Holmes Lewis B, Mittendorf Robert, Shen Aileen, Smith Caitlin R, Hernandez-Diaz Sonia
North American AED Pregnancy Registry, Genetics Unit, MassGeneral Hospital for Children, Boston, MA 02114, USA.
Arch Neurol. 2011 Oct;68(10):1275-81. doi: 10.1001/archneurol.2011.133. Epub 2011 Jun 13.
To determine the frequency of malformations among infants born to women who had taken lamotrigine or carbamazepine as part of polytherapy during the first trimester of pregnancy.
A cohort of women enrolled during pregnancy in the North American AED (Antiepileptic Drug) Pregnancy Registry between February 1, 1997, and June 1, 2010. Information on AED use and demographic characteristics was collected in 3 telephone interviews.
United States and Canada.
A total of 6857 pregnant women taking an AED for any reason.
Major congenital malformations were identified at birth and through the first 12 weeks after delivery. Diagnoses were based on the mother's report and confirmed by medical records. The risks of malformations were compared between polytherapy and monotherapy groups, using exact odds ratios (ORs) and 95% confidence intervals (CIs).
The risk of malformations was 1.9% among infants exposed to lamotrigine as monotherapy (n = 1441). Among the infants exposed to lamotrigine as polytherapy (n = 505), the risks were 9.1% for lamotrigine plus valproate sodium (OR, 5.0; 95% CI, 1.5-14.0) and 2.9% for lamotrigine plus any other AEDs (1.5; 0.7-3.0). The risk of malformations was 2.9% for the infants exposed to carbamazepine monotherapy (n = 1012). For the infants exposed to carbamazepine as polytherapy (n = 365), the risks were 15.4% for carbamazepine plus valproate (OR, 6.2; 95% CI, 2.0-16.5) and 2.5% for carbamazepine plus any other AEDs (0.8; 0.3-1.9). Confounding by factors such as periconceptional vitamin use, cigarette smoking, alcohol use, and chronic maternal diseases did not explain the results.
The risk of malformations among infants exposed to lamotrigine and carbamazepine as polytherapy was higher than the corresponding monotherapies only when the polytherapy includes valproate. These findings suggest that counseling for fetal risks from AED polytherapy should be based on the specific drugs included.
确定在妊娠首三个月接受包括拉莫三嗪或卡马西平在内的联合治疗的女性所生婴儿中畸形的发生频率。
1997年2月1日至2010年6月1日期间在北美抗癫痫药物（AED）妊娠登记处登记入组的妊娠女性队列。通过3次电话访谈收集AED使用情况和人口统计学特征信息。
美国和加拿大。
总共6857名因任何原因服用AED的孕妇。
在出生时及出生后前12周确定主要先天性畸形。诊断基于母亲的报告并经病历证实。使用精确比值比（OR）和95%置信区间（CI）比较联合治疗组和单药治疗组的畸形风险。
接受拉莫三嗪单药治疗的婴儿（n = 1441）中畸形风险为1.9%。在接受拉莫三嗪联合治疗的婴儿（n = 505）中，拉莫三嗪加丙戊酸钠的畸形风险为9.1%（OR，5.0；95% CI，1.5 - 14.0），拉莫三嗪加任何其他AED的畸形风险为2.9%（1.5；0.7 - 3.0）。接受卡马西平单药治疗的婴儿（n = 1012）中畸形风险为2.9%。对于接受卡马西平联合治疗的婴儿（n = 365），卡马西平加丙戊酸的畸形风险为15.4%（OR，6.2；95% CI，2.0 - 16.5），卡马西平加任何其他AED的畸形风险为2.5%（0.8；0.3 - 1.9）。受孕前维生素使用、吸烟、饮酒和慢性母体疾病等因素的混杂并未解释这些结果。
仅当联合治疗包括丙戊酸时，接受拉莫三嗪和卡马西平联合治疗的婴儿的畸形风险高于相应的单药治疗。这些发现表明，关于AED联合治疗对胎儿风险的咨询应基于所包含的具体药物。
