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

Author:

Schroder Theresa H.12,Tan Amy12,Mattman Andre3,Sinclair Graham245,Barr Susan I.1,Vallance Hilary D.245,Lamers Yvonne67

Affiliation:

1. Food, Nutrition and Health Program, Faculty of Land and Food Systems , The University of British Columbia , Vancouver , BC , Canada

2. British Columbia Children’s Hospital Research Institute , Vancouver , BC , Canada

3. Department of Clinical Chemistry and Laboratory Medicine , St Paul’s Hospital , Vancouver , BC , Canada

4. Department of Pathology and Laboratory Medicine, Faculty of Medicine , The University of British Columbia , Vancouver , BC , Canada

5. BC Children’s Hospital and BC Women’s Health Centre , Vancouver , BC , Canada

6. British Columbia Children’s Hospital Research Institute , 950 W 28th Ave, Vancouver , BC V5Z 4H4 , Canada

7. 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

Abstract

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.

Publisher

Walter de Gruyter GmbH

Subject

Biochemistry (medical),Clinical Biochemistry,General Medicine

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