- Baseline 25(OH)D, timing of supplementation initiation and prenatal vitamin D supplementation efficacy to prevent offspring asthma or recurrent wheeze
- 5 ways to reduce asthma risk even more:
- Note: Alveolar developement starts at 32 weeks
- See also VitaminDWiki
- 15+ Intervention pages with ASTHMA in title
Baseline 25(OH)D, timing of supplementation initiation and prenatal vitamin D supplementation efficacy to prevent offspring asthma or recurrent wheeze
Am J Clin Nutr. 2023 Apr 17;S0002-9165(23)46848-7. doi: 10.1016/j.ajcnut.2023.04.019
Iskander L C Shadid 1, Nicklas Brustad 2, Mengdi Lu 3, Bo L Chawes 2, Hans Bisgaard 2, Robert S Zeiger 4, George T O'Connor 5, Leonard B Bacharier 6, Henk-Jan Guchelaar 7, Augusto A Litonjua 8, Scott T Weiss 3, Hooman Mirzakhani 9
Background: Prenatal vitamin D deficiency is associated with asthma or recurrent wheeze in offspring. However, evidence from randomized trials on the efficacy of vitamin D supplementation is inconclusive.
Objective: To examine the differential efficacy of prenatal vitamin D supplementation based on maternal baseline vitamin D status and starting time of supplementation to prevent early life asthma or recurrent wheeze.
Method: We conducted a secondary analysis of the Vitamin D Antenatal Asthma Reduction Trial (VDAART), a randomized double-blind trial of prenatal vitamin D supplementation initiated at 10-18 weeks of gestation (intervention 4400IU/daily vs placebo 400IU/daily) to prevent offspring asthma or recurrent wheeze by age of 6 years. We assessed the effect modification of supplementation by maternal baseline vitamin D status at enrollment and timing of initiation of supplementation.
Results: An inverse relationship was observed between maternal 25(OH)D levels at trial entry and 25(OH)D levels during late pregnancy (32-38 weeks of gestation) in both supplementation arms (p<0.001). Overall, supplementation efficacy was not dependent on maternal baseline 25(OH)D status. However, a trend towards the reduction of asthma or recurrent wheeze was observed across baseline groups in the intervention arm (p=0.01) with the greatest reduction in the most severely vitamin D deficient women (25(OH)D<12 ng/ml, aOR=0.48, CI=0.17-1.34). Gestational age at trial enrollment modified supplementation efficacy, showing a greater reduction of offspring asthma or recurrent wheeze with earlier intervention during pregnancy (aOR=0.85, CI=0.76-0.95), particularly in women at 9-12 weeks pregnant (aOR=0.45, CI=0.24-0.82).
Conclusion: Pregnant women with severe vitamin D deficiency show the greatest 25(OH)D improvement due to the supplementation. In these women, a dose of 4400 IU vitamin D might have a protective effect on early life offspring asthma or recurrent wheeze. Gestational age is suggested to modify the efficacy of prenatal vitamin D supplementation, showing the highest beneficial effect if supplementation is started during the first trimester of pregnancy.
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VDAARDT - 15 year results - Feb 2024
Prenatal vitamin D supplementation to prevent childhood asthma: 15-year results from the Vitamin D Antenatal Asthma Reduction Trial (VDAART)Journal of Allergy and Clinical Immunology Volume 153, Issue 2, February 2024, Pages 378-388 https://doi.org/10.1016/j.jaci.2023.10.003 PDF behind paywall
Scott T. Weiss MD, MS a; Hooman Mirzakhani MD, PhD, MMSc a; Vincent J. Carey PhD a
This article provides an overview of the findings obtained from the Vitamin D Antenatal Asthma Reduction Trial (VDAART) spanning a period of 15 years. The review covers various aspects, including the trial’s rationale, study design, and initial intent-to-treat analyses, as well as an explanation of why those analyses did not achieve statistical significance. Additionally, the article delves into the post hoc results obtained from stratified intent-to-treat analyses based on maternal vitamin D baseline levels and genotype-stratified analyses.
These results demonstrate a statistically significant reduction in asthma among offspring aged 3 and 6 years when comparing vitamin D supplementation (4400 IU/d) to the standard prenatal multivitamin with vitamin D (400 IU/d). Furthermore, these post hoc analyses found that vitamin D supplementation led to a decrease in total serum IgE levels and improved lung function in children compared to those whose mothers received a placebo alongside the standard prenatal multivitamin with vitamin D. Last, the article concludes with recommendations regarding the optimal dosing of vitamin D for pregnant women to prevent childhood asthma as well as suggestions for future trials in this field.
