Intake of Nitrates and Nitrites and Birth Defects in Offspring

ISEE-464 Abstract: N-nitroso compounds are known to induce central nervous system and musculoskeletal malformations in animal models. Nitrate is converted through bacterial and enzyme action to nitrite, which then can react with amines, amino acids, and other compounds to form N-nitroso compounds. Results have been mixed whether nitrates in drinking water and diet are associated with congenital malformations in human offspring. Studies conducted among women in Australia and Canada found higher levels of drinking water nitrate associated with central nervous system abnormalities. Increased risks for anencephaly, but not for spina bifida were noted among California women whose drinking water nitrates were greater than or equal to 5 mg/L. In that study, risk for neural tube defects (NTDs) was inversely associated with dietary intake of nitrates and nitrites, but odds ratios (ORs) were consistent with unity. In a Swedish study, no appreciable risk for congenital cardiac defects was found with maternal exposure to drinking water nitrates greater than or equal to 2 mg/L. We examined the relation between nitrates in drinking water and diet and risk of NTD-affected pregnancies among Mexican American women living along the Texas-Mexico border. In the case-control study, 184 women with NTD-affected pregnancies and 225 women with normal live births were interviewed about their diets during the periconceptional period. For a subset (n=110), water nitrates were also measured from samples obtained from the reported usual periconceptional drinking water source. We noted an inverse relation between NTD risk and increasing levels of intake for both dietary nitrates and nitrites. However, with higher protein intake (116+ gm/day) in conjunction with lower vitamin C intake (<228 mg/day), the ORs for nitrate (65+ vs. <65 mg/day) and total nitrite intake (9+ vs. <9 mg/day) were 2.1 and 3.8, respectively compared with ORs of 0.48 and 0.40 if vitamin C intake was higher (228+ mg/day). Women whose drinking water nitrates measured 3.52 mg/L or greater (median of controls’ samples) were 1.9 times more likely to have an NTD-affected pregnancy (95% confidence interval [CI] = 0.8-4.6). The higher water nitrate levels were associated with an increased risk for spina bifida (OR = 7.8, 95% CI=1.6-74.6), but not for anencephaly (OR=1.0, 95% CI=0.3-2.7). Water nitrates and total dietary nitrites were also found to modify risk of NTDs associated with nitrosatable drug exposure. More research is needed on the interactions of nitrates and nitrites with drugs and dietary nutrients and risk of birth defects.