Levetiracetam versus Phenobarbital for Neonatal Seizures: A Retrospective Cohort Study

Background: Although phenobarbital (PB) is commonly used as a first-line antiseizure medication (ASM) for neonatal seizures, in 2015 we chose to replace it with levetiracetam (LEV), a third-generation ASM. Here, we compared the safety and efficacy of LEV and PB as first-line ASM, considering the years before and after modifying our treatment protocol. Methods: We conducted a retrospective cohort study of 108 neonates with electroencephalography (EEG)-confirmed seizures treated with first-line LEV or PB in 2012 to 2020. Results: First-line ASM was LEV in 33 (31%) and PB in 75 (69%) neonates. The etiology included acute symptomatic seizures in 69% of cases (30% hypoxic-ischemic encephalopathy, 32% structural vascular, 6% infectious, otherwise metabolic) and neonatal epilepsy in 22% (5% structural due to brain malformation, 17% genetic). Forty-two of 108 (39%) neonates reached seizure freedom following first-line therapy. Treatment response did not vary by first-line ASM among all neonates, those with acute symptomatic seizures, or those with neonatal-onset epilepsy. Treatment response was lowest for neonates with a higher seizure frequency, particularly for those with status epilepticus versus rare seizures (P < 0.001), irrespective of gestational age, etiology, or EEG findings. Adverse events were noted in 22 neonates treated with PB and in only one treated with LEV (P < 0.001). Conclusions: Our study suggests a potential noninferiority and a more acceptable safety profile for LEV, which may thus be a reasonable option as first-line ASM for neonatal seizures in place of PB. Treatment should be initiated as early as possible since higher seizure frequencies predispose to less favorable responses. (c) 2022 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).