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

Helene M Wolsk,Augusto A Litonjua,Hans Bisgaard,Jakob Stokholm,Bruce W Hollis,Bo L Chawes,Klaus Bønnelykke,Johannes Waage,Scott T Weiss

doi:10.1371/journal.pone.0186657

Helene M Wolsk, Augusto A Litonjua + Show 7 more

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BackgroundWe 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.ObjectiveTo 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.MethodsVDAART (N = 806) and COPSAC2010. (N = 581) randomized pregnant women to daily high-dose vitamin D3 (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.ResultsThe 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.ConclusionsThis 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.Trial registrationCOPSAC2010: ClinicalTrials.gov NCT00856947; VDAART: ClinicalTrials.gov NCT00920621

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The analysis showed a 25% reduced risk of asthma/recurrent wheeze at 0-3yrs: adjusted odds ratio = 0.74, p = 0.02
Prenatal vitamin D supplementation and childhood asthma/wheeze by private and public research funds all listed on www.copsac.com
There was no effect on the secondary end-points. 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

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We recently conducted two independent randomized controlled trials (RCTs) of increased vitamin D supplementation during pregnancy to prevent childhood asthma/recurrent wheeze in the offspring by age 3 years: the Vitamin D Antenatal Asthma Reduction Trial (VDAART[7]) and the Copenhagen Prospective Studies on Asthma in Childhood 2010 (COPSAC2010[8]). Both trials indicated a clinically important 20% or greater reduced risk of asthma/recurrent wheeze in the offspring, neither found this effect statistically significant in the primary intent-to-treat analyses[9,10].

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