Randomized Controlled Trial: VDAART Continuation Study - CCC

描述（由申请人提供）：哮喘是儿童发病的主要原因之一，大多数病例在儿童早期诊断， 每年的医疗费用。因此，找到可以导致预防这种疾病的因素将具有重大的公共卫生意义。维生素D缺乏症在孕妇中非常普遍，因此是预防疾病的一个潜在的可改变因素。由于维生素D在子宫内对肺和免疫系统发育的影响，我们认为孕妇缺乏维生素D会导致儿童早期发生哮喘和过敏的风险增加。流行病学研究调查了维生素D在生命早期以及哮喘、喘息和过敏发生中的作用，结果不一致。由于维生素D缺乏症的广泛流行，临床试验是唯一能自信地回答怀孕期间较高的维生素D水平是否能预防母亲后代哮喘和过敏的方法。在过去的4年里，我们一直在进行一项关于孕妇补充维生素D的随机、安慰剂对照试验，我们现在正在跟踪儿童（ClinicalTrials.gov标识符：NCT 00920621）。我们招募了881名妇女，并将她们随机分为两组：每天4,000 IU维生素D3加含有400 IU维生素D3的产前维生素与安慰剂加含有400 IU维生素D3的产前维生素。我们对她们进行了整个妊娠期的随访，共有810例活产，其中801例目前正在随访中。目前项目的目标是跟踪儿童到6岁。更新VDAART的具体目标是：（1）确定母亲在怀孕期间补充维生素D是否与儿童在生命最初6年内哮喘发病率的降低有关;（2）确定母亲补充维生素D是否与儿童在生命最初6年内哮喘发病率的降低有关。 妊娠期间维生素D与以下儿童次要结局减少相关：（a）过敏性致敏（总IgE和特异性IgE），（B）医生诊断的湿疹，（c）医生诊断的过敏性鼻炎，（d）食物过敏和（e）6岁时的下呼吸道感染;（3）确定母亲在怀孕期间补充维生素D是否与6岁以下儿童的肺生长有关，如通过脉冲肺量计和肺量计测量的;（4）继续从儿童身上收集生物材料， 与哮喘和过敏症中维生素D相关的机制研究，包括用于基因组和表观基因组研究以及微生物组研究的标本。这项重要研究的结果将对预防儿童哮喘和过敏症具有重大的公共卫生意义。

DESCRIPTION (provided by applicant): Asthma is one of the leading causes of morbidity in children with the majority of all cases diagnosed in early childhood and over 56 billion dollars in health costs annually. Thus, finding factors that can lead to prevention of this disease would be of great public health importance. Vitamin D deficiency is highly prevalent among pregnant women, and thus, represents a potentially modifiable factor for the prevention of disease. Due to the effect of vitamin D in the development of the lung and the immune system in utero, we believe that vitamin D deficiency in pregnant mothers leads to increased risks for developing asthma and allergy in early childhood. Epidemiologic studies that have investigated the role of vitamin D in early life and the development of asthma, wheeze and allergy have inconsistent results. Because of the wide prevalence of vitamin D deficiency, a clinical trial is the only way t confidently answer the question of whether higher vitamin D levels in pregnancy can prevent asthma and allergies in the mother's offspring. Over the past 4 years, we have been conducting a randomized, placebo-controlled trial of maternal vitamin D supplementation in pregnancy, and we are now following the children (ClinicalTrials.gov Identifier: NCT00920621). We recruited 881 women, and randomized them to one of two arms: 4,000 IU vitamin D3 daily plus a prenatal vitamin containing 400 IU vitamin D3 vs. a placebo plus a prenatal vitamin containing 400 IU vitamin D3. We followed them through pregnancy and there were 810 live births with 801 currently under follow-up. The goal of the current project is to follow the children through age 6 years. The specific aims for the renewal of VDAART are: (1) to determine whether maternal supplementation of vitamin D during pregnancy is associated with reduced incidence of asthma in the child during the first 6 years of life; (2) to determine whether maternal supplementation of vitamin D during pregnancy is associated with reduced secondary outcomes in the child of: (a) allergic sensitization (total and specific IgE), (b) doctor's diagnosis of eczema, (c) doctor's diagnosis of allergic rhinitis, (d) food allergies and (e) lower respiratory tract infections by ag 6 years; (3) to determine whether maternal supplementation of vitamin D during pregnancy is associated with greater lung growth in the children up to age 6, as measured by impulse oscillometry and spirometry; and (4) to continue to collect biologic material from the children for mechanistic studies related to vitamin D in asthma and allergies, including specimens for genomic and epigenomic studies and microbiome studies. Findings from this important study will have great public health importance in the prevention of asthma and allergies in childhood.