VCSIP2: CCC - Lead Application

项目摘要/摘要 孕妇吸烟者补充维生素C(500毫克/天)对婴儿有益的结局是 由我们强大的动物模型预审证据和令人信服的人类飞行员数据支持。这一证据 作为我们目前的多中心双盲随机试验的基础 孕期吸烟对婴儿肺功能的影响“(VCSIP；NCT01723696)。招聘工作完成时间为 252名怀孕的吸烟者随机接受维生素C或安慰剂治疗。VCSIP的主要和次要 结果分别是3个月大婴儿的肺功能测试(PFT)，以及PFT和 12个月龄时发生喘息。此申请是VCSIP试验的续订，继续如下 5岁以下的母亲及其子女。时间是关键的，因为研究人群主要是 资源不足使融洽关系对队列保留至关重要，这需要人员和时间。 这项更新建议的目的是确定产前补充维生素C是否可以改善 在吸烟者的后代中，5岁以后，肺功能和减少反复喘息。我们的 假设孕期吸烟者补充维生素C将显著改善其子女的 改善肺功能，减少反复喘息。这是VCSIP试验的逻辑延续，因为 短暂性和复发性喘息直到5岁才能在临床上区分开来。跟随婴儿从 直到5岁的VCSIP：将区分一过性喘息和复发喘息(更有可能是 哮喘的预测指标)；将决定维生素C的早期生命保护作用是否持续到这个较老的年龄； 并将为来自儿童的连续生物样本提供结构，用于未来的机制研究 维生素C的作用。所有研究人员、临床工作人员和参与者将对治疗分配保持盲目。我们 目前正在完成初步结果，根据我们将有的随机吸烟者数量 随机选择3个月大的婴儿进行足够数量的肺功能测量 吸烟者要达到本次分析的预定样本量。VCSIP的第一批婴儿年满1岁 2014年5月；因此，现在提交这项提案，在分析 VCSIP研究，以最大限度地减少在这一宝贵队列的后续行动中的差距。孩子们将被跟随着 每季度一次的呼吸道调查问卷和每年一次的访问，收集以下样本：母婴头发 尼古丁；儿童口腔拭子；母亲呼出的一氧化碳；3、4和5岁时的肺功能测试 几年前。这一竞争性更新将使我们能够研究我们干预的长期结果 维生素C与儿童肺功能和反复喘息的发生 几年前。它还将使我们能够跟踪这一独特的、广泛表型的出生于 将孕妇吸烟者提高到5岁，以解决与母亲吸烟和 儿童呼吸系统健康/喘息/哮喘。

Project Summary/Abstract The beneficial infant outcomes of maternal vitamin C supplementation (500 mg/day) in pregnant smokers is supported by our robust pre-trial evidence in animal models and convincing human pilot data. This evidence served as the basis for our current multi-center double blind randomized trial “Vitamin C to Decrease Effects of Smoking in Pregnancy on Infant Lung Function” (VCSIP; NCT01723696). Recruitment is completed as scheduled with 252 pregnant smokers randomized to vitamin C or placebo. VCSIP's primary and secondary outcomes, respectively, are pulmonary function testing (PFT) of infants at 3 months of age, and PFTs and the incidence of wheeze at 12 months of age. This application is a renewal for the VCSIP trial to continue following mothers and their offspring through 5 years of age. Time is critical, as the study population is predominantly under-resourced making rapport crucial to cohort retention, which requires personnel and time. The aim of this renewal proposal is to determine whether prenatal supplementation with vitamin C can improve pulmonary function and decrease recurrent wheeze through 5 years of age in the offspring of smokers. Our hypothesis is that supplemental vitamin C in pregnant smokers will significantly improve their children's pulmonary function and decrease recurrent wheeze. This is a logical continuation for the VCSIP trial as transient versus recurrent wheeze are not clinical distinguishable until 5 years of age. Following infants from the VCSIP until age 5 years: will differentiate patients with transient versus recurrent wheeze (a more likely predictor of asthma); will determine if early life protective effects of vitamin C are sustained to this older age; and will provide structure for continued biologic samples from the children for future mechanistic studies of vitamin C action. All investigators, clinical staff and participants will remain blinded to treatment allocation. We are currently completing the primary outcome, and based on the number of randomized smokers we will have a sufficient number of pulmonary function measurements at 3 months of age in the infants of randomized smokers to meet the predetermined sample size for this analysis. The first infants of VCSIP turned 1 year old in May 2014; therefore this proposal is being submitted now, prior to the analysis of the primary outcome of the VCSIP study, to minimize gaps in the follow-up of this valuable cohort. The children will be followed with quarterly respiratory questionnaires and yearly visits, collecting the following samples: maternal and child hair for nicotine; child buccal swabs; maternal exhaled carbon monoxide; pulmonary function tests at 3, 4,and 5 years of age. This competitive renewal will allow us to study the longer term outcome of our intervention with vitamin C with regards to childhood pulmonary function and the occurrence of recurrent wheeze through 5 years of age. It will also allow us to follow this unique, extensively phenotyped cohort of children born to pregnant smokers to 5 years of age to address important scientific questions related to maternal smoking and childhood respiratory health/wheeze/asthma.