Revealing environmental chemical exposome in a diverse prenatal population and relationships to maternal and perinatal health (REVEAL)

揭示不同产前人群的环境化学暴露及其与孕产妇和围产期健康的关系 (REVEAL)

• 批准号: 10587408
• 负责人: Tracey J. Woodruff
• 金额: $ 59.41万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-30 至 2028-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10587408
• 关键词: Acceleration; Address; Affect; Analytical Chemistry; Binding; Biological; Biological Markers; Biological Monitoring; Birth Weight; Blood; Blood specimen; Chemical Exposure; Chemicals; Complex; Computational Technique; Computer software; Computing Methodologies; Concentration measurement; Data; Data Analyses; Databases; Development; Disease; Environmental Exposure; Evaluation; Exposure to; Gestational Age; Gestational Diabetes; Goals; Health; Human; Late pregnancy; Left; Link; Low Birth Weight Infant; Mass Spectrum Analysis; Maternal Health; Measurement; Measures; Methods; Modeling; Newborn Infant; Outcome; Output; Participant; Pathway interactions; Pattern; Persons; Phenotype; Plastics; Poly-fluoroalkyl substances; Population; Population Heterogeneity; Predisposition; Pregnancy; Pregnancy Outcome; Pregnancy Trimesters; Premature Birth; Prevalence; Production; Regulation; Research; Resolution; Risk; Rubber; Sampling; Second Pregnancy Trimester; Serum; Shotguns; Siloxanes; Software Tools; Source; Stains; Supercomputing; Techniques; Technology; Third Pregnancy Trimester; advanced analytics; adverse maternal outcomes; adverse pregnancy outcome; analytical method; analytical tool; chemical group; computerized tools; dashboard; data integration; data tools; environmental chemical; fetal; improved; lipid metabolism; machine learning algorithm; maternal serum; metabolome; novel; novel strategies; open source; perinatal health; perinatal outcomes; personal care products; pregnant; prenatal; prenatal exposure; prevent; public health intervention; study population; surfactant

ABSTRACT - Revealing environmental chemical exposome in a diverse prenatal population and relationships to maternal and perinatal health (REVEAL) Our renewal application builds on our original R01 by advancing analytical chemistry and computational techniques to characterize more fully the prenatal chemical exposome and its links to adverse maternal and perinatal health outcomes (e.g., gestational diabetes, preterm birth, and low birthweight). Prevalence of these outcomes has increased and is linked to chemical exposures in the US population. Prenatal exposures to a broad range of environmental chemicals, including plastic related chemicals and per- and polyfluoroalkyl substances (PFAS), have been shown to adversely affect health, but technological challenges have left significant data gaps hindering our ability to characterize environmental exposures and drivers of disease. Over 350,000 chemicals and compound mixtures are registered for production worldwide, and thousands of high–production volume chemicals are used extensively in the US, yet human biomonitoring capacity covers a very small fraction of the chemical exposome. In our previous R01 we pioneered a nontargeted analysis (NTA) workflow, with significantly improved computational and analytical methods using high-resolution mass spectrometry (HRMS) in a demographically diverse population of maternal-newborn pairs. We were the first to identify multiple chemicals in maternal and newborn sample used in high volumes in the US not previously detected in human blood samples including chemicals used in personal care products and fragrances, production of plastics, surfactants, and stain treatment. We also identified over 50 novel chemicals with limited to no information on their uses or sources and found significant associations between exogenous and endogenous compounds, several chemical groups (siloxanes, PFAS, and chemicals used in plastics and rubber) and biomarkers of lipid metabolism and regulation, supporting a link to gestational diabetes. For our renewal project, we propose to expand our study population by analyzing an additional 750 2nd trimester pregnancy samples, 300 of the samples matched to our original 3rd trimester samples. We will contribute to improved understanding of the prenatal chemical exposome by integrating NTA with improved computational methods including a chemical suspect database ~1,000,000 exogenous and endogenous chemical features in combination with upgraded software for supercomputing to identify ~500 chemical prenatal exposures and estimate their concentrations using new machine learning algorithms. We will use this data to characterize complex relationships between multiple exogenous chemical exposures, endogenous effect biomarkers, and maternal and perinatal health outcomes. The overarching goal of this renewal is to develop an integrated package of analytic and computational tools that allow expanded capacity to identify and calculate chemical concentrations and their link to adverse maternal and pregnancy outcomes, critical to information public health interventions to prevent harmful chemical exposures.

