 2021. The population of the study consisted of neonates with gestational age ≥34 weeks and HIE. The main endpoints were overall mortality and the composite outcome of death or severe disability. The certainty of evidence was evaluated with the GRADE approach. Results: Ten studies were included comprising 1,293 neonates. Some concerns of bias were raised due to the nonblinded nature of the intervention. The risk of death was similar between the two groups (risk ratio [RR]: 0.78, 95% confidence interval [CI]: 0.52–1.18). No significant differences were observed in the composite outcome of death or severe disability between the two groups (RR: 0.78, 95% CI: 0.56–1.10, very low quality of evidence). Furthermore, no significant differences were observed in the endpoints of sepsis, shock, acute kidney injury, major arrhythmia, and length of hospital stay. Therapeutic hypothermia was associated with significantly higher risk of thrombocytopenia (RR: 2.13, 95% CI: 1.34–3.38) and clinically significant hemorrhage (RR: 1.57, 95% CI: 1.25–1.97). Conclusion: Therapeutic hypothermia probably results in little to no difference in clinical outcomes among neonates with HIE in LMICs. Further large-scale research targeting proper patient selection is needed to elucidate the utility of therapeutic hypothermia in resource-limited settings. Protocol Registration: The protocol of the study has been prospectively registered by Prospero, CRD42021272284.