Effect of Withholding Phenobarbitone Maintenance in Neonatal Seizures: A Randomized Controlled Trial.

OBJECTIVE: To compare the effect of withholding maintenance phenobarbitone on breakthrough seizures.

DESIGN: A double blind randomized controlled trial.

SETTING: Level II neonatal intensive care unit (NICU) of a teaching hospital in Northern India.

PARTICIPANTS: 152 term and near term neonates (34 weeks of gestation age) with admission weight ≥2 kg with clinically apparent seizures who received intravenous (IV) loading dose of 20 mg/kg of phenobarbitone.

INTERVENTIONS: After 12 hours of seizure free period of the initial loading dose of phenobarbitone, one group received IV maintenance therapy and other 'no maintenance' (saline as placebo).

MAIN OUTCOME MEASURE: Breakthrough seizures from randomization till discharge.

RESULTS: Baseline variables were comparable in the two groups. Breakthrough seizures occurred in 30 (40%) subjects in placebo group and 24 (31.2%) in phenobarbitone group with RR (95% CI) of 1.28 (0.83-1.97) (P=0.19). Seizure recurrence, re-hospitali-sation, mortality and abnormal neurological assessment until 3 months were comparable in the two groups (P>0.05). Babies in either group with breakthrough seizures were more likely to be neurologically abnormal at 1 month than babies who did not have breakthrough seizures, but this difference decreased by 3 months.

CONCLUSION: In term and near-term neonates, those who respond to loading dose of phenobarbitone after a single seizure episode, withholding of phenobarbitone maintenance may not significantly increase the risk of breakthrough seizures.