Volume 85, Issue 1
  • ISSN: 0002-9637
  • E-ISSN: 1476-1645



Pediatric reference intervals for biochemical tests are often derived from studies in Western countries and may not be applicable to the developing world. No such intervals exist for Melanesian populations. The aim of this study was to provide specific reference intervals for children from Papua New Guinea (PNG). We assayed plasma from 327 healthy Melanesian children living in Madang Province for common biochemical and hematological analytes. We used well-validated commercially available assay methodology. Compared with reference intervals from children from Western countries and/or African children, there were substantial differences in hemoglobin, soluble transferrin receptor, ferritin, calcium, phosphate, and C-reactive protein. Differences in the upper limits of reference intervals for bilirubin and alanine aminotransferase were also observed. Available reference intervals from Western and African countries may be inappropriate in PNG and other Melanesian countries. This has implications for clinical care and safety monitoring in pharmaceutical intervention trials and vaccine studies.


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  1. Quinto L, Aponte JJ, Sacarlal J, Espasa M, Aide P, Mandomando I, Guinovart C, Macete E, Navia MM, Thompson R, Menendez C, Alonso PL, , 2006. Haematological and biochemical indices in young African children: in search of reference intervals. Trop Med Int Health 11: 17411748.[Crossref]
  2. Lugada ES, Mermin J, Kaharuza F, Ulvestad E, Were W, Langeland N, Asjo B, Malamba S, Downing R, , 2004. Population-based hematologic and immunologic reference values for a healthy Ugandan population. Clin Diagn Lab Immunol 11: 2934.
  3. Saathoff E, Schneider P, Kleinfeldt V, Geis S, Haule D, Maboko L, Samky E, de Souza M, Robb M, Hoelscher M, , 2008. Laboratory reference values for healthy adults from southern Tanzania. Trop Med Int Health 13: 612625.[Crossref]
  4. Kasvosve I, Gomo ZA, Nathoo KJ, Matibe P, Mudenge B, Gordeuk VR, , 2007. Reference intervals of serum transferrin receptors in pre-school children in Zimbabwe. Clin Chim Acta 382: 138141.[Crossref]
  5. Burchard EG, Ziv E, Coyle N, Gomez SL, Tang H, Karter AJ, Mountain JL, Perez-Stable EJ, Sheppard D, Risch N, , 2003. The importance of race and ethnic background in biomedical research and clinical practice. N Engl J Med 348: 11701175.[Crossref]
  6. National Statistical Office of Papua New Guinea, 2002 Papua New Guinea 2000 Census. Papua New Guinea: Port Moresby.
  7. Cattani JA, Tulloch JL, Vrbova H, Jolley D, Gibson FD, Moir JS, Heywood PF, Alpers MP, Stevenson A, Clancy R, , 1986. The epidemiology of malaria in a population surrounding Madang, Papua New Guinea. Am J Trop Med Hyg 35: 315.
  8. Allen SJ, O'Donnell A, Alexander ND, Alpers MP, Peto TE, Clegg JB, Weatherall DJ, , 1997. alpha+−Thalassemia protects children against disease caused by other infections as well as malaria. Proc Natl Acad Sci USA 94: 1473614741.[Crossref]
  9. Grasbeck R, , 2004. The evolution of the reference value concept. Clin Chem Lab Med 42: 692697.[Crossref]
  10. Ritchie RF, Palomaki G, , 2004. Selecting clinically relevant populations for reference intervals. Clin Chem Lab Med 42: 702709.[Crossref]
  11. Molyneux ME, Taylor TE, Wirima JJ, Borgstein A, , 1989. Clinical features and prognostic indicators in paediatric cerebral malaria: a study of 131 comatose Malawian children. Q J Med 71: 441459.
  12. World Health Organization, 2009. Anthro for Personal Computers: Software for Assessing Growth and Development of the World's Children. Geneva: WHO.
