Prenatal vitamin D supplementation reduces risk of asthma/recurrent wheeze in early childhood: A combined analysis of two randomized controlled trials

Background We recently published two independent randomized controlled trials of vitamin D supplementation during pregnancy, both indicating a >20% reduced risk of asthma/recurrent wheeze in the offspring by 3 years of age. However, neither reached statistical significance. Objective To perform a combined analysis of the two trials and investigate whether maternal 25-hydroxy-vitamin D (25(OH) D) level at trial entry modified the intervention effect. Methods VDAART (N = 806) and COPSAC2010. (N = 581) randomized pregnant women to daily high-dose vitamin D-3 (4,000 IU/d and 2,400 IU/d, respectively) or placebo. All women also received a prenatal vitamin containing 400 IU/d vitamin D3. The primary outcome was asthma/recurrent wheeze from 0-3yrs. Secondary end-points were specific IgE, total IgE, eczema and lower respiratory tract infections (LRTI). We conducted random effects combined analyses of the treatment effect, individual patient data (IPD) meta-analyses, and analyses stratified by 25(OH) D level at study entry. Results The analysis showed a 25% reduced risk of asthma/recurrent wheeze at 0-3yrs: adjusted odds ratio (aOR) = 0.74 (95% CI, 0.57-0.96), p = 0.02. The effect was strongest among women with 25(OH) D level >= 30ng/ml at study entry: aOR = 0.54 (0.33-0.88), p = 0.01, whereas no significant effect was observed among women with 25( OH) D level <30ng/ml at study entry: aOR = 0.84 (0.62-1.15), p = 0.25. The IPD meta-analyses showed similar results. There was no effect on the secondary end-points. Conclusions This combined analysis shows that vitamin D supplementation during pregnancy results in a significant reduced risk of asthma/recurrent wheeze in the offspring, especially among women with 25(OH) D level >= 30 ng/ml at randomization, where the risk was almost halved. Future studies should examine the possibility of raising 25(OH) D levels to at least 30 ng/ml early in pregnancy or using higher doses than used in our studies.