Prenatal exposure to nitrosatable drugs, vitamin C and risk for selected birth defects

Nitrosatable drugs, such as secondary or tertiary amines, and amides react with nitrite in an acidic environment to form N-nitroso compounds, teratogens in animal models. Vitamin C is a known nitrosation inhibitor. Using data from the National Birth Defects Prevention Study, we assessed nitrosatable drug exposure and vitamin C intake during the first trimester among 11,606 case mothers of infants with oral clefts, limb deficiencies (LD)s, or congenital heart defects and 6,807 control mothers of infants without major birth defects during 1997-2005. Daily intake of vitamin C was estimated from maternal interviews and a 58-item food frequency questionnaire. Using mothers with no reported use of nitrosatable drugs as the referent group, mothers with daily vitamin C supplementation and secondary amine drug exposure were less likely (adjusted odds ratio [aOR] 1.2 95% confidence interval [CI] 0.81, 1.7) to have infants with transverse LDs compared to women taking these drugs and reporting no supplementation (aOR 2.5 95% CI 1.5, 4.2). Risk was lower for cleft lip with cleft palate defects in relation to amide drug exposure with daily (aOR 1.1, 95% CI 0.77, 1.5) compared to no vitamin C supplementation (aOR 2.1, 95% CI 1.2, 3.8). Risks of LDs associated with secondary and tertiary amine drug exposure were also lower with daily dietary vitamin C intake above 85 mg compared to less than 85 mg. Prenatal dietary and vitamin C supplement intake may reduce the potential risks of several birth defects associated with nitrosatable drug exposure during pregnancy.