Startseite 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
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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 , Amy Tan , Andre Mattman , Graham Sinclair , Susan I. Barr , Hilary D. Vallance und Yvonne Lamers EMAIL logo
Veröffentlicht/Copyright: 14. Mai 2019
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Clinical Chemistry and Laboratory Medicine (CCLM)
Aus der Zeitschrift Clinical Chemistry and Laboratory Medicine (CCLM) Band 57 Heft 11

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

Acknowledgments

The authors thank the staff at the BC Prenatal Screening Laboratory for their support in sample collection; Benny Chan, Matthew Saunders, Ori Nevares and Pablo Elizondo from UBC for their support in sample processing; Dr. Benjamin Jung for overseeing the serum total vitamin B-12 analyses; and Dr. Arianne Albert from the Women’s Health Research Institute for statistical support.

  1. 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.

  2. 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.

  3. Employment or leadership: None declared.

  4. Honorarium: None declared.

  5. 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.

  6. 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.

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Received: 2018-12-17
Accepted: 2019-03-05
Published Online: 2019-05-14
Published in Print: 2019-10-25

©2019 Walter de Gruyter GmbH, Berlin/Boston

Artikel in diesem Heft

  1. Frontmatter
  2. Editorial
  3. Identification and management of spurious hemolysis: controversies, concerns and criticisms
  4. Reviews
  5. CYP24A1 and SLC34A1 genetic defects associated with idiopathic infantile hypercalcemia: from genotype to phenotype
  6. Meta-analysis: compared with anti-CCP and rheumatoid factor, could anti-MCV be the next biomarker in the rheumatoid arthritis classification criteria?
  7. Opinion Paper
  8. Collection, transport and storage procedures for blood culture specimens in adult patients: recommendations from a board of Italian experts
  9. General Clinical Chemistry and Laboratory Medicine
  10. Using the hemoglobin-binding Staphylococcus aureus protein IsdH to enable plasma analysis of hemolyzed blood samples
  11. Handling of hemolyzed serum samples in clinical chemistry laboratories: the Nordic hemolysis project
  12. Clinical biomarker innovation: when is it worthwhile?
  13. Impact of total automation consolidating first-line laboratory tests on diagnostic blood loss
  14. Diagnostic and prognostic value of the D-dimer test in emergency department patients: secondary analysis of an observational study
  15. Screening of chemical libraries in pursuit of kallikrein-5 specific inhibitors for the treatment of inflammatory dermatoses
  16. Comparison of five automated urine sediment analyzers with manual microscopy for accurate identification of urine sediment
  17. Establishment of an international autoantibody reference standard for human anti-DFS70 antibodies: proof-of-concept study for a novel Megapool strategy by pooling individual specific sera
  18. Only monospecific anti-DFS70 antibodies aid in the exclusion of antinuclear antibody associated rheumatic diseases: an Italian experience
  19. Performance evaluation of an Indoxyl Sulfate Assay Kit “NIPRO”
  20. Variable and inaccurate serum IgG4 levels resulting from lack of standardization in IgG subclass assay calibration
  21. Hematology and Coagulation
  22. Influence of hypertriglyceridemia, hyperbilirubinemia and hemolysis on thrombin generation in human plasma
  23. Reference Values and Biological Variations
  24. 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
  25. Cardiovascular Diseases
  26. Serum concentrations of free fatty acids are associated with 3-month mortality in acute heart failure patients
  27. Letters to the Editor
  28. Management of potassium results in haemolysed plasma samples at the emergency department laboratory
  29. Unexpected analytical interference in isavuconazole UV determination in a child in therapy with lumacaftor/ivacaftor for cystic fibrosis
  30. Total laboratory automation has the potential to be the field of application of artificial intelligence: the cyber-physical system and “Automation 4.0”
  31. 99th percentile upper reference limit of AccuTnI+3 in a Korean reference population: a multicenter study using fresh serum
  32. Roche Troponin T hs-STAT meets all expert opinion analytical laboratory practice recommendations for the use of the differential diagnosis of acute coronary syndrome
  33. A comparison of biotin interference in routine immunoassays on the Roche Cobas 8000, Beckman Coulter DXi and Siemens Advia Centaur XPT immunoassay platforms
  34. The importance of the methodology and sample matrix when interpreting chromogranin A results
  35. The sudden death of the combined first trimester aneuploidy screening, a single centre experience in Belgium
  36. Reply to Luksic et al. Clin Chem Lab Med 2018;56(4):574–581
https://doi.org/10.1515/cclm-2018-1337
Schlagwörter für diesen Artikel
change point analysis; ethnicity; first trimester; holotranscobalamin; methylmalonic acid; pregnancy; reference interval; second trimester; vitamin B12

