Prenatal supplementation with high-dose vitamin D had no impact on asthma and persistent wheezing in 6-year-olds in follow-up of a study that did suggest protection at age 3 years.

Previously reported data from the Vitamin D Antenatal Asthma Reduction Trial (VDAART) showed a reduction in recurrent wheezing in 3-year-olds associated with being born to mothers who took high-dose (4,400 IU daily) vitamin D supplementation during pregnancy.

In the update, Augusto Litonjua, MD, of the University of Rochester Medical Center in New York, and colleagues randomized pregnant women to receive supplementation with either 4,400 IU or 400 IU (control dose) of vitamin D₃ daily starting in week 10 to 18 of pregnancy. Pregnant women were considered eligible for the trial if either they or the biologic father had asthma, allergic rhinitis, or eczema.

The follow-up study, published in the New England Journal of Medicine, showed there was no effect associated with taking vitamin D during pregnancy on either asthma or recurrent wheezing at age 6, suggesting that the earlier reported protective benefit associated with high-dose supplementation was not sustained past the age of 3, the researchers wrote.

In an interview with MedPage Today, Litonjua said while the study failed to show a persistent benefit for prenatal high-dose vitamin D on offspring asthma risk, there is a suggestion in the follow-up data that prenatal supplementation may have some positive effect on lung development. He explained that airway resistance measures obtained using impulse oscillometry were lower in 6-year-old children born to the high-dose vitamin D mothers than among 6-year-olds born to the control mothers, but no treatment effect was seen in traditional measures of lung function, including forced expiratory volume in 1 second (FEV₁), forced vital capacity (FVC), and FEV₁:FVC ratio, he explained.

It is also not known if vitamin D supplementation very early in life protects against asthma and recurrent wheezing, Litonjua continued, noting that the recent D-Wheeze study, which examined postnatal vitamin D supplementation in African-American preterm infants, suggested a protective effect for supplementation against recurrent wheezing.

“It is possible that prenatal and postnatal supplementation designed to keep vitamin D levels [at] a certain level would be protective against asthma, but that study hasn’t been done,” he said.

The VDAART follow-up study included a total of 806 children, including 360 (44.7%) who had a diagnosis of asthma or persistent wheezing by the age of 6. A total of 176 of these children (43.6%) were born to mothers in the high-dose vitamin D group and 184 (45.9%) were born to mothers in the control group.

No effect of maternal vitamin D supplementation on asthma and recurrent wheezing was seen in either an intention-to-treat analysis or analysis with stratification according to maternal blood vitamin D levels during pregnancy, the investigators reported.

Likewise, no significant effects for maternal high-dose vitamin D supplementation were seen on the secondary outcomes of eczema, allergic rhinitis, and lower respiratory tract infection by the age of 6.

In an editorial published with the study, Erika von Mutius, MD, of Helmholtz Centre Munich in Germany, and Fernando Martinez, MD, of the University of Arizona Asthma and Airway Disease Research Center in Tucson, wrote that asthma’s heterogeneity in all age groups remains “an important hurdle for asthma prevention.”

The earlier VDAART finding suggested that protection associated with prenatal supplementation is strongest during the first year of life, with protection waning in the second and third years, von Mutius and Martinez noted. They pointed out that those findings only reached significance when combined in a meta-analysis with a Danish prenatal vitamin D study, which also included data on children up to age 3.

“Taken together, these results suggest that vitamin D supplementation may be effective in preventing the transient forms of wheezing that occur in preschoolers but not allergy-related asthma, the prevailing form of persistent disease during school years,” the editorialists wrote. “Unlike school-age asthma, transient wheezing is unrelated to allergies and the most common cause of wheezing regardless of prognosis in this age group are viral lower respiratory tract illnesses.”

And, while vitamin D supplementation during pregnancy was not found to be effective in preventing asthma in school-age children, prenatal supplementation “may still play a role in averting less persistent forms of wheezing in infants with a parental history of asthma and allergies,” von Mutius and Martinez stated.

“In spite of its good prognosis, transient wheezing can be associated with severe asthma-like symptoms, especially during the virus season,” the editorial continued. “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.”