Asthma is one of the leading causes of morbidity in children with the majority of all cases diagnosed in early childhood and over 56 billion dollars in health costs annually. 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 the development of the lung and the immune system in utero, we believe that vitamin D deficiency in pregnant mothers leads to increased risks for developing asthma and allergy in early childhood. Epidemiologic studies that have investigated the role of vitamin D in early life and the development of asthma, wheeze and allergy have inconsistent results. Because of the wide prevalence of vitamin D deficiency, a clinical trial is the only way t confidently answer the question of whether higher vitamin D levels in pregnancy can prevent asthma and allergies in the mother's offspring. Over the past 4 years, we have been conducting a randomized, placebo-controlled trial of maternal vitamin D supplementation in pregnancy, and we are now following the children ( Identifier: NCT00920621). We recruited 881 women, and randomized them to one of two arms: 4,000 IU vitamin D3 daily plus a prenatal vitamin containing 400 IU vitamin D3 vs. a placebo plus a prenatal vitamin containing 400 IU vitamin D3. We followed them through pregnancy and there were 810 live births with 801 currently under follow-up. The goal of the current project is to follow the children through age 6 years.
The specific aims for the renewal of VDAART are: (1) to determine whether maternal supplementation of vitamin D during pregnancy is associated with reduced incidence of asthma in the child during the first 6 years of life; (2) to determine whether maternal supplementation of vitamin D during pregnancy is associated with reduced secondary outcomes in the child of: (a) allergic sensitization (total and specific IgE), (b) doctor's diagnosis of eczema, (c) doctor's diagnosis of allergic rhinitis, (d) food allergies and (e) lower respiratory tract infections by ag 6 years; (3) to determine whether maternal supplementation of vitamin D during pregnancy is associated with greater lung growth in the children up to age 6, as measured by impulse oscillometry and spirometry; and (4) to continue to collect biologic material from the children for mechanistic studies related to vitamin D in asthma and allergies, including specimens for genomic and epigenomic studies and microbiome studies. Findings from this important study will have great public health importance in the prevention of asthma and allergies in childhood.

Public Health Relevance

Asthma and allergies are among the most common chronic disorders in childhood and they account for over 56 billion dollars in health care costs annually. We are investigating whether vitamin D supplementation in pregnancy can prevent the development of these disorders in children, through a randomized clinical trial. Results of this study could result in an inexpensive way to prevent asthma and allergies in children.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Research Project (R01)
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Clinical Trials Review Committee (CLTR)
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Noel, Patricia
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Washington University
Schools of Medicine
Saint Louis
United States
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Mirzakhani, Hooman; Carey, Vincent J; McElrath, Thomas F et al. (2018) Impact of Preeclampsia on the Relationship of Maternal Asthma with Offspring Asthma: An Observation from the VDAART Clinical Trial. Am J Respir Crit Care Med :
Mirzakhani, Hooman; O'Connor, George; Bacharier, Leonard B et al. (2017) Asthma control status in pregnancy, body mass index, and maternal vitamin D levels. J Allergy Clin Immunol 140:1453-1456.e7
Sordillo, Joanne E; Zhou, Yanjiao; McGeachie, Michael J et al. (2017) Factors influencing the infant gut microbiome at age 3-6 months: Findings from the ethnically diverse Vitamin D Antenatal Asthma Reduction Trial (VDAART). J Allergy Clin Immunol 139:482-491.e14
Al-Garawi, Amal; Carey, Vincent J; Chhabra, Divya et al. (2016) The Role of Vitamin D in the Transcriptional Program of Human Pregnancy. PLoS One 11:e0163832
Weiss, Scott T; Litonjua, Augusto A (2016) Can we prevent childhood asthma before birth? Summary of the VDAART results so far. Expert Rev Respir Med 10:1039-40
Mirzakhani, Hooman; Litonjua, Augusto A; McElrath, Thomas F et al. (2016) Early pregnancy vitamin D status and risk of preeclampsia. J Clin Invest 126:4702-4715
Guilbert, Theresa W; Bacharier, Leonard B (2011) Controversies in the treatment of the acutely wheezing infant. Am J Respir Crit Care Med 183:1284-5