Grant Abstract: Vitamin D and Maternal Offspring Health: The Preg D Trial

Grant Number: 3D43TW009118-06
PI Name: Fuleihan
Project Title: Vitamin D and Maternal Offspring Health: The Preg D Trial

Abstract: Hypovitaminosis D is prevalent worldwide and more so in the Middle East. The deleterious effect of vitamin D deficiency on musculoskeletal outcomes across the life course is undeniable. The impact of more subtle insufficiency on maternal-offspring health in general, and musculoskeletal health in particular, is not clear. Most vitamin D randomized controlled trials (RCTs) conducted during pregnancy measured circulating serum 25 hydroxyvitamin D 25OHD levels using various assays, that often were not calibrated. They also did not assess the impact of changes in vitamin D binding protein (VDBP) on assay performance, nor measured free 25OHD. In Specific Aim 1, we will determine the most optimal assay method to measure serum 25OHD in pregnant women and in cord blood. This will enable investigations on the relationship between the various forms of vitamin D with neonatal outcomes (Aim 2), and placental transporters (Aim 3). Most vitamin D RCTs conducted during pregnancy focused on neonatal anthropometric measurements, and maternal obstetrical outcomes. One RCT from the UK randomized subjects to 1,000 IU/day, or to placebo. It revealed no difference in neonatal whole-body BMC in children born to mothers in the wo groups; there was however a possible beneficial effect in neonates born in the winter. Women from the Middle East western population are more likely to be vitamin D deficient. In Specific aim 2, we will investigate the impact of high dose of vitamin D3 (2,857 IU D3/day) compared to a dose close to the Institute of Medicine (IOM) recommended daily allowance (715 IU D3/day), on neonatal bone mineral density (BMD), bone mineral content (BMC), and bone size, in the Preg D RCT. We will also explore effect modulation by season, and the relationship between the various forms of 25OHD measured and neonatal BMD, BMC, and bone size. In utero, skeletal development depends largely on mineral transfer across the placenta, through transcellular active transport mechanisms. In Specific aim 3, we will compare the impact of vitamin D supplementation, high versus low dose, on the RNA expression of placental calcium transporters, and key hormones, that impact offspring bone mass at birth. We will also explore associations between maternal and cord blood 25OHD and placental transporters. The supplement will enhance the parent D43 award. It will support measurements, and analyses on a completed the Preg D RCT. It will provide a rich dataset to augment three Aims of the parent grant. Trainees will: 1) apply skills learned in SHARP and in the advanced quantitative methods modules (Aim 2); 2) develop competitive research projects to implement under the SHARP Fellowship Initiative (SHARP RFI, Aim 3); and 3) partake in the SHARP mentoring network SHARP CAN (Aim 4). The PI for the RCT, Dr El-Hajj Fuleihan, is the PD on the parent grant. She is an established physician-scientist and mentor of several D-43 trainees

Back to Grants Page