LONG-TERM NEURODEVELOPMENTAL OUTCOMES IN INFANTS TREATED WITH THERAPEUTIC HYPOTHERMIA FOR HIE

Abstract

Hypoxic‐ischemic encephalopathy (HIE) remains a major cause of neonatal morbidity despite widespread adoption of therapeutic hypothermia. In this multicenter prospective cohort study of 150 term infants treated with whole‐body cooling (33–34 °C for 72 h) initiated within six hours of birth, we evaluated neurodevelopmental outcomes at 24 and 60 months and identified clinical, imaging, and biomarker predictors of adverse outcome. At two years, mean BSID-III composite scores were 95.2 ± 12.3 (cognitive), 90.1 ± 14.5 (language), and 92.5 ± 13.1 (motor), and at five years, mean full-scale IQ was 98.3 ± 11.7 with an MABC-2 motor percentile of 42.7 ± 18.4; nevertheless, 40% met criteria for a composite adverse outcome (death, cerebral palsy, or intellectual disability). Multivariable analysis demonstrated that severe HIE (AOR 3.2, p = 0.003), delayed cooling initiation beyond three hours (AOR 2.5, p = 0.014), basal ganglia injury on neonatal MRI (AOR 4.0, p < 0.001), low socioeconomic status (AOR 1.8, p = 0.028), and elevated serum neuron-specific enolase > 18 ng/mL (AOR 2.2, p = 0.049) were independent predictors of adverse outcome. MRI patterns correlated strongly with impairment severity—66% of infants with basal ganglia lesions had moderate to severe deficits versus < 5% with normal imaging. Qualitative interviews underscored barriers in therapy access and emotional coping that may further hinder recovery. These findings emphasize the critical need for rapid initiation of hypothermia, MRI-guided risk stratification, and integrated socioeconomic and psychosocial support to optimize long-term neurodevelopment. Ongoing longitudinal surveillance and investigation of adjunctive neuroprotective and family-centered interventions are warranted to mitigate late-emerging cognitive, motor, and behavioral challenges in this vulnerable population