Abstract
Background: Determination of pediatric reference intervals (RIs) for laboratory quantities, including hematological quantities, is complex. The measured quantities vary by age, and obtaining samples from healthy children is difficult. Many widely used RIs are derived from small sample numbers and are split into arbitrary discrete age intervals. Use of intra-laboratory RIs specific to the examined population and analytical device used is not yet fully established. Indirect methods address these issues by deriving RIs from clinical laboratory databases which contain large datasets of both healthy and pathological samples.
Methods: A refined indirect approach was used to create continuous age-dependent RIs for blood count quantities and sodium from birth to adulthood. The dataset for each quantity consisted of 60,000 individual samples from our clinical laboratory. Patient samples were separated according to age, and a density function of the proportion of healthy samples was estimated for each age group. The resulting RIs were merged to obtain continuous RIs from birth to adulthood.
Results: The obtained RIs were compared to RIs generated by identical laboratory instruments, and to population-specific RIs created using conventional methods. This comparison showed a high concordance of reference limits and their age-dependent dynamics.
Conclusions: The indirect approach reported here is well-suited to create continuous, intra-laboratory RIs from clinical laboratory databases and showed that the RIs generated are comparable to those created using established methods. The procedure can be transferred to other laboratory quantities and can be used as an alternative method for RI determination where conventional approaches are limited.
References
1. Ceriotti F. Establishing pediatric reference intervals: a challenging task. Clin Chem 2012;58:808–10.10.1373/clinchem.2012.183483Search in Google Scholar PubMed
2. Solberg HE. A guide to IFCC recommendations on reference values. J Int Fed Clin Chem 1993;5:162–5.Search in Google Scholar
3. Jones G, Barker A. Reference intervals. Clin Biochem Rev 2008;29(Suppl 1):S93–7.Search in Google Scholar
4. Horowitz GL, Altaie S, Boyd JC, Ceriotti F, Garg U, Horn P, et al. Defining, establishing, and verifying reference intervals in the clinical laboratory; Approved guideline, 3rd ed. Wayne, PA: Clinical and Laboratory Standards Institute, 2008.Search in Google Scholar
5. Abdelhaleem M, Adeli K, Bamforth F, Callahan J, Chan A, Cheung Chan P, et al., An editorial on behalf of the CALIPER investigators. Pediatric reference intervals: critical gap analysis and establishment of a national initiative. Clin Biochem 2006;39:559–60.10.1016/j.clinbiochem.2006.03.009Search in Google Scholar PubMed
6. Jung B, Adeli K. Clinical laboratory reference intervals in pediatrics: the CALIPER initiative. Clin Biochem 2009;42:1589–95.10.1016/j.clinbiochem.2009.06.025http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=000270935700001&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=b7bc2757938ac7a7a821505f8243d9f3Search in Google Scholar PubMed
7. Kulasingam V, Jung BP, Blasutig IM, Baradaran S, Chan MK, Aytekin M, etal. Pediatric reference intervals for 28 chemistries and immunoassays on the Roche cobas 6000 analyzer – a CALIPER pilot study. Clin Biochem 2010;43:1045–50.http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=000281721200003&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=b7bc2757938ac7a7a821505f8243d9f310.1016/j.clinbiochem.2010.05.008Search in Google Scholar PubMed
8. Colantonio DA, Kyriakopoulou L, Chan MK, Daly CH, Brinc D, Venner AA, etal. 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.http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=000303701400014&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=b7bc2757938ac7a7a821505f8243d9f310.1373/clinchem.2011.177741Search in Google Scholar PubMed
