Startseite LMS-based continuous reference percentiles for 14 laboratory parameters in the CALIPER cohort of healthy children and adolescents
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LMS-based continuous reference percentiles for 14 laboratory parameters in the CALIPER cohort of healthy children and adolescents

  • Siobhan M. Wilson , Mary Kathryn Bohn , Andre Madsen , Thomas Hundhausen und Khosrow Adeli EMAIL logo
Veröffentlicht/Copyright: 16. Januar 2023
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Clinical Chemistry and Laboratory Medicine (CCLM)
Aus der Zeitschrift Clinical Chemistry and Laboratory Medicine (CCLM) Band 61 Heft 6

Abstract

Objectives

Marked physiological changes in growth and development present challenges in defining pediatric reference intervals for biomarkers of health and disease. Lambda, Mu, and Sigma (LMS)-based statistical modeling provides a continuous normal distribution by negating skewness and variation, and is commonly used to establish growth charts. Such LMS reference curves are suggested to enhance laboratory test result interpretation. The current study establishes LMS-based continuous reference percentiles for 14 biomarkers in the CALIPER cohort of healthy children and adolescents.

Methods

Data from healthy children and adolescents aged 1–<19 years were used to establish continuous reference percentiles using a novel LMS-based statistical method, including 2.5th, 25th, 50th, 75th, and 97.5th percentiles. The LMS approach applies a Box-Cox data transformation and summarizes continuous distributions by age via three curves: skewness (Lambda), median (Mu), and coefficient of variation (Sigma).

Results

LMS-based percentiles and z-scores were generated for 14 common pediatric biomarkers that demonstrate dynamic concentration patterns with age (e.g., alkaline phosphatase) and/or wherein the magnitude of difference from the population mean may be clinically relevant (e.g., triglycerides). The LMS model captured age- and sex-specific distributions accurately and was not substantially influenced by outlying points.

Conclusions

This is the first study to establish LMS-based continuous reference percentiles for biochemical markers in a healthy Canadian pediatric population. The current LMS-based approach builds upon previous continuous reference interval models by providing graded percentiles to improve test result interpretation, particularly with repeated measures over time. This method may assist in facilitating a patient-centered approach to laboratory medicine.

Keywords: CALIPER; continuous reference interval; immunoassay; LMS; pediatric; reference interval
Corresponding author: Khosrow Adeli, CALIPER Program, Department of Pediatric Laboratory Medicine, The Hospital for Sick Children, 555 University Avenue, Toronto, ON, M5G 1X8 Canada; and Department of Laboratory Medicine & Pathobiology, Faculty of Medicine, 1 King’s College Cir, University of Toronto, Toronto, ON, M5S 1A8 Canada, Phone: 416-813-8682, Fax: 416-813-6257, E-mail:

Funding source: Canadian Institute for Health Research

Award Identifier / Grant number: 353989

Acknowledgments

We would like to thank the CALIPER participants, families, and volunteers who have made this research possible.

  1. Research funding: This work is supported by a Canadian Institute for Health Research (CIHR) Foundation Grant to K.A. [grant number: 353989], a CIHR Doctoral Award to M.K.B, and a CIHR Master’s Award and Banting and Best Diabetes Centre Graduate Studentship to S.W.

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

  3. Competing interests: Authors state no conflict of interest.

  4. Informed consent: Informed consent was obtained from all individuals included in this study.

  5. Ethical approval: Research involving human subjects complied with all relevant national regulations, institutional policies and is in accordance with the tenets of the Helsinki Declaration (as revised in 2013) and has been approved by the authors’ Institutional Review Board at the Hospital for Sick Children.

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Supplementary Material

This article contains supplementary material (https://doi.org/10.1515/cclm-2022-1077).

