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

John C Huber,Jean D Brender,Joseph R Sharkey,Peter H Langlois,Lucina Suarez,Mark A Canfield,The National Birth Defects Prevention Study ,John S Griesenbeck,Peter J Weyer,Paul A Romitti,Mayura U Shinde,Qi Zheng,Ann M Vuong

doi:10.1186/1475-2891-12-34

Abstract

BackgroundDietary 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.MethodsFor 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.ResultsWhile 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).ConclusionsOverall, odds of NTDs, OCs or LDs did not appear to be significantly associated with estimated dietary intake of nitrate, nitrite, and nitrosamines.

Highlights

Dietary intake of nitrates, nitrites, and nitrosamines can increase the endogenous formation of N-nitroso compounds in the stomach
This study examines the relationship between maternal exposure to dietary nitrates, nitrites, and nitrosamines and several types of birth defects including neural tube defects (NTD), orofacial clefts, and limb malformations in a large, population-based case–control study
A majority of the participants were of nonHispanic white race/ethnicity with the second most common group being of Hispanic origin

Summary

Introduction

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. Findings from a few epidemiologic studies have suggested that prenatal exposure to nitrates (from drinking water) [1] and nitrites, especially in conjunction with nitrosatable drugs [2,3], are associated with neural tube defects (NTD)s. In our previous studies of maternal nitrosatable drug exposure among study participants in the National Birth Defects Prevention Study (NBDPS), we found that 24% of the control women

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