Prenatal vitamin D supplementation reduces risk of asthma/recurrent wheeze in early childhood: A combined analysis of two randomized controlled trials
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Prenatal vitamin D supplementation reduces risk of asthma/recurrent wheeze in early childhood : A combined analysis of two randomized controlled trials. / Wolsk, Helene M; Chawes, Bo L; Litonjua, Augusto A; Hollis, Bruce W; Waage, Johannes; Stokholm, Jakob; Bønnelykke, Klaus; Bisgaard, Hans; Weiss, Scott T.
In: PLOS ONE, Vol. 12, No. 10, e0186657, 2017.Research output: Contribution to journal › Journal article › Research › peer-review
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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
Y1 - 2017
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
VL - 12
JO - PLoS ONE
JF - PLoS ONE
SN - 1932-6203
IS - 10
M1 - e0186657
ER -
ID: 194772409