Home Medicine Pediatric reference interval verification for 16 biochemical markers on the Alinity ci system in the CALIPER cohort of healthy children and adolescents
Article
Licensed
Unlicensed Requires Authentication

Pediatric reference interval verification for 16 biochemical markers on the Alinity ci system in the CALIPER cohort of healthy children and adolescents

  • Mary Kathryn Bohn , Randal Schneider , Benjamin Jung and Khosrow Adeli EMAIL logo
Published/Copyright: May 1, 2023
Clinical Chemistry and Laboratory Medicine (CCLM)
From the journal Clinical Chemistry and Laboratory Medicine (CCLM) Volume 61 Issue 11

Abstract

Objectives

Special chemistry parameters are useful in the diagnosis and management of inherited disorders, liver disease, and immunopathology. Evidence-based pediatric reference intervals (RIs) are required for appropriate clinical decision-making and need to be verified as new assays are developed. This study aimed to evaluate the applicability of pediatric RIs established for biochemical markers on the ARCHITECT for use on newer Alinity assays.

Methods

An initial method validation was completed for 16 assays, including precision, linearity, and method comparison. Sera collected from approximately 100 healthy children and adolescents as part of the Canadian Laboratory Initiative on Pediatric Reference Intervals (CALIPER) were also analyzed on the Alinity c system. Percentage of results within established ARCHITECT RIs were calculated and considered verified if ≥90 % fell within established limits. New RIs were established for three electrolytes, glucose, and lactate wherein no data were previously reported.

Results

Of the 11 assays for which CALIPER pediatric RIs were previously established on ARCHITECT assays, 10 met the verification criteria. Alpha-1-antitrypsin did not meet verification criterion and a new RI was established. For the other 5 assays, de novo RIs were derived following analysis of 139–168 samples from healthy children and adolescents. None required age- and sex-partitioning.

Conclusions

Herein, pediatric RIs were verified or established for 16 chemistry markers in the CALIPER cohort on Alinity assays. Findings support excellent concordance between ARCHITECT and Alinity assays with one exception (alpha-1-antitrypsin) as well as robustness of age- and sex-specific patterns originally reported by CALIPER in healthy Canadian children and adolescents.

Keywords: pediatrics; reference intervals; special chemistry
Corresponding author: Khosrow Adeli, Clinical Biochemistry, Pediatric Laboratory Medicine, The Hospital for Sick Children, 555 University Avenue, Toronto, ON, M5G 1X8, Canada; CALIPER Program, Department of Pediatric Laboratory Medicine, The Hospital for Sick Children, Toronto, ON, Canada; and Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada, E-mail:

Funding source: Institute of Nutrition, Metabolism and Diabetes

Funding source: Abbott Laboratories

Acknowledgments

We would like to thank CALIPER participants without whom this work would not be possible.

  1. Research funding: This work was supported by a Canadian Institutes for Health Research (CIHR) foundation grant to Khosrow Adeli. Mary Kathryn Bohn was supported by a CIHR Doctoral Award. Abbott Diagnostics also supported the study and provided all reagents at no cost.

  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: The local Institutional Review Board approved all study procedures.

References

1. Adeli, K, Higgins, V, Trajcevski, K, White-Al Habeeb, N. The Canadian laboratory initiative on pediatric reference intervals: a CALIPER white paper. Crit Rev Clin Lab Sci 2017;54:358–413. https://doi.org/10.1080/10408363.2017.1379945.Search in Google Scholar PubMed

2. Karbasy, K, Lin, DCC, Stoianov, A, Chan, MK, Bevilacqua, V, Chen, Y, et al.. Pediatric reference value distributions and covariate-stratified reference intervals for 29 endocrine and special chemistry biomarkers on the Beckman Coulter Immunoassay Systems: a CALIPER study of healthy community children. Clin Chem Lab Med 2015;54:643–57. https://doi.org/10.1515/cclm-2015-0558.Search in Google Scholar PubMed

