Poster Topical Area: Biomarkers

Location: Auditorium

Poster Board Number: 141

P02-007 - Effects of Maternal Vitamin D Supplementation on Angiogenic Proteins During Pregnancy in Bangladesh

Sunday, Jun 10
8:00 AM – 6:00 PM

Objectives

To examine changes in angiogenic proteins from mid to late pregnancy and to describe the impact of vitamin D on angiogenic proteins.

Methods

This is a substudy of placental angiogenesis (n=695) within the Maternal Vitamin D for Infant Growth randomized controlled trial of vitamin D supplementation. Pregnant women were enrolled at 17-24 (median 20) weeks gestation and randomly assigned to receive: A) placebo, B) 4200 IU, C) 16800 IU or D) 28000 IU vitamin D3 weekly until delivery. Blood samples were taken at baseline and 30 weeks gestation; plasma was stored at -70oC until analysis. Soluble fms-like tyrosine kinase-1 (sFlt-1) was measured by ELISA; all other proteins were measured by multiplex bead-based immunoassay. Pro-angiogenic factors included: vascular endothelial growth factor (VEGF)-A, placental growth factor (PlGF), and angiopoietin-2 (Ang2); anti-angiogenic factors included: sFlt-1 and soluble endoglin (sEng). We calculated the sFlt/PlGF ratio. Concentrations were censored at the lower and upper limits of detection. Tobit regression models were used to estimate the effect of vitamin D on each outcome. Binomial regression was used to estimate the effect of vitamin D on low VEGF-A. Interactions by fetal sex were examined.

Results

Concentrations for all proteins at baseline were similar across treatment groups. For >50% of women, VEGF-A, PlGF, sFlt-1, and sEng increased from mid-pregnancy to 30 weeks gestation, while Ang2 decreased. Median values at 30 weeks for VEGF-A, PlGF, Ang2, sFlt-1, and sEng were 21.4, 661, 7162, 1781, and 984 pg/mL, respectively. In pregnancies carrying females, Ang2 was higher at 30 weeks in group C (7810, 95% CI 1114, 14506 pg/mL) and non-significantly higher in B (7497, p=0.06) vs. placebo; no effect was observed for mothers of males nor for group D. Concentrations of other proteins did not differ between vitamin D groups versus placebo. VEFG-A values were below detection ("low") for 78% of women at baseline and 36% of women at 30 weeks. Risk of low VEGF-A was non-significantly lower in group D vs placebo (RR 0.77, 95% CI 0.59, 1.01), which was attenuated after adjusting for baseline VEGF-A.

Conclusions

Vitamin D starting at mid-pregnancy may alter some angiogenic proteins in maternal blood. Notably, the effect of vitamin D on Ang2 was modified by fetal sex.




Funding Source: Bill and Melinda Gates Foundation
Eunice Kennedy Shriver National Institute of Child Health and Human Development of the National Institutes of Health (NIH) under BIRCWH award number K12HD055882, Career Development Program in Women's Health Research at Penn State

CoAuthors: Eszter Papp, PhD – The Hospital for Sick Children; Jill Korsiak – The Hospital for Sick Children; Kellie Murphy – Mt. Sinai Hospital; Abdullah Mahmud – icddr,b; Daniel Roth, MD, PhD – The Hospital for Sick Children

Alison Gernand

Assistant Professor
The Pennsylvania State University
University Park, Pennsylvania