Applying and advancing modern approaches for studying the joint impacts of environmental chemicals on pregnancy outcomes

应用和推进现代方法来研究环境化学品对妊娠结局的联合影响

• 批准号: 10517508
• 负责人: John D. Meeker
• 金额: $ 60.5万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-01-01 至 2025-10-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10517508
• 关键词: 37 weeks gestation; Arachidonic Acids; Aromatic Polycyclic Hydrocarbons; Behavioral; Biological; Biological Markers; Birth; Boston; Chemical Exposure; Chemicals; Childhood; Cohort Studies; Consensus; Cytochrome P450; Data; Eicosanoids; Environmental Exposure; Environmental Impact; Exposure to; Fetal Growth; Fetal Growth Retardation; Future; Geography; Goals; Health; Individual; Infant Mortality; Intervention; Isoprostanes; Joints; Knowledge; Life; Link; Lipoxygenase; Live Birth; Low Birth Weight Infant; Measurement; Measures; Mediating; Mediation; Mediator; Metals; Methods; Modernization; Morbidity - disease rate; Outcome; Outcome Study; Oxidative Stress; Oxidative Stress Pathway; Pathway interactions; Phase; Policies; Population; Pregnancy; Pregnancy Outcome; Pregnant Women; Premature Birth; Prevalence; Prostaglandin-Endoperoxide Synthase; Public Health; Risk; Risk Factors; Risk Reduction; Role; Sampling; Societies; Source; Statistical Methods; Techniques; Testing; Therapeutic Intervention; Time; Toxicant exposure; Tyrosine; Ultrasonography; Work; adverse pregnancy outcome; economic cost; environmental agent; environmental chemical; environmental chemical exposure; health assessment; high dimensionality; human data; improved; innovation; insight; machine learning method; oxidation; phthalates; prevent; preventive intervention; remediation; reproductive; software development; specific biomarkers; statistical and machine learning; toxicant; ultrasound

Preterm birth is a significant public health challenge due to increasing rates over time, as well as serious consequences for infant mortality, childhood morbidity, and economic costs to society. Conditions that contribute to preterm birth remain unclear, though an influence by environmental chemical exposures is suspected but poorly understood. Establishing links with common environmental chemicals could have huge public health impact since many exposures could be modifiable through remediation, policies or other interventions. Low birth weight and fetal growth restriction also represent a great public health challenge, as they too have increased in recent decades and may be influenced by modifiable exposures to environmental chemicals. This project proposes to leverage the established Boston Lifecodes cohort study (N~4,000) of risk factors for preterm birth and other adverse pregnancy outcomes, with a focus on exposure to mixtures of commonly-encountered chemicals. We propose to select 1,000 singleton births from Lifecodes with detailed information and samples collected at multiple times during pregnancy. We will then utilize state-of-the-art methods to estimate biomarkers of exposure to chemical mixtures (per- and polyfluorinated substances [PFAS], phthalates and phthalate replacement chemicals, polycyclic aromatic hydrocarbons [PAH], and metals/metalloids), in addition to intermediate biomarkers of effect and repeated ultrasound measures of fetal growth, in order to provide much needed human data on environmental and other predictors of pregnancy outcomes and insights on the biological pathways involved. Results from our preliminary work show that oxidative stress may be an important link between exposure and outcome that needs to be explored in more depth using the proposed pathway-specific biomarkers. To accomplish our aims we will develop innovative statistical and machine learning approaches for analyzing mixtures and mediation with high-dimensional mediator sets, with the goal of improving our ability to discover and define these relationships. Finally, a study sub-aim is to identify conditions/activities contributing to high exposures that can inform exposure reduction strategies. The expected outcomes of this study are new and much needed information on the magnitude, sources, and impacts of exposure to commonly encountered chemicals, both individually and in combination, among pregnant women, and innovative methods for identifying relevant biological pathways and assessing health impacts from exposure to mixtures. Our findings will have a significant impact on public health given widespread exposure to the target chemicals, the growing need to identify environmental agents that adversely impact pregnancy, and the need to discover contributors to the high rates of preterm birth in the U.S. and beyond that could be prevented. Our study will also provide new information on the role of oxidative stress in adverse pregnancy outcomes which may inform future therapeutic or preventative interventions, and contribute new statistical and machine learning methods for investigating mixtures, mediation, and birth outcomes.

早产是一个重大的公共卫生挑战，因为随着时间的推移，早产率不断上升，而且 造成婴儿死亡率、儿童发病率和社会经济代价的后果。符合以下条件的条件 导致早产的原因尚不清楚，尽管环境化学物质暴露的影响是 疑似，但知之甚少。与常见的环境化学品建立联系可能会产生巨大的影响 对公共健康的影响，因为许多接触可以通过补救、政策或其他方式进行修改 干预措施。低出生体重和胎儿生长受限也是一个巨大的公共卫生挑战，因为 近几十年来，它们也有所增加，并可能受到环境暴露的影响 化学制品。该项目建议利用已建立的波士顿LIFECODES风险队列研究(N~4000) 早产和其他不良妊娠结局的因素，重点是暴露于 常见的化学物质。我们建议从LIFECODES中挑选1,000名单身新生儿，并详细说明 在怀孕期间多次收集的信息和样本。然后我们将利用最先进的技术 评估接触化学混合物(全氟物质和多氟物质)的生物标志物的方法 [全氟辛烷]、邻苯二甲酸盐和邻苯二甲酸盐替代化学品、多环芳烃[PAH]以及 金属/类金属)，除了影响的中间生物标志物和重复的胎儿超声测量 生长，以便提供急需的关于环境和其他怀孕预测因素的人类数据 关于所涉及的生物途径的结果和见解。我们的初步工作结果表明， 氧化应激可能是暴露和结果之间的重要联系，需要在更多的 使用所提出的路径特异性生物标志物的深度。为了实现我们的目标，我们将发展创新 高维混合与中介分析的统计与机器学习方法 中介者集，目的是提高我们发现和定义这些关系的能力。最后，一项研究 次要目标是确定导致高暴露的条件/活动，以便减少暴露 战略。这项研究的预期结果是关于震级的新的和迫切需要的信息， 单独或合并接触常见化学品的来源和影响， 以及确定相关生物途径和评估的创新方法 暴露在混合物中对健康的影响。我们的发现将对公众健康产生重大影响 广泛接触目标化学品，越来越需要确定对环境有害的物质 影响怀孕，以及需要发现美国早产率高的原因和 超过这一点是可以防止的。我们的研究还将提供有关氧化应激在 不良妊娠结局可能为今后的治疗性或预防性干预提供信息，并有助于 新的统计和机器学习方法，用于研究混合、调解和出生结局。