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Meta-Analysis
. 2017 Oct 27;12(10):e0186657.
doi: 10.1371/journal.pone.0186657. eCollection 2017.

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

Helene M Wolsk  1   2 , Bo L Chawes  1   2 , Augusto A Litonjua  2   3 , Bruce W Hollis  4 , Johannes Waage  1 , Jakob Stokholm  1 , Klaus Bønnelykke  1 , Hans Bisgaard  1 , Scott T Weiss  2   3
Affiliations
Meta-Analysis

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

Helene M Wolsk et al. PLoS One. .

Abstract

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 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.

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.

Trial registration: COPSAC2010: ClinicalTrials.gov NCT00856947; VDAART: ClinicalTrials.gov NCT00920621.

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Conflict of interest statement

Competing Interests: HB has been consultant for Chiesi and Boehringer Ingelheim. AAL reports grants from NIH, during the conduct of the study and author royalties from UpToDate, Inc. and Humana Springer Press. STW reports grants from the NIH, and speakers fees from Illumina Corp during the conduct of the study. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Figures

Fig 1
Fig 1
A) The VDAART participants flow, B) The COPSAC2010 participants flow.
Fig 2
Fig 2. Forest plots of the combined analyses of asthma/recurrent wheeze in COPSAC2010 and VDAART.
A) Combined analysis of the effect of randomization group, B) Combined analysis of women with initial 25(OH)D level ≥ 30 ng/ml, C) Combined analysis of women with initial 25(OH)D level < 30 ng/ml. All analyses are adjusted for gender, birth season and fish-oil intervention in COPSAC2010, and center and maternal education level in VDAART. All analyses of the average 25(OH)D level are also adjusted for intervention group. p<0.05 is shown in italic.
Fig 3
Fig 3. Forest plots of the meta-analysis of asthma/recurrent wheeze in all three published randomized trials of vitamin D intervention in pregnancy and subsequent asthma/recurrent wheeze at age 3 years.
See this image and copyright information in PMC

References

    1. Raby BA, Lazarus R, Silverman EK, Lake S, Lange C, Wjst M, et al. Association of Vitamin D Receptor Gene Polymorphisms with Childhood and Adult Asthma. Am J Respir Crit Care Med. 2004;170: 1057–1065. doi: 10.1164/rccm.200404-447OC - DOI - PubMed
    1. Kho AT, Sharma S, Qiu W, Gaedigk R, Klanderman B, Niu S, et al. Vitamin D related genes in lung development and asthma pathogenesis. BMC Med Genomics. 2013;6: 47 doi: 10.1186/1755-8794-6-47 - DOI - PMC - PubMed
    1. Litonjua AA. Childhood asthma may be a consequence of vitamin D deficiency. Curr Opin Allergy Clin Immunol. 2009;9: 202–207. doi: 10.1097/ACI.0b013e32832b36cd - DOI - PMC - PubMed
    1. Camargo CA, Rifas-Shiman SL, Litonjua AA, Rich-Edwards JW, Weiss ST, Gold DR, et al. Maternal intake of vitamin D during pregnancy and risk of recurrent wheeze in children at 3 y of age. Am J Clin Nutr. 2007;85: 788–795. - PMC - PubMed
    1. Devereux G, Litonjua AA, Turner SW, Craig LC, McNeill G, Martindale S, et al. Maternal vitamin D intake during pregnancy and early childhood wheezing. The American Journal of Clinical Nutrition. 2007;85: 853–859. - PubMed

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