Less Asthma if mother took vitamin D while pregnant

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 16 October 2023 https://doi.org/10.1016/j.jaci.2023.10.003

Scott T. Weiss MD, MS a, Hooman Mirzakhani MD, PhD, MMSc a, Vincent J. Carey PhD a, George T. O’Connor MD b, Robert S. Zeiger MD c, Leonard B. Bacharier MD d, Jeffrey Stokes MD e, Augusto A. Litonjua MD, MPH f

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 . . .

Vitamin D Life - Overview Asthma and Vitamin D contains:

{include}

Vitamin D Life - Severe asthmatics willing to pay 5180 dollars for relief, Vitamin D needed costs only 45 dollars – Sept 2023

18+ Vitamin D Life Pregnancy pages with ASTHMA in the title

This list is automatically updated

{LIST()}

19+ Vitamin D Life Pregnancy pages with AUTISM in the title

This list is automatically updated

{LIST()}