Early Pregnancy Vitamin D Binding Protein Is Independently Associated with the Development of Gestational Diabetes: A Retrospective Cohort Study

Abstract

<jats:p>Background: Vitamin D-binding protein (VDBP) has been implicated in several adverse pregnancy outcomes either directly or indirectly via influencing the concentrations of biologically active vitamin D metabolites. However, human studies exploring these metabolites in pregnancy remain sparse. Here, we examine whether VDBP and total, free, and bioavailable 25-hydroxyvitamin D (25(OH)D) metabolites in early pregnancy are associated with subsequent adverse pregnancy outcomes. Methods: We conducted a retrospective analysis of 304 pregnant women in early pregnancy (&lt;20 weeks gestation). The demographic characteristics, anthropometric data, and total 25(OH)D were measured and plasma or serum samples were collected and bio-banked. Using these samples, we measured VDBP (polyclonal ELISA) and albumin (automated colorimetry), and calculated free and bioavailable 25(OH)D using validated formulae. Pregnancy outcomes were derived from scanned medical records. Regression models were used to analyse the relationships between vitamin D metabolites in early pregnancy and subsequent pregnancy outcomes (gestational diabetes mellitus (GDM), pre-eclampsia, preterm birth), with adjustment for predetermined clinically relevant maternal factors including age, body mass index (BMI), and ethnicity. Results: Lower VDBP concentrations were associated with higher glucose levels and a greater likelihood of developing GDM at 26–28 weeks gestation (odds ratio [OR] (95% CI) = 0.98 (0.97,0.99), p = 0.015). This finding remained significant after adjustment for maternal covariates including age, BMI, and ethnicity (β = −0.003, p = 0.03). Lower total, free and bioavailable 25(OH)D, but not VDBP, were associated with a shorter length of gestation, but only the relationship with total 25(OH)D remained significant after adjustment for the above maternal covariates (β = 0.02, p = 0.006). Conclusions: This is the first study to examine VDBP, and total, free and bioavailable 25(OH)D in relation to pregnancy outcomes in a well characterised multi-ethnic cohort of pregnant women. Our findings show that VDBP and total 25(OH)D are associated with GDM and length of gestation, respectively; however, further investigations using large-scale prospective studies are needed to confirm our findings.</jats:p>

Post Hoc Analysis of National Institute of Child Health and Human Development Vitamin-D Pregnancy Cohort and The Role of Functional Vitamin-D Deficiency in Pregnancy

“…Vitamin D Binding Protein (VDBP) genotype, which is associated with variations in vitamin D status (68), has been recently associated with the occurrence of premature membrane rupture and pregnancy loss as well gestational diabetes and neonatal outcomes such as birth weight (69)(70)(71).…”

“…Vitamin D-binding protein genotype, which is associated with variations in vitamin D status, 68 has been recently associated with the occurrence of premature membrane rupture and pregnancy loss as well gestational diabetes and neonatal outcomes such as birth weight. [69][70][71] Additionally, studies looking into the relationship between iPTH and free 25(OH)D concentrations are also warranted. This study, as well as other similar studies, have only explored the relationship between iPTH and total 25(OH)D, not looking into the possible impact of free 25 (OH)D. Further research is still needed in this area.…”

Vitamin D binding protein correlate with estrogen increase after administration of human chorionic gonadotropin but do not affect ovulation, embryo, or pregnancy outcomes

“…state their results that DBP is highly expressed in the placenta and the decidua in women with spontaneous miscarriages, potentially causing a less efficient transport of vitamin D to the fetus ( 17 ). Further studies showed that DBP is related to pregnancy complications such as pre-eclampsia (up-regulated with fold changes 3.38 in early-onset preeclampsia) ( 18 , 19 ), gestational diabetes (lower DBP concentrations were associated with higher glucose levels and a greater likelihood of developing GDM at 26–28 weeks gestation (odds ratio [OR] (95% CI) = 0.98 (0.97,0.99), P = 0.015)) ( 20 ), preterm birth (DBP is reduced, P=0.04) ( 21 , 22 ), fetal growth restriction (DBP was significantly reduced (control versus FGR, P< 0.05) and strongly associated with idiopathic fetal growth restriction (P< 0.01)) ( 23 ) as well as reduced birthweight ( 24 ).…”

Links Between Vitamin D-Binding Protein, Alpha-1 Antitrypsin and Neutrophil Proteins in Meconium

“…VDBP (58 kDa), an abundant serum protein linked to numerous biological processes during pregnancy, is a glycosylated α 2 -globulin produced in the liver [ 5,6,7,8,9]. VDBP is bound to specific, activated regions on the neutrophil plasma membrane using myeloperoxidase released from the azurophilic granules [10].…”