High-resolution pediatric reference intervals for 15 biochemical analytes described using fractional polynomials

Author:

Zierk Jakob12,Baum Hannsjörg3,Bertram Alexander4,Boeker Martin5,Buchwald Armin6,Cario Holger7,Christoph Jürgen8,Frühwald Michael C.9,Groß Hans-Jürgen10,Groening Arndt4,Gscheidmeier Thomas10,Hoff Torsten11,Hoffmann Reinhard12,Klauke Rainer13,Krebs Alexander14,Lichtinghagen Ralf13,Mühlenbrock-Lenter Sabine11,Neumann Michael15,Nöllke Peter16,Niemeyer Charlotte M.16,Ruf Hans-Georg12,Steigerwald Udo15,Streichert Thomas17,Torge Antje18,Yoshimi-Nöllke Ayami16,Prokosch Hans-Ulrich19,Metzler Markus1,Rauh Manfred1

Affiliation:

1. Department of Pediatrics and Adolescent Medicine , University Hospital Erlangen , Erlangen , Germany

2. Center of Medical Information and Communication Technology, University Hospital Erlangen , Erlangen , Germany

3. Institute for Laboratory Medicine, Regionale Kliniken Holding RKH GmbH , Ludwigsburg , Germany

4. MVZ wagnerstibbe, amedes Gruppe , Hannover , Germany

5. Institute of Medical Biometry and Statistics, Medical Data Science, Faculty of Medicine and Medical Center, University of Freiburg , Freiburg , Germany

6. Institute for Clinical Chemistry and Laboratory Medicine, University of Freiburg , Freiburg , Germany

7. Department of Pediatrics and Adolescent Medicine , University Medical Centre , Ulm , Germany

8. Children’s and Youth Hospital ‘Auf der Bult’ , Hannover , Germany

9. Paediatric and Adolescent Medicine , Medical Faculty and University Hospital Augsburg , Augsburg , Germany

10. Core Facility of Clinical Chemistry , University Medical Centre Ulm , Ulm , Germany

11. Central Laboratory , Gesundheit Nord - Bremen Hospital Group , Bremen , Germany

12. Institute for Laboratory Medicine and Microbiology, Medical Faculty and University Hospital Augsburg , Augsburg , Germany

13. Institute of Clinical Chemistry, MHH , Hannover , Germany

14. MVZ Labor PD Dr. Volkmann und Kollegen , Karlsruhe , Germany

15. Division of Laboratory Medicine, University Hospital of Würzburg , Würzburg , Germany

16. Department of Pediatrics and Adolescent Medicine , Division of Pediatric Hematology and Oncology, Medical Center, Faculty of Medicine, University of Freiburg , Freiburg , Germany

17. Department of Clinical Chemistry , University Hospital of Cologne , Cologne , Germany

18. Institute of Clinical Chemistry, University Hospital Schleswig-Holstein, Campus Kiel , Kiel , Germany

19. Chair of Medical Informatics, Friedrich-Alexander-University Erlangen-Nuremberg , Erlangen , Germany

Abstract

Abstract Objectives Assessment of children’s laboratory test results requires consideration of the extensive changes that occur during physiological development and result in pronounced sex- and age-specific dynamics in many biochemical analytes. Pediatric reference intervals have to account for these dynamics, but ethical and practical challenges limit the availability of appropriate pediatric reference intervals that cover children from birth to adulthood. We have therefore initiated the multi-center data-driven PEDREF project (Next-Generation Pediatric Reference Intervals) to create pediatric reference intervals using data from laboratory information systems. Methods We analyzed laboratory test results from 638,683 patients (217,883–982,548 samples per analyte, a median of 603,745 test results per analyte, and 10,298,067 test results in total) performed during patient care in 13 German centers. Test results from children with repeat measurements were discarded, and we estimated the distribution of physiological test results using a validated statistical approach (kosmic). Results We report continuous pediatric reference intervals and percentile charts for alanine transaminase, aspartate transaminase, lactate dehydrogenase, alkaline phosphatase, γ-glutamyl-transferase, total protein, albumin, creatinine, urea, sodium, potassium, calcium, chloride, anorganic phosphate, and magnesium. Reference intervals are provided as tables and fractional polynomial functions (i.e., mathematical equations) that can be integrated into laboratory information systems. Additionally, Z-scores and percentiles enable the normalization of test results by age and sex to facilitate their interpretation across age groups. Conclusions The provided reference intervals and percentile charts enable precise assessment of laboratory test results in children from birth to adulthood. Our findings highlight the pronounced dynamics in many biochemical analytes in neonates, which require particular consideration in reference intervals to support clinical decision making most effectively.

Publisher

Walter de Gruyter GmbH

Subject

Biochemistry (medical),Clinical Biochemistry,General Medicine

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