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.

Methods: A retrospective, multicenter cohort study was performed in children with NE treated with TH at two 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 (LMM).

Results: Seventy-seven children were analyzed. In LMM, motor Z-scores decreased non-linearly 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 MRI. Cognitive Z-scores decreased among children with mammillary body abnormalities on neonatal MRI, and were significantly lower in children with a lower gestational age and lower socio-economic 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.