Levetiracetam versus Phenobarbitone as First Line Antiepileptic Drug in Management of Neonatal Seizures: A Retrospective Cohort Study

Abstract

Introduction: Neonatal seizures require urgent intervention, yet the optimal first-line treatment remains a subject of ongoing debate. While Phenobarbitone (PB) remains the traditional standard of care, its use is increasingly scrutinised due to adverse effects like respiratory depression and potential neurotoxicity in the developing brain. Levetiracetam (LEV) has emerged as a promising alternative with a more favourable safety profile and superior neurodevelopmental outcomes, but direct comparative data remain limited. Aim: To compare the clinical efficacy and safety profiles of PB versus LEV in the management of neonatal seizures. Materials and Methods: This retrospective cohort study was conducted over 1.5 years (April 2021 to October 2022) in the Neonatal Intensive Care Unit (NICU) at the Department of Paediatrics, Sumandeep Vidyapeeth Deemed to be University, Vadodara, Gujarat, India, comparing 45 neonates treated for seizures with either PB (n=24) or LEV (n=21). Outcomes measured included clinical adverse events, breakthrough seizures, crossover protocols, discharge neurological status, and 6-month neurodevelopmental trajectories using Hammersmith Infant Neurological Examination (HINE) scores. Data entry and statistical analysis were performed using MedCalc software (v20.11), utilising Chi-square, Student’s t-test, or One-way Analysis of Variance (ANOVA) with a significance threshold of p<0.05. Results: Baseline demographics showed no significant differences between the PB and LEV groups regarding mean gestational age (38.87 vs 38.33 weeks), birth weight (2.84 vs 2.82 kg), male predominance, or mode of delivery. Immediate seizure cessation following the initial loading dose was achieved in 10/24 (41.67%) of the PB group compared to 3/21 (14.29%) of the LEV group (p=0.04). Additionally, a secondary reloading dose was required to attain seizure control in 14/24 (58.33%) of the PB cohort versus 18/21 (85.71%) of the LEV cohort (p=0.04). Retrospective data tracking revealed no statistically significant differences between the two treatment groups regarding documented in-hospital adverse effects, postdischarge breakthrough recurrence rates, or short- and longterm neurodevelopmental outcomes at the 6-month milestone. Conclusion: The PB group showed better seizure control as first-line AED as compared to LEV.