Abstract
Objectives
Pediatric Reference Intervals in China (PRINCE) is a nationwide initiative that aims to establish and validate harmonized reference intervals (RIs) for Chinese children and adolescents, in which 15,150 healthy volunteers aged up to 20 years were recruited from 11 centers to establish RIs and 7,557 children and adolescents were enrolled from 21 centers to validate RIs.
Methods
The complete blood cell counts (CBC) of venous whole blood were measured by hematology analyzers through Sysmex systems in different centers. Age- and sex-specific RIs were calculated according to the guidelines.
Results
Unlike adults with certain levels of analyte concentrations, hematological parameters of children changed through growth and development. Red blood cell counts, hemoglobin, and hematocrit increased with age, and revealed higher concentrations in boys than girls after puberty. White blood cell counts and platelet counts showed significant higher levels than adults before 2 years of age, and then gradually decreased without distinct sex differences. In addition, lymphocyte counts decreased with age while neutrophil counts showed an opposite trend. The lower and upper limits of pediatric RIs of CBC were different from those of adults.
Conclusions
The validation of RIs indicated that the PRINCE study provided a version of RIs suitable for most of regions in China. This first harmonized pediatric RIs of CBC across China provided a robust database to understand the dynamic changes of hematologic parameters from birth to adolescence, and will contribute to clinical diagnosis and prognosis evaluation for pediatric patients as well.
Funding source: The Medical Hospital Authority, National Health Commission of the People's Republic of China
Award Identifier / Grant number: No. 2017374
Acknowledgments
We thank Dr. Ali Abbas for his help in language polishing. We thank all of the members of workgroups in 11 medical centers for their hard work in participant recruitment and sample collection. At last, we specially thank all of the healthy children volunteers and their family.
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Research funding: This study was supported by the grant from the Medical Hospital Authority, National Health Commission of the People’s Republic of China (No. 2017374).
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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 each participant’s legally authorized representative (parent or guardian) in the case of the child aged less than 8 years. Otherwise, the informed consent was obtained from both the child and his/her legally authorized representative.
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Ethical approval: The PRINCE study was approved by The Institutional Review Board of Beijing Children’s Hospital (2016-53). At the same time, the protocol was approved by the institutional review boards of other 10 collaborating centers.
References
1. Lv, Y, Feng, G, Ni, X, Song, W, Peng, X. The critical gap for pediatric reference intervals of complete blood count in China. Clin Chim Acta 2017;469:22–5. https://doi.org/10.1016/j.cca.2017.03.017.Search in Google Scholar
2. Wu, X, Zhao, M, Pan, B, Zhang, J, Peng, M, Wang, L, et al.. Complete blood count reference intervals for healthy Han Chinese adults. PLoS One 2015;10:e0119669. https://doi.org/10.1371/journal.pone.0119669.Search in Google Scholar
3. Wang, Y, Song, W, Ren, N, Li, Y, Chen, Z. Investigation of reference intervals of kidney clinical biochemistry tests for healthy children in Beijing [in Chinese]. J Mod Lab Med 2013;28:2631–8.Search in Google Scholar
4. Gao, Y, Zou, C, Jiang, J, Yang, JM, Tian, XM. Determination of normal reference ranges for venous blood count among 526 children aging from 1 year old to 12 years old in Shanghai [in Chinese]. Int J Lab Med 2015;36:2332–4.Search in Google Scholar
5. Yuan, L, Wang, G, Chen, W. The establishment of the reference interval for venous blood leukocyte count and classification among 2213 children in Xi′an [in Chinese]. Int J Lab Med 2016;37:1077–8.Search in Google Scholar
6. 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
7. Peng, X, Lv, Y, Feng, G, Peng, Y, Li, Q, Song, W, et al.. Algorithm on age partitioning for estimation of reference intervals using clinical laboratory database exemplified with plasma creatinine. Clin Chem Lab Med 2018;56:1514–23. https://doi.org/10.1515/cclm-2017-1095.Search in Google Scholar
8. CLSI. Defining, establishing, and verifying reference intervals in the clinical laboratory; approved guideline. CLSI document EP28-A3c, 3rd ed. Wayne, PA: Clinical and Laboratory Standards Institute; 2008.Search in Google Scholar
9. CLSI. Measurement procedure comparison and bias estimation using patient samples; approved guideline. CLSI document EP09-A3, 3rd ed. Wayne, PA: Clinical and Laboratory Standards Institute; 2013.Search in Google Scholar
