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. 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. 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. 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. 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.
Boyd et al. (Wed,) studied this question.