Advanced Reproductive Age and Environmental Health

描述（由申请人提供）：常见的内分泌改变（EA）环境污染物，包括双酚A（BPA）和多溴二苯醚（PBDE），可能是人类神经毒素、免疫调节剂、生殖毒物，或可能干扰生长和发育。虽然有许多动物研究，但迄今为止还没有流行病学研究调查BPA或多溴二苯醚与出生体重、妊娠期和头围等生殖结果之间的关系。我们建议招募200名高龄产妇（AMA）在一个前瞻性的怀孕队列，并组装在产前收集的产妇生物标本库。将招募有AMA适应症的女性，这些女性被转诊到西奈山医疗中心进行常规筛查穿刺术。这一独特的人群将使我们能够评估胎儿暴露于羊水中的EA化学物质。研究的目的是：1）建立一个产前生物样本库; 2）评估羊水和母亲尿液BPA浓度之间的相关性;以及在怀孕过程中母亲尿液BPA浓度的重现性; 3）评估子宫内BPA和多溴二苯醚暴露与出生结果之间的关系，包括出生体重，妊娠时间和头围。该项目将提供所需的初步数据，以衡量这些物质对生殖健康造成的风险。此外，通过比较同时收集的羊水和孕妇尿液中的BPA浓度，我们将能够评估孕妇尿液作为胎儿暴露的替代标志物的适用性，同时还提供了一个严格收集的产前标本库，可用于未来的研究。计划未来的研究包括EA化学品和并发羊膜内细胞因子浓度之间的相互作用;关键代谢酶的遗传多态性对EA化学身体负担的影响;以及EA化学水平和氧化应激生物标志物之间的关联。调查小组包括生殖流行病学和环境暴露评估方面的专家，支持这项研究的基础设施存在于社区和预防医学部。该项目将提供所需的初步数据，以确定高龄产妇产前接触6-苯甲酚和多溴联苯醚的程度，并试图确定这种接触的常见消费者来源及其对出生结果的影响。

DESCRIPTION (provided by applicant): Common endocrine altering (EA) environmental contaminants, including bisphenol A (BPA) and polybrominated diphenyl ethers (PBDEs), are possible human neurotoxins, immune modulators, reproductive toxicants, or may otherwise interfere with growth and development. Although there have been numerous animal studies, to date there have been no epidemiologic studies investigating the relationship between either BPA or PBDEs with reproductive outcomes such as birth weight, length of gestation, and head circumference. We propose to enroll 200 women of advanced maternal age (AMA) in a prospective pregnancy cohort, and to assemble a repository of maternal biological specimens collected in the antenatal period. Women with the indication of AMA, who are referred to Mount Sinai Medical Center for a routine screening amniocentesis, will be recruited. This unique population will allow us to assess fetal exposure to EA chemicals in the amniotic fluid. The study aims are to: 1) Assemble a repository of biological specimens collected in the antenatal period; 2) Evaluate the correlation between amniotic fluid and maternal urine BPA concentration; and the reproducibility of maternal urine BPA concentration over the course of pregnancy; and 3) Assess the relationships between in utero BPA and PBDE exposure and birth outcomes including birth weight, length of gestation, and head circumference. This project will provide needed preliminary data to gauge the reproductive health risks posed by these agents. Moreover, by comparing BPA concentrations in concurrently collected amniotic fluid and maternal urine, we will be able to evaluate the suitability of maternal urine as a surrogate marker of fetal exposure, while also providing a rigorously collected repository of antenatal specimens that can be drawn upon in future studies. Planned future studies include the interaction between EA chemicals and concurrent intra-amniotic cytokine concentrations; the impact of genetic polymorphisms in key metabolizing enzymes on EA chemical body burden; and the association between EA chemical levels and biomarkers of oxidative stress. The investigative team includes experts in reproductive epidemiology and environmental exposure assessment, and the infrastructure to support this study exists in the Department of Community and Preventive Medicine. This project will provide needed preliminary data to determine the level of prenatal exposure to 6/sphenol A and polybrominated diphenyl ethers experienced by women of advanced maternal age, and attempt to identify common consumer sources of this exposure and their effect on birth outcomes.