Pregnancy Changes in Vitamin D Metabolism, Maternal Obesity and the Association with Offspring Bone: A Secondary Analysis of Two US Cohorts

PROJECT SUMMARY/ABSTRACT Maternal vitamin D status during pregnancy will have significant implications for offspring bone health. In order to optimize peak bone mass and deter the development of osteoporosis, a life course approach is needed which begins with improving maternal vitamin D status during pregnancy. Total 25-hydroxyvitamin D (25(OH)D) is commonly used as a biomarker of vitamin D status as it reflects vitamin D exposure. Studies suggest 40-45% of US women have insufficient 25(OH)D concentrations in pregnancy with higher risks among women with obesity. Despite the potential benefits of improving maternal vitamin D status on offspring bone, pregnancy-specific vitamin D guidance does not exist. This has been partly hampered by our incomplete understanding of vitamin D metabolism during pregnancy. Further, high-risk subgroups such as women which begin pregnancy with obesity have been largely understudied in prior work. To better understand the physiological changes in vitamin D metabolism which occur during pregnancy, we propose to characterize multiple vitamin D metabolites and their ratios [termed the “vitamin D metabolome”] in two parallel cohorts of US women collected longitudinally across pregnancy, from early to late phases. In specific aim 1, we will assess the longitudinal changes of total 25(OH)D, 1,25 dihydroxy vitamin D (1,25(OH)2D), the catabolic products: 24,25- dihydroxyvitamin D (24,25(OH)2D), 1,24,25-trihydroxyvitamin D (1,24,25(OH)3D), and 25-hydroxyvitamin D-26,23- lactone (25(OH)D3-26,23-lactone) and their ratios (i.e., 25(OH)D: 24,25(OH)2D, an indicator of CYP24A1 activity), across pregnancy and by maternal pre-pregnancy obesity status. Then in specific aim 2, we will determine the cumulative effect of maternal circulating 25(OH)D level across pregnancy on offspring bone outcomes while considering maternal obesity. This will enable the identification of circulating 25(OH)D thresholds in pregnancy which are associated with optimal offspring bone outcomes and can be used in subsequent clinical trials. This is a secondary analysis in which we will pool participants from two prospective cohorts of pregnant women from the central Arkansas area and with sera available from two or more pregnancy timepoints (12-, 24-, or 36-weeks’ gestation). We will utilize a novel multiplex liquid chromatography tandem mass spectrometry for the assessment of multiple vitamin D metabolites. In addition to offspring bone mass in early childhood, we will use bone turnover markers as a potential adjunctive health outcome of offspring skeletal development. Hence, this proposed research has the potential to significantly contribute towards improving our understanding of the pregnancy-related changes in vitamin D metabolism and also fill gaps regarding these changes among obesity-affected pregnancies. This may lead to identification of novel clinical biomarkers for the assessment of vitamin D during pregnancy. Further, it will identify pregnancy-specific targets for current vitamin D assessment methods and critical time periods for intervention which will directly inform subsequent clinical trials among high-risk subgroups of the US population. Our collaborative research team is well-positioned to do this work with complementary expertise in clinical biochemistry, micronutrient requirements, maternal and child nutrition and development, vitamin D metabolomics, and biostatistics.