Epidemiology of Perfluorinated Compounds in Pregnancy and Risk of Preeclampsia

描述（由申请人提供）：本提案描述了生殖健康和不良妊娠结局（特别是先兆子痫）流行病学方面的培训计划。拟议的研究项目检查了孕妇血浆中全氟化合物的浓度，以及这些污染物与改变的心血管疾病生物标志物之间的可能联系，以及随后的先兆子痫风险。这里描述的项目和指导计划旨在培养申请人将流行病学工具应用于复杂的产科和环境问题的能力，并将这种研究培训整合到未来的职业生涯中，成为独立的医生科学家。导师团队由一名生殖和环境流行病学家组成，一名内科流行病学家，一名妇产科医生，一名妇产科医生和一名来自国家环境健康科学研究所的环境流行病学家，他们将定期会面，以确保研究员朝着她的目标取得足够的进展。 全氟化合物（PFCs）是一种人造化学物质，可持续存在于环境和人体中。虽然接触这些化学品在普通人群中很普遍[1]，但这种接触对人类健康的影响在很大程度上是未知的。动物研究表明，高剂量PFC暴露会对健康产生各种影响，包括血脂异常、发育异常和死胎[11]。有限的人类流行病学证据表明，高剂量接触可能会导致某些代谢效应[4，5]，但孕妇接触低剂量全氟化学品可能产生的后果尚不清楚。孕妇PFC浓度升高的一个合理影响可能是先兆子痫的风险增加。先兆子痫是一种严重的妊娠期疾病，其特征是新发高血压和蛋白尿，通常发生在妊娠20周后。先兆子痫对母亲和胎儿造成严重的健康风险，严重病例中唯一可用的治疗方法是分娩婴儿。这可能导致早产和早产的长期后遗症。先兆子痫被认为有遗传和环境原因，但这些原因仍然不清楚[23]。 本研究的具体目的是：1）检查妊娠中期血浆PFC浓度与先兆子痫之间的可能关联，以及2）检查妊娠中期PFC浓度与某些临床化学之间的关系，这可能阐明PFC影响妊娠生理学的机制。为了实现这些目标，这项研究建议使用现有的人口为基础的挪威母亲和儿童队列研究。该提案直接涉及国家环境健康科学研究所的目标，因为它旨在确定广泛的环境污染物是否可能导致人类疾病。了解这些持久性污染物对人类健康的影响对于负责管理全氟化学品生产和使用的决策者至关重要。

DESCRIPTION (provided by applicant): This proposal describes a training program in reproductive health and the epidemiology of adverse pregnancy outcomes, specifically preeclampsia. The proposed research project examines the plasma concentration of per fluorinated compounds in pregnant women, and the possible association between these contaminants and altered cardiovascular disease biomarkers, and the subsequent risk of preeclampsia. The project and mentoring plan described here aim to develop the applicant's ability to apply epidemiologic tools to complex obstetric and environmental problems and to integrate this research training into a future career as an independent physician-scientist. The mentorship team, composed of a reproductive and environmental epidemiologist at UNC, a physician-epidemiologist at UNC, an obstetrician-gynecologist at UNC, and a biomarker-based environmental epidemiologist at the National Institute of Environmental Health Sciences, will meet regularly to ensure the fellow's adequate progress toward her goal. Per fluorinated compounds (PFCs) are man-made chemicals that persist in the environment and in the human body. While exposure to these chemicals is widespread in the general population [1], the effect of this exposure on human health is largely unknown. Animal studies have shown a variety of health effects resulting from high-dose PFC exposure, including dyslipidemia, developmental abnormalities, and stillbirth [11]. Limited epidemiologic evidence in humans suggests that some metabolic effects may result from high-dose exposure [4, 5], but the possible consequences of PFC exposure at low levels in pregnant women are unknown. One plausible effect of elevated PFC concentration in pregnant women could be an increased risk of preeclampsia. Preeclampsia is a serious disorder of pregnancy characterized by new-onset hypertension and proteinuria, typically after 20 weeks of pregnancy. Preeclampsia poses a serious health risk to mother and fetus, and the only available treatment in severe cases is the delivery of the infant. This may lead to preterm delivery and the long-term sequel of prematurity. Preeclampsia is believed to have both genetic and environmental causes, but these causes remain obscure [23]. This specific aims of this study are: 1) to examine the possible association between mid-pregnancy plasma PFC concentrations and preeclampsia, and 2) to examine the relationship between mid-pregnancy PFC concentrations and certain clinical chemistries, which may elucidate the mechanism by which PFCs affect pregnancy physiology. To accomplish these aims, this study proposes to use the existing population-based Norwegian Mother and Child Cohort Study. This proposal directly addresses the goals of the National Institute of Environmental Health Sciences, in that it aims to identify whether a widespread environmental contaminant may contribute to human disease. Knowledge about the human health effects of these persistent pollutants is essential to decision-makers who are responsible for regulating the production and use of PFCs.