Six-Year Follow-up of a Trial of Antenatal Vitamin D for Asthma Reduction

Abstract

Background: We previously reported the results of a trial of prenatal vitamin D supplementation to prevent asthma and recurrent wheeze in young children, which suggested that supplementation provided a protective effect at the age of 3 years. We followed the children through the age of 6 years to determine the course of asthma and recurrent wheeze.

Methods: In this follow-up study, investigators and participants remained unaware of the treatment assignments through the children's sixth birthday. We aimed to determine whether, when maternal levels of 25-hydroxyvitamin D were taken into account, children born to mothers who had received 4400 IU of vitamin D₃ per day during pregnancy (vitamin D group) would have a lower incidence of asthma and recurrent wheeze at the age of 6 years than would those born to mothers who had received 400 IU of vitamin D₃ per day (control group). Time-to-event methods were used to compare the treatment groups with respect to time to the onset of asthma or recurrent wheeze. Multivariate methods were used to compare longitudinal measures of lung function between the treatment groups.

Results: There was no effect of maternal vitamin D supplementation on asthma and recurrent wheeze in either an intention-to-treat analysis or an analysis with stratification according to the maternal 25-hydroxyvitamin D level during pregnancy. There was no effect of prenatal vitamin D supplementation on most of the prespecified secondary outcomes. We found no effects of prenatal supplementation on spirometric indexes. Although there was a very small effect on airway resistance as measured by impulse oscillometry, this finding was of uncertain significance.

Conclusions: Vitamin D supplementation during the prenatal period alone did not influence the 6-year incidence of asthma and recurrent wheeze among children who were at risk for asthma. (Funded by the National Heart, Lung, and Blood Institute; VDAART ClinicalTrials.gov number, NCT00920621.).

Figure 1.. Enrollment, Randomization, and Follow-up.

IVF denotes in vitro fertilization.

Figure 2.. Intention-to-Treat Analysis of Asthma- and Wheeze-free Time Distributions.

In the primary analysis, a nonparametric test accommodating interval-censored response times indicated that the between-group difference was not significant (P = 0.25). Tick marks indicate censored data, and shading around each line indicates the 95% confidence interval.

Figure 3.. Lung-Function Measures Stratified According to Mean Maternal Vitamin D Level Status during Pregnancy.

Mixed-effects models for repeated lung-function outcome measures were adjusted for age, race, height, and weight. Data points are mean values for each child from at least two successful oscillometry or spirometry tests. Boxes indicate the medians and interquartile ranges, and vertical lines indicate the 95% confidence intervals. FEV₁ denotes forced expiratory volume in 1 second, FVC forced vital capacity, and R5 resistance at 5 Hz (total airway resistance).