Individual study results in VDAART and COPSAC₂₀₁₀ and combined analyses of the effect of vitamin D vs. placebo on the secondary end-points at age 0–3.

<p>All analyses are adjusted for gender, birth season and fish-oil intervention in COPSAC₂₀₁₀, and center and maternal education level in VDAART. Lower respiratory tract infections (LRTI) are analyzed by Poisson regression model. *Random effects meta-analysis.</p

Forest plots of the meta-analysis of asthma/recurrent wheeze in all three published randomized trials of vitamin D intervention in pregnancy and subsequent asthma/recurrent wheeze at age 3 years.

<p>Forest plots of the meta-analysis of asthma/recurrent wheeze in all three published randomized trials of vitamin D intervention in pregnancy and subsequent asthma/recurrent wheeze at age 3 years.</p

Prenatal vitamin D supplementation reduces risk of asthma/recurrent wheeze in early childhood: A combined analysis of two randomized controlled trials - Fig 1

<p>A) The VDAART participants flow, B) The COPSAC₂₀₁₀ participants flow.</p

Meta-analyses of individual patient data (IPD), of vitamin D vs. placebo on the primary and secondary end-points at age 0–3.

<p>All analyses are adjusted for gender, birth season, fish-oil intervention, center and maternal education level. Lower respiratory tract infections (LRTI) are analyzed by Poisson regression model.</p

Forest plots of the combined analyses of asthma/recurrent wheeze in COPSAC₂₀₁₀ and VDAART.

<p>A) Combined analysis of the effect of randomization group, B) Combined analysis of women with initial 25(OH)D level ≥ 30 ng/ml, C) Combined analysis of women with initial 25(OH)D level < 30 ng/ml. All analyses are adjusted for gender, birth season and fish-oil intervention in COPSAC₂₀₁₀, and center and maternal education level in VDAART. All analyses of the average 25(OH)D level are also adjusted for intervention group. p<0.05 is shown in italic.</p

Characteristics of the two trials.

<p>Characteristics of the two trials.</p

The Role of Vitamin D in the Transcriptional Program of Human Pregnancy

<div><p>Background</p><p>Patterns of gene expression of human pregnancy are poorly understood. In a trial of vitamin D supplementation in pregnant women, peripheral blood transcriptomes were measured longitudinally on 30 women and used to characterize gene co-expression networks.</p><p>Objective</p><p>Studies suggest that increased maternal Vitamin D levels may reduce the risk of asthma in early life, yet the underlying mechanisms have not been examined. In this study, we used a network-based approach to examine changes in gene expression profiles during the course of normal pregnancy and evaluated their association with maternal Vitamin D levels.</p><p>Design</p><p>The VDAART study is a randomized clinical trial of vitamin D supplementation in pregnancy for reduction of pediatric asthma risk. The trial enrolled 881 women at 10–18 weeks of gestation. Longitudinal gene expression measures were obtained on thirty pregnant women, using RNA isolated from peripheral blood samples obtained in the first and third trimesters. Differentially expressed genes were identified using significance of analysis of microarrays (SAM), and clustered using a weighted gene co-expression network analysis (WGCNA). Gene-set enrichment was performed to identify major biological pathways.</p><p>Results</p><p>Comparison of transcriptional profiles between first and third trimesters of pregnancy identified 5839 significantly differentially expressed genes (FDR<0.05). Weighted gene co-expression network analysis clustered these transcripts into 14 co-expression modules of which two showed significant correlation with maternal vitamin D levels. Pathway analysis of these two modules revealed genes enriched in immune defense pathways and extracellular matrix reorganization as well as genes enriched in notch signaling and transcription factor networks.</p><p>Conclusion</p><p>Our data show that gene expression profiles of healthy pregnant women change during the course of pregnancy and suggest that maternal Vitamin D levels influence transcriptional profiles. These alterations of the maternal transcriptome may contribute to fetal immune imprinting and reduce allergic sensitization in early life.</p><p>Trial Registration</p><p>clinicaltrials.gov <a href="http://clinicaltrials.gov/ct2/results?term=NCT00920621" target="_blank">NCT00920621</a></p></div

Population Characteristics of 30 pregnant women.

<p>Population Characteristics of 30 pregnant women.</p

Functional Pathway Enrichment of Genes in Green Module.

<p>Functional Pathway analysis of genes in green module revealing most enriched pathways based on InterPro, Pathway Commons and Transcription Factor target databases. The distance between groups of genes reflects the strength of their relationship and groups of genes that are more closely related are clustered together. Black circle = nodes, grey diamonds = enriched functional pathways</p

Transcription factor enrichment analysis of Green module genes.

<p>CREB1 transcription factor network depicting CREB1 in center and known interactions among 72 genes demonstrating various functionality within the green module. Hypergeometric test adjusted for multiple comparisons using Benjamini & Hochberg (<i>p</i><0.05).</p