摘要 - 揭示潜水产前人群中的环境化学杂物体和 与母校和围产期健康的关系（揭示） 我们的续签应用是通过推进分析化学和计算的原始R01建立的 更全面地表征产前化学杂志及其与Mater的链接的技术 围产期健康结果（例如妊娠糖尿病，早产和低出生体重）。这些流行 结果有所增加，并与美国人口的化学暴露有关。产前暴露于 广泛的环境化学物质，包括相关化学品以及每个氟烷基和多氟烷基 已经证明物质（PFA）会对健康产生不利影响，但剩下的技术挑战 严重的数据差距阻碍了我们表征环境暴露和疾病驱动因素的能力。 全球生产的350,000多种化学品和复合混合物已注册，成千上万 在美国广泛使用了高生产量化学品，但是人类的生物监测能力涵盖了A 化学杂志的一小部分。在以前的R01中，我们开创了非目标分析（NTA） 工作流程，使用高分辨率质量可显着改善计算和分析方法 在人口统计学上多样化的母体纽文出生对中的光谱法（HRMS）。我们是第一个 识别在美国大容量中使用的孕产妇和新生儿样品中的多种化学物质 在人类血液样本中检测到，包括用于个人护理产品和香水中的化学物质， 产生塑料，表面活性剂和污渍治疗。我们还确定了50多种新型化学物质，有限 没有有关其用途或来源的信息，发现外源与 内源性化合物，几个化学基（塑料中使用的硅氧烷，PFA和化学物质， 橡胶）和脂质代谢和调节的生物标志物，支持与妊娠糖尿病的联系。为我们 更新项目，我们建议通过分析另外750个孕期扩大研究人群 怀孕样本，300个样品与我们最初的三个月样品相匹配。我们将为 通过将NTA与改进的计算相结合，可以提高对产前化学杂志的理解 包括化学可疑数据库在内的方法〜1,000,000个外源性和内生化学特征 结合升级的软件，用于识别〜500个化学产前暴露和 使用新的机器学习算法来估计其浓度。我们将使用这些数据来表征 多种外源化学暴露，内源性效应生物标志物和 孕产妇和围产期健康结果。这种更新的总体目标是开发一个集成的 分析和计算工具包，允许扩展的能力识别和计算化学 集中度及其与母亲和怀孕成果道歉的联系，对信息公共卫生至关重要 防止有害化学暴露的干预措施。

项目成果

Gaussian graphical modeling of the serum exposome and metabolome reveals interactions between environmental chemicals and endogenous metabolites.

• DOI: 10.1038/s41598-021-87070-9
• 发表时间: 2021-04-07
• 期刊: Scientific reports
• 影响因子: 4.6
• 作者: Bessonneau V;Gerona RR;Trowbridge J;Grashow R;Lin T;Buren H;Morello-Frosch R;Rudel RA
• 通讯作者: Rudel RA

Translating community-based participatory research into broadscale sociopolitical change: insights from a coalition of women firefighters, scientists, and environmental health advocates.

• DOI: 10.1186/s12940-023-01005-7
• 发表时间: 2023-08-30
• 期刊: ENVIRONMENTAL HEALTH
• 影响因子: 6
• 作者: Ohayon, Jennifer Liss;Rasanayagam, Sharima;Rudel, Ruthann A.;Patton, Sharyle;Buren, Heather;Stefani, Tony;Trowbridge, Jessica;Clarity, Cassidy;Brody, Julia Green;Morello-Frosch, Rachel
• 通讯作者: Morello-Frosch, Rachel