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

项目摘要 我们是目前环境对儿童健康结果的影响（ECHO）队列获奖者（队列 标识符“母亲补充维生素C，以减少怀孕期间吸烟对婴儿肺部的影响 功能和健康”[VCSIP]），具有上气道和下气道结局的专业知识， 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。本申请是 将我们参与ECHO计划的时间延长七年（9/2023-8/2030）。总目标 ECHO计划更新的目的是延长现有ECHO队列参与者的纵向随访 并添加新的怀孕参与者。ECHO队列研究通过结合数据和 来自多个母婴队列的生物标本，因此现在有多达 6万名儿童和他们的家人这一强大而持续的数据集提供了一个巨大的机会， 合作调查多重同时暴露对一个或多个健康结果的影响。 多种产前因素可能对肺发育产生不利影响，并使婴儿位于下肺 功能轨迹和增加肺部疾病的风险。怀孕期间吸烟（MSDP）是一个很好的... 胎儿肺发育受损、气道功能下降和 哮喘和气喘的症状我们已经证明，补充维生素C（500毫克/天），以怀孕 吸烟者在5岁时显著改善了其后代的肺功能， 出现喘息。我们还证明了与以下疾病相关的特异性和稳定的表观遗传变化： 与肺发育相关的途径中的MSDP。本申请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， 电子烟和/或大麻以及产后暴露的潜在调节。具体目标1： 利用ECHO队列方案3.0核心数据元素来表征胎盘中的表观遗传特征 和后代与MSDP相关，并检查其相对于额外的产前预测值 和产后暴露。在具体目标2中，我们将利用具有气道专门结局的ECHO队列 （每年） 暴露 产后 肺功能测定和每年两次的呼吸问卷调查），以描述胎儿之间的关系， 根据多因素产前调整的儿童期气道功能和喘息的MSDP， 我们假设MSDP将显著影响临床呼吸结果，包括 哮喘和气道功能轨迹长达21岁。我们还假设，这些影响将是 通过ECHO将测量的多因素暴露进行修改。考虑到我们这群人的优秀记录 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 准备好继续领导上下气道结果领域的科学研究， 在ECHO的更新阶段与这些结果相关的表观遗传机制。

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.