Exploring associations between maternal vitamin D-binding protein, vitamin D, and offspring asthma/recurrent wheeze

BACKGROUND: Vitamin D-binding protein (DBP) transports vitamin D metabolites and regulates vitamin D levels in circulation. Additionally, maternal vitamin D levels during pregnancy play an important role in lung development and childhood asthma occurrence. OBJECTIVES: In this post hoc analysis of a randomized controlled trial, the joint associations of maternal 25-hydroxyvitamin-D (25OHD) and DBP with offspring asthma/recurrent wheeze, for both the full cohort and stratified by maternal asthma status, are analyzed. Additionally, associations between estimated maternal free 25OHD and offspring asthma/recurrent wheeze are investigated. METHODS: A total of 518 participants from the Vitamin D Antenatal Asthma Reduction Trial were included in this analysis. The primary outcome was offspring asthma/recurrent wheeze by age 3 y. Maternal plasma DBP levels were measured for 517 and 516 participants at 10-18 and 32-38 wk of gestation, respectively. Total 25OHD and DBP levels were compared across haplotypes of the group-specific component (GC) gene, which codes for DBP. Logistic regression models estimated the relationships between maternal DBP, total 25OHD, and offspring asthma/recurrent wheeze. In addition, offspring asthma/recurrent wheeze was modeled as a function of estimated maternal free 25OHD. RESULTS: Maternal DBP levels generally increased as pregnancy progressed. Maternal DBP and total 25OHD levels varied significantly across GC haplotypes. A significant positive interaction effect between maternal DBP and total 25OHD on offspring asthma/recurrent wheeze risk was observed for the subset of mothers without asthma. For the subset of mothers with asthma, we observed a significant negative association between estimated maternal free 25OHD and offspring asthma/recurrent wheeze, surpassing the effects of DBP or total 25OHD individually. CONCLUSIONS: Our study gives insight into the interplay between vitamin D metabolites during pregnancy and their associations with offspring asthma/recurrent wheeze. These results also suggest that maternal free vitamin D during pregnancy may be more biologically relevant than total vitamin D for offspring's respiratory health. This trial was registered at clinicaltrials.gov for VDAART as NCT00920621.