Dataset Information

Prenatal Exposure to Nitrate from Drinking Water and Markers of Fetal Growth Restriction: A Population-Based Study of Nearly One Million Danish-Born Children.

ABSTRACT:

Background

High levels of nitrate (NO3-) in drinking water cause methemoglobinemia in infants; however, few studies have examined the potential effects of low-level exposure on fetal growth, and the results have been inconsistent.

Objectives

We sought to assess the association between maternal exposure to nitrate in drinking water during pregnancy and offspring size at birth in a nationwide study of full-term (?37?wk gestation) live-born singletons.

Methods

We estimated maternal nitrate exposure for 898,206 births in Denmark during 1991-2011 by linkage of individual home address(es) with nitrate data from the national monitoring database. Maternal address during pregnancy, infant size at birth [i.e., birth weight, low birth weight (LBW), body length, and birth head circumference] and covariates were compiled from the Danish Civil Registration System, the Danish Medical Birth Register, and The Integrated Database for Longitudinal Labor Market Research. Linear and logistic models with generalized estimating equations were used to account for multiple births to an individual. Nitrate exposure was modeled using five categories and as a log-transformed continuous variable.

Results

There was evidence of a decreasing trend in models for term birth weight using categorical or continuous measures of exposure. Modeling exposure continuously, a difference of -9.71?g (95% confidence interval: -14.60, -4.81) was predicted at 25?mg/L (half the value of the European Union drinking water standard) compared with 0?mg/L?NO3-. Body length also decreased as nitrate concentrations increased in categorical and continuous models. There was little evidence of an association between NO3- and head circumference or LBW.

Discussion

Although the estimated effects were small, our findings for live singleton births to Danish-born parents suggest that maternal intake of nitrate from drinking water may reduce term birth weight and length, which are markers of intrauterine growth. However, there was little evidence for an association between nitrate and head circumference or LBW. Future studies in other populations and with data on dietary sources of nitrate are encouraged to confirm or refute these findings. https://doi.org/10.1289/EHP7331.

SUBMITTER: Coffman VR

PROVIDER: S-EPMC7861494 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

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Publications

Prenatal Exposure to Nitrate from Drinking Water and Markers of Fetal Growth Restriction: A Population-Based Study of Nearly One Million Danish-Born Children.

Coffman Vanessa R VR Jensen Anja Søndergaard AS Trabjerg Betina B BB Pedersen Carsten B CB Hansen Birgitte B Sigsgaard Torben T Olsen Jørn J Schaumburg Inger I Schullehner Jörg J Pedersen Marie M Stayner Leslie T LT

Environmental health perspectives 20210204 2

<h4>Background</h4>High levels of nitrate (NO3-) in drinking water cause methemoglobinemia in infants; however, few studies have examined the potential effects of low-level exposure on fetal growth, and the results have been inconsistent.<h4>Objectives</h4>We sought to assess the association between maternal exposure to nitrate in drinking water during pregnancy and offspring size at birth in a nationwide study of full-term (≥37 wk gestation) live-born singletons.<h4>Methods</h4>We estimated mat ...[more]

PMID: 33539179

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Project description:Evidence is emerging that preterm birth (PTB, birth before 37 completed weeks of gestation), a risk factor for neonatal mortality and future morbidity, may be induced by maternal nitrate ( NO3- ) exposure from drinking water. The objective of this study is to assess the association between maternal exposure to nitrate and the risk of PTB in a nationwide study of liveborn singletons.MethodsWe estimated maternal nitrate exposure from household tap water for 1,055,584 births in Denmark to Danish-born parents during 1991-2015 by linkage of individual home address(es) with nitrate concentrations from a national monitoring database. Nitrate exposure during pregnancy was modeled using four categories and continuously. Logistic models adjusted for sex, birth year, birth order, urbanicity, and maternal age, smoking, education, income, and employment, with generalized estimating equations were used to account for sibling clusters.ResultsA total of 1,009,189 births were included, comprising 51,747 PTB. An increase in the risk of PTB was seen across categories of exposure (P < 0.001) with an odds ratio (OR) in the uppermost category (>25 mg/L nitrate) of 1.05 (95% confidence interval [CI] = 1.00, 1.10). Evidence of an exposure-response relationship was observed in models using continuous nitrate (OR = 1.01 [95% CI = 1.00, 1.03] per 10 mg/L nitrate). In sensitivity analyses, results were robust to the addition of variables for short inter-pregnancy interval (<1 year between births), maternal pre-pregnancy body mass index, paternal socioeconomic status and age, season of birth, and inclusion of post-term births. Results were virtually unchanged when the analysis was restricted to women exposed to less than the current European Union standard of 50 mg/L.ConclusionWe observed an increasing risk of PTB with increases in nitrate in household tap water. These findings add to a growing body of evidence of adverse effects from nitrate in drinking water at levels below current regulatory levels.

