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Maternal vitamin D-related metabolome and offspring risk of asthma outcomes
Min Kim1, Nicklas Brustad2, Mina Ali2
1Copenhagen Prospective Studies on Asthma in Childhood (COPSAC), Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark; Faculty of Health and Biomedical Science, University of Surrey, Guildford, United Kingdom.
Insights
Higher gestational vitamin D levels are linked to specific maternal metabolic changes, particularly in the sphingomyelin pathway. These changes are associated with a reduced risk of recurrent wheeze and asthma exacerbations in early childhood.
Area of Science:
- Perinatal medicine
- Metabolomics
- Respiratory health
Background:
- Gestational vitamin D deficiency is linked to offspring respiratory diseases.
- The underlying mechanisms remain largely unknown.
Purpose of the Study:
- Investigate the association between maternal vitamin D levels during pregnancy and childhood asthma phenotypes.
- Utilize maternal blood metabolomics to uncover potential mechanisms.
Main Methods:
- Analyzed untargeted blood metabolomics from two large mother-child cohorts (COPSAC2010 and VDAART).
- Employed multivariate models and pathway enrichment analysis to identify vitamin D-associated metabolites and pathways.
- Validated findings in a separate cohort and in vitro cellular models.
Main Results:
- Higher maternal vitamin D levels correlated with distinct metabolic profiles, notably involving the sphingomyelin pathway.
- This maternal metabolic profile was associated with a decreased risk of recurrent wheeze and asthma exacerbations in offspring (ages 0-3).
- In vitro studies showed vitamin D3 increased sphingolipid levels in bronchial epithelial cells.
Conclusions:
- Maternal metabolic alterations, particularly within the sphingomyelin pathway, characterize the protective effect of gestational vitamin D on offspring respiratory health.
- This study provides novel insights into the mechanisms linking maternal vitamin D status to childhood asthma.
Background:
Gestational vitamin D deficiency is implicated in development of respiratory diseases in offspring, but the mechanism underlying this relationship is unknown.
Objective:
We sought to study the link between gestational vitamin D exposure and childhood asthma phenotypes using maternal blood metabolomics profiling.
Methods:
Untargeted blood metabolic profiles were acquired using liquid chromatography-mass spectrometry at 1 week postpartum from 672 women in the Copenhagen Prospective Studies on Asthma in Childhood2010 (COPSAC2010) mother-child cohort and at pregnancy weeks 32 to 38 from 779 women in the Vitamin D Antenatal Asthma Reduction Trial (VDAART) mother-child cohort. In COPSAC2010, we employed multivariate models and pathway enrichment analysis to identify metabolites and pathways associated with gestational vitamin D blood levels and investigated their relationship with development of asthma phenotypes in early childhood. The findings were validated in VDAART and in cellular models.
Results:
In COPSAC2010, higher vitamin D blood levels at 1 week postpartum were associated with distinct maternal metabolome perturbations with significant enrichment of the sphingomyelin pathway (P < .01). This vitamin D-related maternal metabolic profile at 1 week postpartum containing 46 metabolites was associated with decreased risk of recurrent wheeze (hazard ratio [HR] = 0.92 [95% CI 0.86-0.98], P = .01) and wheeze exacerbations (HR = 0.90 [95% CI 0.84-0.97], P = .01) at ages 0 to 3 years. The same metabolic profile was similarly associated with decreased risk of asthma/wheeze at ages 0 to 3 in VDAART (odds ratio = 0.92 [95% CI 0.85-0.99], P = .04). Human bronchial epithelial cells treated with high-dose vitamin D3 showed an increased cytoplasmic sphingolipid level (P < .01).
Conclusions:
This exploratory metabolomics study in 2 independent birth cohorts demonstrates that the beneficial effect of higher gestational vitamin D exposure on offspring respiratory health is characterized by specific maternal metabolic alterations during pregnancy, which involves the sphingomyelin pathway.
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