Randomized Controlled Trial: VDAART Continuation Study - CCC

描述(申请人提供)：哮喘是导致儿童发病的主要原因之一，大多数病例是在儿童早期诊断的，超过560亿美元 每年的医疗费用。因此，找到能够导致预防这种疾病的因素将具有重要的公共卫生意义。维生素D缺乏症在孕妇中非常普遍，因此，它是预防疾病的一个潜在的可修改因素。由于维生素D在子宫内对肺部和免疫系统发育的作用，我们认为孕妇缺乏维生素D会增加儿童早期患哮喘和过敏的风险。流行病学研究调查了维生素D在早期生命和哮喘、喘息和过敏发展中的作用，但结果不一致。由于维生素D缺乏的广泛流行，临床试验是唯一自信地回答怀孕期间较高的维生素D水平是否可以预防母亲子女哮喘和过敏的问题。在过去的4年里，我们一直在进行一项关于孕妇在怀孕期间补充维生素D的随机、安慰剂对照试验，现在我们正在跟踪调查儿童(ClinicalTrials.gov标识：NCT00920621)。我们招募了881名妇女，并将她们随机分成两组：每天4000IU维生素D3加含400IU维生素D3的产前维生素，与安慰剂加含400IU维生素D3的产前维生素。我们在怀孕期间对他们进行了跟踪，有810名活产婴儿，其中801名目前正在随访中。目前项目的目标是跟踪这些儿童直到6岁。VDAART更新的具体目标是：(1)确定孕妇在怀孕期间补充维生素D是否与降低儿童在出生后6年内的哮喘发病率有关；(2)确定孕妇补充维生素D是否与婴儿出生后6年内哮喘的发病率下降有关； 妊娠期维生素D与以下儿童的次要结局减少有关：(A)过敏反应(总的和特异性的IgE)，(B)医生对湿疹的诊断，(C)医生对过敏性鼻炎的诊断，(D)食物过敏和(E)6岁以下的下呼吸道感染；(3)通过脉冲振荡法和肺活量测定法确定孕妇补充维生素D是否与6岁以下儿童的肺生长更大有关；以及(4)继续收集儿童的生物材料 与哮喘和过敏有关的维生素D的机制研究，包括基因组和表观基因组研究以及微生物组研究的样本。这项重要研究的结果将对预防儿童哮喘和过敏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.