title: Plasma 3-Epi-25-Hydroxycholecalciferol Can Alter the Assessment of Vitamin D Status Using the Current Reference Ranges for Pregnant Women and Their Newborns.
abstract: BACKGROUND
  Vitamin D is critical for healthy pregnancies and normal fetal development. It is important to accurately ascertain vitamin D status in mothers and their newborns to establish the optimal vitamin D concentration during pregnancy. There are many different metabolites and epimers of vitamin D in peripheral blood and controversy as to the importance of epimers in estimating vitamin D status in maternal and infant health.
  
  
  OBJECTIVE
  We undertook this study to measure 25-hydroxyvitamin D metabolites and epimers and their relations in maternal and cord blood and to evaluate the impact of the inclusion of epimers on assessing vitamin D status.
  
  
  METHODS
  We performed a substudy in a longitudinal cohort of pregnant women and their infants in Alberta, Canada [APrON (Alberta Pregnancy Outcomes and Nutrition) Study]. Maternal and cord blood plasma collected at the time of newborn delivery was stored at -70°C until testing and assayed for 25-hydroxyergocalciferol [25(OH)D2], 25-hydroxycholecalciferol [25(OH)D3], and 3-epi-25-hydroxycholecalciferol [3-epi-25(OH)D3] by using LC-tandem mass spectrometry. The effect of 3-epi-25(OH)D3 on estimates of vitamin D adequacy was explored by using McNemar's chi-square test at both recommended thresholds of 50 and 75 nmol/L.
  
  
  RESULTS
  Ninety-two pairs of maternal and cord blood samples were obtained. 3-Epi-25(OH)D3 was detected in all samples, comprising 6.0% and 7.8% of 25(OH)D3 in maternal and cord blood, respectively. Positive correlations were found between 25(OH)D3 and 3-epi-25(OH)D3 for both maternal and cord blood (maternal blood: r = 0.34, P = 0.01; cord blood: r = 0.44, P = 0.01). In addition, regression analysis showed a significant association between vitamin D supplementation and 3-epi-25(OH)D3 in maternal and cord blood (β: 0.423; 95% CI: 0.173, 0.672). When 3-epi-25(OH)D3 was not included in plasma vitamin D estimations, 38% of women and 80% of neonates were classified as having an insufficient concentration (<75 nmol/L); however, with 3-epi-25(OH)D3 included, the estimates of insufficiency were significantly lower: 33% and 73% for women and neonates, respectively.
  
  
  CONCLUSIONS
  Using LC-MS/MS we showed the presence of 3-epi-25(OH)D3 in all samples of pregnant women and their cord blood, and when the 3-epimer was included in the estimation of status the prevalence of vitamin D insufficiency (<75 nmol/L) was significantly lower. Our data suggest that the high use of dietary supplements in this group of women contributes to 3-epi-25(OH)D3 concentrations in both maternal and cord blood. Further research on the role of the epimers in characterizing vitamin D status in pregnancy and infancy is imperative.
authors.affiliation: Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada; Departments of fariba.aghajafari@ucalgary.ca.
authors.forename: Fariba
authors.initials: F
authors.lastname: Aghajafari
authors.affiliation: Agricultural, Food, and Nutritional Science and.
authors.forename: Catherine J
authors.initials: CJ
authors.lastname: Field
authors.affiliation: Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada; Departments of.
authors.forename: Doreen
authors.initials: D
authors.lastname: Rabi
authors.affiliation: Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada; Departments of.
authors.forename: Bonnie J
authors.initials: BJ
authors.lastname: Kaplan
authors.affiliation: Research and Development, Doctor's Data, Inc., St. Charles, IL; and.
authors.forename: Jack A
authors.initials: JA
authors.lastname: Maggiore
authors.affiliation: Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada; Departments of.
authors.forename: Maeve
authors.initials: M
authors.lastname: O'Beirne
authors.affiliation: Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada; Departments of.
authors.forename: David A
authors.initials: DA
authors.lastname: Hanley
authors.affiliation: Department of Public Health and Community Medicine, Tufts University, Boston, MA.
authors.forename: Misha
authors.initials: M
authors.lastname: Eliasziw
authors.affiliation: Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada; Departments of.
authors.forename: Deborah
authors.initials: D
authors.lastname: Dewey
authors.affiliation: Obstetrics and Gynecology, University of Alberta, Edmonton, Alberta, Canada;
authors.forename: Sue
authors.initials: S
authors.lastname: Ross
mesh_terms: D000328:Adult; D002112:Calcifediol / Q000008:administration & dosage / Q000097:blood*; D002170:Canada / Q000453:epidemiology; D002853:Chromatography, Liquid; D019587:Dietary Supplements; D005260:Female; D005312:Fetal Blood / Q000737:chemistry; D006801:Humans; D007231:Infant, Newborn; D016014:Linear Models; D008137:Longitudinal Studies; D039382:Maternal Nutritional Physiological Phenomena; D008875:Middle Aged; D011247:Pregnancy; D015995:Prevalence; D012016:Reference Values; D012959:Socioeconomic Factors; D053719:Tandem Mass Spectrometry; D014807:Vitamin D / Q000097:blood*; D014808:Vitamin D Deficiency / Q000097:blood / Q000453:epidemiology*; D055815:Young Adult
chemical_list: D014807:Vitamin D; D002112:Calcifediol
keywords: 25(OH)D; 3-epi-25(OH)D3; LC-MS/MS; cord blood; pregnancy