Abstract Objectives Very low birth weight (VLBW) infants are at disproportionately high risk for neonatal seizures, yet optimal first-line antiseizure medication (ASM) strategies in this vulnerable population remain a matter of debate. Over the past decade, levetiracetam (LEV) has emerged as a promising alternative to phenobarbital (PB), driven by growing concerns over PB’s limited efficacy and potential neurotoxic effects. Methods This retrospective cohort study analyzed medical records of VLBW infants treated for seizures at our Neonatal Intensive Care Unit from 2013 to 2023. We compared the efficacy and safety of LEV and PB as initial antiepileptic treatments. Data on gestational age, birth weight, type of seizures, electroencephalogram findings, and treatment outcomes were meticulously collected and analyzed. Results The study included 103 VLBW infants (mean gestational age 26.17±2.31 weeks); 27 received LEV and 76 received PB. Baseline demographic and clinical characteristics were comparable between the two groups. Although the LEV group had a higher proportion of infants with severe intraventricular hemorrhage and necrotizing enterocolitis indicating a potentially more critical baseline, these differences were not statistically significant. The primary outcome revealed that significantly fewer infants in the LEV group were unresponsive to initial treatment compared to the PB group (14.8 vs. 56.6 %; p<0.001). Furthermore, lower gestational age was identified as a significant risk factor for PB unresponsiveness. Conclusions This study supports that LEV is more successful in clinical seizure control compared to PB as the first choice in ASM selection in VLBW. If our study results are supported by randomized controlled prospective studies, LEV, with its potentially fewer side effects, could be included in clinical algorithms as the first-choice ASM especially for VLBW.
Armağan et al. (2026) studied this question.