Congenital defects remain the greatest contributor to infant mortality;yet, the causes for the majority of these defects are either unknown or poorly understood. Amine- and amide-containing (nitrosatable) drugs and other compounds react with nitrite in the stomach to form N-nitroso compounds. In animal models, N-nitroso compounds have been found to induce a variety of congenital malformations. The few epidemiologic studies conducted in the past have focused on the separate effects of nitrates, nitrites, and nitrosatable drugs on risk of congenital malformations without consideration of their interaction in the endogenous formation of N- nitroso compounds. This case-control study will examine the separate and joint effects of prenatal exposures to nitrates, nitrites, and nitrosatable drugs on risk of selected congenital malformations (neural tube defects, limb malformations, oral clefts, and heart defects). Cases and controls will be obtained from the National Birth Defects Prevention Study (NBDPS), a multi-center study that covers populations in 10 different states. Subjects'usual intake of dietary nitrates, nitrites, and nitrosamines will be calculated from the NBDPS food frequency questionnaire. From the NBDPS interview, medications reported taken one month preconception and during the first trimester will be classified as to their likelihood of nitrosatability based on the literature and chemical structure. The periconceptional addresses of Iowa and Texas participants will be linked to community water systems and pertinent water nitrate sampling results. For Texas participants on private wells, we will model and predict nitrate levels with a multi-dimensional flow and transport model. We will analyze the separate and joint effects of nitrosatable precursors on risk of the selected malformations. We will also examine the effects of vitamins C and E (inhibitors of nitrosation) on the relations between nitrate/nitrite intake and nitrosatable drugs and risk of selected congenital malformations. Use of over-the- counter medications is fairly common during pregnancy according to a recently published study. Several over-the-counter preparations contain nitrosatable compounds as active ingredients. The proposed study will help us understand whether pregnant women who take these types of drugs and also consume greater amounts of nitrates and nitrites are at increased risk of having offspring with birth defects. The study is also designed to examine whether higher intakes of vitamin C or E decrease these potential risks.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Research Project (R01)
Project #
5R01ES015634-04
Application #
7885654
Study Section
Infectious Diseases, Reproductive Health, Asthma and Pulmonary Conditions Study Section (IRAP)
Program Officer
Dilworth, Caroline H
Project Start
2007-07-27
Project End
2013-06-30
Budget Start
2010-07-01
Budget End
2013-06-30
Support Year
4
Fiscal Year
2010
Total Cost
$323,281
Indirect Cost
Name
Texas A&M University
Department
Public Health & Prev Medicine
Type
Schools of Public Health
DUNS #
835607441
City
College Station
State
TX
Country
United States
Zip Code
77845
Weyer, Peter J; Brender, Jean D; Romitti, Paul A et al. (2014) Assessing bottled water nitrate concentrations to evaluate total drinking water nitrate exposure and risk of birth defects. J Water Health 12:755-62
Shinde, Mayura U; Vuong, Ann M; Brender, Jean D et al. (2013) Prenatal exposure to nitrosatable drugs, vitamin C, and risk of selected birth defects. Birth Defects Res A Clin Mol Teratol 97:515-31
Huber Jr, John C; Brender, Jean D; Zheng, Qi et al. (2013) Maternal dietary intake of nitrates, nitrites and nitrosamines and selected birth defects in offspring: a case-control study. Nutr J 12:34
Brender, Jean D; Weyer, Peter J; Romitti, Paul A et al. (2013) Prenatal nitrate intake from drinking water and selected birth defects in offspring of participants in the national birth defects prevention study. Environ Health Perspect 121:1083-9
Dwivedi, Dipankar; Mohanty, Binayak P; Lesikar, Bruce J (2013) Estimating Escherichia coli loads in streams based on various physical, chemical, and biological factors. Water Resour Res 49:2896-2906
Arora, B; Mohanty, B P; McGuire, J T (2012) Uncertainty in dual permeability model parameters for structured soils. Water Resour Res 48:WR010500
Brender, Jean D; Werler, Martha M; Shinde, Mayura U et al. (2012) Nitrosatable drug exposure during the first trimester of pregnancy and selected congenital malformations. Birth Defects Res A Clin Mol Teratol 94:701-13
Arora, Bhavna; Mohanty, Binayak P; McGuire, Jennifer T (2011) Inverse estimation of parameters for multidomain flow models in soil columns with different macropore densities. Water Resour Res 47:2010WR009451
Brender, Jean D; Werler, Martha M; Kelley, Katherine E et al. (2011) Nitrosatable drug exposure during early pregnancy and neural tube defects in offspring: National Birth Defects Prevention Study. Am J Epidemiol 174:1286-95
Hansen, David J; McGuire, Jennifer T; Mohanty, Binayak P (2011) Enhanced biogeochemical cycling and subsequent reduction of hydraulic conductivity associated with soil-layer interfaces in the vadose zone. J Environ Qual 40:1941-54

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