3. Colantonio, DA, Kyriakopoulou, L, Chan, MK, Daly, CH, Brinc, D, Venner, AA, et al.. Closing the gaps in pediatric laboratory reference intervals: a caliper database of 40 biochemical markers in a healthy and multiethnic population of children. Clin Chem 2012;58:854–68. https://doi.org/10.1373/clinchem.2011.177741.Search in Google Scholar PubMed

4. Konforte, D, Shea, JL, Kyriakopoulou, L, Colantonio, D, Cohen, AH, Shaw, J, et al.. Complex biological pattern of fertility hormones in children and adolescents: a study of healthy children from the CALIPER cohort and establishment of pediatric reference intervals. Clin Chem 2013;59:1215–27. https://doi.org/10.1373/clinchem.2013.204123.Search in Google Scholar PubMed

5. Bailey, D, Colantonio, D, Kyriakopoulou, L, Cohen, AH, Chan, MK, Armbruster, D, et al.. Marked biological variance in endocrine and biochemical markers in childhood: establishment of pediatric reference intervals using healthy community children from the CALIPER cohort. Clin Chem 2013;59:1393–405. https://doi.org/10.1373/clinchem.2013.204222.Search in Google Scholar PubMed

6. Kelly, J, Raizman, JE, Bevilacqua, V, Chan, MK, Chen, Y, Quinn, F, et al.. Complex reference value distributions and partitioned reference intervals across the pediatric age range for 14 specialized biochemical markers in the CALIPER cohort of healthy community children and adolescents. Clin Chim Acta 2015;450:196–202. https://doi.org/10.1016/j.cca.2015.08.020.Search in Google Scholar PubMed

7. Bevilacqua, V, Chan, MK, Chen, Y, Armbruster, D, Schodin, B, Adeli, K. Pediatric population reference value distributions for cancer biomarkers and covariate-stratified reference intervals in the CALIPER cohort. Clin Chem 2014;60:1532–42. https://doi.org/10.1373/clinchem.2014.229799.Search in Google Scholar PubMed

8. Bohn, MK, Horn, P, League, D, Steele, P, Hall, A, Adeli, K. Pediatric reference intervals for endocrine markers and fertility hormones in healthy children and adolescents on the Siemens Healthineers Atellica immunoassay system. Clin Chem Lab Med 2021;59:1421–30. https://doi.org/10.1515/cclm-2021-0050.Search in Google Scholar PubMed

9. Bohn, MK, Horn, P, League, D, Steele, P, Hall, A, Adeli, K. Pediatric reference intervals for 32 routine biochemical markers using the siemens healthineers atellica® CH assays in healthy children and adolescents. Clin Biochem 2021;99:69–77. https://doi.org/10.1016/j.clinbiochem.2021.10.006.Search in Google Scholar PubMed

10. Tahmasebi, H, Higgins, V, Woroch, A, Asgari, S, Adeli, K. Pediatric reference intervals for clinical chemistry assays on Siemens ADVIA XPT/1800 and Dimension EXL in the CALIPER cohort of healthy children and adolescents. Clin Chim Acta 2019;490:88–97. https://doi.org/10.1016/j.cca.2018.12.011.Search in Google Scholar PubMed

11. Bohn, MK, Higgins, V, Asgari, S, Leung, F, Hoffman, B, MacRi, J, et al.. Paediatric reference intervals for 17 Roche cobas 8000 e602 immunoassays in the CALIPER cohort of healthy children and adolescents. Clin Chem Lab Med 2019;57:1968–79. https://doi.org/10.1515/cclm-2019-0707.Search in Google Scholar PubMed

12. Kohse, KP. KiGGS – the German survey on children’s health as data base for reference intervals and beyond. Clin Biochem 2014;47:742–3. https://doi.org/10.1016/j.clinbiochem.2014.05.039.Search in Google Scholar PubMed

13. Hoq, M, Matthews, S, Karlaftis, V, Burgess, J, Cowley, J, Donath, S, et al.. Reference values for 30 common biochemistry analytes across 5 different analyzers in neonates and children 30 days to 18 years of age. Clin Chem 2019;65:1317–26. https://doi.org/10.1373/clinchem.2019.306431.Search in Google Scholar PubMed

