Abstract
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 (<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.
Highlights
Vitamin D has a well established role in calcium homeostasis and bone mineralisation, and has been shown to contribute to other biological processes including inflammation [1], immunoregulation and cardiometabolic health [2,3]
There were no differences between the two cohorts of women (HLP and creatine and pregnancy outcomes (CPO)) in any demographic or anthropometric characteristics at early pregnancy (
Our results show that women with lower concentrations of Vitamin D-binding protein (VDBP) at early pregnancy had higher glucose levels at Oral glucose tolerance test (OGTT) and a greater likelihood of developing gestational diabetes mellitus (GDM) at 26–28 weeks gestation compared with women with higher VDBP concentrations, irrespective of free and bioavailable 25(OH)D concentrations
Summary
Vitamin D has a well established role in calcium homeostasis and bone mineralisation, and has been shown to contribute to other biological processes including inflammation [1], immunoregulation and cardiometabolic health [2,3]. Vitamin D deficiency in pregnancy has been linked with several adverse pregnancy outcomes including pre-eclampsia, gestational diabetes mellitus (GDM) and preterm birth [2]. 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. 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). Our findings show that VDBP and total 25(OH)D are associated with GDM and length of gestation, respectively; further investigations using large-scale prospective studies are needed to confirm our findings
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