左乙拉西坦治疗妊娠期癫痫疗效及胎儿安全性的Meta分析

The effectiveness and fetal safety of levetiracetam in the treatment of epilepsy during pregnancy:a Meta analysis

目的:评价左乙拉西坦治疗妊娠期癫痫的疗效及其对胎儿的影响。方法:计算机检索Medline、Cochrane library、EMbase、CNKI、万方、维普、CBM数据库,收集有关左乙拉西坦治疗妊娠期癫痫疗效及胎儿安全性的队列研究和病例对照研究。依据纽卡斯-渥太华量表(NOS量表)对符合纳入标准的临床研究进行质量评价,并采用RevMan5.3进行Meta分析。结果:本研究共纳入11篇队列研究进行分析,采用NOS评分评估偏移风险,其中10项研究的得分均在7~9分。Meta分析结果显示,在妊娠期癫痫发作控制率方面,左乙拉西坦组低于丙戊酸钠组,差异有统计学意义(P<0.05);而左乙拉西坦与拉莫三嗪、托吡酯、卡马西平或苯妥因单药治疗相比,两组间差异均无统计学意义(P>0.05)。在新生儿严重先天畸形发生率方面,左乙拉西坦组低于拉莫三嗪、托吡酯、丙戊酸钠、卡马西平或苯巴比妥组,差异均有统计学意义(P<0.05);左乙拉西坦组与奥卡西平组相比,两组间差异无统计学意义(P>0.05);左乙拉西坦单药治疗组明显低于多药治疗组(P<0.05)。左乙拉西坦对宫内死胎发生率的影响与拉莫三嗪、丙戊酸钠、卡马西平无明显区别(P>0.05)。结论:妊娠期癫痫患者服用左乙拉西坦单药治疗,其癫痫控制率可能低于丙戊酸钠,但与拉莫三嗪、托吡酯、卡马西平及苯妥因单药治疗疗效大致相当。在胎儿安全性结局方面,左乙拉西坦致畸性可能优于拉莫三嗪、托吡酯、丙戊酸钠、卡马西平及苯巴比妥,合并使用其他抗癫痫药物增加其致畸风险;左乙拉西坦对宫内死胎发生率的影响与拉莫三嗪、丙戊酸钠、卡马西平无明显区别。本文纳入研究均为队列研究,易受偏移风险的影响,故存在一定局限性。

OBJECTIVE To evaluate the effectiveness and fetal safety of levetiracetam in the treatment of epilepsy during pregnancy.METHODS Literatures were searched from Medline,Cochrane library,EMbase,CNKI,WanFang,VIP and CBM database.The quality of studies was evaluated according to Newcastle-Ottawa Quality Scale（NOS scale）.Meta-analysis was performed by The Cochrane Collaboration＇s software RevMan 5.3.RESULTS Eleven cohort studies were included,ten of which were high quality researches（7-9 according to NOS scale）.The results of Meta-analysis suggested that,in the aspect of seizures during pregnancy,levetiracetam had higher risks than valproate monotherapy（P〈0.05）,but there was no statistically significant difference between levetiracetam and lamotrigine,topiramate,carbamazepine or phenytoin（P〉0.05）.In the aspect of major congenital malformation（MCM）,levetiracetam monotherapy had lower risks than lamotrigine,topiramate,valproate,carbamazepine,phenobarbital or levetiracetam polytherapy（P〈0.05）,but no statistically increased risks than oxcarbazepine（P〉0.05）.There was no statistically significant difference between levetiracetam and lamotrigine,valproate,or carbamazepine in rates of intrauterine death（P〉0.05）.CONCLUSION Levetiracetam monotherapy may be inferior to valproate in the control of epilepsy attack,but effective as lamotrigine,topiramate,carbamazepine or phenytoin.Levetiracetam monotherapy has lower risks of MCM than lamotrigine,topiramate,valproate,carbamazepine,phenobarbital or levetiracetam polytherapy,and significant differences compared to lamotrigine,valproate,or carbamazepine in rates of intrauterine death.