14. Ni, X, Song, W, Peng, X, Shen, Y, Peng, Y, Li, Q, et al.. Pediatric reference intervals in China (PRINCE): design and rationale for a large, multicenter collaborative cross-sectional study. Sci Bull 2018;63:1626–34. https://doi.org/10.1016/j.scib.2018.11.024.Search in Google Scholar PubMed

15. Zierk, J, Baum, H, Bertram, A, Boeker, M, Buchwald, A, Cario, H, et al.. High-resolution pediatric reference intervals for 15 biochemical analytes described using fractional polynomials. Clin Chem Lab Med 2021;59:1267–78. https://doi.org/10.1515/cclm-2020-1371.Search in Google Scholar PubMed

16. Bohn, MK, Wilson, S, Hall, A, Massamiri, Y, Randell, E, Adeli, K. Pediatric reference interval verification for common biochemical assays on the Abbott Alinity system. Clin Chem Lab Med 2021;59:1554–62. https://doi.org/10.1515/cclm-2021-0336.Search in Google Scholar PubMed PubMed Central

17. Bohn, MK, Wilson, S, Hall, A, Adeli, K. Pediatric reference interval verification for endocrine and fertility hormone assays on the Abbott Alinity system. Clin Chem Lab Med 2021;59:1680–7. https://doi.org/10.1515/cclm-2021-0337.Search in Google Scholar PubMed

18. Bohn, MK, Wilson, S, Schneider, R, Massamiri, Y, Randell, EW, Adeli, K. Pediatric reference interval verification for 17 specialized immunoassays and cancer markers on the Abbott Alinity i system in the CALIPER cohort of healthy children and adolescents. Clin Chem Lab Med 2022;61:123–32. https://doi.org/10.1515/cclm-2022-0709.Search in Google Scholar PubMed PubMed Central

19. EP06-A evaluation of the linearity of quantitative measurement procedures: a statistical approach; Approved Guideline; 2003.Search in Google Scholar

20. Higgins, V, Asgari, S, Chan, MK, Adeli, K. Pediatric reference intervals for calculated LDL cholesterol, non-HDL cholesterol, and remnant cholesterol in the healthy CALIPER cohort. Clin Chim Acta 2018;486:129–34. https://doi.org/10.1016/j.cca.2018.07.028.Search in Google Scholar PubMed

21. Horowitz, GL, Altaie, S, Boyd, JC. Defining, establishing, and verifying reference intervals in the clinical laboratory; approved guideline, 3rd ed. Wayne, PA, USA: CLSI; 2010.Search in Google Scholar

22. Harris, EK, Boyd, JC. On dividing reference data into subgroups to produce separate reference ranges. Clin Chem 1990;36:265–70. https://doi.org/10.1093/clinchem/36.2.265.Search in Google Scholar

23. Horn, PS, Pesce, AJ. Reference intervals: an update. Clin Chim Acta 2003;334:5–23. https://doi.org/10.1016/s0009-8981(03)00133-5.Search in Google Scholar PubMed

24. Garcia-Prat, M, Vila-Pijoan, G, Martos Gutierrez, S, Gala Yerga, G, García Guantes, E, Martínez-Gallo, M, et al.. Age‐specific pediatric reference ranges for immunoglobulins and complement proteins on the OptiliteTM automated turbidimetric analyzer. J Clin Lab Anal 2018;32:e22420. https://doi.org/10.1002/jcla.22420.Search in Google Scholar PubMed PubMed Central

25. Lepage, N, Huang, SHS, Nieuwenhuys, E, Filler, G. Pediatric reference intervals for immunoglobulin G and its subclasses with Siemens immunonephelometric assays. Clin Biochem 2010;43:694–6. https://doi.org/10.1016/j.clinbiochem.2010.02.003.Search in Google Scholar PubMed

