Plasma 3-Epi-25-Hydroxycholecalciferol Can Alter the Assessment of Vitamin D Status Using the Current Reference Ranges for Pregnant Women and Their Newborns

J Nutr. 2016 Jan;146(1):70-5. doi: 10.3945/jn.115.220095. Epub 2015 Nov 25.

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.

Objectives: 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.

Keywords: 25(OH)D; 3-epi-25(OH)D3; LC-MS/MS; cord blood; pregnancy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Calcifediol / administration & dosage
  • Calcifediol / blood*
  • Canada / epidemiology
  • Chromatography, Liquid
  • Dietary Supplements
  • Female
  • Fetal Blood / chemistry
  • Humans
  • Infant, Newborn
  • Linear Models
  • Longitudinal Studies
  • Maternal Nutritional Physiological Phenomena*
  • Middle Aged
  • Pregnancy
  • Prevalence
  • Reference Values
  • Socioeconomic Factors
  • Tandem Mass Spectrometry
  • Vitamin D / blood*
  • Vitamin D Deficiency / blood
  • Vitamin D Deficiency / epidemiology*
  • Young Adult

Substances

  • Vitamin D
  • Calcifediol