Exposure to phthalates and OP flame retardants and long-term maternal cardiovascular and metabolic health

接触邻苯二甲酸盐和 OP 阻燃剂与长期孕产妇心血管和代谢健康

• 批准号: 10515782
• 负责人: Lidia Minguez Alarcon
• 金额: $ 71.64万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-07-05 至 2027-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10515782
• 关键词: Accounting; Adherence; Age; Anthropometry; Archives; Attention; Binding; Biological Markers; Birth; Birth Rate; Blood Pressure; Body mass index; Cardiovascular Diseases; Cardiovascular system; Cause of Death; Cessation of life; Chemicals; Chronic Disease; Clinic; Collection; Couples; Databases; Diabetes Mellitus; Diet; Disease; Eating; Enrollment; Environment; Environmental Exposure; Environmental Impact; Etiology; Exposure to; Female; Fertility; Flame Retardants; Future; General Population; Gestational Diabetes; Glucose; Guidelines; Health; Health Status; Human; Hypertension; Impairment; Individual; Inflammatory; Investigation; Joints; Knowledge; Length; Life Style; Link; Lipids; Live Birth; Longterm Follow-up; Maternal Health; Measures; Medical Device; Menopause; Metabolic; Modification; Nuclear Receptors; Obesity; Organophosphates; Outcome; Outcome Measure; PPAR alpha; Participant; Physical activity; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Pregnancy loss; Premature Birth; Recommendation; Regulation; Reproductive Health; Research Priority; Risk Factors; Sampling; Series; Smoke; Smoking; Symptoms; Syndrome; Testing; Time; Urine; Weight; Woman; cardiometabolism; cardiovascular disorder prevention; cardiovascular disorder risk; cardiovascular health; cardiovascular risk factor; clinical care; cohort; consumer product; disorder risk; environmental chemical; experimental study; gestational weight gain; glucose metabolism; healthy lifestyle; high risk; lipid metabolism; men; middle age; offspring; personal care products; phthalates; preventive intervention; recruit; reproductive; screening; urinary

ABSTRACT Cardiovascular disease (CVD) is the leading cause of death among U.S. women, accounting for approximately 1 of every 3 female deaths. Cumulative evidence has identified pregnancy complications as well as fertility measures, as CVD risk factors. However, there is very limited knowledge on the impact of environmental exposures during pregnancy and both short and long-term maternal cardiovascular and metabolic health. Environmental chemicals with potential cardiometabolic impact include phthalates and organophosphate (OP) flame retardants, which widespread use leads to ubiquitous general population exposure. Experimental studies demonstrated that both phthalates and OP flame retardants bind to human peroxisome proliferator-activated receptors (PPARs), a master nuclear receptor that is involved in lipid metabolism regulation. Among subfertile women enrolled in the Environment and Reproductive Health (EARTH) Study, we observed worse pregnancy outcomes, including decreased live birth rates, increased pregnancy loss and elevated glucose levels during pregnancy, with increasing urinary concentrations of phthalate and/or OP flame retardant metabolites. However, it is unstudied whether phthalate and OP flame retardant exposure during pregnancy is associated with long-term (midlife) maternal cardiovascular and metabolic health. We propose to evaluate associations of preconception, pregnancy and midlife urinary phthalate and OP flame retardant metabolite concentrations (individually and as a mixture) with long-term cardiometabolic health (anthropometry, glucose and lipid metabolism, blood pressure and inflammatory biomarkers). We will also identify the most important window(s) of exposure associated with cardiometabolic health, evaluate the joint and interactive effects of urinary metabolite concentrations and modifiable lifestyle risk factors for CVD (BMI, diet, physical activity, smoking) with cardiometabolic health, and investigate trajectories of cardiovascular health outcomes from pregnancy to midlife. We embed our proposal within the EARTH Study (2004-2021), a cohort of subfertile couples attending a single fertility center to identify environmental predictors of reproductive health. Strengths of EARTH Study include collection of urine samples both before and during pregnancy and its comprehensive and rich database of covariates. We will contact and re-enroll former female EARTH participants who will provide additional urine samples comprising the midlife window of exposure for phthalate and OP flame retardant metabolites and we will assess their current health status. Women with impaired fertility are at higher risk of CVD, thus this proposal provides an exceptional opportunity to explore cardiovascular and metabolic health among women within the well-established EARTH Study, which so far, has focused on fertility, pregnancy and offspring outcomes. Results from the proposed series of investigations will inform clinical care for women from the reproductive years through midlife, CVD guidelines regarding screening and long-term follow-up, and future research priorities.

抽象的 心血管疾病（CVD）是美国妇女死亡的主要原因，大约为 每3名女性死亡中有1人。累积证据已经确定了妊娠并发症和生育能力 措施，作为CVD风险因素。但是，关于环境影响的知识非常有限 怀孕期间的暴露以及短期和长期母体心血管和代谢健康。 具有潜在心脏代谢影响的环境化学物质包括邻苯二甲酸盐和有机磷酸盐（OP） 广泛使用的阻燃剂会导致普遍存在的一般人口暴露。实验研究 证明邻苯二甲酸盐和op火焰阻燃剂与人过氧化物酶体增殖物结合了激活 受体（PPARS），一种参与脂质代谢调节的主要核受体。在子系列中 妇女参加了环境和生殖健康（Earth）研究，我们观察到怀孕较差 结果，包括降低活出生率，妊娠损失增加和葡萄糖水平升高 妊娠，邻苯二甲酸酯和/或OP火焰阻燃代谢产物的浓度增加。 但是，尚未研究邻苯二甲酸盐和op火焰在怀孕期间的阻燃暴露与 长期（中年）的孕产妇心血管和代谢健康。我们建议评估 先选，怀孕和中年尿邻苯二甲酸酯和蛋白阻燃代谢物浓度 （单独和作为混合物）长期心脏代谢健康（人体测量法，葡萄糖和脂质 代谢，血压和炎症生物标志物）。我们还将确定最重要的窗口 与心脏代谢健康相关的暴露，评估尿的关节和互动效应 CVD的代谢物浓度和可修改的生活方式危险因素（BMI，饮食，体育锻炼，吸烟） 具有心脏代谢健康，并研究从怀孕到心血管健康结果的轨迹 中年。我们将提议嵌入了地球研究（2004-2021），这是一群参与的副夫妇 一个单一的生育中心，以确定生殖健康的环境预测指标。地球研究的优势 包括在怀孕之前和期间收集尿液样品及其全面且丰富的数据库 协变量。我们将联系并重新注册以前的女性地球参与者，他们将提供额外的尿液 样品包括邻苯二甲酸酯和op燃料阻燃代谢物的中年窗户，我们 将评估他们当前的健康状况。生育不良的妇女的CVD风险较高，因此 提案为妇女探索心血管和代谢健康提供了极大的机会 到目前为止，在良好的地球研究中，集中于生育能力，妊娠和后代 结果。拟议的一系列调查的结果将为女性的临床护理提供信息 通过中年生命的生殖年，有关筛查和长期随访的CVD指南以及未来 研究重点。