Poster Topical Area: Biomarkers
Poster Board Number: 141
To examine changes in angiogenic proteins from mid to late pregnancy and to describe the impact of vitamin D on angiogenic proteins.
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.
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.
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.
The Pennsylvania State University
University Park, Pennsylvania