Prenatal vitamin D supplementation failed to prevent asthma in at-risk children

Children whose mothers received high-dose vitamin D supplementation while pregnant were not less likely to develop asthma or recurrent wheeze at age 6 years than children whose mothers did not receive supplementation, according to follow-up data from the Vitamin D Antenatal Asthma Reduction Trial.

In the initial randomized, double-blind, placebo-controlled VDAART trial, researchers randomly assigned women aged 18 to 39 years who were 10 to 18 weeks pregnant to 4,000 IU of vitamin D daily or placebo. Both study arms also received a daily multivitamin containing 400 IU of vitamin D. All women were nonsmokers and had a history of asthma, eczema or allergic rhinitis or had a partner with a history of asthma, eczema or allergic rhinitis. Asthma, recurrent wheeze or both served as the primary outcome.

Children were originally followed through their third birthday and this study, recently published in The New England Journal of Medicine, extended follow-up through age 6 years. This analysis comprised 806 children.

No effect of prenatal vitamin D

By age 6 years, 43.5% of children in the vitamin D group and 45.9% of children in the control group had asthma or recurrent wheeze. The researchers observed no difference in incidence of the primary outcome when comparing the control group with the vitamin D group (interval-censored HR = 1.12; P = .25). Similarly, maternal vitamin D supplementation did not appear to affect secondary outcomes – including eczema, allergic rhinitis or lower respiratory tract infection – by age 6.

Childhood lung function was assessed using impulse oscillometry and spirometry. The researchers found that, after adjustment for race/ethnicity, clinical center and sex, total airway resistance and lower peripheral airway resistance were lower among children in the vitamin D group compared with the control group. No association was noted, however, between maternal vitamin D supplementation and spirometric indexes.

The researchers also evaluated childhood lung function in relation to maternal prenatal 25-hydroxyvitamin D (25-[OH]D). Results showed that children born to women with mean 25-(OH)D less than 30 ng/mL vs. those with higher levels differed in terms of total airway resistance (adjusted mean resistance at 5 Hz, 1.01 kPa/L/second vs. 0.96 kPa/L/second), peripheral airway resistance (adjusted mean resistance at 5 Hz to 20 Hz, 0.35 kPa/L/second vs. 0.32 kPa/L/second), FEV1 (adjusted mean, 0.97 L vs. 1 L) and FVC (adjusted mean, 1.06 L vs. 1.12 L).

“Prenatal vitamin D supplementation alone did not affect the development of asthma and recurrent wheeze in young children through the age of 6 years. The effect of prenatal supplementation on airway resistance through the age of 6 years suggests that there may be prenatal programming of lung airways, but these small effects will need to be validated in future studies,” the researchers wrote.

Looking ahead

In an accompanying editorial, Erika von Mutius, MD, from the Institute of Asthma and Allergy Prevention at Helmholtz Centre Munich, and Fernando D. Martinez, MD, from Asthma and Airway Disease Research Center at University of Arizona in Tucson, noted that this trial was “appropriately powered and skillfully conducted” and, when coupled with similar results from a study in Denmark, provides a definitive conclusion that “vitamin D supplementation should not be used to prevent school-age asthma, which is most often associated with aeroallergen sensitization.”

Both the VDAART study and the Danish study, however, suggested that prenatal vitamin D supplementation may protect against wheezing illnesses through age 3 years, according to von Mutius and Martinez.

“Although supplementation in the VDAART trial was not effective in preventing school-age asthma, vitamin D supplementation during pregnancy may still play a role in averting less persistent forms of wheezing in infants with a parental history of asthma and allergies,” they wrote. “In spite of its good prognosis, transient wheezing can be associated with severe asthma-like symptoms, especially during the virus season. If future studies confirm the preventive effect of high-dose vitamin D supplementation in pregnancy for preschool viral lower respiratory tract illnesses, then routine supplementation with higher doses than those currently recommended may be considered.” – by Melissa Foster

Disclosure: Litonjua reports he has received personal fees from UpToDate Inc. Please see the full study for all other authors’ relevant financial disclosures. Martinez reports he has received grants from Johnson and Johnson, NIH/National Heart, Lung, and Blood Institute, NIH/National Institute of Environmental Health Sciences, NIH/National Institute of Allergy and Infectious Diseases and NIH/Office of Director. von Mutius reports she has received personal fees from Boehringer Ingelheim International GmbH, HiPP GmbH and Co KG, OM Pharma S.A., Peptinnovate Ltd, Pharmaventures Ltd; she has received non-financial support from Nestlé Deutschland AG; she has received grants from the European Commission; and she has a patents with royalties paid and licensed to Protectimmun GmbH.