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.

项目摘要 我们是当前对儿童健康成果（ECHO）队列奖的环境影响（队列 识别剂“补充母体维生素C，以减少妊娠期吸烟对婴儿肺的影响 功能和健康” [VCSIP]）具有上下气道结果的专业知识，并分析相关的 表观遗传机制。自2016年成立以来，我们一直是Echo队列的一部分。此申请是 为了续签我们参与Echo计划的另外七年（9/2023-8/2030）。总体目标 回声计划的续约是扩展现有Echo队列参与者的纵向随访 并添加新的怀孕参与者。回声队列是通过组合数据和 来自多个母子队列的生物测量，以便现在有数据和生物测量。 60,000名儿童及其家人。这个强大而持续的数据集为 协作对一个或多个健康结果进行多次简单暴露。 多种产前因素会对肺发育产生不利影响并将婴儿放在下肺上 功能轨迹并增加肺部疾病的风险。怀孕期间的孕产妇吸烟（MSDP）是一个很好的 胎儿肺发育受损，气道功能降低以及增加风险的危险因素 后代的鞭打和哮喘。我们已经表明，孕妇补充维生素C（500 mg/天） 吸烟者在5岁时显着改善了后代的肺功能，并降低了 喘息的发生。我们还展示了与 与肺发育有关的途径中的MSDP。该应用的重点是子宫暴露的影响 在子宫暴露于空气污染中所修饰的后代肺功能和呼吸健康的吸烟， 蒸发和/或大麻以及产后暴露的潜在调节。在特定目标1中，我们将 利用回声队列协议3.0核心数据元素以表征plapeta中的表观遗传特征 和与MSDP相关的后代，并检查其相对于其他产前的添加性预测价值 和产后暴露。在特定的目标2中，我们将利用Echo COHORTS和AIRWAY PECTECIALIZED结果 （每年 接触 产后 肺活量测定法和每年两次呼吸问卷）表征胎儿之间的关系 通过多因素产前和 我们假设MSDP将显着影响 Wheeleze和气道功能轨迹长达21岁。我们还假设这些影响将是 通过回声将测量的多因素暴露进行修改。鉴于我们队列的出色记录 在Echo的初始阶段（2016年至今）中，如特定的AIM 3和我们的科学背景所述，我们 有毒的毒品继续领导上下气道结果领域的科学研究 与这些结果相关的表观遗传机制在回声的更新阶段。