Efficacy and safety of levetiracetam in the off-label treatment of neonatal seizures

Background: Treatment of neonatal seizures includes etiotropic and anticonvulsant treatments. However, anticonvulsant use in neonates is off-label and requires ethical review. Objective: To investigate the efficacy and safety of levetiracetam for neonatal seizures and to establish a predictive model. Methods: We retrospectively analyzed 125 neonatal seizure cases (phenobarbital 66 cases, levetiracetam 59 cases). The efficacy, safety and tolerability of levetiracetam were evaluated by cox regression survival analysis and a regression tree prediction model for the 16-week time point. Results: There was no significant difference between phenobarbital and levetiracetam treatment group in short-term efficacy (p > 0.05). But the cumulative survival function suggested that levetiracetam treatment group was better than phenobarbital (p = 0.026) in long-term efficacy evaluation. Neurodevelopmental assessments at 16 weeks showed that levetiracetam had better effect on the neurodevelopmental level (Gesell scores in response) than phenobarbital (p = 0.011). The main adverse events with levetiracetam were irritability and anorexia. According to the regression tree prediction model, the top three factors influencing the therapeutic effect were pre-treatment seizure frequency, age of onset and etiological classification. Conclusion: Levetiracetam shows good efficacy, safety and tolerability for the long-term neonatal seizure treatment.