Supplementary Material for: Neurological outcomes beyond epilepsy following electroencephalographically verified neonatal seizures: A Swedish nationwide cohort study

Introduction: Neonatal seizures affect 1-3 per 1000 live term newborns and are most often acute provoked. Seizure verification with electroencephalogram (EEG) or amplitude-integrated EEG (aEEG) is of major importance for correct diagnosis. The aim of this study was to investigate the risks of developmental delay (DD), intellectual disability (ID), autism, attention-deficit hyperactivity disorder (ADHD), and cerebral palsy (CP) after EEG/aEEG-verified neonatal seizures of any cause in a Swedish population-based cohort. Methods: Data from five national health care registers was used. Infants with EEG/aEEG-verified seizures, born from January 1, 2009, to December 31, 2020, were matched with controls, negative for neonatal seizure diagnosis. Follow-up time was from January 1, 2009, to December 31, 2021. Cumulative incidences, unadjusted and adjusted hazard ratios (aHRs) with 95% confidence intervals (CIs) from Cox regression analysis of each outcome, were explored. In infants with neonatal seizures, the occurrence of pre-specified etiologies was investigated. Results: In total, 1062 infants with neonatal seizures were matched with 5310 controls. Overall, the cumulative incidences were greater in infants with neonatal seizures compared to controls, and CP presented with the highest incidence of 21.9% (95% CI: 19.4-24.6%) in children with neonatal seizures at 10 years of age and 0.42% (95% CI: 0.27-0.64%) in controls. The greatest aHR of 42.6 (95% CI: 26.3-69.1) was found for CP, followed by an aHR of 18.9 (95% CI: 11.8-30.4) for ID when children with neonatal seizures were compared with controls. In children with neonatal seizures, 57.1% (n=606) were registered with any of the pre-specified etiologies. Conclusion: Neonatal seizures were associated with overall increased risks of DD, ID, autism, ADHD, and CP. The findings emphasize the risks of adverse developmental trajectories in the exposed children and the importance of standardized follow-up programs to initiate clinical interventions when needed.