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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 / Lackner, Karl J. / Lippi, Giuseppe / Melichar, Bohuslav / Payne, Deborah A. / Schlattmann, Peter

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Volume 56, Issue 6


Pediatric reference intervals for 1,25-dihydroxyvitamin D using the DiaSorin LIAISON XL assay in the healthy CALIPER cohort

Victoria Higgins
  • Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada
  • CALIPER Program, Pediatric Laboratory Medicine, The Hospital for Sick Children, Toronto, ON, Canada
  • Other articles by this author:
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/ Dorothy Truong
  • Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada
  • Other articles by this author:
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/ Nicole M.A. White-Al Habeeb
  • Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada
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/ Angela W.S. Fung
  • Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada
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/ Barry Hoffman / Khosrow Adeli
  • Corresponding author
  • Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada
  • Clinical Biochemistry, DPLM, CALIPER Program, Pediatric Laboratory Medicine, The Hospital for Sick Children, 555 University Avenue, Toronto, ON, M5G 1X8, Canada
  • Email
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
Published Online: 2018-02-01 | DOI: https://doi.org/10.1515/cclm-2017-0767



1,25-dihydroxyvitamin D (1,25(OH)2D), the biologically active vitamin D metabolite, plays a critical role in calcium and phosphate homeostasis. 1,25(OH)2D is measured to assess calcium and phosphate metabolism, particularly during periods of profound growth and development. Despite its importance, no reliable pediatric reference interval exists, with those available developed using adult populations or out-dated methodologies. Using the fully automated chemiluminescence immunoassay by DiaSorin, we established 1,25(OH)2D pediatric reference intervals using healthy children and adolescents from the CALIPER cohort.


Serum samples from healthy subjects (0 to <19 years) were analyzed for 1,25(OH)2D using the DiaSorin LIAISON XL assay and age-specific reference intervals were established. The Mann-Whitney U-test was used to determine seasonal differences. Pooled neonatal and infantile samples were quantified using liquid chromatography tandem mass spectrometry (LC-MS/MS) to determine if elevated concentrations during the first year of life may be attributed to cross-reacting moieties.


Three reference interval age partitions were required with highest levels in subjects 0 to <1 year (77–471 pmol/L), which declined and narrowed after 1 year (113–363 pmol/L) and plateaued at 3 years (108–246 pmol/L). 1,25(OH)2D concentration was not significantly affected by seasonal variation or sex. Elevated 1,25(OH)2D concentrations in neonatal and infantile samples may be the result of an interfering substance. The absence of 3-epi-1,25-dihydroxyvitamin D in the pooled samples makes it unlikely to be the interfering moiety.


Pediatric reference intervals for 1,25(OH)2D were established to improve test result interpretation in children and adolescents. 1,25(OH)2D is elevated in a proportion of neonates and infants, which may be the result of a cross-reacting moiety.

Keywords: DiaSorin; 1,25-dihydroxyvitamin D; mass spectrometry; pediatric; reference intervals


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About the article

aVictoria Higgins and Dorothy Truong contributed equally to this work.

Received: 2017-08-28

Accepted: 2017-12-18

Published Online: 2018-02-01

Published in Print: 2018-05-24

Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

Research funding: Canadian Institutes of Health Research (CIHR); Grant no. 201509FDN-353989-FDN-CEAB-10158. VH is a recipient of a CIHR graduate scholarship.

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.

Citation Information: Clinical Chemistry and Laboratory Medicine (CCLM), Volume 56, Issue 6, Pages 964–972, ISSN (Online) 1437-4331, ISSN (Print) 1434-6621, DOI: https://doi.org/10.1515/cclm-2017-0767.

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