Therapeutic Hypothermia in Sudden Unexpected Postnatal Collapse: Feasibility, Risks, and Long-Term Outcomes—A Systematic Review

<b>Background/Objectives</b>: Sudden unexpected postnatal collapse (SUPC) is a rare but catastrophic event affecting apparently healthy neonates during the first days of life. Therapeutic hypothermia has been increasingly applied in this setting due to pathophysiological overlap with hypoxic-ischemic encephalopathy, but its effectiveness remains uncertain. The aim of this review is to systematically identify, appraise, and synthesize the evidence on therapeutic hypothermia for SUPC. <b>Methods</b>: We searched MEDLINE, Scopus, Embase, Web of Science, and Cochrane up to February 2025. Eligible studies included term or near-term infants with SUPC within seven days of life who underwent therapeutic hypothermia. Data were extracted on demographics, collapse circumstances, therapeutic hypothermia protocol, mortality, seizures, neuroimaging, and neurodevelopment. <b>Results</b>: Thirteen studies were included, encompassing 70 infants. Most events occurred within two hours of life, during skin-to-skin or breastfeeding, and were strongly associated with primiparity. Therapeutic hypothermia was typically initiated within six hours of collapse, using whole-body cooling at 33-34 °C for 72 h. Mortality was approximately 10% (widely ranging from 0 to 50%). Seizures were frequent (70-90%), and MRI abnormalities were reported in about half of cases. Approximately half of survivors demonstrated normal neurodevelopment at one year. Study quality was low to moderate, and risk of bias substantial. <b>Conclusions</b>: Therapeutic hypothermia is feasible in SUPC and survival with favorable outcomes has been documented, but the certainty of evidence is very low. Given recurrent risk factors such as primiparity and early skin-to-skin/breastfeeding, enhanced vigilance and preventive strategies are essential. Therapeutic hypothermia should be considered case by case, ideally within specialized centers and supported by registries.