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)
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Clinical Trials Review Committee (CLTR)
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Noel, Patricia
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Brigham and Women's Hospital
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Mirzakhani, Hooman; Carey, Vincent J; McElrath, Thomas F et al. (2018) The Association of Maternal Asthma and Early Pregnancy Vitamin D with Risk of Preeclampsia: An Observation From Vitamin D Antenatal Asthma Reduction Trial (VDAART). J Allergy Clin Immunol Pract 6:600-608.e2
Lee-Sarwar, Kathleen; Litonjua, Augusto A (2018) As You Eat It: Effects of Prenatal Nutrition on Asthma. J Allergy Clin Immunol Pract 6:711-718
Mirzakhani, Hooman; Carey, Vincent J; Zeiger, Robert et al. (2018) Impact of Parental Asthma, Prenatal Maternal Asthma Control and Vitamin D Status on Risk of Asthma and Recurrent Wheeze in 3-Year Old Children. Clin Exp Allergy :
Savage, Jessica H; Lee-Sarwar, Kathleen A; Sordillo, Joanne et al. (2018) A prospective microbiome-wide association study of food sensitization and food allergy in early childhood. Allergy 73:145-152
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 :
Blighe, Kevin; Chawes, Bo L; Kelly, Rachel S et al. (2017) Vitamin D prenatal programming of childhood metabolomics profiles at age 3 y. Am J Clin Nutr 106:1092-1099
Litonjua, Augusto A; Weiss, Scott T (2017) Vitamin D status through the first 10 years of life: A vital piece of the puzzle in asthma inception. J Allergy Clin Immunol 139:459-461
Weiss, Scott T (2017) Emerging mechanisms and novel targets in allergic inflammation and asthma. Genome Med 9:107
Weiss, Scott T; Litonjua, Augusto A (2017) Vitamin D in Host Defense: Implications for Future Research. Am J Respir Cell Mol Biol 56:692-693
Wolsk, Helene M; Chawes, Bo L; Litonjua, Augusto A et al. (2017) Prenatal vitamin D supplementation reduces risk of asthma/recurrent wheeze in early childhood: A combined analysis of two randomized controlled trials. PLoS One 12:e0186657

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