Timing of therapeutic hypothermia and outcomes in neonatal HIE

Background. Therapeutic hypothermia improves survival and neurodevelopmental 22 outcomes in neonates with hypoxic-ischemic encephalopathy when initiated within 23 6 hours of birth. However, in low- and middle-income countries, delays in referral 24 and access to tertiary care often preclude early initiation, and the benefits of 25 therapeutic hypothermia initiated beyond the recommended window remain 26 uncertain. We aimed to assess whether initiating therapeutic hypothermia between 27 6 and 12 h after birth is associated with a higher risk of mortality and/or brain injury 28 compared to initiation within 6 h in neonates with moderate or severe hypoxic29 ischemic encephalopathy. 30 Methods. We conducted a retrospective cohort study of 173 neonates with moderate 31 or severe hypoxic-ischemic encephalopathy treated with servo-controlled whole32 body therapeutic hypothermia at a tertiary care center in Colombia. Neonates were 33 categorized based on the timing of therapeutic hypothermia initiation as =6 h or >6 34 to =12 h after birth. The primary outcome was a composite of in-hospital mortality 35 and/or brain injury confirmed by magnetic resonance imaging during the first week 36 of life. Multivariate logistic regression was used to adjust for confounding variables. Results. Of the 173 neonates, 44.5% received therapeutic hypothermia within 6 38 hours and 55.5% after 6–12 hours. A composite outcome was observed in 40.6% of 39 the patients. Delayed therapeutic hypothermia was not significantly associated with 40 an increased risk of the composite outcome compared to early initiation (adjusted 41 odds ratio [OR]: 1.83; 95% CI: 0.86–3.90).