The Road Not So Travelled: Should Measurement of Vitamin D Epimers during Pregnancy Affect Our Clinical Decisions?

Abstract

Observational studies suggest an adverse effect of maternal hypovitaminosis D during pregnancy. However, intervention studies failed to show convincing benefit from vitamin D supplementation during pregnancy. With analytical advances, vitamin D can now be measured in ten forms—including as epimers—which were thought to be biologically inactive, but can critically impair immunoassays. The aim of this commentary is to highlight the potential clinical and analytical significance of vitamin D epimers in the interpretation of vitamin D roles in pregnancy. Epimers may contribute a considerable proportion of total vitamin D—especially in the neonate—which renders the majority of common assays questionable. Furthermore, epimers have been suggested to have activity in laboratory studies, and evidence suggests that the fetus contributes significantly to epimer production. Maternal epimer levels contribute significantly to predict neonate circulating 25-hydroxyvitamin D concentrations. In conclusion, the existence of various vitamin D forms (such as epimers) has been established, and their clinical significance remains obscure. These results underscore the need for accurate measurements to appraise vitamin D status, in order to understand the current gap between observational and supplementation studies on the field.

Vitamin D-Binding Protein in Pregnancy and Reproductive Health

“…Indeed, total 25(OH)D concentration often correlates to free 25(OH)D, except in states such as pregnancy where the concentrations of the carrier proteins undergo significant changes themselves [47,48]. Because VDBP levels change drastically during pregnancy, this can influence the concentration of free 25(OH)D as well as other vitamin D metabolites, leading to measurements of total 25(OH)D being no longer representative of vitamin D status in this population [50][51][52]. In fact, this increase in the primary carrier protein is accompanied by an increase in total 25(OH)D and a consistent decline in free 25(OH)D from 15 to 36 weeks gestational age [53].…”

Deconvoluting the Biological Roles of Vitamin D-Binding Protein During Pregnancy: A Both Clinical and Theoretical Challenge

“…In addition, although the existence of various vitamin D forms (such as epimers) has been established, their clinical significance remains obscure. Furthermore, recent data show that at least one epimer form has activity in vitro ( 72 , 73 ). With the development of more advanced assays, a thorough understanding of the interplay among the various vitamin D forms could be achieved.…”

Upregulation of Irisin and Vitamin D-Binding Protein Concentrations by Increasing Maternal 25-Hydrovitamin D Concentrations in Combination with Specific Genotypes of Vitamin D-Binding Protein Polymorphisms

“…In this regard, free 25(OH)D may be a better indicator compared to total 25(OH)D since it remains comparable to levels reported in nonpregnant women [ 41 ]. The analytical significance of several vitamin D metabolites including epimers during pregnancy has been vastly questionable [ 42 ]. Recent studies are shedding light on a plausible biologically active role for epimers in vitamin D metabolism and hence its importance upon interpretation of serum 25(OH)D levels based on the measurement assay being used.…”