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

基本信息

批准号：
10659212
负责人：
Lidia Minguez Alarcon
金额：
$ 66.31万
依托单位：
BRIGHAM AND WOMEN'S HOSPITAL
依托单位国家：
美国
项目类别：
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/10659212
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 Conceptions 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 Participant Peroxisome Proliferator-Activated Receptors 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

项目摘要

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）是美国女性死亡的主要原因，约占美国女性死亡的主要原因每 3 名女性死亡中就有 1 名。累积证据已确定妊娠并发症以及生育能力措施，作为 CVD 危险因素。然而，人们对环境影响的认识非常有限。怀孕期间的暴露以及短期和长期的母亲心血管和代谢健康。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) 阻燃剂的广泛使用导致普遍人群普遍接触阻燃剂。实验研究证明邻苯二甲酸盐和 OP 阻燃剂均与人过氧化物酶体增殖物激活的结合受体（PPAR），一种参与脂质代谢调节的主要核受体。生育能力低下者中参加环境与生殖健康 (EARTH) 研究的女性，我们观察到怀孕情况更差结果，包括活产率下降、妊娠丢失增加以及妊娠期间血糖水平升高怀孕期间，尿中邻苯二甲酸酯和/或 OP 阻燃剂代谢物浓度增加。然而，尚未研究怀孕期间接触邻苯二甲酸盐和 OP 阻燃剂是否存在相关性长期（中年）产妇心血管和代谢健康。我们建议评估协会孕前、怀孕和中年尿液中邻苯二甲酸盐和 OP 阻燃剂代谢物浓度（单独和作为混合物）与长期心脏代谢健康（人体测量、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，评估尿的联合和相互作用的影响 CVD 的代谢浓度和可改变的生活方式危险因素（BMI、饮食、体力活动、吸烟）与心脏代谢健康，并调查从怀孕到心血管健康结果的轨迹中年。我们将我们的提案纳入“地球研究”（2004-2021 年）中，该研究由一群生育力低下的夫妇参加一个单一的生育中心来确定生殖健康的环境预测因素。地球研究的优势包括怀孕前和怀孕期间的尿液样本采集及其全面丰富的数据库协变量。我们将联系并重新招募前女性 EARTH 参与者，她们将提供额外的尿液样品包含邻苯二甲酸酯和 OP 阻燃剂代谢物的中年暴露窗口，我们将评估他们目前的健康状况。生育能力受损的女性患 CVD 的风险较高，因此该提案提供了一个探索女性心血管和代谢健康的绝佳机会迄今为止，该研究的重点是生育、怀孕和后代结果。拟议的一系列调查的结果将为妇女的临床护理提供信息生育年龄到中年、CVD 筛查和长期随访指南以及未来研究重点。