A preconception cohort study of environmental chemicals, fertility, and miscarriage

环境化学物质、生育力和流产的孕前队列研究

• 批准号: 10057270
• 负责人: ELIZABETH E HATCH
• 金额: $ 60.14万
• 依托单位: BOSTON UNIVERSITY MEDICAL CAMPUS
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-01-01 至 2023-10-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10057270
• 关键词: Acids; Affect; Age; Benzophenones; Biological; Biological Assay; Blood; Blood specimen; Boston; Canada; Centers for Disease Control and Prevention (U.S.); Chemicals; Clinic; Cohort Studies; Collection; Conceptions; Confounding Factors (Epidemiology); Cost efficiency; Couples; Cyclohexanes; Data; Data Collection; Denmark; Dicarboxylic Acids; Diethylhexyl Phthalate; Endocrine Disruptors; Enrollment; Environmental Pollutants; Esters; Evaluation; Exposure to; Female; Fertility; Financial Hardship; Future; General Population; Geography; Grant; Health; Health Care Costs; High Prevalence; Home; Human; Infertility; Infrastructure; Laboratory Study; Measurement; Measures; Methods; Minority; Modeling; National Institute of Child Health and Human Development; North America; Online Systems; Outcome; Parabens; Participant; Persons; Phenols; Pilot Projects; Poly-fluoroalkyl substances; Population; Pregnancy; Probability; Prospective cohort; Prospective cohort study; Public Health; Research; Research Design; Retrospective Studies; Risk; Risk Factors; Sample Size; Sampling; Selection Bias; Serum; Ships; Site; Specimen; Spontaneous abortion; Sum; Testing; Time; United States; Urine; Woman; Work; adverse pregnancy outcome; aged; analytical method; base; bisphenol A; chemical standard; child bearing; cohort; cost effective; cost estimate; design; early pregnancy; early pregnancy loss; environmental chemical; feasibility testing; follow-up; health goals; high risk; improved; infertility treatment; innovation; male; modifiable risk; phthalates; pregnant; prospective; psychologic; random forest; recruit; reproductive; subfertility; time-to-pregnancy; trying to conceive; urinary; Acids; Affect; Age; Benzophenones; Biological; Biological Assay; Blood; Blood specimen; Boston; Canada; Centers for Disease Control and Prevention (U.S.); Chemicals; Clinic; Cohort Studies; Collection; Conceptions; Confounding Factors (Epidemiology); Cost efficiency; Couples; Cyclohexanes; Data; Data Collection; Denmark; Dicarboxylic Acids; Diethylhexyl Phthalate; Endocrine Disruptors; Enrollment; Environmental Pollutants; Esters; Evaluation; Exposure to; Female; Fertility; Financial Hardship; Future; General Population; Geography; Grant; Health; Health Care Costs; High Prevalence; Home; Human; Infertility; Infrastructure; Laboratory Study; Measurement; Measures; Methods; Minority; Modeling; National Institute of Child Health and Human Development; North America; Online Systems; Outcome; Parabens; Participant; Persons; Phenols; Pilot Projects; Poly-fluoroalkyl substances; Population; Pregnancy; Probability; Prospective cohort; Prospective cohort study; Public Health; Research; Research Design; Retrospective Studies; Risk; Risk Factors; Sample Size; Sampling; Selection Bias; Serum; Ships; Site; Specimen; Spontaneous abortion; Sum; Testing; Time; United States; Urine; Woman; Work; adverse pregnancy outcome; aged; analytical method; base; bisphenol A; chemical standard; child bearing; cohort; cost effective; cost estimate; design; early pregnancy; early pregnancy loss; environmental chemical; feasibility testing; follow-up; health goals; high risk; improved; infertility treatment; innovation; male; modifiable risk; phthalates; pregnant; prospective; psychologic; random forest; recruit; reproductive; subfertility; time-to-pregnancy; trying to conceive; urinary

