Nitrosatable Drug Exposure During Early Pregnancy and Neural Tube Defects in Offspring National Birth Defects Prevention Study
Nitrosatable Drug Exposure During Early Pregnancy and Neural Tube Defects in Offspring National Birth Defects Prevention Study
复制标题
DOI：
10.1093/aje/kwr254
复制
发表时间：
2011-12-01
影响因子：
5
通讯作者：
Canfield, Mark A.
中科院分区：
文献类型：
--
作者：
Brender, Jean D.;Werler, Martha M.;Canfield, Mark A.
可亚硝基化的药物，如仲胺或叔胺和酰胺，在亚硝酸盐存在下形成N-亚硝基化合物。在动物模型中，各种N-亚硝基化合物与神经管缺陷有关。使用来自国家出生缺陷预防研究的数据，作者检查了1997年至2005年期间1，223例受神经管缺陷影响的妊娠病例母亲和6，807例分娩无重大先天性异常婴儿的对照母亲在受孕前1个月和受孕后1个月的亚硝化药物暴露。亚硝酸盐的摄入量是根据母亲对食物频率问卷的回答来估计的。调整后的母亲种族/民族，教育水平，叶酸补充剂，病例妇女比对照组妇女更有可能采取叔胺（比值比= 1.60，95%置信区间（CI）：1.31，1.95）。这种关联在无脑儿出生时最强（比值比= 1.96，95% CI：1.40，2.73）;从亚硝酸盐摄入量的最低三分位数到最高三分位数，与叔胺相关的比值比为1.16（95% CI：0.59，2.29）、2.19（95% CI：1.25，3.86）和2.51（95% CI：1.45，4.37）。在每天服用含有维生素C的维生素补充剂的妇女中，暴露于亚硝化药物的无脑畸形的比值比降低。产前暴露于亚硝化药物可能会增加神经管缺陷的风险，特别是在母亲饮食中亚硝酸盐摄入量较高的情况下，但维生素C可能会调节这种关联。
Nitrosatable drugs, such as secondary or tertiary amines and amides, form N-nitroso compounds in the presence of nitrite. Various N-nitroso compounds have been associated with neural tube defects in animal models. Using data from the National Birth Defects Prevention Study, the authors examined nitrosatable drug exposure 1 month before and 1 month after conception in 1,223 case mothers with neural tube defect-affected pregnancies and 6,807 control mothers who delivered babies without major congenital anomalies from 1997 to 2005. Nitrite intakes were estimated from mothers' responses to a food frequency questionnaire. After adjustment for maternal race/ethnicity, educational level, and folic acid supplementation, case women were more likely than were control women to have taken tertiary amines (odds ratio = 1.60, 95% confidence interval (CI): 1.31, 1.95). This association was strongest with anencephalic births (odds ratio = 1.96, 95% CI: 1.40, 2.73); odds ratios associated with tertiary amines from the lowest tertile of nitrite intake to the highest tertile were 1.16 (95% CI: 0.59, 2.29), 2.19 (95% CI: 1.25, 3.86), and 2.51 (95% CI: 1.45, 4.37), respectively. Odds ratios for anencephaly with nitrosatable drug exposure were reduced among women who also took daily vitamin supplements that contained vitamin C. Prenatal exposure to nitrosatable drugs may increase the risk of neural tube defects, especially in conjunction with a mother's higher dietary intake of nitrites, but vitamin C might modulate this association.