Abstract
Background
Accurate pediatric reference intervals (RIs) for laboratory tests determined in a healthy pediatric population are essential for correct laboratory test interpretation and clinical decision-making. In pediatrics, RIs require partitioning by age and/or sex; however, the need for partitioning based on ethnicity is unclear. Here, we assessed the influence of ethnicity on biomarker concentrations in the Canadian Laboratory Initiative on Pediatric Reference Intervals (CALIPER) cohort of healthy children and adolescents and compared the results with the National Health and Nutrition Examination Survey (NHANES).
Methods
A total of 52 biomarkers were measured in a multiethnic population of 846–1179 healthy children (aged 5 to <19 years) upon informed consent. Biomarker concentrations were retrospectively compared between four major ethnic groups (i.e. Black, Caucasian, East Asian, and South Asian, determined by parental ethnicity). Retrospective results were verified prospectively using an additional 500 healthy pediatric samples with equal sample size across ethnicities. Ethnic-specific differences were assessed based on statistical significance and biological and analytical variations. Appropriate age-, sex-, and ethnic-specific RIs were calculated.
Results
Ethnic-specific differences were not observed for 34 biomarkers examined in the retrospective analysis, while 18 demonstrated statistically significant ethnic differences. Among these, seven analytes demonstrated ethnic-specific differences in the prospective analysis: vitamin D, amylase, ferritin, follicle-stimulating hormone (FSH), immunoglobulin A (IgA), immunoglobulin G (IgG), and immunoglobulin M (IgM). Analysis of select NHANES data confirmed CALIPER findings.
Conclusions
This is the first comprehensive Canadian pediatric study examining ethnic-specific differences in common biomarkers. While the majority of biomarkers did not require ethnic partitioning, ethnic-specific RIs were established for seven biomarkers showing marked differences. Further studies in other populations are needed to confirm our findings.
Funding source: Canadian Institutes of Health Research
Award Identifier / Grant number: 353989
Funding statement: This research was supported by the Canadian Institutes of Health Research (funder Id: http://dx.doi.org/10.13039/501100000024, Grant Number: 353989).
Acknowledgments
We thank all study participants and their families, without whom this study would not have been possible.
Author contributions: KA and HT conceptualized the research question and designed the study plan. AH, AC, RT, MKB, and JM were involved in participant recruitment and sample collection. VT and SA contributed to retrospective and prospective data analysis, in addition to HT. All authors contributed to drafting and revising the final manuscript. All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.
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.
References
1. 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
2. Tahmasebi H, Trajcevski K, Higgins V, Adeli K. Influence of ethnicity on population reference values for biochemical markers. Crit Rev Clin Lab Sci 2018;55:359–75.10.1080/10408363.2018.1476455Search in Google Scholar
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;58:854–68.10.1373/clinchem.2011.177741Search in Google Scholar
4. 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;59:1393–405.10.1373/clinchem.2013.204222Search in Google Scholar
5. Konforte D, Shea JL, Kyriakopoulou L, Colantonio D, Cohen AH, Shaw J, et al. Complex biological pattern of fertility hormones inchildren and adolescents: a study of healthy children from the CALIPER cohort and establishment of pediatric reference intervals. Clin Chem 2013;59:1215–27.10.1373/clinchem.2013.204123Search in Google Scholar
6. Tsianos EB, Jalali MT, Gowenlock AH, Braganza JM. Ethnic “hyperamylasaemia”: clarification by isoamylase analysis. Clin Chim Acta Int J Clin Chem 1982;124:13–21.10.1016/0009-8981(82)90314-XSearch in Google Scholar
7. Wang C, Berman NG, Veldhuis JD, Der T, McDonald V, Steiner B, et al. Graded testosterone infusions distinguish gonadotropin negative-feedback responsiveness in Asian and white —men – a Clinical Research Center study. J Clin Endocrinol Metab 1998;83:870–6.10.1210/jc.83.3.870Search in Google Scholar
8. van Houten ME, Gooren LJ. Differences in reproductive endocrinology between Asian men and Caucasian men – a literature review. Asian J Androl 2000;2:13–20.Search in Google Scholar
9. Boucai L, Surks MI. Reference limits of serum TSH and free T4 are significantly influenced by race and age in an urban outpatient medical practice. Clin Endocrinol (Oxf) 2009;70: 788–93.10.1111/j.1365-2265.2008.03390.xSearch in Google Scholar PubMed
