Background: Atrazine and nitrate are common contaminants in water, and there is limited evidence that they are associated with adverse birth outcomes. The objective of this study was to examine whether atrazine and nitrate in water are associated with an increased risk of preterm delivery (PTD) and term low birth weight (LBW).

Methods: The study included a total of 134,258 singletons births born between January 1, 2004 and December 31, 2008 from 46 counties in four Midwestern states with public water systems that were included in the U.S. Environmental Protection Agency (EPA)'s atrazine monitoring program (AMP). Counties with a population of >300,000 were eliminated from the analyses in order to avoid confounding by urbanicity. Monthly child's sex, race and Hispanic ethnicity specific data were obtained from the states for estimating rates of PTD (<37 weeks) and very preterm (VPTD, <32 weeks), term LBW (<2.5kg among infants born at term) and very low birth weight (VLBW, <1.5kg). The rates were linked with county specific monthly estimates of the concentration of atrazine and nitrate in finished water. Multivariable negative binomial models were fitted to examine the association between the exposures and the adverse birth outcomes. Models were fitted with varying restrictions on the percentage of private well usage in the counties in order to limit the degree of exposure misclassification.

Results: Estimated water concentrations of atrazine (mean=0.42 ppb) and nitrate (mean=0.95ppm) were generally low. Neither contaminant was associated with an increased risk of term LBW. Atrazine exposure was associated with a significant increased rate of PTD when well use was restricted to 10% and the exposure was averaged over 4-6 months prior to birth (Rate Ratio for 1ppm increase [RR_1ppm]=1.08, 95%CI=1.05,1.11) or over 9 months prior to birth (RR_1ppm=1.10, 95%CI=1.01,1.20). Atrazine exposure was also associated with an increased rate of VPTD when when well use was restricted to 10% and the exposure was averaged over 7-9 months prior to birth (RR_1ppm=1.19, 95%CI=1.04,1.36). Exposure to nitrate was significantly associated with an increased rate of VPTD (RR_1ppm=1.08, 95%CI=1.02,1.15) and VLBW (RR_1ppm=1.17, 95%CI=1.08,1.25) when well use was restricted to 20% and the exposure was averaged over 9 months prior to birth.

Conclusion: The positive and negative findings from our study need to be interpreted cautiously given its ecologic design, and limitations in the data for the exposures and other risk factors. Nonetheless, our findings do raise concerns about the potential adverse effects of these common water contaminants on human development and health, and the adequacy of current regulatory standards. Further studies of these issues are needed with individual level outcome data and more refined estimates of exposure.