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: 10323275
• 负责人: John D. Meeker
• 金额: $ 61.78万
• 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/10323275
• 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 of activation protein; 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; 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.

自早产是由于随着时间的推移增加的速度而引起的重大公共卫生挑战，而且严重 婴儿死亡率，儿童发病率和社会经济成本的后果。条件 尽管环境化学暴露的影响是 怀疑但知之甚少。与通用环境化学品建立联系可能具有巨大 公共卫生影响，因为许多暴露可以通过补救，政策或其他情况进行修改 干预措施。低出生体重和胎儿生长限制也代表了一个巨大的公共卫生挑战，因为 他们最近几十年也有所增加，可能会受到环境的可修改暴露的影响 化学物质。该项目提议利用既定的波士顿生命码队列研究（N〜4,000）风险 早产和其他不良怀孕结果的因素，重点是暴露于 通常遇到的化学物质。我们建议从生命模型中选择1,000个单身人士的出生 怀孕期间多次收集的信息和样品。然后，我们将利用最先进的 估计暴露于化学混合物的生物标志物（每个氟化物质和多氟化物质） [PFA]，邻苯二甲酸盐和邻苯二甲酸盐替代化学物质，多环芳烃[PAH]和 金属/金属），除了效应的中间生物标志物和胎儿重复的超声测量 增长，为了提供急需的人类有关怀孕的环境和其他预测指标的数据 对所涉及的生物途径的结果和见解。我们的初步工作的结果表明 氧化应激可能是暴露与结果之间的重要联系，需要更多地探索 使用拟议的途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 统计和机器学习方法，用于分析混合物和高维的混合物和调解 调解员设置，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 Sub-aim是确定有助于高暴露的条件/活动，以减少暴露 策略。这项研究的预期结果是有关大小的新的急需信息， 来源，以及暴露于单独和结合的常见化学物质的影响， 在孕妇中，以及确定相关生物学途径和评估的创新方法 健康对混合物的影响会影响。我们的发现将对公共卫生产生重大影响 广泛暴露于目标化学物质，越来越需要确定不利的环境药物 影响怀孕，并需要发现美国早产率高的贡献者和 除此之外，还可以避免。我们的研究还将提供有关氧化应激中作用的新信息 不良怀孕结果可能为未来的治疗或预防性干预提供依据，并做出贡献 用于研究混合物，调解和出生结果的新统计和机器学习方法。