Abstract Randomized controlled trials have demonstrated the safety and efficacy of mild hypothermia in the treatment of neonatal hypoxic-ischemic encephalopathy (HIE), which can reduce mortality or the incidence of severe neurological sequelae. Mild hypothermia has been used in the neonatal intensive care unit (NICU) as a routine treatment method for neonatal HIE in many developed countries, and it is increasingly applied in some NICUs in China. However, 40%-50% of the neonates treated with mild hypothermia die or develop severe neurological disability. Thus, to achieve the best neuroprotective effect, issues such as selection of patients with indications for mild hypothermia, cooling method, optimal time for mild hypothermia, duration of mild hypothermia, optimal target temperature, and the safety and long-term effects of mild hypothermia combined with other therapies, need to be further discussed. This article reviews the latest progress in clinical research on these issues.
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