Nonpersistent chemical exposure, placental development, and maternal pre- and post-pregnancy cardiovascular health

项目摘要/摘要 在美国，越来越多的女性经历着怀孕并发症，如 先兆子痫、子痫和妊娠期高血压会把自己和孩子的直接 以及长期的健康面临风险。特别是，这些妊娠高血压疾病与 女性产后心血管疾病发病率增加。链接似乎是胎盘，一个 调节营养流向发育中的胎儿并影响母体心血管功能的器官。 非持久性内分泌干扰物(EDCs)，包括塑料和邻苯二甲酸酯中的双酚 在个人护理产品中发现，与心血管疾病有关，也可能 与胎盘功能障碍有关。在我的硕士、博士和博士后培训课程中，我 已经开始在环境和生殖流行病学方面开发一系列已发表的研究成果， 并特别强调确定潜在的生物机制。我以前的教育背景和经验 让我很好地承担我提议的K99/R00研究项目：检查母体之间的关系 暴露于非持续性内皮细胞、胎盘功能障碍的生物标志物和母体的指标 怀孕前后的心血管疾病。这一独立之路奖将提供 我需要更多的指导和专业知识来过渡到教职员工，并成功地竞争资金 首席调查员。我的培训计划包括正式课程、讲习班和研讨会、定向阅读、 和学徒期，以发展1)EDC、环境流行病学和暴露评估方面的技能，2) 先进的统计方法，以及3)胎盘和心血管健康的交集。在K99公路上 在我的研究阶段，我将利用纽约大学(NYU)目前收集的数据 儿童健康与环境研究(CHES)，包括产前孕妇生物标志物和 调查问卷数据以及产后产妇心血管指标。在R00阶段，我将合并 来自纽约大学影响生殖成功和怀孕时间因素的额外先入为主的数据 (一)学习。具体目标包括1)检查孕妇产前尿邻苯二甲酸盐与 双酚水平对母体胎盘发育生物标志物的影响以及内分泌细胞对胎盘发育的影响 出生时胎盘大小，2)检查产前尿邻苯二甲酸盐和双酚水平的关系 妊娠三个月对产妇产后1年和2年临床心血管危险因素的影响 CHES，以及3)评估母亲怀孕前邻苯二甲酸盐和双酚暴露之间的关系， 先入为主的心血管危险因素、怀孕时间和胎盘生长发育 组合CHS和FIRST数据。这些培训和研究活动将增加我作为一名 环境流行病学家和我做好准备，以独立的身份成功竞争R01资金 以生殖和妇女健康为重点的调查员。

PROJECT SUMMARY/ABSTRACT In the United States, increasing numbers of women are experiencing pregnancy complications such as preeclampsia, eclampsia, and gestational hypertension that can put their own and their children’s immediate and long-term health at risk. In particular, these hypertensive disorders of pregnancy are associated with increased incidence of postnatal cardiovascular disease in women. The link appears to be the placenta, an organ that both regulates nutrient flow to the developing fetus and influences maternal cardiovascular function. Nonpersistent endocrine disrupting chemicals (EDCs), including bisphenols found in plastics and phthalates found in personal care products, have been associated with cardiovascular disease and may also be associated with placental dysfunction. Over the course of my masters, doctoral, and postdoctoral training, I have begun to develop a portfolio of published research in both environmental and reproductive epidemiology, with a particular emphasis on identifying underlying biological mechanisms. My prior education and experience positions me well to undertake my proposed K99/R00 research project: examining relations among maternal exposure to nonpersistent EDCs, biomarkers of placental dysfunction, and indicators of maternal cardiovascular disease both before and after pregnancy. This Pathway to Independence Award will provide the additional mentorship and expertise I need to transition to faculty and successfully compete for funding as a principal investigator. My training plan includes formal courses, workshops and seminars, directed readings, and apprenticeships to develop skills in 1) EDCs, environmental epidemiology, and exposure assessment, 2) advanced statistical methods, and 3) the intersection between placental and cardiovascular health. In the K99 phase of my research, I will leverage data currently being collected in the New York University (NYU) Children’s Health and Environment Study (CHES) that includes both prenatal maternal biomarker and questionnaire data as well as postnatal maternal cardiovascular measures. In the R00 phase, I will incorporate additional preconception data from the NYU Factors Influencing Reproductive Success and Time to Pregnancy (FIRST) Study. Specific Aims include 1) examining relations of maternal prenatal urinary phthalate and bisphenol levels to maternal biomarkers of placental development, and trimester-specific effects of EDCs on placental size at birth, 2) examining relations of prenatal urinary phthalate and bisphenol levels measured in three trimesters of pregnancy to maternal clinical cardiovascular risk factors at 1 and 2 years postpartum in CHES, and 3) assessing relations among maternal preconception phthalate and bisphenol exposure, preconception cardiovascular risk factors, time to pregnancy, and placental growth and development using combined CHES and FIRST data. These training and research activities will increase my expertise as an environmental epidemiologist and prepare me to successfully compete for R01 funding as an independent investigator with a focus on reproductive and women’s health.