Prenatal and Early Childhood Pathways To Health:  An Integrated Model of Chemical and Social Exposures, Biological Mechanisms, and Sex-Specific Effects on Neurodevelopment and Respiratory Outcomes

产前和幼儿期健康之路：化学和社会暴露、生物机制以及对神经发育和呼吸结果的性别特异性影响的综合模型

• 批准号: 10473537
• 负责人: Nicole Renee Bush
• 金额: $ 733.63万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-21 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10473537
• 关键词: Address; Affect; Age; Air Pollutants; Air Pollution; Airway Disease; American; Anxiety; Area; Aromatic Polycyclic Hydrocarbons; Asthma; Attention deficit hyperactivity disorder; Biological; Biological Markers; Biological Specimen Banks; Birth; Blood; CRH gene; Chemical Models; Chemicals; Child; Child Health; Childhood; Chronic; Clinical; Cognition; Cohort Studies; Corticotropin-Releasing Hormone; Data; Databases; Development; Diagnosis; Diethylhexyl Phthalate; Dimensions; Disease model; Elderly; Elements; Environmental Exposure; Evaluation; Exposure to; Fetal Development; Gene Expression; Genes; Growth; Health; Hormones; Hypersensitivity; IgE; Individual; Inflammatory; Joints; Learning; Life Cycle Stages; Link; Liquid substance; Maternal Exposure; Measures; Mental Depression; Mental Health; Modeling; Morbidity - disease rate; Mothers; Neighborhoods; Nitrogen Dioxide; Obesity; Obstruction; Outcome; Oxidative Stress; Ozone; Participant; Pathway interactions; Phase; Phenotype; Pilot Projects; Placenta; Plastics; Policies; Positioning Attribute; Pregnancy; Pregnant Women; Process; Protocols documentation; Psychosocial Stress; Resolution; Resources; Sample Size; Sampling; Science; Scientific Advances and Accomplishments; Second Pregnancy Trimester; Stress; Testing; Third Pregnancy Trimester; Tissues; Urine; Wheezing; Woman; Work; ambient air pollution; biobank; brain health; cohort; critical period; data repository; disorder risk; early childhood; epidemiologic data; experience; fine particles; follow-up; health data; innovation; middle childhood; multidisciplinary; neurodevelopment; offspring; perinatal outcomes; phthalates; postnatal; prenatal; prenatal environmental exposure; prenatal exposure; programs; prospective; psychosocial; psychosocial stressors; pulmonary function; respiratory; respiratory health; sex; social; social adversity; spatiotemporal; stressor; transcriptome; transcriptome sequencing; urinary; whole genome

ABSTRACT Pregnant women are exposed daily to multiple chemical and non-chemical stressors, including air pollutants, phthalates, and psychosocial stress. The Developmental Origins of Health and Disease model (DOHaD) states that exposure to these stressors in pregnancy affects fetal development in a manner that impacts offspring health across the life course. Yet epidemiologic data in these areas is limited, particularly with U.S. samples. It is also poorly understood whether these exposures prenatally affect childhood neurodevelopment and airway health in an independent or combined manner, and likely moderators of effects, such as the sex of the child, are infrequently addressed. We propose to unify three diverse extant pregnancy cohorts—TIDES (N=717, 2010-12), GAPPS (N=1133, 2012-16), and CANDLE (N=1385, 2007-11), for a combined sample size of 3235 mother-child dyads in the PATHWAYS study. PATHWAYS will investigate how chemical (air pollutants and phthalates) and non-chemical (psychosocial stress) exposures during pregnancy are related to placental gene expression (transcriptome) and childhood neurodevelopment and airway health (at ages 4-6, 8-9, and 10-11 years). Each cohort has rich resources of prenatal data and banked specimens (urine, blood, and placenta) that will be harmonized for the PATHWAYS study and will contribute to the ECHO consortium. We will develop a national model with high spatiotemporal resolution of key air pollutants and assess urinary markers of maternal exposure. A composite measure will capture multilevel maternal psychosocial stress across pregnancy, and urinary phthalate and blood stress hormone (CRH) levels in the second and third trimesters will provide individual assessment of those exposures in potential critical periods. We will characterize the placental transcriptome using RNA sequencing and will assess neurodevelopment and airway health prospectively into middle childhood. PATHWAYS will examine how these prenatal exposures are related to the placental transcriptome and child health outcomes in main effect and interactive models, with emphasis on sex-specific associations. For both neurodevelopment and airway health, we propose to measure both phenotypic precursors of health outcomes (i.e. fluid cognition, lung function growth), which yield dimensional tests of proposed associations, as well as clinically meaningful and policy relevant outcomes (i.e. asthma, mental health). Our study is powered to assess interactive effects of chemical and non-chemical stressors and will be the first study to characterize how prenatal environmental exposures relate to placental transcriptome pathways in relation to childhood health outcomes. This represents a significant scientific advance in testing DOHaD hypotheses. Major contributions to the ECHO Consortium include: 1) the development of a state of the art national model of air pollution, 2) a large, diverse pregnancy cohort with extensive biorepositories and extant prenatal and postnatal biomarkers, placental transcriptome, psychosocial and environmental data, and 3) an experienced, interdisciplinary team that will contribute meaningfully to the ECHO program of work.

