RANDOMIZED TRIAL: MATERNAL VITAMIN D SUPPLEMENTATION TO PREVENT CHILDHOOD ASTHMA

Summary

Principal Investigator: Scott T Weiss
Abstract: 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.
Funding Period: 2009-03-01 - 2014-08-28
more information: NIH RePORT

Top Publications

  1. pmc Modulation of Lgl1 by steroid, retinoic acid, and vitamin D models complex transcriptional regulation during alveolarization
    Katia Nadeau
    Montreal Children s Hospital Research Institute, McGill University, Montreal, Quebec, Canada H3A 1B1
    Pediatr Res 67:375-81. 2010
  2. pmc Fat-soluble vitamins and atopic disease: what is the evidence?
    Augusto A Litonjua
    Channing Laboratory and Division of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women s Hospital, Harvard Medical School, 181 Longwood Avenue, Boston, MA 02115, USA
    Proc Nutr Soc 71:67-74. 2012
  3. pmc Vitamin D deficiency as a risk factor for childhood allergic disease and asthma
    Augusto A Litonjua
    Channing Laboratory and Division of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women s Hospital and Harvard Medical School, Boston, Massachusettes, USA
    Curr Opin Allergy Clin Immunol 12:179-85. 2012
  4. ncbi Vitamin D status among preterm and full-term infants at birth
    Heather H Burris
    1 Harvard Medical School, Boston, Massachusetts 2 Department of Neonatology, Beth Israel Deaconess Medical Center, Boston, Massachusetts 3 Division of Newborn Medicine, Boston Children s Hospital, Boston, Massachusetts
    Pediatr Res 75:75-80. 2014
  5. pmc Asthma, allergy, and responses to methyl donor supplements and nutrients
    Sunita Sharma
    Channing Division of Network Medicine, Department of Medicine, Brigham and Women s Hospital, and Harvard Medical School, Boston, Mass Division of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women s Hospital, Boston, Mass Electronic address
    J Allergy Clin Immunol 133:1246-54. 2014
  6. pmc The Vitamin D Antenatal Asthma Reduction Trial (VDAART): rationale, design, and methods of a randomized, controlled trial of vitamin D supplementation in pregnancy for the primary prevention of asthma and allergies in children
    Augusto A Litonjua
    Channing Division of Network Medicine, Department of Medicine, Brigham and Women s Hospital, Boston, MA, United States Division of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women s Hospital, Boston, MA, United States Harvard Medical School, Boston, MA, United States Electronic address
    Contemp Clin Trials 38:37-50. 2014

Detail Information

Publications9

  1. pmc Modulation of Lgl1 by steroid, retinoic acid, and vitamin D models complex transcriptional regulation during alveolarization
    Katia Nadeau
    Montreal Children s Hospital Research Institute, McGill University, Montreal, Quebec, Canada H3A 1B1
    Pediatr Res 67:375-81. 2010
    ..Complex integration of the effects of GC, RA, and VitD on gene expression in the postnatal lung is likely to contribute to the timely advance of alveolarization without attendant inflammation...
  2. pmc Fat-soluble vitamins and atopic disease: what is the evidence?
    Augusto A Litonjua
    Channing Laboratory and Division of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women s Hospital, Harvard Medical School, 181 Longwood Avenue, Boston, MA 02115, USA
    Proc Nutr Soc 71:67-74. 2012
    ..Ongoing clinical trials will help determine whether results of observational studies can be applied to the clinical setting...
  3. pmc Vitamin D deficiency as a risk factor for childhood allergic disease and asthma
    Augusto A Litonjua
    Channing Laboratory and Division of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women s Hospital and Harvard Medical School, Boston, Massachusettes, USA
    Curr Opin Allergy Clin Immunol 12:179-85. 2012
    ..The purpose of this review is to update the last review in this journal and examine the evidence of the relationship between vitamin D deficiency and childhood asthma and allergies...
  4. ncbi Vitamin D status among preterm and full-term infants at birth
    Heather H Burris
    1 Harvard Medical School, Boston, Massachusetts 2 Department of Neonatology, Beth Israel Deaconess Medical Center, Boston, Massachusetts 3 Division of Newborn Medicine, Boston Children s Hospital, Boston, Massachusetts
    Pediatr Res 75:75-80. 2014
    ..We aimed to determine the associations between 25(OH)D levels and gestational age...
  5. pmc Asthma, allergy, and responses to methyl donor supplements and nutrients
    Sunita Sharma
    Channing Division of Network Medicine, Department of Medicine, Brigham and Women s Hospital, and Harvard Medical School, Boston, Mass Division of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women s Hospital, Boston, Mass Electronic address
    J Allergy Clin Immunol 133:1246-54. 2014
    ..Future studies will need to account for both the interrelationships between these nutrients and the effects of the microbiome. ..
  6. pmc The Vitamin D Antenatal Asthma Reduction Trial (VDAART): rationale, design, and methods of a randomized, controlled trial of vitamin D supplementation in pregnancy for the primary prevention of asthma and allergies in children
    Augusto A Litonjua
    Channing Division of Network Medicine, Department of Medicine, Brigham and Women s Hospital, Boston, MA, United States Division of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women s Hospital, Boston, MA, United States Harvard Medical School, Boston, MA, United States Electronic address
    Contemp Clin Trials 38:37-50. 2014
    ..Ancillary studies will investigate neonatal T-regulatory cell function, maternal vaginal flora, and maternal and child intestinal flora...

Research Grants30

  1. RANDOMIZED TRIAL: MATERNAL VITAMIN D SUPPLEMENTATION TO PREVENT CHILDHOOD ASTHMA
    Robert Strunk; Fiscal Year: 2013
    ..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. ..
  2. Mechanisms of Health Effects of Exercise in Children
    Dan M Cooper; Fiscal Year: 2013
    ..Collectively, the PPG will promote novel preventive and adjunctive exercise therapies in children with chronic inflammation- therapies grounded in a firm understanding of biological mechanisms. ..
  3. Nutrition, Deregulation of Imprinted Genes
    Cathrine Hoyo; Fiscal Year: 2013
    ....
  4. Exploratory Trial of Choline Supplementation for Fetal Alcohol Syndrome
    Sandra W Jacobson; Fiscal Year: 2013
    ..Maternal and infant nutritional intake will be evaluated by dietary history and biological assay. Infants will be assessed for birth size, growth, and EBC and neurocognitive function at 6.5 months postpartum. ..
  5. COBRE Center for Central Nervous System Function
    Jerome N Sanes; Fiscal Year: 2013
    ..The COBRE Center will leverage the administrative resources available through the Brown Institute for Brain Science to ensure efficient operation and coordinate with other brain science research activities at Brown. ..
  6. Vitamin D supplementation in pregnancy: impact on neonatal immune phenotype
    GEORGE T O'CONNOR; Fiscal Year: 2013
    ....