Abstract
Animal studies and epidemiological evidence suggest an association between prenatal exposure to drinking water with elevated nitrate (NO3-N) concentrations and incidence of congenital anomalies. This study used Geographic Information Systems (GIS) to derive individual-level prenatal drinking-water nitrate exposure estimates from measured nitrate concentrations from 140 temporally monitored private wells and 6 municipal water supplies. Cases of major congenital anomalies in Kings County, Nova Scotia, Canada, between 1988 and 2006 were selected from province-wide population-based perinatal surveillance databases and matched to controls from the same databases. Unconditional multivariable logistic regression was performed to test for an association between drinking-water nitrate exposure and congenital anomalies after adjusting for clinically relevant risk factors. Employing all nitrate data there was a trend toward increased risk of congenital anomalies for increased nitrate exposure levels though this was not statistically significant. After stratification of the data by conception before or after folic acid supplementation, an increased risk of congenital anomalies for nitrate exposure of 1.5–5.56 mg/L (2.44; 1.05–5.66) and a trend toward increased risk for >5.56 mg/L (2.25; 0.92–5.52) was found. Though the study is likely underpowered, these results suggest that drinking-water nitrate exposure may contribute to increased risk of congenital anomalies at levels below the current Canadian maximum allowable concentration.
Highlights
Congenital anomalies complicate 2% to 3% of Canadian births and the incidence of neural tube defects, congenital heart defects and Down’s syndrome in Nova Scotia are among the highest in Canada [1].The etiologies of many congenital anomalies remain unknown; their widespread health impacts warrant further investigation into risk factors, environmental causes and means of prevention [1].Teratogens in the environment, such as nitrate, may cause 8%–12% of congenital anomalies [1,2].Nitrate (NO3) is one of the most prevalent forms of biologically-available nitrogen, and may be created naturally or anthropogenically [3,4,5]
The mean and median drinking-water nitrate levels were below the Maximum Allowable Concentration (MAC) in both municipalities and rural areas, though the mean, median and maximum drinking-water nitrate concentrations were higher in rural areas compared to those within municipalities
This study builds on previous work to examine the association between drinking-water nitrate concentrations and incidence of major congenital anomalies in the agricultural region of Kings County, Nova Scotia, Canada by employing the use of province-wide population-based birth registry data which enabled controlling for factors that may have introduced confounding in previous studies and which allowed for inclusion of cases diagnosed in-utero with congenital anomalies in pregnancies that had been electively terminated before birth
Summary
Congenital anomalies complicate 2% to 3% of Canadian births and the incidence of neural tube defects, congenital heart defects and Down’s syndrome in Nova Scotia are among the highest in Canada [1].The etiologies of many congenital anomalies remain unknown; their widespread health impacts warrant further investigation into risk factors, environmental causes and means of prevention [1].Teratogens in the environment, such as nitrate, may cause 8%–12% of congenital anomalies [1,2].Nitrate (NO3) is one of the most prevalent forms of biologically-available nitrogen, and may be created naturally or anthropogenically [3,4,5]. Teratogens in the environment, such as nitrate, may cause 8%–12% of congenital anomalies [1,2]. Ingested nitrate may be converted to nitrite by microbial reduction in saliva, or in the stomach during instances of increased pH or infections with diarrhea-producing bacteria [6,7]. Several animal studies have shown that nitrates and other nitrogenous compounds can cross the placenta and have a teratogenic effect on the developing fetus during pregnancy, impacting the central nervous system [8,9,10]. Several case-control studies have shown a positive association between drinking-water nitrate levels and incidence of congenital anomalies among humans [11,12,13,14,15]
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