Artikel in diesem Heft

  1. Frontmatter
  2. Editorial
  3. Identification and management of spurious hemolysis: controversies, concerns and criticisms
  4. Reviews
  5. CYP24A1 and SLC34A1 genetic defects associated with idiopathic infantile hypercalcemia: from genotype to phenotype
  6. Meta-analysis: compared with anti-CCP and rheumatoid factor, could anti-MCV be the next biomarker in the rheumatoid arthritis classification criteria?
  7. Opinion Paper
  8. Collection, transport and storage procedures for blood culture specimens in adult patients: recommendations from a board of Italian experts
  9. General Clinical Chemistry and Laboratory Medicine
  10. Using the hemoglobin-binding Staphylococcus aureus protein IsdH to enable plasma analysis of hemolyzed blood samples
  11. Handling of hemolyzed serum samples in clinical chemistry laboratories: the Nordic hemolysis project
  12. Clinical biomarker innovation: when is it worthwhile?
  13. Impact of total automation consolidating first-line laboratory tests on diagnostic blood loss
  14. Diagnostic and prognostic value of the D-dimer test in emergency department patients: secondary analysis of an observational study
  15. Screening of chemical libraries in pursuit of kallikrein-5 specific inhibitors for the treatment of inflammatory dermatoses
  16. Comparison of five automated urine sediment analyzers with manual microscopy for accurate identification of urine sediment
  17. Establishment of an international autoantibody reference standard for human anti-DFS70 antibodies: proof-of-concept study for a novel Megapool strategy by pooling individual specific sera
  18. Only monospecific anti-DFS70 antibodies aid in the exclusion of antinuclear antibody associated rheumatic diseases: an Italian experience
  19. Performance evaluation of an Indoxyl Sulfate Assay Kit “NIPRO”
  20. Variable and inaccurate serum IgG4 levels resulting from lack of standardization in IgG subclass assay calibration
  21. Hematology and Coagulation
  22. Influence of hypertriglyceridemia, hyperbilirubinemia and hemolysis on thrombin generation in human plasma
  23. Reference Values and Biological Variations
  24. 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
  25. Cardiovascular Diseases
  26. Serum concentrations of free fatty acids are associated with 3-month mortality in acute heart failure patients
  27. Letters to the Editor
  28. Management of potassium results in haemolysed plasma samples at the emergency department laboratory
  29. Unexpected analytical interference in isavuconazole UV determination in a child in therapy with lumacaftor/ivacaftor for cystic fibrosis
  30. Total laboratory automation has the potential to be the field of application of artificial intelligence: the cyber-physical system and “Automation 4.0”
  31. 99th percentile upper reference limit of AccuTnI+3 in a Korean reference population: a multicenter study using fresh serum
  32. Roche Troponin T hs-STAT meets all expert opinion analytical laboratory practice recommendations for the use of the differential diagnosis of acute coronary syndrome
  33. A comparison of biotin interference in routine immunoassays on the Roche Cobas 8000, Beckman Coulter DXi and Siemens Advia Centaur XPT immunoassay platforms
  34. The importance of the methodology and sample matrix when interpreting chromogranin A results
  35. The sudden death of the combined first trimester aneuploidy screening, a single centre experience in Belgium
  36. Reply to Luksic et al. Clin Chem Lab Med 2018;56(4):574–581
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