Yerby Mark S
Department of Obstetrics and Gynecology, Oregon Health & Science University, North Pacific Epilepsy Research Center, Portland, OR 97201, USA.
Neurology. 2003 Sep 1;61(6 Suppl 2):S23-6. doi: 10.1212/wnl.61.6_suppl_2.s23.
For infants exposed to antiepileptic drugs (AEDs) in utero, the risk for congenital malformations is approximately 4 to 6%, twice the rate reported in the general population. A variety of malformations have been reported in association with prenatal exposure to AEDs. However, a particular association of valproate and carbamazepine with neural tube defects (NTDs)--specifically, with spina bifida aperta (SB)--has been identified. The prevalence of SB is approximately 1 to 2% with valproate exposure and 0.5% with carbamazepine. Reported risk factors for NTDs include previous pregnancy with an NTD, maternal insulin-dependent diabetes mellitus, various nutritional deficiencies and occupational exposures, and high prepregnancy weight. Deficiencies of folate have been implicated in the development of birth defects, including NTDs. The value of periconceptional folic acid supplementation for women in the general population is accepted. However, it is unclear whether folic acid supplementation protects against the embryotoxic and teratogenic effects of AEDs because animal and human studies and case reports have shown variable results. Nevertheless, folic acid supplementation is recommended for women with epilepsy as it is for other women of childbearing age. Even with supplementary folic acid, women taking valproate or carbamazepine should undergo perinatal diagnostic ultrasound to rule out NTDs.
对于在子宫内接触抗癫痫药物（AEDs）的婴儿，先天性畸形的风险约为4%至6%，是普通人群报告发生率的两倍。已有多种畸形被报道与产前接触AEDs有关。然而，已确定丙戊酸盐和卡马西平与神经管缺陷（NTDs）——特别是与开放性脊柱裂（SB）——存在特定关联。接触丙戊酸盐时SB的患病率约为1%至2%，接触卡马西平时为0.5%。已报道的NTDs风险因素包括既往有NTDs妊娠史、母亲胰岛素依赖型糖尿病、各种营养缺乏和职业暴露以及孕前体重过高。叶酸缺乏与包括NTDs在内的出生缺陷的发生有关。普通人群中妇女在受孕前补充叶酸的价值已得到认可。然而，尚不清楚补充叶酸是否能预防AEDs的胚胎毒性和致畸作用，因为动物和人体研究以及病例报告显示结果不一。尽管如此，仍建议癫痫女性补充叶酸，就如同对其他育龄女性的建议一样。即使补充了叶酸，服用丙戊酸盐或卡马西平的妇女仍应接受围产期诊断性超声检查以排除NTDs。
