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：
8234978
负责人：
AUGUSTO A LITONJUA
金额：
$ 202.62万
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/8234978
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）：哮喘是儿童发病的主要原因之一，其中 60% 的病例是在 3 岁之前诊断出来的。因此，找到能够预防这种疾病的因素对于公共卫生具有重要意义。维生素 D 缺乏症在孕妇中非常普遍，因此，维生素 D 缺乏症是预防疾病的一个潜在可改变因素。由于维生素 D 具有调节免疫反应的作用，我们认为孕妇缺乏维生素 D 会导致新生儿免疫系统发育缺陷，使他们容易患哮喘和过敏。我们从两项独立出生队列研究中获得的观察数据表明，母亲在怀孕期间摄入较高的维生素 D 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，为了推荐将此作为预防哮喘的普遍治疗方法，需要进行随机、对照的临床试验。因此，我们建议开展一项维生素 D 的双组、双盲、安慰剂对照、随机临床试验，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 岁时孩子的哮喘和过敏。从参与本试验的三个临床中心的产科诊所确定患有哮喘或过敏的孕妇或其伴侣患有哮喘或过敏的孕妇。我们将招募 870 名怀孕前三个月的孕妇，并将她们随机分配到为期 4 年的临床试验的两个治疗组之一：除了常规的产前维生素外，还服用 4000 IU 维生素 D，n=435；和单独使用常规产前维生素，n=435。我们的主要具体目标是确定怀孕母亲补充足够的维生素 D 是否与降低孩子出生后 3 年内的哮喘发病率有关。该研究的子目标将包括 (1) 确定怀孕母亲补充足够的维生素 D 是否与减少孩子的继发后果有关：(a) 过敏性过敏，(b) 医生对湿疹的诊断，以及 (c)出生后 3 年内发生过下呼吸道感染； (2) 通过测量母亲血浆、脐带血和儿童血液中的 25(OH)D 水平，确定怀孕母亲补充足够的维生素 D 是否与母亲及其后代维生素 D 状况的改善相关。 3岁。公共健康相关性：我们认为，维生素 D 缺乏可能对 1980 年代初开始的哮喘流行产生了重大影响。呆在室内的时间增加以及使用防晒霜会导致阳光照射减少和维生素 D 生成减少；并且缺乏足够的膳食补充剂来补偿这些行为变化，导致维生素 D 水平非常低。我们相信，如果孕妇服用足够的维生素 D，我们可以预防其后代一半的哮喘病例，并最终将疾病患病率降低到 1980 年前的水平。如果成功，该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。这种干预措施廉价、安全，并将带来重大的公共卫生效益。它还代表了过去 30 年来最具创新性和新颖性的哮喘治疗和预防方法。