Vitamin D Disappoints: Prenatal Supplementation and Childhood Asthma

William T. Basco, Jr, MD, MS


April 04, 2016

Effect of Prenatal Supplementation With Vitamin D on Asthma or Recurrent Wheezing and Offspring by Age 3 Years: the VDAART Randomized Clinical Trial

Litonjua AA, Carey VJ, Laranjo N, et al
JAMA. 2016;315:362-370


Maternal Vitamin D and Infant Outcomes

Previous observational studies have failed to establish a definitive link between maternal vitamin D status during pregnancy and the risk for wheezing and asthma among offspring. Two recent clinical trials examined maternal supplementation with vitamin D and postpregnancy offspring outcomes for asthma and wheezing.

In the study by Litonjua and colleagues, pregnant women (aged 18-39 years) were enrolled at three clinical sites in the United States at 18-20 weeks of pregnancy. All mothers had a history of atopic disease or had a partner with atopic disease, suggesting that the offspring would be at higher risk for asthma, allergies, or other atopic phenomena.

This was a double-blind, placebo-controlled study. The active treatment group received a multivitamin daily that contained 400 IU of vitamin D, plus an additional 4000-IU vitamin D supplement daily. The placebo group received only the multivitamin containing 400 IU of vitamin D. The mothers were monitored throughout pregnancy, and their offspring were evaluated monthly and followed through age 3 years.

There were two outcomes of interest. The first was a physician diagnosis of asthma or recurrent wheeze during the first 3 years of life. This outcome was ascertained by parental report on surveys filled out every 3 months during follow-up. The second outcome of interest was whether the mothers achieved a serum 25-hydroxyvitamin D level of 30 ng/mL. Other outcomes of interest were whether the child developed eczema or allergies, as measured by immunoglobulin E (IgE) levels.

Each group comprised 400 women, with a mean age of 27 years and mean 25-hydroxyvitamin D level of 23 ng/mL at baseline. Approximately 40% of the mothers had asthma, 64% had allergic rhinitis, and 32% had eczema. With respect to race/ethnicity, 43% of the mothers were black, 13% were Hispanic, and 26% were non-Hispanic white.

Vitamin D supplementation at the treatment arm dose was successful in raising third-trimester levels among the mothers to a mean of 39.2 ng/mL in the intervention group and 26.8 ng/mL in the control group. Furthermore, 24.3% of offspring in the intervention group developed asthma or recurrent wheeze by age 3 years, compared with 30.4% of the offspring in the placebo group. The 95% confidence interval (CI) for the difference ranged from -30 to 18, resulting in a P value of .051—not significant. Similarly, the hazard ratio for development of asthma or recurrent wheeze among the offspring of treated mothers was 0.80 (95% CI, 0.6-1.0), also a nonsignificant difference.

Almost 75% of the intervention-group mothers achieved a serum 25-hydroxyvitamin D level ≥ 30 ng/mL during the third trimester, compared with 34% of the placebo mothers. The frequency of eczema in offspring was essentially the same (21% in the treatment group vs 23% in the placebo group), a difference that did not reach statistical significance. Similarly, the frequency of lower respiratory tract infections and IgE concentrations did not differ between the two groups of children. The frequency of any allergic sensitization was also approximately 50% in both groups.

The authors concluded that the trial was successful in increasing vitamin D levels in the women, with no difference in the primary outcome of asthma or allergic sensitization among offspring.


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