Objective: To determine the effects of therapeutic hypothermia (TH) in encephalopathic asphyxiated newborn infants on mortality, long-term neurodevelopmental disability and side effects by summarizing the data of hypoxic-ischemic encephalopathy(HIE) newborns undergoing mild hypothermia using meta-analysis.
Methods: The standard searching strategy of the Neonatal Review Group as outlined in the Cochrane Library was used to retrieve all clinical literatures about TH on HIE. RevMan 5.1 software was used to perform the meta-analysis of target papers. The primary outcome measure was a combination of death and severe major neurodevelopmental disabilities at 18 - 24 months of age. Secondary outcomes included mortality, cerebral palsy (CP), neurodevelopmental delay, blindness, deafness and main side effects of cooling therapy.
Results: A total of 276 papers fulfilled the search strategy and 11 trials were included. Overall TH resulted in a statistically significant and clinically important reduction in the combined outcome of death or major neurodevelopmental disabilities to 18-24 months of age (RR = 0.76, 95%CI: 0.68 - 0.84, P < 0.01). Moreover, as compared with the control group, TH significantly decreased the incidence of mortality (RR = 0.76, 95%CI: 0.65 - 0.90, P < 0.01), psychomotor development index(RR = 0.69, 95%CI: 0.55 - 0.87, P < 0.01), mental development index (RR = 0.66, 95%CI: 0.53 - 0.83, P < 0.01), CP (RR = 0.70, 95%CI: 0.54 - 0.91, P < 0.01) and blindness (RR = 0.54, 95%CI: 0.33 - 0.90, P < 0.05)except for severe hearing loss (deafness) (RR = 0.69, 95%CI: 0.35 - 1.34, P = 0.3000) in survivors. Adverse effects included significant thrombocytopenia in the TH group (P = 0.0400) but without deleterious consequences. There were no significant differences in arrhythmia, coagulopathy, hypotension requiring inotropic supports, sepsis and pulmonary hypertension between the TH and control groups (all P > 0.05).
Conclusions: Mild hypothermia is effective in reducing death and major disabilities in infants with moderate-to-severe HIE without significant side effects. Infants presenting within the first hours after birth with the signs and symptoms of moderate-to-severe encephalopathy should be cooled in accordance with the established protocols of previous randomized controlled trials.