Prenatal vitamin D supplementation reduces risk of asthma/recurrent wheeze in early childhood: A combined analysis of two randomized controlled trials.
PLoS One. 2017 Oct 27;12(10):e0186657. doi: 10.1371/journal.pone.0186657. eCollection 2017.
Wolsk HM1,2, Chawes BL1,2, Litonjua AA2,3, Hollis BW4, Waage J1, Stokholm J1, Bønnelykke K1, Bisgaard H1, Weiss ST2,3.
Reduces before Birth
- Reduction of infant asthma may require good vitamin D when lung development starts (4 weeks) – March 2017
- Smoking while pregnant lowers vitamin D and increases child asthma by 3.6 X – Aug 2011
Smoking reduces vitamin D
Reduces after Birth
- Overview Asthma and Vitamin D
- Vitamin D supplements could halve risk of serious asthma attacks – Cochrane conclusion – Sept 2016
- Childhood asthma problems eliminated for months by 600,000 IU of Vitamin D – June 2017
- Asthma reduced 60 percent with vitamin D supplementation – meta-analysis 2014, 2015
- Asthma attacks reduced in half if Vitamin D level higher than 42 nanograms – RCT May 2014
- The worse the bronchial asthma, the lower the vitamin D – Jan 2017
- Maternal vitamin D status during pregnancy and risk of childhood asthma: A meta-analysis of prospective studies May 2017
Sweet spot = 70 nmol. Meta-analaysis of 15 studies found that 28 ng resulted in the least asthma in offspring
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.
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.
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.
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.
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.
PMID: 29077711 DOI: 10.1371/journal.pone.0186657