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

TY - JOUR

T1 - Prenatal vitamin D supplementation reduces risk of asthma/recurrent wheeze in early childhood

T2 - A combined analysis of two randomized controlled trials

AU - Wolsk, Helene M

AU - Chawes, Bo L

AU - Litonjua, Augusto A

AU - Hollis, Bruce W

AU - Waage, Johannes

AU - Stokholm, Jakob

AU - Bønnelykke, Klaus

AU - Bisgaard, Hans

AU - Weiss, Scott T

PY - 2017/10

Y1 - 2017/10

N2 - 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.

AB - 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.

KW - Asthma/prevention & control

KW - Child, Preschool

KW - Female

KW - Humans

KW - Placebos

KW - Pregnancy

KW - Prenatal Care

KW - Randomized Controlled Trials as Topic

KW - Recurrence

KW - Respiratory Sounds

KW - Vitamin D/administration & dosage

U2 - 10.1371/journal.pone.0186657

DO - 10.1371/journal.pone.0186657

M3 - Journal article

C2 - 29077711

SN - 1932-6203

VL - 12

JO - PLoS Computational Biology

JF - PLoS Computational Biology

IS - 10

M1 - e0186657

ER -