VCSIP2: CCC - Lead Application

项目总结/摘要 孕妇吸烟者补充维生素C（500 mg/天）对婴儿的有益结果是 我们在动物模型和令人信服的人类飞行员数据中获得了强大的试验前证据。这一证据 作为我们目前多中心双盲随机试验的基础， 妊娠期吸烟对婴儿肺功能的影响”（VCSIP; NCT 01723696）。招聘已完成， 252名孕妇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个月龄婴儿的肺功能测试（PFT），PFT和 12个月龄时喘息的发生率。本申请是VCSIP试验的延续， 母亲和5岁以下的孩子。时间至关重要，因为研究人群主要是 由于资源不足，因此融洽关系对留住学员至关重要，这需要人员和时间。 这项更新提案的目的是确定产前补充维生素C是否能改善 肺功能，并减少吸烟者后代在5岁时的反复喘息。我们 一种假设是，怀孕吸烟者补充维生素C将显着改善其子女的 肺功能和减少反复喘息。这是VCSIP试验的合理延续， 在5岁之前，暂时性喘息与复发性喘息在临床上是无法区分的。婴儿从 VCSIP直到5岁：将区分短暂性喘息与复发性喘息的患者（更可能是 预测哮喘）;将确定维生素C的早期生命保护作用是否持续到这个年龄; 并将为儿童的持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。所有研究者、临床工作人员和受试者将对治疗分配保持盲态。我们 目前正在完成主要结局，根据随机吸烟者的数量， 在3个月大的婴儿中进行足够数量的肺功能测量， 吸烟者以满足本分析的预定样本量。VCSIP的第一批婴儿满1岁 2014年5月;因此，在分析2014年5月的主要成果之前， VCSIP研究，以最大限度地减少这一有价值队列的随访差距。孩子们将被跟踪 每季度进行一次呼吸问卷调查，每年进行一次访问，收集以下样本： 尼古丁;儿童口腔拭子;母亲呼出的一氧化碳; 3、4和5时的肺功能测试 岁的这种竞争性的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5岁以下反复喘息发生率的关系 岁的它还将使我们能够跟踪这个独特的，广泛的表型队列的儿童出生， 5岁以下的孕妇吸烟者，以解决与母亲吸烟有关的重要科学问题， 儿童呼吸道健康/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.