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.