What question did this study set out to answer?

The aim is to compare the efficacy and safety of levetiracetam (LEV) and phenobarbital (PB) as first-line treatments for neonatal seizures.

February 13, 2026Open Access

Levetiracetam versus phenobarbital as first-line therapy for neonatal seizures: a comprehensive systematic review and meta-analysis with meta-regression of 26 studies involving 9,854 neonates

Key Points

The aim is to compare the efficacy and safety of levetiracetam (LEV) and phenobarbital (PB) as first-line treatments for neonatal seizures.
Comprehensive systematic review of 26 studies
Meta-analysis of data involving 9,854 neonates
Meta-regression to assess treatment effects
LEV and PB show comparable efficacy in treating neonatal seizures
LEV has a better safety profile, particularly for cardiopulmonary stability
Findings suggest LEV may be preferred for neonates at risk for respiratory issues

Abstract

LEV and PB demonstrate comparable efficacy for first-line treatment of neonatal seizures; however, LEV provides a more favorable safety and tolerability profile, particularly with respect to cardiopulmonary stability. These findings support the consideration of LEV as an alternative first-line agent, especially in neonates at risk for hemodynamic or respiratory compromise. Further large, high-quality RCTs with standardized EEG confirmation and long-term neurodevelopmental follow-up are warranted.

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