Abstract
AIM: To estimate the cumulative risk of epilepsy after neonatal seizures and identify subpopulations at increased risk. METHOD: This was a nationwide register-based cohort study including all children born in Denmark between 1997 and 2018. The cumulative risk of epilepsy in children with and without neonatal seizures was compared. Furthermore, neonatal seizures were stratified according to aetiology. RESULTS: We followed 1 294 377 children and identified 1998 neonatal survivors with neonatal seizures. The cumulative risk of epilepsy was 20.4% (95% confidence interval [CI] = 18.5-22.3) among children with neonatal seizures, compared to 1.15% (95% CI = 1.12-1.18) among children without. Epilepsy was diagnosed before 1 year of age in 11.4% of children with neonatal seizures, in an additional 4.5% between 1 year and 5 years, 3.1% between 5 years and 10 years, and 1.4% between 10 years and 22 years. The aetiologies of neonatal cerebral infarction, haemorrhage, or malformations (adjusted hazard ratio = 2.49, 95% CI = 1.98-3.14) and low Apgar score (1.49, 95% CI = 1.12-1.98) were associated with the highest risk of epilepsy, compared to children with seizures of unknown aetiology. INTERPRETATION: Epilepsy after neonatal seizures is common and remains a substantial risk throughout childhood. Aetiological risk factors are identifiable and relevant when planning appropriate information for parents and follow-up.