9. Dortschy R, Rosario AS, Scheidt-Nave C, Thierfelder W, Thamm M, Gutsche J, etal. Bevölkerungsbezogene Verteilungswerte ausgewählter Laborparameter aus der Studie zur Gesundheit von Kindern und Jugendlichen in Deutschland (KiGGS). Berlin: Robert Koch-Institut, 2009.Search in Google Scholar
10. Friedberg RC, Souers R, Wagar EA, Stankovic AK, Valenstein PN. The origin of reference intervals. Arch Pathol Lab Med 2007;131:348–57.10.5858/2007-131-348-TOORISearch in Google Scholar PubMed
11. Soldin SJ, Brugnara C, Wong EC. Pediatric reference ranges, 4th ed. Washington, DC: AACC Press, 2003.Search in Google Scholar
12. Arzideh F, Brandhorst G, Gurr E, Hinsch W, Hoff T, Roggenbuck L, etal. An improved indirect approach for determining reference limits from intra-laboratory data bases exemplified by concentrations of electrolytes. J Lab Med 2009;33:52–66.Search in Google Scholar
13. Arzideh F, Wosniok W, Haeckel R. Reference limits of plasma and serum creatinine concentrations from intra-laboratory data bases of several German and Italian medical centres: comparison between direct and indirect procedures. Clin Chim Acta 2010;411:215–21.http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=000274102700016&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=b7bc2757938ac7a7a821505f8243d9f310.1016/j.cca.2009.11.006Search in Google Scholar PubMed
14. Concordet D, Geffre A, Braun JP, Trumel C. A new approach for the determination of reference intervals from hospital-based data. Clin Chim Acta 2009;405:43–8.http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=000267448300008&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=b7bc2757938ac7a7a821505f8243d9f310.1016/j.cca.2009.03.057Search in Google Scholar PubMed
15. Solberg HE. Using a hospitalized population to establish reference intervals: pros and cons. Clin Chem 1994;40:2205–6.10.1093/clinchem/40.12.2205Search in Google Scholar PubMed
16. Grossi E, Colombo R, Cavuto S, Franzini C. The REALAB project: a new method for the formulation of reference intervals based on current data. Clin Chem 2005;51:1232–40.10.1373/clinchem.2005.047787Search in Google Scholar PubMed
17. Kouri T, Kairisto V, Virtanen A, Uusipaikka E, Rajamaki A, Finneman H, etal. Reference intervals developed from data for hospitalized patients: computerized method based on combination of laboratory and diagnostic data. Clin Chem 1994;40:2209–15.10.1093/clinchem/40.12.2209Search in Google Scholar PubMed
18. R Development Core Team. R: a language and environment for statistical computing. Vienna: R Foundation for Statistical Computing, 2010.Search in Google Scholar
19. Ceriotti F, Hinzmann R, Panteghini M. Reference intervals: the way forward. Ann Clin Biochem 2009;46:8–17.10.1258/acb.2008.008170Search in Google Scholar PubMed
20. Richtlinie der Bundesärztekammer zur Qualitätssicherung laboratoriumsmedizinischer Untersuchungen. Dt Ärzteblatt 2008;105:A341–55.Search in Google Scholar
21. Arceci R, Hann IM, Smith OP. Pediatric hematology. Malden, MA: Blackwell Publishing, 2006.10.1002/9780470987001Search in Google Scholar
22. Orkin SH, Nathan DG. Nathan and Oski’s hematology of infancy and childhood, 7th ed. Philadelphia: Saunders/Elsevier, 2009.Search in Google Scholar
23. Irwin JJ, Kirchner JT. Anemia in children. Am Fam Physician 2001;64:1379–86.Search in Google Scholar
24. Saarinen UM, Siimes MA. Developmental changes in red blood cell counts and indices of infants after exclusion of iron deficiency by laboratory criteria and continuous iron supplementation. J Pediatr 1978;92:412–6.10.1016/S0022-3476(78)80429-6Search in Google Scholar PubMed
25. Virtanen A, Kairisto V, Uusipaikka E. Regression-based reference limits: determination of sufficient sample size. Clin Chem 1998;44:2353–8.10.1093/clinchem/44.11.2353Search in Google Scholar PubMed
©2013 by Walter de Gruyter Berlin Boston
