Preschool Outcome After Therapeutic Hypothermia in Neonatal Hypoxic-Ischemic Encephalopathy: Insights from Early Neurodevelopmental Assessment

Background: Therapeutic hypothermia has significantly improved the prognosis of infants with hypoxic–ischemic encephalopathy (HIE), shifting the focus of follow-up toward the identification of early predictors of preschool neurodevelopmental outcome. This study aimed to evaluate the predictive value of early neurological, developmental and neuroradiological assessments in children with HIE treated with therapeutic hypothermia. Methods: We conducted a prospective longitudinal study including 105 children with HIE treated with therapeutic hypothermia between 2015 and 2022 at a tertiary neonatal center. Early neurological examination using the Hammersmith Infant Neurological Examination (HINE), Griffiths Mental Development Scales at 24 months, brain magnetic resonance imaging (MRI), and neonatal clinical variables were evaluated as predictors of preschool neurodevelopmental outcome. Outcome was classified as favourable or adverse according to cognitive performance and the presence of major neurodevelopmental impairment. Results: Of the 105 children included in the preschool follow-up, 84 (80.0%) had a favourable neurodevelopmental outcome and 21 (20.0%) an adverse outcome. Moderate-to-severe neonatal MRI abnormalities were observed in 11/84 (13.1%) children with favourable outcome and 12/21 (57.1%) with adverse outcome (p < 0.001). Children with adverse outcomes had lower HINE scores at 12 months (p < 0.001) and lower Griffiths Global Developmental Quotients at 24 months (p < 0.001). ROC analyses showed high discrimination for HINE (AUC 0.920), Griffiths Global Developmental Quotient (AUC 0.917), and Griffiths Hearing and Speech Scale (AUC 0.915). Conclusions: Most children with moderate-to-severe HIE treated with therapeutic hypothermia achieved favorable preschool outcomes. Neonatal MRI, followed by standardized neurological and developmental assessments during infancy and toddlerhood, provides complementary information that may progressively refine neurodevelopmental prognostication.