ABSTRACT Infertility and spontaneous abortion (SAB) are significant public health problems, affecting up to 25% of reproductive age couples in the United States. Health care costs attributable to infertility and SAB exceed $5 billion per year, and several studies have shown an association between infertility treatments and adverse pregnancy outcomes. Thus, identifying modifiable risk factors for subfertility and SAB is an important public health goal. The potential effects of exposure to endocrine-disrupting chemicals (EDCs) on risk of subfertility and SAB are understudied. The few existing human studies have limitations including small sample size, enrollment after conception, retrospective study design, suboptimal assessment of exposure and outcome, inadequate control for potential confounding variables, and limited generalizability. The proposed study will prospectively assess the relation of exposure to selected EDCs, including phenols, phthalates, and per- and poly-fluoroalkyl substances (PFAS), to risk of subfertility and SAB in a preconception subcohort of 950 pregnancy planners. We will use data from two NICHD-supported prospective cohorts of pregnancy planners in North America and Denmark. With web-based recruitment and data collection, we have enrolled over 17,000 women attempting pregnancy into these cohorts. In a subset of 200 participants, we have successfully pilot tested in-person collection of urine and blood specimens during the preconception and early pregnancy periods. In this application, we propose to expand in-person biospecimen collection, increasing the number of women with preconception and early pregnancy urine and blood samples from 200 to 950. At each of our three biospecimen collection sites (Boston, Detroit, and Aarhus), we will enroll 250 women and collect three urine samples and one blood sample (in preconception) and three urine samples and one blood sample (in early pregnancy). We will ship the samples to the CDC for the analysis of urinary phthalates, urinary phenols, and serum PFAS. To increase cost efficiency, we will pool three urine samples in each exposure window before assaying for phthalates and phenols; and we will assay one preconception blood specimen for PFAS, a persistent chemical, in analyses of subfertility and SAB. Finally, we will conduct a pilot study among 100 U.S. participants to assess the feasibility of collecting urine by mail, which would allow us to take advantage of our full geographically-diverse cohort in the future. Strengths of this application include the prospective design, preconception enrollment of pregnancy planners, repeated measurement of exposure during preconception and early pregnancy, excellent control for confounding via bimonthly prospective data collection on a wide range of covariates, and use of the latest analytic methods for mixtures modeling. We have generated compelling preliminary data to support our aims. The present grant is cost-effective in leveraging already-established cohort studies with data collection and follow-up supported by other grants. The results generated will be translatable by directly informing future regulatory decisions about EDC standards in a manner that could reduce rates of infertility and SAB.

抽象的 不育和自发流产（SAB）是重大的公共卫生问题，影响多达25％ 美国的生殖年龄夫妇。归因于不育和SAB超过$ 5的医疗保健费用 每年十亿美元，几项研究表明，不育治疗与不良治疗之间存在关联 怀孕结果。因此，识别可修改的危险因素和SAB是重要的公众 健康目标。暴露于内分泌中断化学物质（EDC）的潜在影响对不属性的风险和 SAB被研究了。现有的人类研究有局限性，包括小样本量，注册 经过构想，回顾性研究设计，暴露和结果的次优评估，不足 控制潜在的混杂变量和有限的概括性。拟议的研究将前瞻性地 评估接触所选EDC的关系，包括苯酚，邻苯二甲酸酯和氟氟烷基 物质（PFA），在950个怀孕计划者的先入为主的亚群中出现副生物和SAB的风险。我们 将使用来自北美和 丹麦。通过基于Web的招聘和数据收集，我们已经招募了17,000多名妇女 怀孕这些队列。在200名参与者的子集中，我们已经成功地进行了亲自测试 在预选和怀孕早期期间收集尿液和血液标本。在这个 应用，我们建议扩大面对面的生物循环收集，增加了 先入为主和早期妊娠尿液和血液样本200至950。 收集地点（波士顿，底特律和阿尔胡斯），我们将注册250名妇女，并收集三个尿液样本和一个 血液样本（以前）和三个尿液样本和一个血液样本（在怀孕初期）。我们将 将样品运送到CDC上，以分析尿邻苯二甲酸酯，尿酚和血清PFA。到 提高成本效率，在分析之前，我们将在每个曝光窗口中汇集三个尿液样本 邻苯二甲酸盐和苯酚；我们将分析一个持续化学物质PFA的一个先入血液标本， 在分析和SAB的分析中。最后，我们将对100名美国参与者进行试点研究，以评估 通过邮件收集尿液的可行性，这将使我们能够利用我们的完整地理多样性 将来的队列。此应用的优势包括前瞻性设计 怀孕策划者，重复测量在先入前和怀孕早期期间暴露的测量 通过在各种协变量上通过两次前瞻性数据收集进行混淆的控制，并使用 混合物建模的最新分析方法。我们已经生成了引人入胜的初步数据，以支持我们的 目标。目前的赠款在利用已经建立的队列研究的数据收集方面具有成本效益 以及其他赠款支持的后续行动。通过直接告知未来，产生的结果将是可以翻译的 关于EDC标准的监管决策，可以降低不育和SAB的速度。