Petersen Irene, Collings Shuk-Li, McCrea Rachel L, Nazareth Irwin, Osborn David P, Cowen Phil J, Sammon Cormac J
Department of Primary Care and Population Health, University College London, London, UK; Department of Clinical Epidemiology, Aarhus University, Aarhus N, Denmark.
Department of Primary Care and Population Health, University College London, London, UK; OXON Epidemiology, London, UK.
Clin Epidemiol. 2017 Feb 16;9:95-103. doi: 10.2147/CLEP.S118336. eCollection 2017.
The aim of this study was to examine the prevalence of major congenital malformations associated with antiepileptic drug (AED) treatment in pregnancy.
Using data from The Health Improvement Network, we identified women who have given live birth and their offspring. Four subgroups were selected based on the AED treatment in early pregnancy, valproate, carbamazepine, lamotrigine and women not receiving AED treatment. We compared the prevalence of major congenital malformations within children of these four groups and estimated prevalence ratios (PRs) using Poisson regression adjusted for maternal age, sex of child, quintiles of Townsend deprivation score and indication for treatment.
In total, 240,071 women were included in the study. A total of 229 women were prescribed valproate in pregnancy, 357 were prescribed lamotrigine and 334 were prescribed carbamazepine and 239,151 women were not prescribed AEDs. Fifteen out of 229 (6.6%) women prescribed valproate gave birth to a child with a major congenital malformation. The figures for lamotrigine, carbamazepine and women not prescribed AEDs were 2.7%, 3.3% and 2.2%, respectively. The prevalence of major congenital malformation was similar for women prescribed lamotrigine or carbamazepine compared to women with no AED treatment in pregnancy. For women prescribed valproate in polytherapy, the prevalence was fourfold higher. After adjustments, the effect of estimates attenuated, but the prevalence remained two- to threefold higher in women prescribed valproate.
The results of our study suggest that lamotrigine and carbamazepine are safer treatment options than valproate in pregnancy and should be considered as alternative treatment options for women of childbearing potential and in pregnancy.
本研究旨在调查孕期使用抗癫痫药物（AED）治疗与主要先天性畸形的患病率。
利用健康改善网络的数据，我们确定了已生育活产儿的女性及其后代。根据孕早期使用的AED治疗情况，选择了四个亚组，即丙戊酸盐组、卡马西平组、拉莫三嗪组以及未接受AED治疗的女性组。我们比较了这四组儿童中主要先天性畸形的患病率，并使用泊松回归估计患病率比（PRs），同时对产妇年龄、孩子性别、汤森贫困评分五分位数和治疗指征进行了校正。
本研究共纳入240,071名女性。孕期共229名女性使用丙戊酸盐，357名使用拉莫三嗪，334名使用卡马西平，239,151名女性未使用AED。使用丙戊酸盐的229名女性中有15名（6.6%）生下患有主要先天性畸形的孩子。拉莫三嗪组、卡马西平组以及未使用AED组的这一数字分别为2.7%、3.3%和2.2%。与孕期未接受AED治疗的女性相比，使用拉莫三嗪或卡马西平的女性中主要先天性畸形的患病率相似。对于联合使用丙戊酸盐的女性，患病率高出四倍。校正后，估计效应减弱，但使用丙戊酸盐的女性患病率仍高出两至三倍。
我们的研究结果表明，孕期使用拉莫三嗪和卡马西平比丙戊酸盐更安全，对于有生育潜力的女性和孕期女性，应考虑将其作为替代治疗选择。