26. Khan, SR, van der Burgh, AC, Peeters, RP, van Hagen, PM, Dalm, VASH, Chaker, L. Determinants of serum immunoglobulin levels: a systematic Review and meta-analysis. Front Immunol 2021;12:664526. https://doi.org/10.3389/fimmu.2021.664526.Search in Google Scholar PubMed PubMed Central

27. Durandy, A, Kracker, S. Immunoglobulin class-switch recombination deficiencies. Arthritis Res Ther 2012;14:218. https://doi.org/10.1186/ar3904.Search in Google Scholar PubMed PubMed Central

28. Stoller, JK, Aboussouan, LS. Alpha1-antitrypsin deficiency. Lancet 2005;365:2225–36. https://doi.org/10.1016/s0140-6736(05)66781-5.Search in Google Scholar

29. Tanash, HA, Nystedt-Duzakin, M, Montero, LC, Sveger, T, Piitulainen, E. The Swedish alpha1-antitrypsin screening study: health status and lung and liver function at age 34. Ann Am Thorac Soc 2015;12:807–12. https://doi.org/10.1513/annalsats.201410-452oc.Search in Google Scholar PubMed

30. Strnad, P, McElvaney, NG, Lomas, DA. Alpha1-Antitrypsin deficiency. N Engl J Med 2020;382:1443–55.10.1056/NEJMra1910234Search in Google Scholar PubMed

31. American Thoracic Society/European Respiratory Society. Standards for the diagnosis and management of individuals with alpha-1 antitrypsin deficiency. Am J Respir Crit Care Med 2003;168:818–900. https://doi.org/10.1164/rccm.168.7.818.Search in Google Scholar PubMed

32. Donato, LJ, Jenkins, SM, Smith, C, Katzmann, JA, Snyder, MR. Reference and interpretive ranges for α1-antitrypsin quantitation by phenotype in adult and pediatric populations. Am J Clin Pathol 2012;138:398–405. https://doi.org/10.1309/ajcpmeejk32acyfp.Search in Google Scholar PubMed

33. Dati, F, Baudner, S, Schumann, G, Thomas, L, Aguzzi, F, Bienvenu, J, et al.. Consensus of a group of professional societies and diagnostic companies on guidelines for interim reference ranges for 14 proteins in serum based on the standardization against the IFCC/BCR/CAP reference material (CRM 470). Clin Chem Lab Med 1996;34:517–20.Search in Google Scholar

34. Primhak, RA, Tanner, MS. Alpha-1 antitrypsin deficiency. Arch Dis Child 2001;85:2–5. https://doi.org/10.1136/adc.85.1.2.Search in Google Scholar PubMed PubMed Central

35. Kim, JA, Kim, HJ, Cho, JM, Oh, SH, Lee, BH, Kim, GH, et al.. Diagnostic value of ceruloplasmin in the diagnosis of pediatric Wilson’s disease. Pediatr Gastroenterol Hepatol Nutr 2015;18:187–92. https://doi.org/10.5223/pghn.2015.18.3.187.Search in Google Scholar PubMed PubMed Central

36. Wilson, S, Earle, H, Bohn, MK, Hall, A, Adeli, K. Pediatric reference intervals for point-of-care random glucose in healthy children and adolescents. J Appl Lab Med 2022;7:582–8. https://doi.org/10.1093/jalm/jfab155.Search in Google Scholar PubMed

37. Bohn, MK, Hall, A, Wilson, S, Henderson, T, Adeli, K. Pediatric reference intervals for critical point-of-care whole blood assays in the CALIPER cohort of healthy children and adolescents. Am J Clin Pathol 2021;156:1030–7. https://doi.org/10.1093/ajcp/aqab064.Search in Google Scholar PubMed

38. Dodd, A, El-Farhan, N, Moat, S. Are commonly used paediatric reference intervals for water and electrolyte balance appropriate for clinical use? Ann Clin Biochem 2015;52:44–52. https://doi.org/10.1177/0004563214531557.Search in Google Scholar PubMed

Supplementary Material

This article contains supplementary material (https://doi.org/10.1515/cclm-2023-0256).

