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Licensed Unlicensed Requires Authentication Published by De Gruyter April 22, 2019

Next-generation reference intervals for pediatric hematology

  • Jakob Zierk EMAIL logo , Johannes Hirschmann , Dennis Toddenroth , Farhad Arzideh , Rainer Haeckel , Alexander Bertram , Holger Cario , Michael C. Frühwald , Hans-Jürgen Groß , Arndt Groening , Stefanie Grützner , Thomas Gscheidmeier , Torsten Hoff , Reinhard Hoffmann , Rainer Klauke , Alexander Krebs , Ralf Lichtinghagen , Sabine Mühlenbrock-Lenter , Michael Neumann , Peter Nöllke , Charlotte M. Niemeyer , Oliver Razum , Hans-Georg Ruf , Udo Steigerwald , Thomas Streichert , Antje Torge , Wolfgang Rascher , Hans-Ulrich Prokosch , Manfred Rauh and Markus Metzler



Interpreting hematology analytes in children is challenging due to the extensive changes in hematopoiesis that accompany physiological development and lead to pronounced sex- and age-specific dynamics. Continuous percentile charts from birth to adulthood allow accurate consideration of these dynamics. However, the ethical and practical challenges unique to pediatric reference intervals have restricted the creation of such percentile charts, and limitations in current approaches to laboratory test result displays restrict their use when guiding clinical decisions.


We employed an improved data-driven approach to create percentile charts from laboratory data collected during patient care in 10 German centers (9,576,910 samples from 358,292 patients, 412,905–1,278,987 samples per analyte). We demonstrate visualization of hematology test results using percentile charts and z-scores ( and assess the potential of percentiles and z-scores to support diagnosis of different hematological diseases.


We created percentile charts for hemoglobin, hematocrit, red cell indices, red cell count, red cell distribution width, white cell count and platelet count in girls and boys from birth to 18 years of age. Comparison of pediatricians evaluating complex clinical scenarios using percentile charts versus conventional/tabular representations shows that percentile charts can enhance physician assessment in selected example cases. Age-specific percentiles and z-scores, compared with absolute test results, improve the identification of children with blood count abnormalities and the discrimination between different hematological diseases.


The provided reference intervals enable precise assessment of pediatric hematology test results. Representation of test results using percentiles and z-scores facilitates their interpretation and demonstrates the potential of digital approaches to improve clinical decision-making.


We thank the members of the German Society for Clinical Chemistry and Laboratory Medicine’s working group on guide limits (“AG Richtwerte der DGKL”) for their valuable input.

  1. Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

  2. Research funding: Supported by the Interdisciplinary Center for Clinical Research (IZKF) at the University Hospital of the University of Erlangen-Nuremberg.

  3. Employment or leadership: None declared.

  4. Honorarium: None declared.

  5. 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.


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Supplementary Material

The online version of this article offers supplementary material (

Article note:

Prior presentations: 22th Congress of the European Hematology Association (EHA), Madrid, Spain, June 2017 (abstract/e-poster); 14th Annual Congress of the German Society of Clinical Chemistry and Laboratory Medicine (DGKL), Oldenburg, Germany, October 2017 (talk and poster); XIVth International Congress of Paediatric Laboratory Medicine, Durban, South Africa October 2017 (talk and poster), IFCC WorldLab 2017, Durban, South Africa, October 2017 (poster); preliminary percentile charts have been published by the German Society for Paediatric Oncology and Haematology (GPOH) at

Received: 2018-11-18
Accepted: 2019-03-02
Published Online: 2019-04-22
Published in Print: 2019-09-25

©2019 Walter de Gruyter GmbH, Berlin/Boston

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