Dietary nitrites and nitrates, nitrosatable drugs, and neural tube defects.
BACKGROUND
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Brender
Jean D
JD
Department of Health Services Research, Texas State University at San Marcos, San Marcos, Texas 78666, USA. jb52@txstate.edu
Olive
Janus M
JM
Felkner
Marilyn
M
Suarez
Lucina
L
Marckwardt
Wendy
W
Hendricks
Katherine A
KA
D000293:Adolescent; D000328:Adult; D016022:Case-Control Studies; D016001:Confidence Intervals; D019587:Dietary Supplements; D004347:Drug Interactions; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015994:Incidence; D008423:Maternal Age; D017058:Mexican Americans; D009436:Neural Tube Defects / Q000139:chemically induced* / Q000208:ethnology*; D009566:Nitrates / Q000008:administration & dosage / Q000009:adverse effects*; D009573:Nitrites / Q000008:administration & dosage / Q000009:adverse effects*; D009603:Nitroso Compounds / Q000008:administration & dosage / Q000009:adverse effects*; D016017:Odds Ratio; D011247:Pregnancy; D018566:Pregnancy, High-Risk; D011295:Prenatal Care; D012016:Reference Values; D018570:Risk Assessment; D011795:Surveys and Questionnaires; D013781:Texas / Q000453:epidemiology
D009566:Nitrates; D009573:Nitrites; D009603:Nitroso Compounds