Efficacy And Safety Of Levetiracetam For Neonatal Seizure:A Meta-Analysis

Objective:To evaluate the efficacy and safety of levetiracetam(LEV)for neonatal seizure,and compare the efficacy,side effects,mortality and neurological outcomes betweenlevetiracetam(LEV)and phenobarbital(PB)in the treatment of neonatal seizure.Methods:The keywords of LEV、PB and neonatal seizure were searched in Pub Med,MEDLINE,the Cochrane Library,wed of science,EMBASE clinicaltrials.gov to collect high-quality studies.We collected studies studying the efficacy or safety of LEV and PB in the treatment of neonatal seizure from 1960 to 2021 years.Data were extracted through the strict inclusion and exclusion criteria.Outcome measures including efficacy,side effects rate,neurological score,mortality were performed by Revman 5.3 software.Results:1.The efficacy of LEV as a first-line drug for neonatal seizure was28%-86% in 24 hours,79%-100% in 6-7 days,and 35%-100% when it was used as second-line or third-line drug.2.The incidence rate of side effects of LEV was 0%-12%.The most common side effects were hypotension and respiratory depression,with the incidence rate of 0%-5% and 0%-12% respectively.Most of the newborns with seizure who received LEV had good neurodevelopmental outcomes and less severe neurological sequelae such as cerebral、growth retardation or epilepsy.3.Ten articles were finally included in the meta-analysis,including 4RCTs,2 prospective cohort studies and 4 retrospective studies.Meta-analysis showed that there was no difference in efficacy between LEV and PB in the treatment of neonatal seizure(P=0.68).However,there was heterogeneous in the studies,and the heterogeneity mainly comes from the different measures of seizure diagnosis and the different doses of PB.Compared with LEV,PB was less effective in the treatment of neonates with clinically confirmed seizure(P=0.002),but there was no difference between LEV and PB in the treatment of neonates with EEG confirmed seizure(P=0.68).4.Compared with PB,the incidence rate of side effects of LEV was lower(P<0.0001).The incidence rate of hypotension and respiratory depression in LEV group was significantly lower than that in PB(P=0.001,P=0.04).5.In terms of long-term neurodevelopmental outcome,there was no significant difference in the cognitive and motor scores of BSID between the LEV group and the PB group(P=0.57,P=0.47).Conclusion: PB is a first-line AEDs drug recommended by WHO in the treatment of neonatal seizure.However,the new AEDs levetiracetam(LEV)has good efficacy and high safety.And LEV has important value in the treatment of neonatal seizure.At the same time,it is important to normalize the diagnosis of neonatal seizure and evaluate the efficacy of AEDs through c EEG monitoring.