Relationships between Total, Free and Bioavailable Vitamin D and Vitamin D Binding Protein in Early Pregnancy with Neonatal Outcomes: A Retrospective Cohort Study

Maternal vitamin D deficiency has been associated with adverse neonatal outcomes, however, existing results are inconsistent. Current data focus on total 25-hydroxyvitamin D (25(OH)D) as the common measure of vitamin D status, while additional measures including vitamin D-binding protein (VDBP) and free and bioavailable metabolites have not been explored in relation to neonatal outcomes. We examined whether VDBP and total, free, and bioavailable vitamin D metabolites in early pregnancy are associated with subsequent neonatal outcomes. In this retrospective analysis of 304 women in early pregnancy (<20 weeks gestation), demographic and anthropometric data were collected and total 25(OH)D (chemiluminescent assay), VDBP (polyclonal enzyme-linked immunosorbent assay (ELISA)) and albumin (automated colorimetry) were measured in bio-banked samples. Free and bioavailable 25(OH)D were calculated using validated formulae. Neonatal outcomes were derived from a medical record database. Higher maternal total and free 25(OH)D concentrations were associated with higher neonatal birthweight (β = 5.05, p = 0.002 and β = 18.06, p = 0.02, respectively), including after adjustment for maternal covariates including age, body mass index (BMI) and ethnicity (all p ≤ 0.04). Higher total 25(OH)D and VDBP concentrations were associated with a lower likelihood of neonatal jaundice (odds ratio [OR] [95%CI] = 0.997 [0.994, 1.000], p = 0.04 and 0.98 [0.96, 0.99], p = 0.03, respectively), but these were attenuated after adjustment for the above maternal covariates (both p = 0.09). Our findings suggest a novel association between free 25(OH)D and neonatal birthweight. Total 25(OH)D concentrations were also associated with birthweight, and both total 25(OH)D and VDBP were associated with jaundice, but the latter were not significant after adjustment. These results suggest a potential link between these metabolites and neonatal outcomes; however, further large-scale prospective studies are warranted.

Clinical Usefulness of Bioavailable Vitamin D and Impact of GC Genotyping on the Determination of Bioavailable Vitamin D in a Korean Population

Background. Bioavailable 25-hydroxy vitamin D (25(OH)D) has been suggested for the accurate determination of vitamin D status. The purpose of this study was to determine the utility of bioavailable 25(OH)D in assessing vitamin D status when vitamin D-binding protein (VDBP) was significantly altered by pregnancy and liver cirrhosis (LC). The role of genotyping of GC, a gene encoding VDBP, in the determination of bioavailable 25(OH)D concentration in a Korean population was also evaluated. Methods. This prospective study enrolled a total of 136 subjects (53 healthy controls, 45 patients with LC, and 38 pregnant women) from 2017 to 2018. The concentrations of total 25(OH)D and VDBP were measured, and bioavailable 25(OH)D concentrations were calculated. GC genotyping was performed to determine rs4588 and rs7041 polymorphisms. Clinical and laboratory data were compared among the three groups of subjects. Results. Median VDBP and total 25(OH)D concentrations were 165.2 μg/ml and 18.5 ng/ml in healthy controls, 76.9 μg/ml and 10.5 ng/ml in patients with LC, and 368.9 μg/ml and 17.7 ng/ml in pregnant women, respectively. Compared with controls, patients diagnosed with LC had significantly lower VDBP and total 25(OH)D concentrations (all P<0.001) while pregnant women had significantly higher VDBP concentrations (P<0.001). Although total 25(OH)D concentrations in pregnant women were similar to those in controls (P=0.394), their bioavailable 25(OH)D concentrations were significantly lower (1.2 vs. 3.0 ng/ml; P<0.001). Among all the three groups combined, the genotype-specific bioavailable 25(OH)D and the genotype-independent bioavailable 25(OH)D concentrations did not differ significantly (P=0.299). Conclusions. Our study has demonstrated that bioavailable 25(OH)D concentration reflects vitamin D status more accurately than the total 25(OH)D concentration, especially in pregnant women. In addition, GC genotyping did not significantly affect bioavailable 25(OH)D concentration. Therefore, if VDBP concentration is significantly altered, the measurement of bioavailable 25(OH)D concentration might facilitate the accurate determination of vitamin D status. However, GC genotyping might be unnecessary.