Serial Assessment of Neurodevelopmental Outcome Following Neonatal Encephalopathy and Therapeutic Hypothermia

OBJECTIVE: To compare the neurodevelopmental outcome at 18-24 months, 5-6 years, and 8-10 years of age among children who received therapeutic hypothermia (TH) for neonatal encephalopathy (NE) following perinatal asphyxia. STUDY DESIGN: A retrospective, multicenter cohort study was performed in children with NE treated with TH at 2 level III neonatal intensive care units between January 2008 and December 2015, with neurodevelopmental testing at 18-24 months (visit 1), 5-6 years (visit 2), and 8-10 years (visit 3). Motor, cognitive, and behavioral scores, derived from standardized neurodevelopmental tests, were converted to Z-scores and compared across the visits using linear mixed modeling. RESULTS: Seventy-seven children were analyzed. In linear mixed modeling, motor Z-scores decreased nonlinearly throughout the follow-up visits, being lower among children with a lower total IQ at 8-10 years and deep gray matter injury on neonatal brain magnetic resonance imaging. Cognitive Z-scores decreased among children with mammillary body abnormalities on neonatal magnetic resonance imaging, and were significantly lower in children with a lower gestational age and lower socioeconomic status. Z-scores indicating internalizing behavioral problems increased linearly (visit 1: median -0.7, IQR 1.4; visit 2: median -0.5, IQR 1.2; visit 3: median -0.1, IQR 1.5). CONCLUSIONS: Motor, cognitive, and behavioral Z-scores significantly worsened from 2 to 8-10 years among children who received TH for NE, highlighting the importance of long-term developmental surveillance.