Section snippets
Evidence of vitamin D and asthma relationship before vitamin D antenatal asthma reduction trial (VDAART)
It is widely recognized that wheezing is prevalent in the first few years of life, with approximately 40% of children wheezing at or before the age of 3. This percentage decreases to 20% by the age of 6. 24 The dynamics of wheezing at an early age are a function of airway size, lung maturity based on gestational age, and viral illnesses. Wheezing syndromes may not be diagnostically separable early in life, but clinically severe and/or persistent wheezing usually signifies asthma. Thus, it is not ....
Design of the VDAART study
This study is an ancillary analysis from the VDAART study, which is registered with ClinicalTrials.gov (NCT00902621). The trial was funded by the US National Heart, Lung, and Blood Institute in 2008 (R01 HL091528 and UH3 OD023268). the VDAART was a double-blind, placebo-controlled trial of pregnant women who had a personal or family history of allergy or asthma. These women were randomly assigned to receive either treatment (4000 IU of vitamin D daily plus a multivitamin [400 IU]) or placebo;;;;
Three-year results
The relationship between prenatal vitamin D supplementation and offspring asthma or recurrent wheeze outcome at age 3 years was published in JAMA in 2016.36 The analysis used a standard intent-to-treat (ITT) approach, and a time-to-event analysis was used. These analyses were specified beforehand, as detailed at ClinicalTrials.gov (NCT00920621). The results are visually presented in Fig 2. The result indicated a 20% reduction of asthma in the treatment group compared to the control group,
What factors influenced the outcome of the ITT analysis?
When examining ITT outcomes at year 3 and year 6, it is important to consider several factors that influenced the findings. The first factor was that the dose of vitamin D provided to the treatment group was likely too low to timely induce sufficient levels. According to the standards of sufficiency set by either the Institute of Medicine (20 ng/mL) or the Endocrine Society (30 ng/mL), the treatment group achieved significantly higher sufficiency rate compared to the control group at 32 and 38
Meta-analysis
The importance of the misclassification finding can be evaluated through a meta-analysis that retains the ITT analysis approach but includes adjustments for participants’ initial baseline levels of vitamin D at randomization. It is important to note that although this analysis is considered post hoc, it still adheres to the original ITT design. This approach increases statistical power and enables control for baseline differences in vitamin D levels in the treatment and control groups at trial....
Genetic findings that strengthen the possibility of a causal relationship between vitamin D and childhood asthma
The most important and replicated genetic locus associated with childhood asthma is located on chromosome 17q21, which encompasses 4 genes: IKFZ3, ZPBP2, ORMDL3, and GSDMB.44 The protective effect of vitamin D might be influenced by maternal variations in the 17q21 functional single nucleotide polymorphism (SNP) rs12936231. We stratified the VDAART’s results by maternal rs12936231 genotype.45 The post hoc genotype-stratified ITT analysis showed that the maternal GG and the GC genotypes protect....
Summary
Table I summarizes the beneficial effects of vitamin D on asthma prevention. Vitamin D plays a crucial role throughout pregnancy, from conception to delivery and beyond, as the fetus transitions from maternal innate immunity to its own innate and adaptive immunity. Notably, vitamin D sufficiency early in pregnancy has a greater impact on reducing asthma outcomes in the child compared to sufficiency later in pregnancy. It is important to recognize that nutrient trials are fundamentally different ...
Conclusion and recommendations for future studies
We would recommend that all pregnant women consider a daily intake of at least 4400 IU vitamin D3 throughout their pregnancy, starting at the time of conception. It is worth noting that our detailed monitoring of potential adverse events found no attributable adverse events to vitamin D at this dose, during both 3-year and 6-year follow-up intervals, for both mother and child.36,37 However, we would note that this dosage is likely not optimum to achieve a serum level of at least 30 ng/mL for...
Original VDAART study (881 women, etc.) - 2014
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- " ...we are conducting VDAART, a randomized, double-blind, placebo-controlled clinical trial among
881 pregnant women with
either history of asthma or allergies in themselves or the biological father. "
5 ways to reduce asthma risk even more:
- Higher dose
- Start before 9th week
- Use a loading dose
- Use weekly dosing in place of daily
- Also use Vitamin D Receptor activator
Note: Alveolar developement starts at 32 weeks
See also VitaminDWiki
- Overview Asthma and Vitamin D
- Asthma treated by Vitamin D - 13th Meta-analysis – July 2022
- Vitamin D is cost-effective to give to asthmatic children in Columbia - Feb 2023
- Reduction of infant asthma may require good vitamin D when lung development starts (4 weeks) – March 2017
15+ Intervention pages with ASTHMA in title
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