The use of prenatal vitamin D supplementation alone has no effect on the 6-year incidence of asthma and recurrent wheeze in children considered to be at risk, according to the results of a follow-up study1 of the randomized double-blind placebo-controlled Vitamin D Antenatal Asthma Reduction Trial (VDAART; ClinicalTrials.gov Identifier: NCT00920621).2 Results of the follow-up analysis were published in The New England Journal of Medicine.
Investigators sought to determine whether daily prenatal supplementation with 4400 IU of vitamin D3, with maternal levels of 25-hydroxyvitamin D taken into consideration, would be associated with decreased rates of asthma in children aged 6 years. In VDAART, children were evaluated through 3 years of age. The researchers’ aim for the present analysis was to establish whether earlier findings from VDAART with respect to the effect of vitamin D supplementation would carry over to the sixth birthday of the children from VDAART who were currently being evaluated. Women between 18 and 39 years of age were recruited from 3 US clinical sites: Boston Medical Center in Massachusetts; Washington University at St. Louis in Missouri; and Kaiser Permanente Southern California Region in San Diego.
The primary outcome of the study was an extension of the results from VDAART — that is, asthma, recurrent wheeze, or both. Secondary study outcomes included active asthma, parental report of a physician’s diagnosis of allergic rhinitis or eczema, allergen sensitization, total immunoglobulin E (IgE) levels, lung function measures, and lower respiratory tract infections.
A total of 360 children aged 6 years were enrolled in the study and were divided into 2 groups: the vitamin D group, which consisted of 176 children born to mothers who had received 4400 IU of vitamin D3 per day throughout their pregnancies, and the control group, which consisted of 184 children born to mothers who had received 400 IU of vitamin D3 per day throughout their pregnancies. The 2 treatment groups were compared with respect to time to asthma onset or recurrent wheeze.
No effect of maternal vitamin D supplementation on asthma or recurrent wheeze was reported in either an intention-to-treat analysis or an analysis with stratification based on maternal 25-hydroxyvitamin D levels during pregnancy. In addition, the researchers found that prenatal vitamin D supplementation did not affect most of the prespecified secondary outcomes. Finally, no effects of prenatal supplementation with vitamin D were shown on spirometry indices. A very small effect on airway resistance as measured by impulse oscillometry was demonstrated; however, its significance was uncertain.
A major study limitation was the fact that since postnatal supplementation was not undertaken, no conclusions can be drawn about the combined effects of prenatal and postnatal vitamin D supplementation on asthma and recurrent wheeze. The investigators concluded that the small effect of prenatal vitamin D supplementation on airway resistance warrants validation in future studies.
1. Litonjua AA, Carey VJ, Laranjo N, et al. Six-year follow-up of a trial of antenatal vitamin D for asthma reduction. N Engl J Med. 2020;382(6):525-533.
2. Litonjua AA, Lange NE, Carey VJ, et al. 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. Contemp Clin Trials. 2014;38(1):37-50.