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Maternal dietary intake of nitrates, nitrites and nitrosamines and selected birth defects in offspring: a case-control study

John C Huber1, Jean D Brender1*, Qi Zheng1, Joseph R Sharkey2, Ann M Vuong1, Mayura U Shinde1, John S Griesenbeck3, Lucina Suarez4, Peter H Langlois4, Mark A Canfield4, Paul A Romitti5, Peter J Weyer6 and the National Birth Defects Prevention Study

Author Affiliations

1 Department of Epidemiology and Biostatistics, The Texas A&M Health Science Center School of Rural Public Health, MS 1266 TAMU, College Station, TX 77843-1266, USA

2 Department of Health Promotion & Community Health Sciences, The Texas A&M Health Science Center School of Rural Public Health, MS 1266 TAMU, College Station, TX 77843-1266, USA

3 111 Marine Expeditionary Force, Okinawa, Japan

4 Texas Department of State Health Services, PO Box 149347, Austin, Texas 78714-9347, USA

5 Department of Epidemiology, The University of Iowa College of Public Health, C21-E GH, 200 Hawkins Drive, Iowa City, Iowa 52242, USA

6 The University of Iowa Center for Health Effects of Environmental Contamination, N202 Oakdale Hall, Iowa City, Iowa 52242, USA

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Nutrition Journal 2013, 12:34  doi:10.1186/1475-2891-12-34

Published: 21 March 2013



Dietary intake of nitrates, nitrites, and nitrosamines can increase the endogenous formation of N-nitroso compounds in the stomach. Results from animal studies suggest that these compounds might be teratogenic. We examined the relationship between maternal dietary intake of nitrates, nitrites (including plant and animal sources as separate groups), and nitrosamines and several types of birth defects in offspring.


For this population-based case–control study, data from a 58-question food frequency questionnaire, adapted from the short Willett Food Frequency Questionnaire and administered as part of the National Birth Defects Prevention Study (NBDPS), were used to estimate daily intake of dietary nitrates, nitrites, and nitrosamines in a sample of 6544 mothers of infants with neural tube defects (NTD)s, oral clefts (OC)s, or limb deficiencies (LD)s and 6807 mothers of unaffected control infants. Total daily intake of these compounds was divided into quartiles based on the control mother distributions. Odds ratios (OR)s and 95% confidence intervals (CI)s were estimated using logistic regression; estimates were adjusted for maternal daily caloric intake, maternal race-ethnicity, education, dietary folate intake, high fat diet (> 30% of calories from fat), and state of residence.


While some unadjusted ORs for NTDS had 95% (CI)s that excluded the null value, none remained significant after adjustment for covariates, and the effect sizes were small (adjusted odds ratios [aOR] <1.12). Similar results were found for OCs and LDs with the exception of animal nitrites and cleft lip with/without cleft palate (aORs and CIs for quartile 4 compared to quartile 1 =1.24; CI=1.05-1.48), animal nitrites and cleft lip (4th quartile aOR=1.32; CI=1.01-1.72), and total nitrite and intercalary LD (4th quartile aOR=4.70; CI=1.23-17.93).


Overall, odds of NTDs, OCs or LDs did not appear to be significantly associated with estimated dietary intake of nitrate, nitrite, and nitrosamines.

Congenital malformation; Diet; Nitrate; Nitrite; Nitrosamine; Pregnancy