Safety of Moderate Hypothermia for Perinatal Hypoxic-Ischemic Encephalopathy: A Meta-analysis

BACKGROUND: We investigated the safety of therapeutic hypothermia during intervention in infants with hypoxic-ischemic encephalopathy (HIE). METHODS: The MEDLINE, EMBASE, PubMed, and the Cochrane Central Register of Controlled Trials from onset to November 30, 2016 were searched for studies on perinatal HIE. Randomized controlled trials comparing the use of therapeutic hypothermia with normothermia for perinatal HIE were included in the study. Safety and efficacy data for therapeutic hypothermia in 1806 infants with HIE were included in this meta-analysis. The primary outcomes were safety variables, and the secondary outcomes were efficacy variables. A fixed-effect model was used to perform the meta-analysis. Risk ratios (RR), risk differences (RD), and 95% confidence intervals (CI) were calculated. RESULTS: Thirteen trials, including 1806 infants, contained information on safety and efficacy variables. Moderate hypothermia significantly increased the risk of thrombocytopenia (RR 1.18, 95% CI 1.02 to 1.37, P = 0.03; RD 0.06, 95% CI -0.02 to 0.09) and cardiac arrhythmia (RR 2.52, 95% CI 1.62 to 3.93, P < 0.0001; RD 0.19, 95% CI 0.09 to 0.03) during intervention. CONCLUSIONS: In infants with HIE, the application of therapeutic hypothermia increases the risk of thrombocytopenia and cardiac arrhythmia during intervention.