Received: 2023-03-12
Accepted: 2023-04-18
Published Online: 2023-05-01
Published in Print: 2023-10-26

© 2023 Walter de Gruyter GmbH, Berlin/Boston

Articles in the same Issue

  1. Frontmatter
  2. Editorial
  3. The development of reference measurement procedures to establish metrological traceability
  4. Opinion Paper
  5. Establishing metrological traceability for small molecule measurands in laboratory medicine
  6. Articles
  7. An isotope dilution-liquid chromatography-tandem mass spectrometry (ID-LC-MS/MS)-based candidate reference measurement procedure (RMP) for the quantification of aldosterone in human serum and plasma
  8. An isotope dilution-liquid chromatography-tandem mass spectrometry (ID-LC-MS/MS)-based candidate reference measurement procedure (RMP) for the quantification of methotrexate in human serum and plasma
  9. An isotope dilution-liquid chromatography-tandem mass spectrometry (ID-LC-MS/MS)-based candidate reference measurement procedure (RMP) for the quantification of lamotrigine in human serum and plasma
  10. An isotope dilution-liquid chromatography-tandem mass spectrometry (ID-LC-MS/MS)-based candidate reference measurement procedure for the quantification of topiramate in human serum and plasma
  11. An isotope dilution-liquid chromatography-tandem mass spectrometry (ID-LC-MS/MS)-based candidate reference measurement procedure (RMP) for the quantification of gabapentin in human serum and plasma
  12. An isotope dilution-liquid chromatography-tandem mass spectrometry (ID-LC-MS/MS)-based candidate reference measurement procedure for the quantification of levetiracetam in human serum and plasma
  13. Review
  14. Recent advances of drugs monitoring in oral fluid and comparison with blood
  15. Genetics and Molecular Diagnostics
  16. One fits all: a highly sensitive combined ddPCR/pyrosequencing system for the quantification of microchimerism after hematopoietic and solid organ transplantation
  17. General Clinical Chemistry and Laboratory Medicine
  18. Design of an algorithm for the detection of intravenous fluid contamination in clinical laboratory samples
  19. Sex-specific disparities of serum pepsinogen I in relation to body mass index
  20. Rapid and efficient LC-MS/MS diagnosis of inherited metabolic disorders: a semi-automated workflow for analysis of organic acids, acylglycines, and acylcarnitines in urine
  21. Persistently elevated serum concentrations of human chorionic gonadotropin (hCG)
  22. Reference Values and Biological Variations
  23. Pediatric reference interval verification for 16 biochemical markers on the Alinity ci system in the CALIPER cohort of healthy children and adolescents
  24. Serum GFAP – pediatric reference interval in a cohort of Danish children
  25. Cardiovascular Diseases
  26. Higher troponin T serum concentrations in hospital patients without diagnosed cardiac diseases compared to a population-based cohort
  27. Infectious Diseases
  28. Neopterin and kynurenine in serum and urine as prognostic biomarkers in hospitalized patients with delta and omicron variant SARS-CoV-2 infection
  29. Letters to the Editor
  30. Limitations in using the EFLM WG-A/ISO approach for assessment of reagent lot variability
  31. In reply to: Limitations in using the EFLM WG-A/ISO approach for assessment of reagent lot variability
  32. ChatGPT, critical thing and ethical practice
  33. AI, diabetes and getting lost in translation: a multilingual evaluation of Bing with ChatGPT focused in HbA1c
  34. UK diagnostics in the era of ‘permacrisis’: is it fit for purpose and able to respond to the challenges ahead?
  35. The underestimated potential of vibrational spectroscopy in clinical laboratory medicine: a translational gap to close
  36. A universal reference interval for serum immunoglobulins free light chains may be outdated
  37. The likelihood ratios of FIB-4-values for diagnosing advanced liver fibrosis in patients with NAFLD
https://doi.org/10.1515/cclm-2023-0256
Keywords for this article
pediatrics; reference intervals; special chemistry

