Validating CALIPER pediatric reference intervals in a U.S. population using retrospective outpatient data and RefineR

IF 4.1 3区医学 Q2 MEDICAL LABORATORY TECHNOLOGY

Clinica Chimica Acta Pub Date : 2026-03-15 Epub Date: 2026-01-19 DOI:10.1016/j.cca.2026.120846

Jillian Kodger , Thomas J.S. Durant , Nalan Yurtsever , Joe M. El-Khoury

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引用次数: 0

Abstract

Background

Accurate pediatric reference intervals (RIs) are critical for proper interpretation of laboratory results, yet their development is challenged by age-related physiological variation, limited sample sizes, and preanalytical variability. This study evaluates the applicability of the Canadian Laboratory Initiative on Pediatric Reference Intervals (CALIPER) RIs to a US-based, diverse pediatric outpatient population using both the RefineR inverse modeling approach and the Clinical and Laboratory Standards Institute (CLSI) EP28-A3c recommended approach.

Methods

Outpatient laboratory data from 51,863 patients under 19 years of age were collected from a single institution between January 2023 and December 2024. Nine commonly ordered chemistry analytes were evaluated. RIs were derived using both RefineR and CLSI guidelines with bootstrap resampling. These were compared to CALIPER RIs using a color-coded flagging system based on 95% confidence intervals and total allowable error (TAE).

Results

RefineR-based RIs aligned with CALIPER values in 86 out of 88 age- and gender-specific analyte groups, whereas CLSI-derived RIs aligned in 79 out of 88. Notable discrepancies involved alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and blood urea nitrogen, often influenced by known preanalytical and physiological variables such as sample type, body mass index (BMI), and hydration status.

Conclusions

RefineR demonstrated superior alignment with CALIPER RIs compared to CLSI guidelines, highlighting its robustness in outpatient pediatric populations. Given its tolerance to mixed data and skewed distributions, RefineR offers a more practical and accurate method for deriving population-specific RIs in pediatric laboratory medicine, and helps verify the implementation of external RIs, such as CALIPER.

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使用回顾性门诊数据和RefineR在美国人群中验证CALIPER儿科参考间隔。

背景：准确的儿科参考区间（RIs）对于正确解释实验室结果至关重要，但其发展受到年龄相关生理变化、有限样本量和分析前变异性的挑战。本研究使用RefineR逆建模方法和临床与实验室标准协会（CLSI） EP28-A3c推荐方法，评估加拿大儿科参考区间RIs （CALIPER）实验室倡议在美国不同儿科门诊人群中的适用性。方法：2023年1月至2024年12月，从一家机构收集51863例年龄在19岁以下 患者的门诊实验室数据。对9种常用化学分析物进行了评价。RIs是使用RefineR和CLSI指南和自举重采样得到的。使用基于95%置信区间和总允许误差（TAE）的颜色编码标记系统将这些与CALIPER RIs进行比较。结果：基于refiner的RIs在88个年龄和性别特定分析组中有86个与CALIPER值一致，而clsi衍生的RIs在88个组中有77个与CALIPER值一致。显著差异包括丙氨酸转氨酶、天冬氨酸转氨酶、碱性磷酸酶和血尿素氮，通常受到已知的分析前和生理变量的影响，如样品类型、体重指数（BMI）和水合状态。结论：与CLSI指南相比，RefineR与CALIPER RIs的一致性更好，突出了其在门诊儿科人群中的稳健性。鉴于RefineR对混合数据和偏态分布的容忍，它为儿科检验医学中获得人群特异性RIs提供了一种更实用、更准确的方法，并有助于验证外部RIs（如CALIPER）的实施。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Clinica Chimica Acta 医学-医学实验技术

CiteScore

10.10

自引率

2.00%

发文量

1268

审稿时长

23 days

期刊介绍： The Official Journal of the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) Clinica Chimica Acta is a high-quality journal which publishes original Research Communications in the field of clinical chemistry and laboratory medicine, defined as the diagnostic application of chemistry, biochemistry, immunochemistry, biochemical aspects of hematology, toxicology, and molecular biology to the study of human disease in body fluids and cells. The objective of the journal is to publish novel information leading to a better understanding of biological mechanisms of human diseases, their prevention, diagnosis, and patient management. Reports of an applied clinical character are also welcome. Papers concerned with normal metabolic processes or with constituents of normal cells or body fluids, such as reports of experimental or clinical studies in animals, are only considered when they are clearly and directly relevant to human disease. Evaluation of commercial products have a low priority for publication, unless they are novel or represent a technological breakthrough. Studies dealing with effects of drugs and natural products and studies dealing with the redox status in various diseases are not within the journal''s scope. Development and evaluation of novel analytical methodologies where applicable to diagnostic clinical chemistry and laboratory medicine, including point-of-care testing, and topics on laboratory management and informatics will also be considered. Studies focused on emerging diagnostic technologies and (big) data analysis procedures including digitalization, mobile Health, and artificial Intelligence applied to Laboratory Medicine are also of interest.