Meador Kimford, Reynolds Matthew W, Crean Sheila, Fahrbach Kyle, Probst Corey
Department of Neurology, University of Florida, Gainesville, FL 32610-0236, USA.
Epilepsy Res. 2008 Sep;81(1):1-13. doi: 10.1016/j.eplepsyres.2008.04.022. Epub 2008 Jun 18.
To conduct a systematic review and meta-analysis to quantify the incidence of congenital malformations (CMs) and other pregnancy outcomes as a function of in utero anti-epileptic drug (AED) exposure.
We performed a systematic literature review to identify all published registries and cohort studies of births from pregnant women with epilepsy (WWE) that reported incidence of CMs. Overall incidences were calculated using a random effects model.
The review included 59 studies that met inclusion/exclusion criteria, involving 65,533 pregnancies in WWE and 1,817,024 in healthy women. The calculated incidence of births with CM in WWE [7.08%; 95% CIs 5.62, 8.54] was higher than healthy women [2.28%; CIs 1.46, 3.10]. Incidence was highest for AED polytherapy [16.78%; CIs 0.51, 33.05]. The AED with the highest CM incidence was valproate, which was 10.73% [CIs 8.16, 13.29] for valproate monotherapy.
Results of this systematic literature review suggest that the overall incidence of CMs in children born of WWE is approximately threefold that of healthy women. The risk is elevated for all AED monotherapy and further elevated for AED polytherapy compared to women without epilepsy. The risk was significantly higher for children exposed to valproate monotherapy and to polytherapy of 2 or more drugs when the polytherapy combination included phenobarital, phenytoin, or valproate. Further research is needed to delineate the specific risk for each individual AED and to determine underlying mechanisms including genetic risk factors.
进行一项系统评价和荟萃分析，以量化先天性畸形（CMs）的发生率以及其他妊娠结局与宫内抗癫痫药物（AED）暴露的关系。
我们进行了一项系统的文献综述，以确定所有已发表的关于癫痫孕妇（WWE）分娩的登记研究和队列研究，这些研究报告了CMs的发生率。总体发生率采用随机效应模型计算。
该综述纳入了59项符合纳入/排除标准的研究，涉及WWE的65533例妊娠和健康女性的1817024例妊娠。WWE中CMs分娩的计算发生率[7.08%；95%可信区间5.62，8.54]高于健康女性[2.28%；可信区间1.46，3.10]。AED联合治疗的发生率最高[16.78%；可信区间0.51，33.05]。CMs发生率最高的AED是丙戊酸盐，丙戊酸盐单药治疗的发生率为10.73%[可信区间8.16，13.29]。
这项系统文献综述的结果表明，WWE所生儿童中CMs的总体发生率约为健康女性的三倍。与无癫痫的女性相比，所有AED单药治疗的风险均升高，AED联合治疗的风险进一步升高。暴露于丙戊酸盐单药治疗以及联合使用2种或更多药物（联合治疗组合包括苯巴比妥、苯妥英或丙戊酸盐）的儿童风险显著更高。需要进一步研究来确定每种AED的具体风险，并确定包括遗传风险因素在内的潜在机制。
