Effect of early withdrawal of phenobarbitone on the recurrence of neonatal seizures: An open-label randomized controlled trial

Abstract

BackgroundThe long-term administration of phenobarbitone in neonates may be associated with adverse neurological outcome. The timing of stopping phenobarbitone maintenance after acute seizure control in neonates is a matter of debate. ObjectivesTo study the effect of early withdrawal of phenobarbitone on recurrence of neonatal seizures. Study designOpen-label randomized controlled trial. ParticipantsOutborn neonates (≥34 weeks of gestation to <28 days of postnatal period) with seizures (n = 221) admitted to Neonatal unit in Pediatric emergency of a tertiary care hospital in north India over 1 year. InterventionAfter a loading dose of phenobarbitone (20 mg/kg), neonates who remained seizure free for at least 12 h were enrolled after written informed consent from parents, and randomized (computer generated block randomization) to ‘phenobarbitone withdrawal group’ (n = 112) where phenobarbitone maintenance was stopped and ‘phenobarbitone continued group’ (n = 109) where phenobarbitone maintenance was continued until discharge and further as per clinician’s discretion. OutcomesThe primary outcome was seizure recurrence until discharge and secondary outcomes were time to reach full enteral feeds, duration of hospital stay, abnormal neurological status at discharge, and mortality in two groups. ResultsThe baseline variables were comparable in 2 groups. The incidence of seizure recurrence was similar in the phenobarbitone withdrawal and phenobarbitone continued groups (50% vs. 37.6%, respectively, p = 0.078). Among secondary outcomes, the phenobarbitone withdrawal and continued groups had similar time to reach full enteral feeds (4.02 days vs. 4.2 days, p = 0.75), duration of hospital stay (6.3 days vs. 6.5 days, p = 0.23), abnormal neurological status at discharge (45.6% vs. 38%, p = 0.39), and mortality (11.6% vs. 8.3%, p = 0.50). ConclusionEarly withdrawal of phenobarbitone in neonatal seizures does not lead to a significant increase in the rate of seizure recurrence.