10. 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
11. Box, G, Cox, D. An analysis of transformations. J Roy Stat Soc 1964;B26:211–52. https://doi.org/10.1111/j.2517-6161.1964.tb00553.x.Search in Google Scholar
12. Dixon, WJ. Processing data for outliers. Biometrics 1953;9:74–89. https://doi.org/10.2307/3001634.Search in Google Scholar
13. 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
14. Daly, CH, Higgins, V, Adeli, K, Grey, VL, Hamid, JS. Reference interval estimation: methodological comparison using extensive simulations and empirical data. Clin Biochem 2017;50:1145–58. https://doi.org/10.1016/j.clinbiochem.2017.07.005.Search in Google Scholar PubMed
15. Li, K, Hu, L, Peng, Y, Yan, R, Li, Q, Peng, X, et al.. Comparison of four algorithms on establishing continuous reference intervals for pediatric analytes with age-dependent trend. BMC Med Res Methodol 2020;20:136. https://doi.org/10.1186/s12874-020-01021-y.Search in Google Scholar PubMed PubMed Central
16. Wang, GC, Li, N, Niu, C, Ma, WB, Wang, ZL, Guo, H, et al.. Establishment of complete blood count reference intervals for Chinese preschoolers. J Clin Lab Anal 2017;31:e22095. https://doi.org/10.1002/jcla.22095.Search in Google Scholar PubMed PubMed Central
17. Zhang, X, Ding, Y, Zhang, Y, Xing, J, Dai, Y, Yuan, E. Age- and sex-specific reference intervals for hematologic analytes in Chinese children. Int J Lab Hematol 2019;41:331–7. https://doi.org/10.1111/ijlh.12979.Search in Google Scholar PubMed
18. Li, J, Zhang, H, Huang, X, Zhang, J, Wu, X. Establishment of reference intervals for complete blood count parameters in venous blood for children in the Xiamen area, China. Int J Lab Hematol 2019;41:691–6. https://doi.org/10.1111/ijlh.13095.Search in Google Scholar PubMed
19. Nah, EH, Kim, S, Cho, S, Cho, HI. Complete blood count reference intervals and patterns of changes across pediatric, adult, and geriatric ages in Korea. Ann Lab Med 2018;38:503–11. https://doi.org/10.3343/alm.2018.38.6.503.Search in Google Scholar PubMed PubMed Central
20. Adeli, K, Raizman, JE, Chen, Y, Higgins, V, Nieuwesteeg, M, Abdelhaleem, M, et al.. Complex biological profile of hematologic markers across pediatric, adult, and geriatric ages: establishment of robust pediatric and adult reference intervals on the basis of the Canadian Health Measures Survey. Clin Chem 2015;61:1075–86. https://doi.org/10.1373/clinchem.2015.240531.Search in Google Scholar PubMed
21. 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
22. Bachman, E, Travison, TG, Basaria, S, Davda, MN, Guo, W, Li, M, et al.. Testosterone induces erythrocytosis via increased erythropoietin and suppressed hepcidin: evidence for a new erythropoietin/hemoglobin set point. J Gerontol A Biol Sci Med Sci 2014;69:725–35. https://doi.org/10.1093/gerona/glt154.Search in Google Scholar PubMed PubMed Central
23. Joint World Health Organization/centers for disease control and prevention technical consultation on the assessment of iron status at the population level (2004: Geneva, Switzerland). Assessing the iron status of populations: including literature reviews: report of a Joint World Health Organization/Centers for Disease Control and Prevention Technical Consultation on the Assessment of Iron Status at the Population Level, 6–8 April 2004, 2nd ed. Geneva, Switzerland: World Health Organization; 2007. https://apps.who.int/iris/handle/10665/75368.Search in Google Scholar
24. Miao, G, Xinping, L, Haiyan, F, Zhilun, W, Yanfang, Z, Jian, Z, et al.. Normal reference value of hemoglobin of middleaged women and altitude. Yale J Biol Med 2004;77:117–23.Search in Google Scholar
25. Xu, XM, Zhou, YQ, Luo, GX, Liao, C, Zhou, M, Chen, PY, et al.. The prevalence and spectrum of alpha and beta thalassaemia in Guangdong Province: implications for the future health burden and population screening. J Clin Pathol 2004;57:517–22. https://doi.org/10.1136/jcp.2003.014456.Search in Google Scholar PubMed PubMed Central
26. Wang, X, Jiang, H, Jia, J, Zhou, J, Liao, J, Zuo, C. Screening and genetic analysis of thalassemia in Sichuan District [in Chinese]. Sheng Wu Yi Xue Gong Cheng Xue Za Zhi 2011;28:135–7.Search in Google Scholar
27. Xu, JH, Hao, XK, Mu, RQ, Pan, BS, Zhang, J, Peng, MT, et al.. The effect of thalassemia on erythrocyte reference intervals in a representative Han Chinese adult population. Clin Lab 2015;61:405–14. https://doi.org/10.7754/clin.lab.2014.140905.Search in Google Scholar PubMed
28. Ishiguro, A, Nakahata, T, Matsubara, K, Hayashi, Y, Kato, T, Suzuki, Y, et al.. Age-related changes in thrombopoietin in children: reference interval for serum thrombopoietin levels. Br J Haematol 1999;106:884–8. https://doi.org/10.1046/j.1365-2141.1999.01641.x.Search in Google Scholar PubMed
Supplementary Material
The online version of this article offers supplementary material (https://doi.org/10.1515/cclm-2022-0304).
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