Department Of Neurology, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Trivandrum 695011, India.
Kerala Registry of Epilepsy and Pregnancy, Department of Neurology, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Trivandrum 695011, India.
Epilepsy Res. 2018 Oct;146:121-125. doi: 10.1016/j.eplepsyres.2018.07.017. Epub 2018 Jul 25.
The management of Women With Epilepsy (WWE) in pregnancy is a challenge that demands balancing the risks of Major Congenital Malformation (MCM) on one hand with adequate seizure control on the other. While most studies have analysed the risks of Anti-Epileptic Drugs (AED) exposure in the first trimester, AED changes during the second and third trimester and their effects on fetal outcome has not been studied adequately.
Data of WWE who were prospectively followed up and completed pregnancy with live birth under the Kerala registry of epilepsy and pregnancy (KREP) between 1998 and 2014 were analysed. The AED addition, dose escalation, unchanged continuation, dose reduction or stoppage during the second or third trimester in comparison to the first trimester was tabulated for each drug. The outcome measures evaluated were malformation status and Developmental Quotient (DQ) at one year as extracted from the clinical records of the registry.
The first trimester AED exposure was nil for 231, monotherapy for 925 and polytherapy for 391 WWE. WWE on monotherapy in first trimester were more likely to remain on the same number of AEDs in second or third trimester than those who were on polytherapy (OR 3.1, 95% CI 2.2 - 4.46). AED naïve women had a higher likelihood (OR 16.7; 95% CI 10.9-25.8) of being started on AED than women on monotherapy being switched to polytherapy. At least one AED was reduced or stopped during second or third trimester more often in women on polytherapy (15.1%) than in women on monotherapy (3.7%) (OR 4.7; 95% CI 2.9-7.2). Malformation rates for the infants of women whose AED dosage was increased or added were not significantly different from those of others. There was no statistically significant change in DQ with increase in dose or addition of drugs in the second or third trimester.
AEDs were reduced in a significant proportion of patients on polytherapy while more than a third of women who were not on AEDs in the first trimester were subsequently started on AEDs. Increase in dose or addition of AEDs after the first trimester is unlikely to influence malformation outcome but the potential adverse effect on the DQ needs to be explored on a larger set of data.
管理妊娠合并癫痫女性（WWE）是一项具有挑战性的任务，需要在权衡重大先天畸形（MCM）风险和确保充足的癫痫发作控制之间取得平衡。虽然大多数研究都分析了抗癫痫药物（AED）在妊娠早期暴露的风险，但AED 在妊娠第二和第三阶段的变化及其对胎儿结局的影响尚未得到充分研究。
分析了 1998 年至 2014 年间在喀拉拉邦癫痫与妊娠登记处（KREP）前瞻性随访并完成活产妊娠的 WWE 患者的数据。比较了每种药物在妊娠第二或第三阶段与第一阶段时的 AED 添加、剂量调整、不变的持续治疗、剂量减少或停药情况。从登记处的临床记录中提取了畸形状况和一岁时的发育商（DQ）作为结局测量指标。
231 例 WWE 患者在第一阶段无 AED 暴露，925 例患者接受单药治疗，391 例患者接受多药治疗。在第一阶段接受单药治疗的 WWE 患者在第二或第三阶段继续使用相同数量 AED 的可能性高于接受多药治疗的患者（OR 3.1，95%CI 2.2-4.46）。与接受单药治疗转为多药治疗的患者相比，AED 初治女性开始使用 AED 的可能性更高（OR 16.7；95%CI 10.9-25.8）。在多药治疗患者中，第二或第三阶段更常减少或停止至少一种 AED（15.1%），而在单药治疗患者中（3.7%）（OR 4.7；95%CI 2.9-7.2）。AED 剂量增加或添加的婴儿畸形率与其他婴儿无显著差异。在第二或第三阶段增加剂量或添加药物不会导致 DQ 统计学上的显著变化。
多药治疗患者中，AED 减少的比例相当大，而在第一阶段未使用 AED 的三分之一以上的女性随后开始使用 AED。妊娠第一阶段后增加剂量或添加 AED 不太可能影响畸形结局，但需要在更大的数据集上探索其对 DQ 的潜在不良影响。
