RANDOMIZED TRIAL: MATERNAL VITAMIN D SUPPLEMENTATION TO PREVENT CHILDHOOD ASTHMA

随机试验：母体维生素 D 补充剂预防儿童哮喘

• 批准号: 7584414
• 负责人: Robert Strunk
• 金额: $ 45.02万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-03-01 至 2014-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7584414
• 关键词: Age; Allergic; Asthma; Behavioral; Birth; Blood; Child; Childhood Asthma; Clinic; Clinical; Clinical Trials; Cohort Studies; Companions; Computer Systems Development; Data; Data Coordinating Center; Diagnosis; Dietary Supplementation; Discipline of obstetrics; Disease; Dose; Double-Blind Method; Eczema; Epidemic; First Pregnancy Trimester; Grant; Health Benefit; Health Care Costs; Hypersensitivity; Immune response; Immune system; Incidence; Intake; Intervention; Lead; Life; Link; Lower Respiratory Tract Infection; Measurement; Morbidity - disease rate; Mothers; Placebo Control; Plasma; Pregnancy; Pregnant Women; Prevalence; Prevention; Production; Public Health; Randomized; Randomized Clinical Trials; Randomized Controlled Clinical Trials; Recruitment Activity; Recurrence; Risk; Sun Exposure; Supplementation; The Sun; Time; Umbilical Cord Blood; Upper arm; Vitamin D; Vitamin D Deficiency; Vitamins; Wheezing; disorder prevention; improved; innovation; neonate; novel strategies; offspring; pregnant; prenatal; prevent; public health relevance; secondary outcome

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. Public Health Relevance: We believe that it is likely that Vitamin D deficiency has had a significant impact on the asthma epidemic that began in the early 1980's. Greater time spent indoors, and use of sun screen has resulted in reduced sun exposure and decreased production of vitamin D; and lack of adequate dietary supplementation to compensate for these behavioral changes, results in very low vitamin D levels. We believe that with adequate dosing of vitamin D in pregnant women, we can prevent half of all asthma cases in their offspring and ultimately reduce disease prevalence to pre-1980 levels. If successful, this trial will ultimately decrease asthma incidence by 50% and consequently decrease health care costs by 8 billion dollars. This intervention is cheap, safe, and will result in major public health benefit. It also represents the most innovative and novel approach to asthma treatment and prevention in the last 30 years.

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。公共卫生相关性：我们认为维生素D缺乏很可能对始于20世纪80年代初的哮喘流行产生了重大影响，S。更多的时间在室内，使用防晒霜导致阳光照射减少，维生素D的产生减少；缺乏足够的饮食补充来弥补这些行为变化，导致维生素D水平非常低。我们相信，如果孕妇服用足够剂量的维生素D，我们可以在她们的后代中预防一半的哮喘病例，并最终将疾病患病率降低到1980年前的水平。如果成功，这项试验最终将使哮喘发病率降低50%，从而减少80亿美元的医疗费用。这种干预是廉价、安全的，并将带来重大的公共卫生利益。它也代表了过去30年来哮喘治疗和预防的最具创新性和新颖性的方法。