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 我们是当前环境对儿童健康结果的影响(ECHO)队列获奖者(队列 孕妇补充维生素C可减少孕期吸烟对婴儿肺的影响 功能和健康“[VCSIP])，具有上、下呼吸道结果和相关分析的专业知识 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。此应用程序是 将我们参加ECHO计划的时间再延长七年(2023年9月8日)。总目标 更新ECHO计划的目的是延长现有ECHO队列参与者的纵向跟踪 并增加新的怀孕参与者。通过将数据和数据相结合成功地建立了回声队列 来自多个母婴队列的生物样本，因此现在有来自 6万名儿童和他们的家人。这一强大且持续的数据集提供了一个巨大的机会 协作性地调查多个同时暴露于一个或多个健康后果的情况。 多种产前因素，可能对肺部发育产生不利影响，并使婴儿处于低肺状态 功能轨迹和增加肺部疾病的风险。孕妇怀孕期间吸烟(MSDP)是一个很好的- 已确定的胎儿肺发育受损、呼吸道功能下降的危险因素，以及 子代出现喘息和哮喘。我们已经证明，补充维生素C(500毫克/天)对孕妇来说 吸烟者在5岁时显著改善其子女的肺功能，并降低 喘息的发生。我们还展示了与以下相关的特定和稳定的表观遗传学变化 MSDP在与肺发育相关的途径中。这项应用的重点是宫内暴露的影响 吸烟对子代肺功能和呼吸健康的影响因宫内暴露在空气污染中而改变， 蒸发、和/或大麻以及出生后暴露的潜在调制。在具体目标1中，我们将 利用Echo Cohort协议3.0核心数据元素表征胎盘的表观遗传学特征 和与MSDP相关的后代，并检查它们相对于额外产前的相加预测值 以及产后暴露。在具体目标2中，我们将利用具有呼吸道专门化成果的回声队列 (每年 暴露 产后 肺活量测定和一年两次的呼吸问卷)，以表征胎儿和 MSDP对儿童呼吸道功能和喘息的影响，经多因素产前和 我们假设MSDP将显著影响临床呼吸结局，包括 21岁以下儿童的喘息和呼吸道功能指标。我们还假设这些影响将是 被ECHO将测量的多因素曝光所修正。考虑到我们这群人的出色记录 在具体目标3和我们的科学背景中概述的ECHO的初始阶段(2016年至今)，我们 已经做好准备，继续领导上、下呼吸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学机制。

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.