Nitrate in drinking water and the risk of adverse birth outcomes

饮用水中的硝酸盐和不良出生结果的风险

• 批准号: 9764364
• 负责人: Leslie Thomas Stayner
• 金额: $ 44.35万
• 依托单位: UNIVERSITY OF ILLINOIS AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-30 至 2021-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9764364
• 关键词: Address; Alcohols; Anemia; Animals; Birth; Birth length; Body mass index; Cohort Studies; Congenital Abnormality; Consumption; Cox Proportional Hazards Models; Data; Denmark; Diet; Dietary intake; Drug Prescriptions; Drug usage; Education; Epidemiology; Evaluation; Exposure to; Fetal Growth Retardation; Folic Acid; Food; Frequencies; Gestational Age; Goals; Head circumference; Income; Individual; Infant; Influentials; Intake; Length; Limb structure; Linear Regressions; Link; Low Birth Weight Infant; Medical; Methemoglobinemia; Modeling; Modification; Mothers; Neural tube; Newborn Infant; Nitrates; Nitrites; Nitrosamines; Outcome; Pharmaceutical Preparations; Policies; Population-Based Registry; Pregnancy; Premature Birth; Public Health; Questionnaires; Recommendation; Recording of previous events; Registries; Reporting; Resources; Risk; Risk Factors; Severities; Smoking; Socioeconomic Status; Source; Statistical Methods; Steroid biosynthesis; Suggestion; Syndrome; Teratogens; Term Birth; Thyroid Function Tests; Uncertainty; United States; Water; Water Supply; Water consumption; base; cleft lip and palate; cohort; contaminated drinking water; contaminated water; design; development policy; drinking water; epidemiology study; experimental study; maternal cigarette smoking; parity; patient registry; population based; prenatal exposure; prepregnancy; prospective

Abstract/Summary Nitrate is the most commonly found contaminant in the world's aquifers and a major contaminant of drinking water in the U.S. Nitrate causes fetal growth restriction (FGR), low birth weight (LBW), and birth defects (BD) in studies of experimental animals, but only at high concentrations. High levels of nitrate in drinking water are also a well-recognized cause of a potentially fatal form of anemia (methemoglobinemia or blue baby syndrome) in newborns. However, surprisingly few epidemiologic studies have examined the risk of adverse birth outcomes from contemporary lower levels of nitrate in water. There is suggestive evidence from these studies that nitrate in drinking water may increase the risk of FGR, preterm delivery (PTD) and neural tube, limb deficiencies and cleft palate/lip BD. Most of the prior studies are limited by their ecologic design, small size, uncertain estimates of exposure, poor control of other risk factors, and lack of consideration of dietary intake of nitrate and nitrite. There is a clear need for larger and better studies at contemporary levels of exposure, which this proposal is designed to address. The goal of this proposal is to evaluate whether maternal consumption of nitrate contaminated water increases the risk of adverse birth outcomes. Specifically we aim to examine whether nitrate in drinking water is associated with an increased risk of: 1) PTD (< 37 weeks) and very PTD (<32 weeks), 2) FGR based on being small (<10th percentile) for gestational age, LBW (<2.5 kg among infants born at term), reduced birth head circumference and body length, 3) neural tube, limb deficiencies and cleft palate/lip BD, and 4) interacts with the use of nitrosatable drugs for BD, which has been reported in one study. To address these aims we will capitalize on unique resources available in Denmark, which permit estimation of concentrations of nitrate in drinking water for all addresses and linkage of these estimates with complete address histories, data on birth outcomes, prescription drug use and other risk factors (e.g. maternal smoking, parity, and socio-economic status) from Danish registries to create a population based cohort study of all liveborn singleton births in Denmark from 1997 to 2013 (~1 million births). We will also link these data with the Danish National Birth Cohort (DNBC), which has extensive information on diet (for ~67000 births) which will be used for estimating dietary intake of nitrate and nitrite. The DNBC also has useful data on water consumption, drug use (prescription and non-prescription), and extensive information on other risk factors. Our study will be the largest ever conducted, with comprehensive data on nitrate intake from water and food and on other risk factors. Our findings should be highly influential in the development of policies and recommendations concerning nitrate in drinking water, which would have a very large public health impact given the ubiquity of nitrate in drinking water and the severity of these outcomes.

摘要/概要 硝酸盐是世界含水层中最常见的污染物，也是饮用水的主要污染物 硝酸盐导致胎儿生长受限（FGR），低出生体重（LBW）和出生缺陷（BD）， 实验动物的研究，但只有在高浓度。饮用水中硝酸盐含量高， 也是一种公认的潜在致命性贫血（高铁血红蛋白血症或蓝婴综合征）的原因 在新生儿中。然而，令人惊讶的是，很少有流行病学研究调查了不良出生的风险 结果从当代较低水平的硝酸盐在水中。从这些研究中有暗示性的证据 饮用水中的硝酸盐可能会增加FGR、早产（PTD）和神经管、肢体的风险。 缺陷和腭裂/唇BD。大多数先前的研究受到其生态设计，小尺寸， 暴露估计不确定，对其他风险因素控制不力，以及缺乏对膳食摄入的考虑， 硝酸盐和亚硝酸盐。显然需要在当代暴露水平上进行更大规模和更好的研究， 这项建议旨在解决。 这项建议的目的是评估产妇是否饮用硝酸盐污染的水 增加了不良生育结果的风险。具体来说，我们的目标是检查饮用水中的硝酸盐是否 与以下风险增加相关：1）PTD（< 37周）和非常PTD（<32周），2）基于 小于胎龄（<第10百分位数），低出生体重（足月出生婴儿<2.5 kg），减少出生 头围和体长，3）神经管，肢体缺陷和腭裂/唇BD，和4）相互作用 在一项研究中报告了使用可亚硝基化药物治疗BD。 为了实现这些目标，我们将利用丹麦的独特资源， 所有地址的饮用水中硝酸盐浓度，并将这些估计数与 处理病史、出生结果数据、处方药使用和其他风险因素（如产妇吸烟， 性别、社会经济地位），以创建一项基于人群的队列研究， 1997年至2013年丹麦活产单胎分娩（约100万例）。我们还将这些数据与 丹麦国家出生队列（DNBC），它有广泛的饮食信息（约67000出生），这将是 用于估计硝酸盐和亚硝酸盐的膳食摄入量。DNBC也有关于水消耗的有用数据， 药物使用（处方药和非处方药），以及关于其他风险因素的广泛信息。我们的研究将是 这是有史以来规模最大的一次，有关于水和食物中硝酸盐摄入量以及其他风险的全面数据。 因素我们的研究结果应该对政策和建议的制定具有很大的影响力 关于饮用水中的硝酸盐，鉴于普遍存在的 饮用水中的硝酸盐以及这些后果的严重性。