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Levetiracetam Vs. Phenobarbital For Neonatal Seizures: Evaluation of A Paradigm Shift

Objective: Although phenobarbital (PB) is commonly used as a first-line anti-seizure drug (ASD) for neonatal seizures, in 2015 we chose to replace it with levetiracetam (LEV), a third-generation ASD. In this study, we compared the safety and efficacy of LEV and PB as first-line ASDs, considering the years before and after modifying our treatment protocol for neonatal seizures. Methods: We performed a retrospective study of 108 consecutive neonates with EEG-confirmed seizures treated with first-line LEV or PB in 2012-2020. Results: First-line ASD was LEV in 33 (31%) and PB in 75 (69%) neonates. The etiology included hypoxic-ischemic encephalopathy (HIE) in 31% of cases, intracranial hemorrhage in 15%, ischemic stroke in 9%, and neonatal-onset genetic epilepsy in 19%. Forty-two of 108 (39%) neonates achieved seizure freedom following first-line therapy. Treatment response did not vary by first-line ASD in the full cohort (p = 0.28) or in the HIE subgroup (p = 0.52). Treatment response was lowest for neonates with a higher seizure burden, particularly for neonates with status epilepticus than those with rare seizures (p<0.001) but did not differ by sex, gestational age, etiology, or EEG background. Adverse events were noted in 22 neonates treated with PB and only in one treated with LEV (p<0.001). Conclusion: PB was associated with more adverse events than LEV, and the two ASDs were equally but incompletely effective in treating neonatal seizures, thus confirming LEV as a safe and effective alternative to PB as a first-line therapy in these neonates.

Linda Bättig
University Children’s Hospital Zurich
Switzerland

Corinne Dünner
University Children’s Hospital Zurich
Switzerland

Dorottya Cserpan
University Children’s Hospital Zurich
Switzerland

Andrea Rüegger
University Children’s Hospital Zurich
Switzerland

Cornelia Hagmann
University Children’s Hospital Zurich
Switzerland

Bernhard Schmitt
University Children’s Hospital Zurich
Switzerland

Francesco Pisani
University of Parma
Italy

Georgia Ramantani
University Children’s Hospital Zurich
Switzerland

 


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