TY - JOUR
T1 - High-resolution pediatric reference intervals for 15 biochemical analytes described using fractional polynomials
AU - Zierk, Jakob
AU - Baum, Hannsjörg
AU - Bertram, Alexander
AU - Boeker, Martin
AU - Buchwald, Armin
AU - Cario, Holger
AU - Christoph, Jürgen
AU - Frühwald, Michael C.
AU - Groß, Hans Jürgen
AU - Groening, Arndt
AU - Gscheidmeier, Thomas
AU - Hoff, Torsten
AU - Hoffmann, Reinhard
AU - Klauke, Rainer
AU - Krebs, Alexander
AU - Lichtinghagen, Ralf
AU - Mühlenbrock-Lenter, Sabine
AU - Neumann, Michael
AU - Nöllke, Peter
AU - Niemeyer, Charlotte M.
AU - Ruf, Hans Georg
AU - Steigerwald, Udo
AU - Streichert, Thomas
AU - Torge, Antje
AU - Yoshimi-Nöllke, Ayami
AU - Prokosch, Hans Ulrich
AU - Metzler, Markus
AU - Rauh, Manfred
N1 - Publisher Copyright:
© 2021 De Gruyter. All rights reserved.
PY - 2021/6/1
Y1 - 2021/6/1
N2 - 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.
AB - 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.
KW - Continuous reference intervals
KW - Data mining
KW - Indirect reference intervals
KW - Pediatric reference intervals
KW - Percentile charts
UR - http://www.scopus.com/inward/record.url?scp=85100980476&partnerID=8YFLogxK
U2 - 10.1515/cclm-2020-1371
DO - 10.1515/cclm-2020-1371
M3 - Article
C2 - 33565284
AN - SCOPUS:85100980476
SN - 1434-6621
VL - 59
SP - 1267
EP - 1278
JO - Clinical Chemistry and Laboratory Medicine
JF - Clinical Chemistry and Laboratory Medicine
IS - 7
ER -