Abstract
Objectives
In adults, the elevation of cardiac troponin (cTn) above the 99th percentile upper reference limit defines myocardial injury. The use and interpretation of cTn in a paediatric population, however, is difficult given the 99th percentile for different assays is not well established. Using paediatric blood samples from healthy neonates, infants and children we derived continuous and partitioned 97.5th and 99th percentiles for the Ortho VITROS hs-TnI assay.
Methods
A total of 328 samples for infants, children and adolescents aged 0–17.8 years were obtained. Age partitioned reference limits were derived in accordance with CLSI EP28-A3C. Continuous reference limits were established as described previously by the HAPPI Kids Study team.
Results
hs-TnI as measured by the Ortho VITROS Assay is highly elevated above the adult 99th percentile at birth and declines to lower levels within the first 6 months of life. The 99th centile upper reference limit for ages 0–3 months was 72 ng/L (90% CI: 52–91) and 9 ng/L (90% CI: 5.2–17.4) for ages 3 months to 18 years. Continuous upper 99th centile reference limits were comparable.
Conclusions
Partitioned and continuous 99th percentiles for hs-TnI were derived for the new Ortho VITROS assay in healthy neonates and older children. This will assist clinicians to appropriately assess for the presence of myocardial injury in this population.
Acknowledgments
The authors thank staff of the Pathology Collection, Anaesthetic, Surgical, and Neonatal and Post-Natal Departments at the Royal Children’s Hospital, Royal Women’s Hospital, Northern Hospital, and Western Health–Sunshine Hospital, Melbourne. The authors also acknowledge the contribution of scientists and clinical biochemists at The Royal Children’s Hospital.
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Research funding: This study was funded by The Royal Children’s Hospital Foundation, with supplementary funding from Ortho Clinical Diagnostics.
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Author contributions: All authors have accepted responsibility for the entire content of this manuscript and approved its submission.
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Competing interests: Authors state no conflict of interest.
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Informed consent: Informed consent was obtained from all individuals included in this study.
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Ethical approval: The study protocol was approved by The Royal Children’s Hospital, Melbourne, Australia Ethics in Human Research Committee (HREC) (HREC 34183 A).
References
1. Thygesen, K, Alpert, JS, Jaffe, AS, Chaitman, BR, Bax, JJ, Morrow, DA, et al.. Fourth universal definition of myocardial infarction (2018). J Am Coll Cardiol 2018;72:2231–64. https://doi.org/10.1016/j.jacc.2018.08.1038.Search in Google Scholar PubMed
2. Clerico, A, Aimo, A, Cantinotti, M. High-sensitivity cardiac troponins in pediatric population. Clin Chem Lab Med 2022;60:18–32. https://doi.org/10.1515/cclm-2021-0976.Search in Google Scholar PubMed
3. Bohn, MK, Steele, S, Hall, A, Poonia, J, Jung, B, Adeli, K. Cardiac biomarkers in pediatrics: an undervalued resource. Clin Chem 2021;67:947–58. https://doi.org/10.1093/clinchem/hvab063.Search in Google Scholar PubMed PubMed Central
4. Kavsak, PA, Rezanpour, A, Chen, Y, Adeli, K. Assessment of the 99th or 97.5th percentile for cardiac troponin I in a healthy pediatric cohort. Clin Chem 2014;60:1574–6. https://doi.org/10.1373/clinchem.2014.228619.Search in Google Scholar PubMed
5. Karlen, J, Karlsson, M, Eliasson, H, Bonamy, AE, Halvorsen, CP. Cardiac troponin T in healthy full-term infants. Pediatr Cardiol 2019;40:1645–54. https://doi.org/10.1007/s00246-019-02199-9.Search in Google Scholar PubMed PubMed Central
6. Hickman, PE, Badrick, T, Wilson, SR, McGill, D. Reporting of cardiac troponin – problems with the 99th population percentile. Clin Chim Acta 2007;381:182–3. https://doi.org/10.1016/j.cca.2007.03.012.Search in Google Scholar PubMed
