Real-World Therapeutic Hypothermia for Neonatal HIE: Neurodevelopmental Outcomes and Predictors

Aim: This study assessed neurodevelopmental outcomes in neonates with hypoxic-ischemic encephalopathy (HIE) treated with therapeutic hypothermia (TH) outside randomised controlled trials (RCTs). It also aimed to identify predictors of outcomes and evaluate TH practices across centres. Methods: A prospective, area-based observational study was conducted in eight Italian NICUs (2016–2021), including neonates treated with TH for any grade of HIE. A 2-year neurodevelopmental follow-up was performed. Severe functional disability (SFD) was defined as cerebral palsy (Gross Motor Function Classification Level > 2), cognitive score < 2 SD, bilateral blindness/deafness, or epilepsy. Demographic, clinical and MRI data were analysed. Results: Among 283 cooled infants, 11 (3.8%) died and 272 (96.2%) survived. HIE severity was mild (14.0%), moderate (76.1%) and severe (9.9%). Follow-up data were available for 232 (85.3%) survivors, with SFD diagnosed in 27 (11.6%). No infants with mild HIE developed SFD. Severe MRI anomalies were found in 51.9% of SFD cases, while 90.7% of non-SFD children had normal findings. cEEG/aEEG-confirmed seizures (OR = 12.9, CI 3.5–65.0) and severe MRI anomalies (OR = 0.24, CI 0.13–0.44) were strong SFD predictors (AUC = 0.95). Conclusion: Mortality and SFD rates were lower than in RCTs. Seizures and severe MRI anomalies predicted poor outcomes. Further RCTs are needed to refine treatment criteria.