  13. Payne RB, Little AJ, Williams RB, Milner JR, , 1973. Interpretation of serum calcium in patients with abnormal serum proteins. BMJ 4: 643646.[Crossref]
  14. Solberg HE, , 1983. The theory of reference values Part 5. Statistical treatment of collected reference values. Determination of reference limits. J Clin Chem Clin Biochem 21: 749760.
  15. Clinical and Laboratory Standards Institute, 2008. Defining, Establishing, and Verifying Reference Intervals in the Clinical Laboratory; Approved Guideline. Third edition. (CLSI Document C28-A3). Wayne, PA.
  16. Bland JM, Altman DG, , 1996. Transforming data. BMJ 312: 770.[Crossref]
  17. Soldin S, Brugnara C, Hicks J, , 1999. Pediatric Reference Ranges. Washington, DC: American Association for Clinical Chemistry.
  18. Sinton TJ, Cowley DM, Bryant SJ, , 1986. Reference intervals for calcium, phosphate, and alkaline phosphatase as derived on the basis of multichannel-analyzer profiles. Clin Chem 32: 7679.
  19. Reed AH, Henry RJ, Mason WB, , 1971. Influence of statistical method used on the resulting estimate of normal range. Clin Chem 17: 275284.
  20. Kratovil T, DeBerardinis J, Gallagher N, Luban NL, Soldin SJ, Wong EC, , 2007. Age specific reference intervals for soluble transferrin receptor (sTfR). Clin Chim Acta 380: 222224.[Crossref]
  21. Randers E, Krue S, Erlandsen EJ, Danielsen H, Hansen LG, , 1999. Reference interval for serum cystatin C in children. Clin Chem 45: 18561858.
  22. Ceriotti F, Boyd JC, Klein G, Henny J, Queralto J, Kairisto V, Panteghini M, , 2008. Reference intervals for serum creatinine concentrations: assessment of available data for global application. Clin Chem 54: 559566.[Crossref]
  23. Samba C, Galan P, Luzeau R, Amedee-Manesme O, , 1990. Vitamin A deficiency in pre-school age Congolese children during malarial attacks. Part 1: utilization of the impression cytology with transfer in an equatorial country. Int J Vitam Nutr Res 60: 215223.
  24. Landis JR, Koch GG, , 1977. The measurement of observer agreement for categorical data. Biometrics 33: 159174.[Crossref]
  25. Cicchetti DV, Feinstein AR, , 1990. High agreement but low kappa: II. Resolving the paradoxes. J Clin Epidemiol 43: 551558.[Crossref]
  26. Mei Z, Grummer-Strawn LM, , 2007. Standard deviation of anthropometric Z-scores as a data quality assessment tool using the 2006 WHO growth standards: a cross country analysis. Bull World Health Organ 85: 441448.[Crossref]
  27. Mahe A, , 2001. Bacterial skin infections in a tropical environment. Curr Opin Infect Dis 14: 123126.[Crossref]
  28. Grant CC, Wall CR, Crengle S, Scragg R, , 2009. Vitamin D deficiency in early childhood: prevalent in the sunny South Pacific. Public Health Nutr 12: 18931901.[Crossref]
  29. Rejnmark L, Jorgensen ME, Pedersen MB, Hansen JC, Heickendorff L, Lauridsen AL, Mulvad G, Siggaard C, Skjoldborg H, Sorensen TB, Pedersen EB, Mosekilde L, , 2004. Vitamin D insufficiency in Greenlanders on a westernized fare: ethnic differences in calcitropic hormones between Greenlanders and Danes. Calcif Tissue Int 74: 255263.[Crossref]
  30. Pepys MB, Hirschfield GM, , 2003. C-reactive protein: a critical update. J Clin Invest 111: 18051812.[Crossref]
  31. Hurt N, Smith T, Teuscher T, Tanner M, , 1994. Do high levels of C-reactive protein in Tanzanian children indicate malaria morbidity. Clin Diagn Lab Immunol 1: 437444.
  32. Food and Drug Administration, 2009. Guidance for industry. Drug-Induced Liver Injury: Premarketing Clinical Evaluation. Silver Spring, MD.

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  • Received : 15 Feb 2011
  • Accepted : 01 Mar 2011

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