Project description:BackgroundNitrosatable drugs commonly prescribed during pregnancy can react with nitrite to form N-nitroso compounds which have been associated with an increased risk of stillbirth. Whether maternal residential drinking water nitrate modifies this association is unknown. We investigated, if household drinking water nitrate was associated with stillbirth, and if it modified the association between nitrosatable prescription drug intake and the risk of stillbirth.MethodsWe conducted an individual-level register- and population-based cohort study using 652,810 women with the first recorded singleton pregnancy in the Danish Medical Birth Registry between 1997 and 2017. Nitrosatable drug exposure was recorded by use of the Danish National Patient Registry defined as women with a first redeemed prescription of a nitrosatable drug the first 22 weeks of pregnancy. The reference group was women with no redeemed prescription of a nitrosatable drug in this period. The average individual drinking water nitrate concentration level (mg/L) was calculated in the same period. We categorized nitrosatable drugs as secondary amines, tertiary amines, and amides. Cox hazard regression was used to estimate crude and adjusted hazard ratios with 95% confidence intervals for stillbirth stratified into five categories of nitrate concentrations: ≤1 mg/L, > 1- ≤ 2 mg/L, > 2- ≤ 5 mg/L, > 5- ≤ 25 mg/L, and > 25 mg/L.ResultsDrinking water nitrate exposure in the population was not associated with the risk of stillbirth. Among 100,244 women who had a nitrosatable prescription drug redeemed ≤22 weeks of pregnancy of pregnancy, 418 (0.42%) had a stillbirth compared to 1993 stillbirths (0.36%) among 552,566 referent women. Women with any nitrosatable prescription drug intake and > 1- ≤ 2 mg/L nitrate concentration had an increased risk of stillbirth [adjusted hazard ratio 1.55 (95% confidence interval, 1.15-2.09)] compared with referent women. In the stratified analyses, the highest risk of stillbirth was found among women with secondary amine intake and > 25 mg/L nitrate concentrations [adjusted hazard ratio 3.11 (95% CI, 1.08-8.94)].ConclusionsThe association between nitrosatable prescription drug intake and the risk of stillbirth may depend on the level of nitrate in household drinking water. Evaluations of the effect of nitrosatable drug intake on perinatal outcomes might consider nitrate exposure from drinking water.

Project description:BackgroundDue to the incomplete standardization of the etiology and diagnostic criteria for fetal growth restriction (FGR), there has been uncertainty in the early prediction of FGR. The comprehensive estimation of FGR was mainly based on various factors, such as maternal characteristics and medical history, nuchal translucency (NT), and serum biochemical markers [pregnancy-associated plasma protein-A (PAPP-A) and free beta human chorionic gonadotropin (free β-hCG)]. Herein, we performed a retrospective cohort study to investigate the correlation and diagnostic value of maternal markers such as PAPP-A, free β-hCG, and NT in the first trimester with maternal characteristics, so as to provide theoretical basis for perinatal care and the application of low-dose aspirin.MethodsA retrospective cohort study was conducted to analyze the data of an FGR group and a non-FGR group. Chi-square test and Mann-Whitney U test were used for univariate analysis of qualitative or quantitative data, respectively. Modified Poisson regression calculated the relative risk (RR) and 95% confidence interval (CI) of perinatal variables; P<0.05 was considered statistically significant.ResultsThe multiple of median (MoM) of PAPP-A level and NT in the FGR group were lower than those of the non-FGR group [0.63 (0.12-2.08) vs. 1.01 (0.28-2.41) MoM, 1.30 (0.80-2.07) vs. 1.40 (0.80-2.20) cm, P<0.05]. The weight, score, and length of newborns in the FGR group were lower than those in the non-FGR group (all P<0.001). Modified Poisson regression analysis showed that gestational hypertension (GH) [RR =1.836 (95% CI: 1.188-2.836)], oligohydramnios [1.420 (95% CI: 1.022-1.973)], premature rupture of membranes (PROM) [0.641 (95% CI: 0.425-0.969)], female infant [1.539 (95% CI: 1.098-2.157)], low infant length [5.700 (95% CI: 3.416-9.509)], low birth weight [1.609 (95% CI: 1.012-2.559), and increased PAPP-A MoM [0.533 (95% CI: 0.369-0.769)] were associated with FGR. The cut-off value of PAPP-A + free β-hCG + NT for predicting FGR was 0.190, with a sensitivity of 0.547 and a specificity of 0.778.ConclusionsEarly screening markers combined with perinatal characteristics have better diagnostic value in predicting FGR and provide a scientific basis for the clinical use of low-dose aspirin to prevent FGR.

