Adverse neurodevelopmental outcomes after exposure to phenobarbital and levetiracetam for the treatment of neonatal seizures

OBJECTIVE: Compare neurodevelopment after levetiracetam (LEV) and phenobarbital (PB) for neonatal seizures. STUDY DESIGN: Retrospective study of infants who received antiepileptic drugs (AEDs) for neonatal seizures. Effect of cumulative exposure to LEV and PB on outcomes of death, cerebral palsy (CP), and Bayley Scales of Infant Development (BSID) scores were evaluated at 24 months corrected age. Analyses were adjusted for number of electrographic seizures and gestational age. RESULTS: In 280 infants with comparable seizure etiology and cranial imaging results, increased exposure to PB was associated with worse BSID cognitive and motor scores (8.1- and 9-point decrease per 100 mg/kg; p=0.01). The effect was less with LEV (2.2- and 2.6-point decrease per 300 mg/kg LEV (p=0.01). CP probability increased by 2.3-fold per 100 mg/kg PB and was not associated with increasing LEV. CONCLUSION: Increased exposure to PB is associated with worse neurodevelopmental outcomes than LEV. Prospective studies of outcomes of neonatal exposure to AEDs are essential.