Prenatal Nitrate Intake from Drinking Water and Selected Birth Defects in Offspring of Participants in the National Birth Defects Prevention Study

Abstract

Background: Previous studies of prenatal exposure to drinking-water nitrate and birth defects in offspring have not accounted for water consumption patterns or potential interaction with nitrosatable drugs.Objectives: We examined the relation between prenatal exposure to drinking-water nitrate and selected birth defects, accounting for maternal water consumption patterns and nitrosatable drug exposure.Methods: With data from the National Birth Defects Prevention Study, we linked addresses of 3,300 case mothers and 1,121 control mothers from the Iowa and Texas sites to public water supplies and respective nitrate measurements. We assigned nitrate levels for bottled water from collection of representative samples and standard laboratory testing. Daily nitrate consumption was estimated from self-reported water consumption at home and work.Results: With the lowest tertile of nitrate intake around conception as the referent group, mothers of babies with spina bifida were 2.0 times more likely (95% CI: 1.3, 3.2) to ingest ≥ 5 mg nitrate daily from drinking water (vs. < 0.91 mg) than control mothers. During 1 month preconception through the first trimester, mothers of limb deficiency, cleft palate, and cleft lip cases were, respectively, 1.8 (95% CI: 1.1, 3.1), 1.9 (95% CI: 1.2, 3.1), and 1.8 (95% CI: 1.1, 3.1) times more likely than control mothers to ingest ≥ 5.42 mg of nitrate daily (vs. < 1.0 mg). Higher water nitrate intake did not increase associations between prenatal nitrosatable drug use and birth defects.Conclusions: Higher water nitrate intake was associated with several birth defects in offspring, but did not strengthen associations between nitrosatable drugs and birth defects.Citation: Brender JD, Weyer PJ, Romitti PA, Mohanty BP, Shinde MU, Vuong AM, Sharkey JR, Dwivedi D, Horel SA, Kantamneni J, Huber JC Jr., Zheng Q, Werler MM, Kelley KE, Griesenbeck JS, Zhan FB, Langlois PH, Suarez L, Canfield MA, and the National Birth Defects Prevention Study. 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 121:1083–1089; http://dx.doi.org/10.1289/ehp.1206249

Hot Spots and Persistence of Nitrate in Aquifers Across Scales

“…Furthermore, nitrate-N can persist in groundwater for a long time (years to decades); it can further increase to high levels as more nitrogen is used at the land surface due to anthropogenic activities. Several studies have noted that high nitrate-N (>10 mg/L of NO 3 --N) concentration in drinking water is a threat to human health, particularly for infants and pregnant women [3][4][5][6]. To mitigate health risks, cleaning up nitrate-contaminated groundwater is an expensive and infeasible solution, especially for large aquifers [7].…”

A study of adverse birth outcomes and agricultural land use practices in Missouri

“…There is some evidence from epidemiologic studies that exposure to nitrate from drinking water sources may increase the incidence of neural tube defects, oral cleft defects, limb deficiencies (Brender et al, 2004;Brender et al, 2013), cardiac defects (Cedergren et al, 2002), SGA and spontaneous abortions (Manassaram et al, 2006). Animal studies also show moderate associations with fetal loss, neonatal mortality, and decreased litters and live births (Manassaram et al, 2006).…”

Preventing birth defects: The value of the NBDPS case–control approach

“…The results confirmed a higher risk of neural tube defects, especially spina bifida, in the highest tertile of nitrate intake, as well as higher risks of oral clefts and limb deficiency, but not congenital heart defects, in this tertile. Water is usually not an important source of nitrate intake compared with diet and medications (Brender et al, 2013), so these results suggest that emphasis needs to be placed on hotspots of high nitrate water content. Brender et al moreover suggest that nitrate in drinking water may also be associated with other contaminants such as pesticides, arsenic, trace metals, and water disinfection byproducts which contribute to the risk, and in their original study, Dorsch et al (1984) also comment that "previous groundwater studies have suggested that the most consistent and significant indicator of manmade pollution in the region (whether it be from municipal, agricultural or industrial sources) is the nitrate ion".…”

“…NBDPS studies have involved experts in nitrate exposure assessment to examine this. Brender et al (2013), using NBDPS data for Iowa and Texas only, made use of a module added to the NBDPS interview on water sources and use, linked maternal addresses to municipal water supplies and their standard monitored nitrate measurements, or to modeling of nitrate levels in aquifers supplying private wells, and incorporated estimates of nitrates in bottled water. The results confirmed a higher risk of neural tube defects, especially spina bifida, in the highest tertile of nitrate intake, as well as higher risks of oral clefts and limb deficiency, but not congenital heart defects, in this tertile.…”