Maternal-fetal-infant dynamics of the C3-epimer of 25-hydroxyvitamin D

Abstract

Background: Poor vitamin D status (i.e. low serum 25-hydroxyvitamin D (25(OH)D)) has been associated with adverse clinical outcomes during pregnancy and childhood. However, the interpretation of serum 25(OH)D levels may be complicated by the presence of the C3-epimer of 25(OH)D. We aimed to quantify C3-epi-25(OH)D3 in pregnant women and fetuses, to explore the relationship of the C3-epimer between maternal and cord samples, and to establish whether infant C3-epimer abundance is explained by prenatal formation.

Methods: In a sub-study of a randomized trial of prenatal vitamin D3, 25(OH)D3 and C3-epi-25(OH)D3 were quantified by LC-MS/MS in 71 sets of mother-fetus-infant serum samples, including maternal delivery specimens, cord blood, and infant specimens acquired at 3-28 weeks of age.

Results: Without supplementation, median concentrations of C3-epi-25(OH)D₃ were higher in infants (6.80 nmol/L) than mothers (0.45 nmol/L) and cord blood (0 nmol/L). However, there was substantial variation such that C3-epi-25(OH)D₃ accounted for up to 11% (maternal), 14% (cord), and 25% (infant) of the total 25(OH)D₃. Supplemental vitamin D₃ significantly increased maternal-fetal C3-epi-25(OH)D₃, and was a preferential source of C3-epi-25(OH)D₃ compared to basal vitamin D, possibly due to C3-epi-cholecalciferol in the supplement. Multivariate regression did not suggest transplacental transfer of C3-epi-25(OH)D₃, but rather indicated its generation within the fetal-placental unit from maternally-derived 25(OH)D₃. Neither maternal nor fetal C3-epi-25(OH)D₃ is accounted for the relatively high concentrations of infant C3-epi-25(OH)D₃, suggesting rapid postnatal generation.

Conclusions: C3-epi-25(OH)D₃ is present in some pregnant women and fetuses, but does not appear to be efficiently transferred transplacentally. High C3-epimer concentrations in infancy are probably due to postnatal formation rather than fetal stores.

Keywords: 25-Hydroxyvitamin D; C3-epi-25-hydroxyvitamin D; Cord; LC–MS/MS; Maternal.