Randomized Trial: Maternal Vitamin D Supplementation to Prevent Childhood Asthma

随机试验：母亲补充维生素 D 可预防儿童哮喘

基本信息

批准号：
8541924
负责人：
AUGUSTO A LITONJUA
金额：
$ 5.47万
依托单位：
BRIGHAM AND WOMEN'S HOSPITAL
依托单位国家：
美国
项目类别：
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/8541924
关键词：
3 year old Address Affect Age Allergic Area Asthma Autoimmune Diseases Awareness Behavioral Birth Blood Cells Child Childhood Childhood Asthma Chronic Disease Cities Clinic Clinical Clinical Trials Cohort Studies Consensus Control Groups Data Developing Countries Diagnosis Diet Dietary Supplementation Dietary intake Discipline of obstetrics Disease Dose Double-Blind Method Eczema Environmental Risk Factor Epidemic Exposure to Fatty acid glycerol esters First Pregnancy Trimester Health Benefit Health Care Costs Healthcare Hormones Hypersensitivity IgE Immune System Diseases Immune response Immune system Incidence Inflammation Inflammatory Bowel Diseases Insulin-Dependent Diabetes Mellitus Intake Interleukin-10 Intervention Lead Life Lower Respiratory Tract Infection Lung Maintenance Measurement Morbidity - disease rate Mothers Multi-Institutional Clinical Trial Multiple Sclerosis National Heart, Lung, and Blood Institute Nutrient Placebo Control Placebos Plasma Population Pregnancy Pregnant Women Prevalence Prevention Production Public Health Randomized Randomized Clinical Trials Randomized Controlled Clinical Trials Recruitment Activity Recurrence Regulation Respiratory Tract Infections Rheumatoid Arthritis Risk Rural Seasonal Variations Second Pregnancy Trimester Skin Cancer Spontaneous abortion Sun Exposure Sunlight Supplementation Systems Development TGFB1 gene The Sun Time Umbilical Cord Blood Variant Vitamin D Vitamin D Deficiency Vitamins Wheezing Withdrawal arm asthma prevention burden of illness disorder prevention disorder risk follow-up improved in utero innovation interest neonate novel strategies offspring pregnant prenatal prevent primary outcome public health relevance randomized trial secondary outcome stillbirth

项目摘要

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）：哮喘是在3岁诊断的所有病例中有60％的儿童发病的主要原因之一。因此，发现可以预防这种疾病的因素将具有很大的公共健康重要性。维生素D缺乏症在孕妇中非常普遍，因此代表了预防疾病的潜在可修改因素。由于维生素D在调节免疫反应中的作用，我们认为怀孕母亲的维生素D缺乏会导致新生儿的免疫系统发育有故障，使它们易于哮喘和过敏。我们从两项独立的出生队列研究中获得了观察性数据，即怀孕期间的较高的母体摄入量与3岁和5岁儿童的复发性喘息和哮喘的风险降低了50％。但是，为了推荐这种通用治疗以防止哮喘，需要进行随机，受控的临床试验。因此，我们提出了一个两臂，双盲，安慰剂控制，随机，维生素D的临床试验，以确定较高的维生素D摄入量和怀孕母亲的水平是否会预防3岁儿童的哮喘和过敏。我们将确定患有哮喘或过敏的孕妇，或者其伴侣或其伴侣的哮喘或过敏症中的哮喘或临床中的临床临床中的临床中心都参与了三个临床中心。我们将在怀孕的头三个月中招募870名孕妇，并将其随机为4年临床试验的两个治疗组之一：4000 IU维生素D除了通常的产前维生素外，n = 435;和通常的产前维生素，n = 435。我们的主要目的是确定怀孕母亲中足够的维生素D是否与儿童哮喘发病率降低有关。该研究的子IAM将包括（1）确定怀孕母亲中足够的维生素D补充剂是否与（a）过敏性敏化的孩子的次要结局降低有关，（b）医生诊断出湿疹和（c）在生命的最初三年中的湿疹和（c）下呼吸道感染。（2）确定怀孕母亲中补充维生素D是否与母亲的维生素D状况提高有关，并通过测量孕妇血浆，脐带血和1岁和3岁的儿童血液中的25（OH）d水平来改善其后代。公共卫生相关性：我们认为，维生素D缺乏症可能对1980年代初期开始的哮喘流行有重大影响。在室内花费的时间更长，使用防晒霜导致阳光的暴露减少和维生素D的产生减少。缺乏足够的饮食补充来补偿这些行为变化，导致维生素D水平非常低。我们认为，随着孕妇维生素D的足够剂量，我们可以防止其后代所有哮喘病例中一半的剂量，并最终将疾病患病率降低到1980年前的水平。如果成功，该试验最终将使哮喘发病率降低50％，从而将医疗保健成本降低80亿美元。这种干预措施便宜，安全，并将带来重大的公共卫生益处。它还代表了过去30年来最具创新性和最新的哮喘治疗方法和预防方法。