RANDOMIZED TRIAL: MATERNAL VITAMIN D SUPPLEMENTATION TO PREVENT CHILDHOOD ASTHMA

描述(由申请人提供)： 哮喘是儿童发病的主要原因之一，所有病例中有60%是在3岁之前确诊的。因此，找到能够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在调节免疫反应中的作用，我们认为孕妇缺乏维生素D会导致新生儿免疫系统发育不良，使他们容易哮喘和过敏。我们有来自两项独立出生队列研究的观察数据，即孕妇在怀孕期间摄入较高的维生素D分别与3岁和5岁儿童反复喘息和哮喘的风险降低50%独立相关。然而，为了推荐将其作为预防哮喘的普遍治疗方法，有必要进行随机对照临床试验。因此，我们提出了一项双臂、双盲、安慰剂对照、随机的维生素D临床试验，以确定孕妇较高的维生素D摄入量和水平是否可以预防3岁儿童的哮喘和过敏。我们将从参与这项试验的三个临床中心的产科诊所识别患有哮喘或过敏的孕妇，或其伴侣患有哮喘或过敏的孕妇。我们将在怀孕的前三个月招募870名孕妇，并将她们随机分配到为期4年的临床试验的两个治疗组中：435名孕妇在常规产前维生素的基础上服用4000国际单位的维生素D；以及435名孕妇单独服用普通产前维生素。我们的主要目标是确定孕妇补充足够的维生素D是否与儿童出生后3年内哮喘发病率的降低有关。该研究的次级目标将包括(1)确定孕妇补充足够的维生素D是否与减少婴儿的继发性结局有关；(2)通过测量1岁和3岁时孕妇血浆、脐带血和儿童血液中25(OH)D的水平，确定孕妇补充充足的维生素D是否与改善母亲及其子女的维生素D状况有关；(3)通过测量1岁和3岁婴儿的血浆、脐带血和儿童血液中的25(OH)D水平，确定孕妇补充充足的维生素D是否与减少1岁和3岁儿童患上湿疹和下呼吸道感染有关。

DESCRIPTION (provided by applicant): Asthma is one of the leading causes of morbidity in children with 60% of all cases diagnosed by age 3. 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 modulating immune responses, we believe that vitamin D deficiency in pregnant mothers leads to faulty immune system development in the neonate, predisposing them to asthma and allergy. We have observational data from two independent birth cohort studies that higher maternal intakes of vitamin D during pregnancy are each independently associated with a 50% reduction in risk for recurrent wheezing and asthma in 3- and 5-yr old children. However, in order to recommend this as a universal treatment to prevent asthma, a randomized, controlled, clinical trial is necessary. Therefore, we propose a two arm, double-blind, placebo controlled, randomized, clinical trial of Vitamin D, to determine whether higher vitamin D intake and levels in the pregnant mother will prevent asthma and allergy in the child at age 3. We will identify pregnant women who have asthma or allergies or whose partner has asthma or allergies, from obstetric clinics in the three clinical centers participating in this trial. We will recruit 870 pregnant women during the first trimester of pregnancy and randomize them to one of two treatment arms of a 4-year clinical trial: 4000 IU of Vitamin D in addition to usual prenatal vitamins, n=435; and usual prenatal vitamins alone, n=435. Our primary specific aim is to determine whether adequate vitamin D supplementation in the pregnant mother is associated with reduced incidence of asthma in the child during the first 3 years of life. The sub-aims of the study will include (1) To determine whether adequate vitamin D supplementation in the pregnant mother is associated with reduced secondary outcomes in the child of (a) allergic sensitization, (b) doctor's diagnosis of eczema and (c) lower respiratory tract infections during the first 3 years of life; and (2) To determine whether adequate vitamin D supplementation in the pregnant mother is associated with improved vitamin D status in the mothers and their offspring through measurement of 25(OH)D levels in maternal plasma, cord blood, and children's blood at 1 and 3 yrs of age.