Department of Neurology, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
Epilepsy Behav. 2022 Oct;135:108904. doi: 10.1016/j.yebeh.2022.108904. Epub 2022 Sep 9.
The management of pregnant women with epilepsy (WWE) treated with antiepileptic drugs (AEDs) polytherapy poses a great challenge. The purpose of this study was to evaluate the major congenital malformations (MCMs) associated with AED polytherapy, to assess the impacts of polytherapy regimens on seizure control and breastfeeding, and to determine the potential predictors for pregnancy outcomes.
This study was based on prospectively acquired data from a registry enrolling WWE in early pregnancy from Feb 2010 to July 2019, in which 123 pregnancies in 110 WWE were exposed to 27 different AED combinations.
There were 123 pregnancies in 110 WWE analyzed in our study. The live birth rate was 86.2 % and the risk of MCMs was 10.4 %. Multivariate analysis indicated that prenatal exposure to phenobarbital (odds ratio [OR], 17.424; 95 %CI, 1.510-201.067; P = 0.022) and topiramate (OR, 9.469; 95 %CI, 1.149-62.402; P = 0.036) was associated with increased risk of MCMs. Valproate (OR, 4.441; 95 %CI, 1.165-16.934; P = 0.029), phenobarbital (OR, 13.636; 95 %CI, 2.146-86.660; P = 0.006) and topiramate (OR, 7.527; 95 %CI, 1.764-32.118; P = 0.006) were significantly correlated with adverse pregnancy outcomes. Among 67 pregnancies in four combinations over 10 patients, 15 (22.4 %) remained seizure free through pregnancy, seizure frequency increased in 17 (25.4 %), decreased in 24 (35.8 %) women, in 26 (38.8 %) remained unchanged. Only 23.6 % of mothers undertook exclusive breastfeeding. Planned pregnancy was the only independent factor significantly associated with decreased risk of adverse pregnancy outcomes (OR, 0.139; 95 % CI, 0.051-0.382; P < 0.001). Notably, no adverse pregnancy outcome was recorded in pregnancies exposed to the combination of lamotrigine plus levetiracetam.
Prenatal exposure to the combinations containing valproate, phenobarbital, or topiramate was associated with increased risk of adverse pregnant outcomes. AED-related teratogenicity may be reduced by planned pregnancy in WWE exposed to polytherapy. Our findings also suggest the combination of lamotrigine and levetiracetam seems to be most desirable to balance seizure control and fetal safety.
治疗癫痫（WWE）的孕妇使用抗癫痫药物（AED）联合治疗带来了巨大挑战。本研究旨在评估与 AED 联合治疗相关的主要先天畸形（MCM），评估联合治疗方案对癫痫控制和母乳喂养的影响，并确定妊娠结局的潜在预测因素。
本研究基于 2010 年 2 月至 2019 年 7 月期间前瞻性收集的早期妊娠 WWE 登记数据，其中 110 例 WWE 中有 123 例妊娠暴露于 27 种不同的 AED 联合治疗中。
在我们的研究中，对 110 例 WWE 中的 123 例妊娠进行了分析。活产率为 86.2%，MCM 风险为 10.4%。多变量分析表明，产前暴露于苯巴比妥（比值比[OR]，17.424；95%CI，1.510-201.067；P=0.022）和托吡酯（OR，9.469；95%CI，1.149-62.402；P=0.036）与 MCM 风险增加相关。丙戊酸（OR，4.441；95%CI，1.165-16.934；P=0.029）、苯巴比妥（OR，13.636；95%CI，2.146-86.660；P=0.006）和托吡酯（OR，7.527；95%CI，1.764-32.118；P=0.006）与不良妊娠结局显著相关。在四种组合中有超过 10 例患者的 67 例妊娠中，15 例（22.4%）在妊娠期间无癫痫发作，17 例（25.4%）癫痫发作频率增加，24 例（35.8%）减少，26 例（38.8%）保持不变。只有 23.6%的母亲进行了纯母乳喂养。计划妊娠是唯一与不良妊娠结局风险降低显著相关的独立因素（OR，0.139；95%CI，0.051-0.382；P<0.001）。值得注意的是，在暴露于拉莫三嗪加左乙拉西坦联合治疗的妊娠中，未记录到不良妊娠结局。
产前暴露于包含丙戊酸、苯巴比妥或托吡酯的联合治疗与不良妊娠结局风险增加相关。在接受联合治疗的 WWE 中，计划妊娠可能会降低 AED 相关的致畸性。我们的研究结果还表明，拉莫三嗪加左乙拉西坦的联合治疗似乎是平衡癫痫控制和胎儿安全性的最佳选择。
