Am J Epidemiol. 2015 Oct 15;182(8):675-84. doi: 10.1093/aje/kwv126. Epub 2015 Sep 29.
Nitrosatable drugs (NSDs) can, in the presence of nitrosating agents and highly acidic conditions, form N-nitroso compounds that have been found to be teratogenic in animal models. Using data from the Slone Epidemiology Center Birth Defects Study collected from 1998 to 2012, we compared maternal periconceptional NSD use between 334 neural tube defect cases and 7,619 nonmalformed controls. We categorized NSDs according to their functional group (secondary amine, tertiary amine, and amide). With logistic regression models, we estimated adjusted odds ratios and 95% confidence intervals. Neural tube defect risk was associated with maternal periconceptional use of secondary (adjusted odds ratio (aOR) = 1.7, 95% confidence interval (CI): 1.1, 2.4) and tertiary (aOR = 1.7, 95% CI: 1.2, 2.5) amines; an association was observed for amides, but the 95% confidence interval included the null (aOR = 1.4, 95% CI: 0.7, 2.5). Within the secondary amine group, elevated adjusted odds ratios were observed for 3 drugs but were null for the remaining medications. Increases in risk were observed for both strata of folic acid intake (<400 µg/day, ≥400 µg/day), with a slightly higher risk in the ≥400-µg/day stratum. Our findings support previously reported positive associations between neural tube defects and periconceptional exposure to NSDs containing a secondary or tertiary amine or amide.
可亚硝化药物（NSD）在亚硝化试剂和强酸性条件下可形成 N-亚硝胺化合物，这些化合物在动物模型中被发现有致畸性。我们利用 Slone 流行病学中心出生缺陷研究（1998 年至 2012 年）的数据，比较了 334 例神经管缺陷病例和 7619 例非畸形对照的母亲围孕期 NSD 使用情况。我们根据功能基团（仲胺、叔胺和酰胺）对 NSD 进行分类。通过逻辑回归模型，我们估计了调整后的优势比和 95%置信区间。神经管缺陷风险与母亲围孕期使用仲胺（调整后的优势比（aOR）=1.7，95%置信区间（CI）：1.1，2.4）和叔胺（aOR = 1.7，95% CI：1.2，2.5）有关；酰胺也存在相关性，但 95%置信区间包含零值（aOR = 1.4，95% CI：0.7，2.5）。在仲胺组中，3 种药物的调整后优势比升高，但其余药物的优势比为零。在叶酸摄入量较低（<400μg/天）和较高（≥400μg/天）的两个亚组中均观察到风险增加，在≥400μg/天的亚组中风险略高。我们的研究结果支持先前报道的神经管缺陷与围孕期暴露于含有仲胺或叔胺或酰胺的 NSD 之间存在正相关关系。
