Interactive Effects of Maternal Vitamin D Binding Protein and Vitamin D on Offspring Asthma

RationaleVitamin-D-binding-protein transports vitamin-D metabolites and regulates vitamin-D levels in circulation. Additionally, maternal vitamin-D levels during pregnancy plays an important role in lung development and childhood asthma occurrence. ObjectivesThis study analyzes the joint effect of maternal 25-hydroxyvitamin-D and vitamin-D-binding-protein on offspring asthma. Methods806 mother-child pairs who participated in the Vitamin D Antenatal Asthma Reduction Trial were included in this analysis. The primary outcome was offspring asthma by age 3. Maternal plasma vitamin-D-binding-protein levels were measured for 515 participants at 10-18 and 32-38 weeks of gestation. Logistic regression models estimated the relationships between maternal vitamin-D-binding-protein, total 25-hydroxyvitamin-D, and offspring asthma. In addition, offspring asthma was modeled as a function of estimated free 25-hydroxyvitamin-D. A bootstrap approach was used for robust confidence interval estimation. Measurements and Main ResultsMaternal vitamin-D-binding-protein levels generally increased as pregnancy progressed. A significant positive interaction effect between maternal vitamin-D-binding-protein and total 25-hydroxyvitamin-D on offspring asthma risk was observed for both the full cohort and the subset of mothers with asthma, suggesting that the protective effect of total 25-hydroxyvitamin-D increases with lower levels of vitamin-D-binding-protein. For mothers with asthma, estimated maternal free 25-hydroxyvitamin-D was found to have a significant protective effect against offspring asthma, surpassing the effects of vitamin-D-binding-protein or total 25-hydroxyvitamin-D individually. ConclusionsThese results highlight the interplay between vitamin-D metabolites during pregnancy and their protective effects for offspring asthma. These results also provide evidence for the free hormone hypothesis, which suggests that free vitamin-D is more biologically relevant than total vitamin-D.