Project description:BackgroundNitrate is a common water contaminant that has been associated with birth defects, although the evidence is limited. The purpose of this study was to examine whether maternal consumption of nitrate through drinking water is associated with an increased risk of congenital anomalies.MethodsThe study included a total of 348,250 singletons births from the state of Missouri between January 1, 2004 and December 31, 2008. Individual-level birth defect data and maternal and child characteristics were obtained from the Missouri birth defects registry and state vital statistics records. Outcomes were linked with county-specific monthly estimates of the nitrate concentration in finished water, based on data collected for compliance with the Safe Drinking Water Standard. Poisson models were fit to examine the association between nitrate exposure and birth defects. Average nitrate exposure during the first trimester and over 12 months prior to birth were modeled as continuous variables. Sensitivity analyses included restriction of the sample to counties with <20% and <10% private well usage to reduce exposure misclassification as well as limiting the analyses to residents of rural counties only to account for potential confounding by urbanicity.ResultsEstimated water concentrations of nitrate were generally low and below the Environmental Protection Agency's maximum contaminant level of 10 mg/L. Nitrate exposure was associated with a significantly increased risk of limb deficiencies (RR for 1 mg/L (RR1) = 1.26, 95% CI = 1.05, 1.51) in models without well restriction. Nitrate was also weakly associated with an increased risk of congenital heart defects (RR1 = 1.13, 95%CI = 0.93, 1.51) and neural tube defects (RR1 = 1.18, 95%CI = 0.93, 1.51) in models with well restriction (<10%).ConclusionThe positive associations found between nitrate exposure via drinking water and congenital abnormalities are largely consistent with some previous epidemiologic studies. The results of this study should be interpreted with caution given limitations in our ability to estimate exposures and the lack information on some risk factors for congenital abnormalities. Our findings may have serious policy implications given that exposure levels in our study were well below current EPA standards for nitrate in drinking water.

Project description:BackgroundEmerging studies suggest that ambient temperature during pregnancy may be associated with fetal growth, but the existing evidence is limited and inconsistent.ObjectivesWe aimed to evaluate the association of trimester-specific temperature with risk of being born small for gestational age (SGA) and birth weight-markers of fetal growth-among term births in the contiguous United States.MethodsWe included data on 29,597,735 live singleton births between 1989 and 2002 across 403 U.S. counties. We estimated daily county-level population-weighted mean temperature using a spatially refined gridded climate data set. We used logistic regression to estimate the association between trimester-specific temperature and risk of SGA and linear regression to evaluate the association between trimester-specific temperature and term birth weight z-score, adjusting for parity, maternal demographics, smoking or drinking during pregnancy, chronic hypertension, and year and month of conception. We then pooled results overall and by geographic regions and climate zones.ResultsHigh ambient temperatures ([Formula: see text] percentile) during the entire pregnancy were associated with higher risk of term SGA {odds ratio [OR] [Formula: see text] 1.041 [95% confidence interval (CI): 1.029, 1.054]} and lower term birth weight [standardized to [Formula: see text] (95% CI: [Formula: see text], [Formula: see text]) reduction in birth weight for infants born at 40 weeks of gestation]. Low temperatures ([Formula: see text] percentile) during the entire pregnancy were not associated with SGA [OR [Formula: see text] 1.003 (95% CI: 0.991, 1.015)] but were associated with a small decrement in term birth weight [standardized to [Formula: see text] (95% CI: [Formula: see text], [Formula: see text])]. Risks of term SGA and birth weight were more strongly associated with temperature averaged across the second and third trimesters, in areas the Northeast, and in areas with cold or very cold climates.ConclusionsAbove-average temperatures during pregnancy were associated with lower fetal growth. Our findings provide evidence that temperature may be a novel risk factor for reduced fetal growth. https://doi.org/10.1289/EHP4648.

Dataset Information

Prenatal Exposure to Nitrate from Drinking Water and Markers of Fetal Growth Restriction: A Population-Based Study of Nearly One Million Danish-Born Children.

Background

Objectives

Methods

Results

Discussion

Publications

Prenatal Exposure to Nitrate from Drinking Water and Markers of Fetal Growth Restriction: A Population-Based Study of Nearly One Million Danish-Born Children.

Similar Datasets

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