Received: 2022-10-25
Accepted: 2023-01-02
Published Online: 2023-01-16
Published in Print: 2023-05-25

© 2023 Walter de Gruyter GmbH, Berlin/Boston

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https://doi.org/10.1515/cclm-2022-1077
Schlagwörter für diesen Artikel
CALIPER; continuous reference interval; immunoassay; LMS; pediatric; reference interval

Artikel in diesem Heft

  1. Frontmatter
  2. Editorial
  3. Improving access to diagnostic testing in conflict-affected areas: what is needed?
  4. Review
  5. Deciphering the role of monocyte and monocyte distribution width (MDW) in COVID-19: an updated systematic review and meta-analysis
  6. Opinion Paper
  7. From research cohorts to the patient – a role for “omics” in diagnostics and laboratory medicine?
  8. EFLM Paper
  9. The European Register of Specialists in Clinical Chemistry and Laboratory Medicine: code of conduct, version 3 – 2023
  10. Guidelines and Recommendations
  11. Cardiac troponin measurement at the point of care: educational recommendations on analytical and clinical aspects by the IFCC Committee on Clinical Applications of Cardiac Bio-Markers (IFCC C-CB)
  12. Genetics and Molecular Diagnostics
  13. A new and improved method of library preparation for non-invasive prenatal testing: plasma to library express technology
  14. Multiplex proteomics using proximity extension assay for the identification of protein biomarkers predictive of acute graft-vs.-host disease in allogeneic hematopoietic cell transplantation
  15. General Clinical Chemistry and Laboratory Medicine
  16. Assessment of laboratory capacity in conflict-affected low-resource settings using two World Health Organization laboratory assessment tools
  17. Challenge in hyponatremic patients – the potential of a laboratory-based decision support system for hyponatremia to improve patient’s safety
  18. Evaluation of hemolysis, lipemia, and icterus interference with common clinical immunoassays
  19. Serum bicarbonate stability study at room temperature – influence of time to centrifugation and air exposure on bicarbonate measurement reported according to the CRESS checklist
  20. Effects of lipemia on capillary serum protein electrophoresis in native ultra-lipemic material and intravenous lipid emulsion added sera
  21. C-reactive protein interacts with amphotericin B liposomes and its potential clinical consequences
  22. Evaluation of analytical performance of homocysteine LC-MS/MS assay and design of internal quality control strategy
  23. A reliable and high throughput HPLC–HRMS method for the rapid screening of β-thalassemia and hemoglobinopathy in dried blood spots
  24. Dynamics of the vitamin D C3-epimer levels in preterm infants
  25. Comparison of ANA testing by indirect immunofluorescence or solid-phase assays in a low pre-test probability population for systemic autoimmune disease: the Camargo Cohort
  26. Reference Values and Biological Variations
  27. LMS-based continuous reference percentiles for 14 laboratory parameters in the CALIPER cohort of healthy children and adolescents
  28. Indirectly determined reference intervals for automated white blood cell differentials of pediatric patients in Berlin and Brandenburg
  29. Infectious Diseases
  30. Evaluation of a high-sensitivity SARS-CoV-2 antigen test on the fully automated light-initiated chemiluminescent immunoassay platform
  31. Letters to the Editor
  32. Non-esterified fatty acids (NEFA): sample stability and effect of haemolysis and icterus
  33. Frozen serum sample pool should not be used as internal quality assessment for lipemia (L) index
  34. Stability of SARS-CoV-2 respiratory samples in non-freezing condition: importance for tropical countries under heavy diagnostic demand
  35. A rare case of both macro-TSH and macro-LH: laboratory analysis of the pathogenesis
  36. A new method for early cancer detection based on platelet transcriptomics will have low positive predictive value
  37. Comparison of near-infrared and UV–vis-based non-contact hematocrit prediction of dried blood spots from patients on immunosuppressants
  38. The diagnostics of heparin-induced thrombocytopenia in Italy and the possible impact of vaccine-induced immune thrombotic thrombocytopenia on it
  39. Pitfall in the analysis of the alcohol biomarkers ethyl glucuronide and ethyl sulfate by laboratory-caused contamination with disinfectants
  40. Growing your own food is like printing money, don’t let it make you mad as a hatter
  41. Congress Abstracts
  42. 43rd annual conference of the association of clinical biochemists in Ireland (ACBI 2021)
  43. 44th Annual Conference of the Association of Clinical Biochemists in Ireland (ACBI 2022)
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