Zierk Jakob, Baum Hannsjörg, Bertram Alexander, Boeker Martin, Buchwald Armin, Cario Holger, Christoph Jürgen, Frühwald Michael C, Groß Hans-Jürgen, Groening Arndt, Gscheidmeier Thomas, Hoff Torsten, Hoffmann Reinhard, Klauke Rainer, Krebs Alexander, Lichtinghagen Ralf, Mühlenbrock-Lenter Sabine, Neumann Michael, Nöllke Peter, Niemeyer Charlotte M, Ruf Hans-Georg, Steigerwald Udo, Streichert Thomas, Torge Antje, Yoshimi-Nöllke Ayami, Prokosch Hans-Ulrich, Metzler Markus, Rauh Manfred
Department of Pediatrics and Adolescent Medicine, University Hospital Erlangen, Erlangen, Germany.
Center of Medical Information and Communication Technology, University Hospital Erlangen, Erlangen, Germany.
Clin Chem Lab Med. 2021 Feb 10;59(7):1267-1278. doi: 10.1515/cclm-2020-1371. Print 2021 Jun 25.
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 project (Next-Generation Pediatric Reference Intervals) to create pediatric reference intervals using data from laboratory information systems.
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 ().
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, -scores and percentiles enable the normalization of test results by age and sex to facilitate their interpretation across age groups.
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.
评估儿童实验室检测结果时，需要考虑生理发育过程中发生的广泛变化，这些变化导致许多生化分析物出现明显的性别和年龄特异性动态变化。儿科参考区间必须考虑这些动态变化，但伦理和实际挑战限制了涵盖从出生到成年儿童的适当儿科参考区间的可用性。因此，我们启动了多中心数据驱动项目（下一代儿科参考区间），以利用实验室信息系统的数据创建儿科参考区间。
我们分析了德国13个中心在患者护理期间对638683名患者进行的实验室检测结果（每种分析物有217883 - 982548个样本，每种分析物的检测结果中位数为603745个，总共10298067个检测结果）。重复测量儿童的检测结果被排除，我们使用经过验证的统计方法估计生理检测结果的分布。
我们报告了丙氨酸转氨酶、天冬氨酸转氨酶、乳酸脱氢酶、碱性磷酸酶、γ-谷氨酰转移酶、总蛋白、白蛋白、肌酐、尿素、钠、钾、钙、氯、无机磷酸盐和镁的连续儿科参考区间和百分位数图表。参考区间以表格和分数多项式函数（即数学方程）的形式提供，可整合到实验室信息系统中。此外，z分数和百分位数能够按年龄和性别对检测结果进行标准化，以便于跨年龄组解读。
提供的参考区间和百分位数图表能够精确评估从出生到成年儿童的实验室检测结果。我们的研究结果突出了新生儿许多生化分析物的明显动态变化，在参考区间中需要特别考虑这些变化，以最有效地支持临床决策。
