Asthma and wheezing begin early in life, and prenatal vitamin D deficiency has been variably associated with these disorders. For this study, published in JAMA, researchers sought to determine whether prenatal vitamin D (cholecalciferol) supplementation can prevent asthma or recurrent wheeze in early childhood.

The Vitamin D Antenatal Asthma Reduction Trial (VDAART) was a randomized, double-blind, placebo-controlled trial conducted in three centers across the U.S. Enrollment began in October 2009 and completed follow-up in January 2015. A total of 881 pregnant women between the ages of 18 and 39 years at high risk of having children with asthma were randomized at 10-18 weeks’ gestation. Five participants were deemed ineligible shortly after randomization and were discontinued. A total of 440 women were randomized to receive daily 4,000 IU vitamin D plus a prenatal vitamin containing 400 IU vitamin D, and 436 women were randomized to receive a placebo plus a prenatal vitamin containing 400 IU vitamin D. Main outcomes and measures included coprimary outcomes of 1) parental report of physician-diagnosed asthma or recurrent wheezing through 3 years of age and 2) third trimester maternal 25-hydroxyvitamin D levels.

A total of 810 infants were born in the study, and 806 were included in the analyses for the 3-year outcomes. Two hundred eighteen children developed asthma or recurrent wheeze: 98 of 405 (24.3%; 95% CI, 18.7%-28.5%) in the 4,400-IU group vs. 120 of 401 (30.4%, 95% CI, 25.7%-73.1%) in the 400-IU group (hazard ratio, 0.8; 95% CI, 0.6-1.0; P = .051). Of the women in the 4,400-IU group whose blood levels were checked, 289 (74.9%) had 25-hydroxyvitamin D levels of 30 ng/mL or higher by the third trimester of pregnancy compared with 133 of 391 (34.0%) in the 400-IU group (difference, 40.9%; 95% CI, 34.2%-47.5%, P < .001).

Researchers concluded that in pregnant women at risk of having a child with asthma, supplementation with 4,400 IU/d of vitamin D compared with 400 IU/d significantly increased vitamin D levels in the women. The incidence of asthma and recurrent wheezing in their children at age 3 years was lower by 6.1%, but this did not meet statistical significance; however, the study may have been underpowered. Longer follow-up of the children is ongoing.