Continued follow-up of the Vitamin C and Smoking in Pregnancy (VCSIP) cohorts through the ECHO consortium, focus on Echo-wide protocols, respiratory outcomes, airway function, and epigenetic changes

通过 ECHO 联盟继续跟踪维生素 C 和妊娠期吸烟 (VCSIP) 队列，重点关注 Echo 范围内的方案、呼吸结果、气道功能和表观遗传变化

• 批准号: 10743723
• 负责人: Cynthia T McEvoy
• 金额: $ 118.08万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 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 2025-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10743723
• 关键词: 21 year old; 5 year old; Adult; Affect; Air Pollution; Airway Disease; American; Antismoking; Area; Ascorbic Acid; Asthma; Biological Markers; Birth; Cannabis; Child; Child Health; Childhood; Clinical; Collaborations; Conceptions; Consent; DNA Methylation; Data; Data Element; Data Set; Development; Elderly; Environmental Exposure; Epigenetic Process; Exposure to; Family; Fetal Lung; Genetic; Goals; Habits; Health; Health Care Costs; Impairment; Inequity; Infant; Investigation; Lead; Life; Link; Longitudinal Studies; Lung diseases; Measures; Mediating; Medical; Mothers; Nasal Epithelium; Outcome; Outcome Study; Participant; Pathway interactions; Phase; Placenta; Population Heterogeneity; Predictive Value; Pregnancy; Protocols documentation; Proxy; Questionnaires; Respiratory Disease; Respiratory physiology; Risk; Risk Factors; Smoking; Specificity; Spirometry; Supplementation; Time; Tobacco use; Wheezing; Woman; cohort; comorbidity; data harmonization; emerging adult; fetal; follow-up; improved; lung development; lung health; marijuana use; marijuana use in pregnancy; maternal cigarette smoking; maternal vaping; medical specialties; methylation biomarker; neglect; novel; offspring; postnatal; postnatal period; pregnant; prenatal; prenatal cigarette smoking; prenatal exposure; programs; pulmonary function; respiratory; respiratory health; respiratory morbidity; smoking during pregnancy; social; success; synergism; vaping

Project Summary We are a current Environmental influences on Children's Health Outcomes (ECHO) Cohort awardee (Cohort Identifier “Maternal Vitamin C Supplementation to Decrease Effects of Smoking during Pregnancy on Infant Lung Function and Health” [VCSIP]) with expertise in upper and lower airway outcomes and analysis of associated epigenetic mechanisms. We have been part of the ECHO cohort since its inception in 2016. This application is to renew our participation in the ECHO Program for an additional seven years (9/2023-8/2030). The overall goal of this renewal of the ECHO program is to extend the longitudinal follow-up of existing ECHO Cohort participants and add new pregnant participants. The ECHO Cohort was successfully established by combining data and biospecimens from multiple maternal-child cohorts such that there is now data and biospecimens from up to 60,000 children and their families. This robust and ongoing data set offers a tremendous opportunity to collaboratively investigate multiple simultaneous exposures on one or more health outcomes. Multiple prenatal factors that can adversely affect lung development and place an infant on a lower lung function trajectory and increase risk of lung disease. Maternal smoking during pregnancy (MSDP) is a well- established risk factor for impaired fetal lung development, decreased airway function, and an increased risk for wheeze and asthma in the offspring. We have shown that supplemental vitamin C (500 mg/day) to pregnant cigarette smokers significantly improves their offspring's lung function through 5 years of age and decreases the occurrence of wheeze. We have also demonstrated specific and stable epigenetic changes associated with MSDP in pathways linked to lung development. The focus of this application are the effects of in utero exposure to smoking on offspring lung function and respiratory health as modified by in utero exposure to air pollution, vaping, and/or cannabis as well as the potential modulation by postnatal exposures. In specific aim 1, we will leverage ECHO Cohort Protocol 3.0 core data elements to characterize the epigenetic signatures in placenta and offspring associated with MSDP, and examine their additive predictive value relative to additional prenatal and postnatal exposures. In specific aim 2, we will leverage ECHO cohorts with airway-specialized outcomes (yearly exposure postnatal spirometry and twice-yearly respiratory questionnaires) to characterize the relationships between fetal to MSDP on airway function and wheeze during childhood as modified by multi-factorial prenatal and exposures.We hypothesize that MSDP will significantly affect clinical respiratory outcomes including wheeze and airway function trajectories up to 21 years of age. We also hypothesize that these effects will be modified by the multi-factorial exposures that ECHO will be measuring. Given our cohort's excellent track record during the initial phase of ECHO (2016-present) as outlined in specific aim 3 and our scientific background, we are well poised to continue to lead scientific investigations in the area of upper and lower airway outcomes and epigenetic mechanisms associated with these outcomes in the renewal phase of the ECHO.

项目概要 我们是当前环境对儿童健康结果 (ECHO) 队列获奖者（队列 标识符“母亲补充维生素 C 可减少怀孕期间吸烟对婴儿肺部的影响” 功能与健康”[VCSIP]），具有上、下呼吸道结果和相关分析的专业知识 自 2016 年成立以来，我们一直是 ECHO 队列的一部分。该应用程序是 将我们对 ECHO 计划的参与再延长七年（9/2023-8/2030） 总体目标。 ECHO 计划更新的目的是延长现有 ECHO 队列参与者的纵向随访 通过结合数据和添加新的怀孕参与者，成功建立了 ECHO 队列。 来自多个母婴队列的生物样本，因此现在有来自多达 这个强大且持续的数据集为 60,000 名儿童及其家庭提供了巨大的机会。 合作研究多种同时暴露对一种或多种健康结果的影响。 多种产前因素可能对肺部发育产生不利影响并使婴儿处于下肺 怀孕期间吸烟（MSDP）是一个很好的因素。 已确定胎儿肺发育受损、气道功能下降以及胎儿风险增加的危险因素 我们已经证明，怀孕期间补充维生素 C（500 毫克/天）会导致后代出现喘息和哮喘。 吸烟者可显着改善其后代 5 岁时的肺功能，并降低 我们还证明了与喘息相关的特定且稳定的表观遗传变化。 MSDP 在与肺部发育相关的途径中的作用 该应用的重点是子宫内暴露的影响。 吸烟对后代肺功能和呼吸系统健康的影响（因子宫内暴露于空气污染而改变） 在具体目标 1 中，我们将考虑电子烟和/或大麻以及产后暴露的潜在调节。 利用 ECHO Cohort Protocol 3.0 核心数据元素来表征胎盘中的表观遗传特征 以及与 MSDP 相关的后代，并检查其相对于额外产前的附加预测价值 在具体目标 2 中，我们将利用具有气道专门结果的 ECHO 队列。 （每年 接触 产后 肺活量测定和每年两次的呼吸问卷）来表征胎儿之间的关系 MSDP 对儿童时期气道功能和喘息的影响经多因素产前和 我们认为 MSDP 将显着影响临床呼吸系统结果，包括 我们还发现，直到 21 岁，喘息和气道功能轨迹都会受到这些影响。 考虑到我们队列的出色记录，ECHO 将测量多因素暴露情况。 在 ECHO 的初始阶段（2016 年至今），如具体目标 3 和我们的科学背景所述，我们 已做好准备继续领导上呼吸道和下呼吸道结果领域的科学研究， 在 ECHO 更新阶段与这些结果相关的表观遗传机制。