Abstract

Background/Aim: Findings from studies examining the effects of prenatal exposure to nitrate from drinking water on fetal growth have been inconsistent, small, and mostly ecologic in nature and none have explicitly examined infant size as measured by body length (BL) or head circumference (HC) at birth. The aim of this study was to assess maternal exposure to nitrate in drinking water and BL and HC at birth in a large population-based cohort.Methods: Estimates of water contamination by nitrate at each maternal address during pregnancy were linked with individual-level birth registry data to create a cohort of full-term singleton live births in Denmark from Danish parents during 1991-2011, with 848,106 measures of BL and 588,981 of HC. Exposures were modeled both categorically and as log-transformed continuous estimates. Multivariate linear regression with generalized estimating equations was used to assess associations.Results: A negative trend in BL was observed in both categorical (p<0.001) and continuous models (p=0.01) of nitrate exposure. When comparing the European Union action level of 25mg/L to 0mg/L NO3- exposure, a 0.3mm reduction in BL was estimated. There was no evidence of an exposure-response relationship in either categorical (p=0.52) or continuous (p=0.69) models of nitrate exposure for HC. Conclusions: To the best of our knowledge, our study is the first to examine the relationship between nitrate in drinking water and body length and head circumference. Estimated maternal nitrate exposure was associated with decreased BL, but not HC at birth. However, HC was not recorded until 1997 and has less overall variation, making it harder to observe effects of environmental exposures. While the reduction in BL is not clinically relevant at the individual level, it may important from a public health point of view given the widespread exposure to nitrate in drinking water worldwide.

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