Long-term safety of early discontinuation of antiseizure medication after resolution of acute provoked neonatal seizures.

OBJECTIVE: To assess long-term safety of antiseizure medication (ASM) discontinuation after resolution of acute provoked neonatal seizures and prior to hospital discharge. METHODS: Prospective, observational, comparative effectiveness cohort study of neonates with acute provoked seizures born from July 2015 to March 2018, and followed until September 2024, at nine U.S. Neonatal Seizure Registry centers with Level IV neonatal intensive care units and Level IV pediatric epilepsy programs. Duration of ASM treatment was quantified as (1) discontinuation before discharge from the neonatal seizure admission or (2) maintenance at the time of hospital discharge. Outcomes were adjusted for propensity to receive ASM at discharge. Propensity for ASM maintenance was defined among enrolled participants by a logistic regression model including seizure etiology, gestational age, therapeutic hypothermia, worst electroencephalography (EEG) background, days of EEG seizures, and discharge neurological exam (all p ≤ .1 in a joint model, except etiology, which was included for face validity). The primary outcome was non-inferiority of cognition (Wechsler Preschool and Primary Scale of Intelligence assessed at age 5-6 years). Secondary outcomes were non-inferiority of functional development (Vineland Adaptive Behavior Scale, 3rd Edition, assessed at 3-8 years) and post-neonatal epilepsy (assessed at 1-8 years). RESULTS: Among 284 children with at least one follow-up, outcomes were similar in the discontinued vs maintained ASM groups for full-scale IQ at age 5 years (adjusted difference +10 points), functional development at ages 3-8 years (adjusted difference 0 points), and post-neonatal epilepsy at ages 1-8 years (adjusted hazard ratio .93, 95% confidence interval [CI] .48-1.80). SIGNIFICANCE: Prolonged administration of ASM for several months after resolution of acute provoked neonatal seizures may expose infants to unnecessary medications. These results provide additional evidence for safety of discontinuing ASM for most neonates soon after the resolution of acute provoked seizures-a practice that is recommended in the International League Against Epilepsy (ILAE) guideline for neonatal seizure management.

Duke Scholars

Author Monica Elizabeth Lemmon Pediatrics, Neurology