抽象的 孕妇每天暴露于多种化学和非化学应力，包括空气污染物，邻苯二甲酸酯和社会心理压力。健康和疾病模型（DOHAD）的发展起源指出，怀孕中这些压力的暴露会影响胎儿发育，以影响整个生活过程中后代健康的方式。然而，这些领域的流行病学数据受到限制，尤其是在美国样本中。它也很糟糕地了解这些暴露是否会独立或联合综合的方式影响儿童的神经发育和气道健康，并且很可能会涉及效应的主持人，例如儿童的性别。我们建议在途径研究中统一三个潜水员的妊娠队列，即（n = 717，2010-12），GAPP（n = 1133，2012-16）和蜡烛（n = 1385，2007-11），用于途径研究中的3235个母亲二元组的组合组合。途径将调查怀孕期间的化学（空气污染物和邻苯二甲酸盐）和非化学（心理社会应激）暴露与占地基因表达（转录组）以及儿童神经发育和气道健康（4-6、8-9和10-11岁）有关。每个队列都有丰富的产前数据和库存标本（尿，血液和胎盘）的资源，这些标本将在途径研究中进行协调，并将为回声财团做出贡献。我们将开发一个国家模型，其主要空间污染物的空间时间分辨率和孕产妇暴露的评估标志物。综合测量将捕获整个怀孕的多级孕产妇社会心理压力，第二和第三个三个诊断者中的邻苯二甲酸酯和血液应激水平（CRH）水平将在潜在的关键时期内对这些暴露进行个人评估。我们将使用RNA测序表征位置转录组，并将神经发育和气道健康前瞻性地评估到中期。途径将检查这些产前暴露与主要效果和交互模型中的斑点转录组和儿童健康结果有关，重点是性别特定的关联。对于神经发育和气道健康，我们建议衡量健康结果的表型前体（即流体认知，肺功能生长），该前体产生了拟议关联的维度测试，以及临床意义和政策相关的结果（即哮喘，心理健康）。我们的研究旨在评估化学和非化学应激源的交互作用，并将成为第一个表征产前环境暴露与胎盘转录组与儿童健康结果有关的研究。这代表了测试DOHAD假设的显着科学进步。对回声联盟的主要贡献包括：1）发展国家风污污染的状态，2）一个大型，多样化的怀孕群体，具有广泛的生物疗法，以及广泛的产前和产后生物标志物，胎盘后trapentum转录组，心理社会和环境数据，以及经验，经验，一项互助的工作。

项目成果

Sleep-related items on the school-age CBCL and the PROMIS sleep disturbance 4-item short-form: A psychometric comparison from the Environmental Influences on Child Health Outcomes (ECHO) program.

学龄 CBCL 和 PROMIS 睡眠障碍 4 项简表中的睡眠相关项目：来自环境对儿童健康结果 (ECHO) 计划的心理测量比较。

• DOI: 10.1037/pas0001220
• 发表时间: 2023
• 期刊: Psychological assessment
• 影响因子: 3.6
• 作者: Mansolf,Maxwell;Blackwell,CourtneyK
• 通讯作者: Blackwell,CourtneyK

Associations of Dietary Intake with Urinary Melamine and Derivative Concentrations among Children in the GAPPS Cohort.

• DOI: 10.3390/ijerph19094964
• 发表时间: 2022-04-19
• 期刊: INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH
• 作者: Melough, Melissa M.;Day, Drew B.;Fretts, Amanda M.;Wang, Sarah;Flynn, Joseph T.;de Boer, Ian H.;Zhu, Hongkai;Kannan, Kurunthachalam;Sathyanarayana, Sheela
• 通讯作者: Sathyanarayana, Sheela

Long-term ozone exposure and lung function in middle childhood.

长期臭氧暴露与儿童中期的肺功能。

• DOI: 10.1016/j.envres.2023.117632
• 发表时间: 2024
• 期刊: Environmental research
• 影响因子: 8.3
• 作者: Hazlehurst,MarnieF;Dearborn,LoganC;Sherris,AllisonR;Loftus,ChristineT;Adgent,MargaretA;Szpiro,AdamA;Ni,Yu;Day,DrewB;Kaufman,JoelD;Thakur,Neeta;Wright,RosalindJ;Sathyanarayana,Sheela;Carroll,KeciaN;Moore,PaulE;Karr,C
• 通讯作者: Karr,C