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Clinical Chemistry and Laboratory Medicine (CCLM)

Published in Association with the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM)

Editor-in-Chief: Plebani, Mario

Ed. by Gillery, Philippe / Greaves, Ronda / Lackner, Karl J. / Lippi, Giuseppe / Melichar, Bohuslav / Payne, Deborah A. / Schlattmann, Peter


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Reference intervals for serum total vitamin B12 and holotranscobalamin concentrations and their change points with methylmalonic acid concentration to assess vitamin B12 status during early and mid-pregnancy

Theresa H. Schroder
  • Food, Nutrition and Health Program, Faculty of Land and Food Systems, The University of British Columbia, Vancouver, BC, Canada
  • British Columbia Children’s Hospital Research Institute, Vancouver, BC, Canada
  • Other articles by this author:
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/ Amy Tan
  • Food, Nutrition and Health Program, Faculty of Land and Food Systems, The University of British Columbia, Vancouver, BC, Canada
  • British Columbia Children’s Hospital Research Institute, Vancouver, BC, Canada
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/ Andre Mattman
  • Department of Clinical Chemistry and Laboratory Medicine, St Paul’s Hospital, Vancouver, BC, Canada
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/ Graham Sinclair
  • British Columbia Children’s Hospital Research Institute, Vancouver, BC, Canada
  • Department of Pathology and Laboratory Medicine, Faculty of Medicine, The University of British Columbia, Vancouver, BC, Canada
  • BC Children’s Hospital and BC Women’s Health Centre, Vancouver, BC, Canada
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/ Susan I. Barr
  • Food, Nutrition and Health Program, Faculty of Land and Food Systems, The University of British Columbia, Vancouver, BC, Canada
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/ Hilary D. Vallance
  • British Columbia Children’s Hospital Research Institute, Vancouver, BC, Canada
  • Department of Pathology and Laboratory Medicine, Faculty of Medicine, The University of British Columbia, Vancouver, BC, Canada
  • BC Children’s Hospital and BC Women’s Health Centre, Vancouver, BC, Canada
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/ Yvonne Lamers
  • Corresponding author
  • British Columbia Children’s Hospital Research Institute, 950 W 28th Ave, Vancouver, BC V5Z 4H4, Canada
  • Food, Nutrition and Health Program, Faculty of Land and Food Systems, The University of British Columbia, FNH 245, 2205 East Mall, Vancouver, BC V6T 1Z4, Canada
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Published Online: 2019-05-14 | DOI: https://doi.org/10.1515/cclm-2018-1337

Abstract

Background

Maternal vitamin B12 (B-12) adequacy is important for maternal health and optimal fetal growth. However, pregnancy-specific cut-offs for B-12 biomarkers are lacking.

Methods

Reference intervals for serum total B-12, holotranscobalamin (holoTC) and methylmalonic acid (MMA) concentrations were calculated following CLSI EP28-A3c guidelines in 723 pregnant women of European (50%) and South Asian (50%) ethnicity, residing in British Columbia, Canada, at median (range) 11.4 (8.3–13.9) and 16.1 (14.9–20.9) weeks of gestation. Change point analyses described relationships between log serum MMA concentration with serum total B-12 and holoTC concentrations, assuming linear-linear relationships.

Results

The central 95% reference interval limits indicated that serum total B-12 <89.9 and <84.0 pmol/L, holoTC <29.5 and <26.0 pmol/L and MMA >371 and >374 nmol/L, in the first and second trimesters, respectively, may indicate B-12 deficiency in pregnant women. The lower limits of total B-12 and holoTC and the upper limits of MMA significantly differed by ethnicity in both trimesters. According to the change point analysis, total B-12 <186 and <180 pmol/L and holoTC <62.2 and <67.5 pmol/L in the first and second trimesters, respectively, suggested an increased probability of impaired intracellular B-12 status, with no difference between ethnicities.

Conclusions

We present novel reference limits and change points for B-12 biomarkers, which may be employed to identify possible B-12 deficiency in women during early and mid-pregnancy. Future research is needed to validate these cut-offs and determine the predictors and functional outcomes associated with impaired B-12 status in ethnically diverse populations.

Keywords: change point analysis; ethnicity; first trimester; holotranscobalamin; methylmalonic acid; pregnancy; reference interval; second trimester; vitamin B12

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About the article

aTheresa H. Schroder and Amy Tan shared first authorship.


Received: 2018-12-17

Accepted: 2019-03-05

Published Online: 2019-05-14


Author contributions: THS and YL designed the study and led the sample analysis; AT led the data retrieval from the Perinatal Data Registry; AT and YL led the data analysis; AM, GS and HDV provided input on study design, execution and data interpretation. SIB contributed to data analysis and interpretation. THS wrote the first draft of the manuscript; AT and YL are main contributors to the manuscript writing; and AM, GS, SIB and HDV provided critical evaluation and input into the manuscript. All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

Research funding: This study was supported by the Canadian Institutes for Health Research/Canada Research Chair Program, and a grant of no charge materials from Abbott Laboratories.

Employment or leadership: None declared.

Honorarium: None declared.

Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.

Disclaimer: All inferences, opinions, and conclusions drawn in this publication are those of the authors, and do not reflect the opinions or policies of Perinatal Services BC.


Citation Information: Clinical Chemistry and Laboratory Medicine (CCLM), 20181337, ISSN (Online) 1437-4331, ISSN (Print) 1434-6621, DOI: https://doi.org/10.1515/cclm-2018-1337.

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