Brender Jean D, Olive Janus M, Felkner Marilyn, Suarez Lucina, Marckwardt Wendy, Hendricks Katherine A
Department of Health Services Research, Texas State University at San Marcos, San Marcos, Texas 78666, USA.
Epidemiology. 2004 May;15(3):330-6. doi: 10.1097/01.ede.0000121381.79831.7b.
Amine-containing (nitrosatable) drugs can react with nitrite to form N-nitroso compounds, some of which are teratogenic. Data are lacking on whether dietary intake of nitrates and nitrites modifies the association between maternal nitrosatable drug exposure and neural tube defects (NTDs) in offspring.
We examined nitrosatable drug exposure and NTD-affected pregnancies in relation to dietary nitrite and total nitrite intake in a case-control study of Mexican American women. We interviewed 184 women with NTD-affected pregnancies and 225 women with normal live births, including questions on periconceptional drug exposures and dietary intake. For 110 study participants, nitrate was also measured in the usual source of drinking water.
Women who reported taking drugs classified as nitrosatable were 2.7 times more likely to have an NTD-affected pregnancy than women without this exposure (95% confidence interval [CI] = 1.4-5.3). The effect of nitrosatable drugs was observed only in women with higher intakes of dietary nitrite and total nitrite (dietary nitrite + 5% dietary nitrate). Women within the highest tertile (greater than 10.5 mg/day) of total nitrite were 7.5 times more likely to have an NTD-affected pregnancy if they took nitrosatable drugs (95% CI = 1.8-45.4). The association between nitrosatable drug exposure and NTDs was also stronger in women whose water nitrate levels were higher.
Findings suggest that effects of nitrosatable drug exposure on risk for neural tube defects in offspring could depend on the amounts of dietary nitrite and total nitrite intake.
含胺（可亚硝化）药物可与亚硝酸盐反应形成N-亚硝基化合物，其中一些具有致畸性。关于膳食中硝酸盐和亚硝酸盐的摄入量是否会改变母亲接触可亚硝化药物与后代神经管缺陷（NTDs）之间的关联，目前尚无相关数据。
在一项针对墨西哥裔美国女性的病例对照研究中，我们研究了可亚硝化药物暴露以及受NTD影响的妊娠与膳食亚硝酸盐和总亚硝酸盐摄入量之间的关系。我们采访了184名有NTD影响妊娠的女性和225名正常活产女性，包括有关受孕前后药物暴露和膳食摄入的问题。对于110名研究参与者，还测量了其日常饮用水源中的硝酸盐含量。
报告服用可亚硝化药物的女性发生NTD影响妊娠的可能性是未接触此类药物女性的2.7倍（95%置信区间[CI]=1.4-5.3）。仅在膳食亚硝酸盐和总亚硝酸盐（膳食亚硝酸盐+5%膳食硝酸盐）摄入量较高的女性中观察到可亚硝化药物的这种影响。总亚硝酸盐摄入量处于最高三分位数（大于10.5毫克/天）的女性，如果服用可亚硝化药物，发生NTD影响妊娠的可能性要高7.5倍（95%CI=1.8-45.4）。在饮用水硝酸盐水平较高的女性中，可亚硝化药物暴露与NTDs之间的关联也更强。
研究结果表明，可亚硝化药物暴露对后代神经管缺陷风险的影响可能取决于膳食亚硝酸盐和总亚硝酸盐的摄入量。