7. Daly, CH, Liu, X, Grey, VL, Hamid, JS. A systematic review of statistical methods used in constructing pediatric reference intervals. Clin Biochem 2013;46:1220–7. https://doi.org/10.1016/j.clinbiochem.2013.05.058.Search in Google Scholar PubMed
8. Wu, AHB, Christenson, RH, Greene, DN, Jaffe, AS, Kavsak, PA, Ordonez-Llanos, J, et al.. Clinical laboratory practice recommendations for the use of cardiac troponin in acute coronary syndrome: expert opinion from the academy of the American association for clinical chemistry and the task force on clinical applications of cardiac bio-markers of the international federation of clinical chemistry and laboratory medicine. Clin Chem 2018;64:645–55. https://doi.org/10.1373/clinchem.2017.277186.Search in Google Scholar PubMed
9. Hoq, M, Karlaftis, V, Mathews, S, Burgess, J, Donath, SM, Carlin, J, et al.. A prospective, cross-sectional study to establish age-specific reference intervals for neonates and children in the setting of clinical biochemistry, immunology and haematology: the HAPPI Kids study protocol. BMJ Open 2019;9:e025897. https://doi.org/10.1136/bmjopen-2018-025897.Search in Google Scholar PubMed PubMed Central
10. 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
11. Kavsak, PA, Edge, T, Roy, C, Malinowski, P, Bamford, K, Clark, L, et al.. Analytical assessment of ortho clinical diagnostics high-sensitivity cardiac troponin I assay. Clin Chem Lab Med 2020;59:749–55.10.1515/cclm-2020-1115Search in Google Scholar
12. Ortho Clinical, Diagnostics. immunodiagnostic products hs troponin, I reagent pack. Instructions for use. Version 1., Rochester, NY, USA: Ortho-Clinical Diagnostics, Inc.; 2022.Search in Google Scholar
13. Masotti, S, Musetti, V, Prontera, C, Storti, S, Passino, C, Clerico, A. Evaluation and comparison with other high-sensitivity methods of analytical performance and measured values of a new laboratory test for cardiac troponin I assay. J Appl Lab Med 2021;6:1237–50. https://doi.org/10.1093/jalm/jfab017.Search in Google Scholar
14. Bohn, MK, Higgins, V, Kavsak, P, Hoffman, B, Adeli, K. High-sensitivity generation 5 cardiac troponin T sex – and age-specific 99th percentiles in the CALIPER cohort of healthy children and adolescents. Clin Chem 2019;65:589–91. https://doi.org/10.1373/clinchem.2018.299156.Search in Google Scholar
15. CLSI. Defining, establishing, and verifying reference intervals in the clinical laboratory; approved guideline – third edition. CLSI document EP28-A3c. Wayne, PA: Clinical and Laboratory Standards Institute; 2008.Search in Google Scholar
16. R Core Team. R: a language and environment for statistical computing. Vienna, Austria: R Foundation for Statistical Computing; 2018.Search in Google Scholar
17. 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
18. Reed, AH, Henry, RJ, Mason, WB. Influence of statistical method used on the resulting estimate of normal range. Clin Chem 1971;17:275–84. https://doi.org/10.1093/clinchem/17.4.275.Search in Google Scholar
19. 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
20. Lam, E, Higgins, V, Zhang, L, Chan, MK, Bohn, MK, Trajcevski, K, et al.. Normative values of high-sensitivity cardiac troponin T and N-terminal pro-B-type natriuretic peptide in children and adolescents: a study from the caliper cohort. J Appl Lab Med 2021;6:344–53. https://doi.org/10.1093/jalm/jfaa090.Search in Google Scholar PubMed
21. Mondal, T, Ryan, PM, Gupta, K, Radovanovic, G, Pugh, E, Chan, AKC, et al.. Cord-blood high-sensitivity troponin-I reference interval and association with early neonatal outcomes. Am J Perinatol 2021. https://doi.org/10.1055/s-0041-1722944 [Epub ahead of print].Search in Google Scholar PubMed
22. Sandoval, Y, Apple, FS. The global need to define normality: the 99th percentile value of cardiac troponin. Clin Chem 2014;60:455–62. https://doi.org/10.1373/clinchem.2013.211706.Search in Google Scholar PubMed
23. Clerico, A, Zaninotto, M, Ripoli, A, Masotti, S, Prontera, C, Passino, C, et al.. The 99th percentile of reference population for cTnI and cTnT assay: methodology, pathophysiology and clinical implications. Clin Chem Lab Med 2017;55:1634–51. https://doi.org/10.1515/cclm-2016-0933.Search in Google Scholar PubMed
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