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

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 - © 2021 Walter de Gruyter GmbH, Berlin/Boston.

PY - 2021/6/25

Y1 - 2021/6/25

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.

U2 - 10.1515/cclm-2020-1371

DO - 10.1515/cclm-2020-1371

M3 - SCORING: Journal article

C2 - 33565284

VL - 59

SP - 1267

EP - 1278

JO - CLIN CHEM LAB MED

JF - CLIN CHEM LAB MED

SN - 1434-6621

IS - 7

ER -