Maternal-fetal-infant dynamics of the C3-epimer of 25-hydroxyvitamin D.
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.
Clinical Biochemistry, Department of Pediatric Laboratory Medicine, Hospital for Sick Children, Canada; Department of Laboratory Medicine and Pathobiology, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada; Gamma-Dynacare Medical Laboratories, London, Ontario, Canada.
Dana
D
Bailey
Department of Paediatrics, Hospital for Sick Children and University of Toronto, Toronto, Ontario, Canada.
Nandita
N
Perumal
Clinical Biochemistry, Department of Pediatric Laboratory Medicine, Hospital for Sick Children, Canada.
Mehrdad
M
Yazdanpanah
International Center for Diarrheal Disease Research, Bangladesh (ICDDR,B), Dhaka, Bangladesh.
Abdullah
A
Al Mahmud
International Center for Diarrheal Disease Research, Bangladesh (ICDDR,B), Dhaka, Bangladesh; International Center for Maternal and Newborn Health, Department of International Health, The Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
Abdullah H
AH
Baqui
Clinical Biochemistry, Department of Pediatric Laboratory Medicine, Hospital for Sick Children, Canada; Department of Laboratory Medicine and Pathobiology, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada.
Khosrow
K
Adeli
Department of Paediatrics, Hospital for Sick Children and University of Toronto, Toronto, Ontario, Canada.
Daniel E
DE
Roth
D000328:Adult; D002762:Cholecalciferol / Q000008:administration & dosage* / Q000493:pharmacokinetics; D004311:Double-Blind Method; D005260:Female; D005312:Fetal Blood / Q000378:metabolism; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008431:Maternal-Fetal Exchange; D011247:Pregnancy; D011248:Pregnancy Complications / Q000097:blood* / Q000188:drug therapy; D016032:Randomized Controlled Trials as Topic; D053719:Tandem Mass Spectrometry; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000097:blood; D014808:Vitamin D Deficiency / Q000097:blood* / Q000188:drug therapy; D014815:Vitamins / Q000008:administration & dosage* / Q000493:pharmacokinetics
D014815:Vitamins; D014807:Vitamin D; D002762:Cholecalciferol; C104450:25-hydroxyvitamin D
25-Hydroxyvitamin D; C3-epi-25-hydroxyvitamin D; Cord; LC–MS/MS; Maternal