Retrospective Evaluation of First-line Levetiracetam use for Neonatal Seizures after Congenital Heart Defect repair with or without Extracorporeal Membrane Oxygenation.

Objective: Levetiracetam (LEV) efficacy for neonatal seizures is debated. We evaluated LEV as a first line anti-seizure medicine (ASM) in neonates following neonatal congenital heart defect (CHD) repair who did not require extracorporeal membrane oxygenation (ECMO) vs neonates who required ECMO.

Methods: A single center retrospective review of neonates with CHD from 2015 to 2020 was conducted. Neonates were included if seizures were present on continuous EEG after CHD repair either on or off ECMO, and they received LEV as a first line ASM. Primary outcomes were seizure resolution with LEV, adverse events and response to subsequent ASM.

Results: Eighteen total neonates were evaluated, 10 with seizures post-CHD repair who did not require ECMO and 8 who required ECMO. In the non-ECMO cohort, nine of ten were successfully treated with LEV monotherapy with no adverse events. In comparison, the eight neonates who required ECMO had a higher initial seizure burden (1.6% vs 17%, p=0.003), were more likely to have injury on neuroimaging (12.5 vs 75%, p= 0.04), and all neonates required multiple ASMs. Seizure burden did not decrease with LEV, but significantly decreased with phenobarbital and fosphenytoin (14.4% and 10.5%, p = 0.024).

Conclusions: Neonates with CHD and seizures on and off ECMO demonstrated divergent seizure characteristics including seizure burden and response to LEV. LEV may reduce neonatal seizure burden after uncomplicated CHD repair. However, in neonates requiring ECMO, multiple ASMs were required. A prospective evaluation of ASM efficacy and safety in this high-risk population is urgently needed.