Articles in the same Issue

  1. Frontmatter
  2. Editorial
  3. The development of reference measurement procedures to establish metrological traceability
  4. Opinion Paper
  5. Establishing metrological traceability for small molecule measurands in laboratory medicine
  6. Articles
  7. An isotope dilution-liquid chromatography-tandem mass spectrometry (ID-LC-MS/MS)-based candidate reference measurement procedure (RMP) for the quantification of aldosterone in human serum and plasma
  8. An isotope dilution-liquid chromatography-tandem mass spectrometry (ID-LC-MS/MS)-based candidate reference measurement procedure (RMP) for the quantification of methotrexate in human serum and plasma
  9. An isotope dilution-liquid chromatography-tandem mass spectrometry (ID-LC-MS/MS)-based candidate reference measurement procedure (RMP) for the quantification of lamotrigine in human serum and plasma
  10. An isotope dilution-liquid chromatography-tandem mass spectrometry (ID-LC-MS/MS)-based candidate reference measurement procedure for the quantification of topiramate in human serum and plasma
  11. An isotope dilution-liquid chromatography-tandem mass spectrometry (ID-LC-MS/MS)-based candidate reference measurement procedure (RMP) for the quantification of gabapentin in human serum and plasma
  12. An isotope dilution-liquid chromatography-tandem mass spectrometry (ID-LC-MS/MS)-based candidate reference measurement procedure for the quantification of levetiracetam in human serum and plasma
  13. Review
  14. Recent advances of drugs monitoring in oral fluid and comparison with blood
  15. Genetics and Molecular Diagnostics
  16. One fits all: a highly sensitive combined ddPCR/pyrosequencing system for the quantification of microchimerism after hematopoietic and solid organ transplantation
  17. General Clinical Chemistry and Laboratory Medicine
  18. Design of an algorithm for the detection of intravenous fluid contamination in clinical laboratory samples
  19. Sex-specific disparities of serum pepsinogen I in relation to body mass index
  20. Rapid and efficient LC-MS/MS diagnosis of inherited metabolic disorders: a semi-automated workflow for analysis of organic acids, acylglycines, and acylcarnitines in urine
  21. Persistently elevated serum concentrations of human chorionic gonadotropin (hCG)
  22. Reference Values and Biological Variations
  23. Pediatric reference interval verification for 16 biochemical markers on the Alinity ci system in the CALIPER cohort of healthy children and adolescents
  24. Serum GFAP – pediatric reference interval in a cohort of Danish children
  25. Cardiovascular Diseases
  26. Higher troponin T serum concentrations in hospital patients without diagnosed cardiac diseases compared to a population-based cohort
  27. Infectious Diseases
  28. Neopterin and kynurenine in serum and urine as prognostic biomarkers in hospitalized patients with delta and omicron variant SARS-CoV-2 infection
  29. Letters to the Editor
  30. Limitations in using the EFLM WG-A/ISO approach for assessment of reagent lot variability
  31. In reply to: Limitations in using the EFLM WG-A/ISO approach for assessment of reagent lot variability
  32. ChatGPT, critical thing and ethical practice
  33. AI, diabetes and getting lost in translation: a multilingual evaluation of Bing with ChatGPT focused in HbA1c
  34. UK diagnostics in the era of ‘permacrisis’: is it fit for purpose and able to respond to the challenges ahead?
  35. The underestimated potential of vibrational spectroscopy in clinical laboratory medicine: a translational gap to close
  36. A universal reference interval for serum immunoglobulins free light chains may be outdated
  37. The likelihood ratios of FIB-4-values for diagnosing advanced liver fibrosis in patients with NAFLD
Sign up now to receive a 20% welcome discount
Institutional Access
How does access work?
Have an idea on how to improve our website?
Please write us.
© 2026 De Gruyter Brill
Downloaded on 28.1.2026 from https://www.degruyterbrill.com/document/doi/10.1515/cclm-2023-0256/html
Scroll to top button