10. Lim E, Miyamura J, Chen JJ. Racial/ethnic-specific reference intervals for common laboratory tests: a comparison among Asians, Blacks, Hispanics, and White. Hawaii J Med Public Health J Asia Pac Med Public Health 2015;74:302–10.Search in Google Scholar
11. Ichihara K, Ceriotti F, Tam TH, Sueyoshi S, Poon PM, Thong ML, et al. The Asian project for collaborative derivation of reference intervals: (1) strategy and major results of standardized analytes. Clin Chem Lab Med 2013;51:1429–42.10.1515/cclm-2012-0421Search in Google Scholar PubMed
12. Ichihara K, Ceriotti F, Kazuo M, Huang Y-Y, Shimizu Y, Suzuki H, et al. The Asian project for collaborative derivation of reference intervals: (2) results of non-standardized analytes and transference of reference intervals to the participating laboratories on the basis of cross-comparison of test results. Clin Chem Lab Med 2013;51:1443–57.10.1515/cclm-2012-0422Search in Google Scholar PubMed
13. Statistics Canada. Census Profile, 2016 Census [Internet]. [cited 2018 Aug 30]. Available from: https://www12.statcan.gc.ca/census-recensement/2016/dp-pd/prof/details/Page.cfm?Lang=E&Geo1=PR&Code1=35&Geo2=&Code2=&Data=Count&SearchText=Ontario&SearchType=Begins&SearchPR=01&B1=All&GeoLevel=PR&GeoCode=35.Search in Google Scholar
14. Bugdayci G, Oguzman H, Arattan HY, Sasmaz G. The use of reference change values in clinical laboratories. Clin Lab 2015;61:251–7.10.7754/Clin.Lab.2014.140906Search in Google Scholar PubMed
15. Brescia V, Tampoia M, Cardinali R. Biological variability of serum 25-hydroxyvitamin D and other biomarkers in healthy subjects. Lab Med 2013;44:20–4.10.1309/LMF62NSLERYC8PADSearch in Google Scholar
16. Bailey D, Bevilacqua V, Colantonio DA, Pasic MD, Perumal N, Chan MK, et al. Pediatric within-day biological variation and quality specifications for 38 biochemical markers in the CALIPER cohort. Clin Chem 2014;60:518–29.10.1373/clinchem.2013.214312Search in Google Scholar PubMed
17. Ricós C, Cava F, García-Lario JV, Hernández A, Iglesias N, Jiménez CV, et al. The reference change value: a proposal to interpret laboratory reports in serial testing based on biological variation. Scand J Clin Lab Invest 2004;64:175–84.10.1080/00365510410004885Search in Google Scholar PubMed
18. Willeman T, Casez O, Faure P, Gauchez AS. Evaluation of biotin interference on immunoassays: new data for troponin I, digoxin, NT-Pro-BNP, and progesterone. Clin Chem Lab Med 2017;55:e226–9.10.1515/cclm-2016-0980Search in Google Scholar PubMed
19. Lowe NM, Bhojani I. Special considerations for vitamin D in the south Asian population in the UK. Ther Adv Musculoskelet Dis 2017;9:137–44.10.1177/1759720X17704430Search in Google Scholar PubMed PubMed Central
20. Langer-Gould A, Lucas RM, Xiang AH, Wu J, Chen LH, Gonzales E, et al. Vitamin D-binding protein polymorphisms, 25-hydroxyvitamin D, sunshine and multiple sclerosis. Nutrients 2018;10:184.10.3390/nu10020184Search in Google Scholar PubMed PubMed Central
21. Makanji Y, Harrison CA, Robertson DM. Feedback regulation by inhibins A and B of the pituitary secretion of follicle-stimulating hormone. Vitam Horm 2011;85:299–321.10.1016/B978-0-12-385961-7.00014-7Search in Google Scholar PubMed
22. Yu S, Qiu L, Liu M, Li S, Tao Z, Zhang Q, et al. Establishing reference intervals for sex hormones and SHBG in apparently healthy Chinese adult men based on a multicenter study. Clin Chem Lab Med 2018;56:1152–60.10.1515/cclm-2017-0749Search in Google Scholar PubMed
23. Harris EL, McLaren CE, Reboussin DM, Gordeuk VR, Barton JC, Acton RT, et al. Serum ferritin and transferrin saturation in Asians and Pacific Islanders. Arch Intern Med 2007;167: 722–6.10.1001/archinte.167.7.722Search in Google Scholar PubMed
24. Yenson PR, Yoshida EM, Li CH, Chung HV, Tsang PW. Hyperferritinemia in the Chinese and Asian community: a retrospective review of the University of British Columbia experience. Can J Gastroenterol 2008;22:37–40.10.1155/2008/245096Search in Google Scholar PubMed PubMed Central
25. Buckley CE, Dorsey FC. Serum immunoglobulin levels throughout the life-span of healthy man. Ann Intern Med 1971;75:673–82.10.7326/0003-4819-75-5-673Search in Google Scholar PubMed
26. Tollerud DJ, Brown LM, Blattner WA, Weiss ST, Maloney EM, Kurman CC, et al. Racial differences in serum immunoglobulin levels: relationship to cigarette smoking, T-cell subsets, and soluble interleukin-2 receptors. J Clin Lab Anal 1995;9:37–41.10.1002/jcla.1860090107Search in Google Scholar PubMed
27. Satoh T, Brown LM, Blattner WA, Maloney EM, Kurman CC, Nelson DL, et al. Serum neopterin, beta2-microglobulin, soluble interleukin-2 receptors, and immunoglobulin levels in healthy adolescents. Clin Immunol Immunopathol 1998;88:176–82.10.1006/clin.1998.4568Search in Google Scholar PubMed
Supplementary Material
The online version of this article offers supplementary material (https://doi.org/10.1515/cclm-2019-0876).
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