Validating Pediatric Reference Intervals in U.S. Populations
Publication Title: Validating CALIPER pediatric reference intervals in a U.S. population using retrospective outpatient data and RefineR
Summary
- Question
- This study evaluated whether pediatric reference intervals (RIs)—standard ranges for interpreting lab test results—developed by the Canadian Laboratory Initiative on Pediatric Reference Intervals (CALIPER) align with the characteristics of a diverse U.S. pediatric population. The researchers specifically compared the performance of two methods for deriving RIs: the RefineR statistical algorithm and the Clinical and Laboratory Standards Institute (CLSI) guidelines.
- Why it Matters
- Accurate pediatric RIs are essential for correctly interpreting lab results in children, who undergo rapid physiological changes as they grow. Using incorrect RIs can lead to misdiagnosis or unnecessary treatments. While CALIPER has established comprehensive RIs for children, these may not perfectly apply to diverse populations like those in the U.S. Verifying their accuracy can improve pediatric care and ensure lab results are interpreted correctly across varying demographics.
- Methods
- The researchers analyzed outpatient lab test data from 51,863 individuals under 19 years of age collected between January 2023 and December 2024. They focused on nine common blood chemistry tests, such as those measuring liver enzymes and kidney function. Using RefineR and CLSI guidelines, they calculated RIs and compared them to CALIPER’s values, using a color-coded system to rate agreement.
- Key Findings
- The RefineR method aligned with CALIPER RIs in 97.7% of test groups, compared to 89.8% alignment using CLSI guidelines. RefineR showed better agreement, particularly for tests like liver enzymes, which are influenced by factors like body mass index (BMI) and hydration. However, some discrepancies were observed, notably for tests like alkaline phosphatase and creatinine, likely due to population-specific differences such as age distribution and lifestyle factors.
- Implications
- RefineR proved to be a more accurate and practical tool for validating pediatric RIs in diverse outpatient settings. Its ability to handle mixed and skewed data makes it particularly valuable for hospitals with limited access to healthy pediatric volunteers. Using this method could help ensure more reliable lab result interpretation, reducing diagnostic errors and improving care for children.
- Next Steps
- The researchers recommend further studies to validate these findings in other U.S. populations and to address preanalytical factors like sample type and processing variability. They also suggest integrating RefineR into routine clinical workflows to improve RI accuracy across diverse healthcare settings.
- Funding Information
- This research was supported by Yale University.
Full Citation
Kodger J, Durant T, Yurtsever N, El-Khoury J. Validating CALIPER pediatric reference intervals in a U.S. population using retrospective outpatient data and RefineR. Clinica Chimica Acta 2026, 584: 120846. PMID: 41565092, DOI: 10.1016/j.cca.2026.120846.
This AI-assisted summary has been reviewed and approved by at least one of the study's authors to ensure it accurately reflects the research.
Authors
Jillian Kodger
First AuthorJoe El-Khoury, PhD, DABCC
Last AuthorProfessor
Additional Yale School of Medicine Authors
Research Themes
Keywords
Concepts
- Pediatric reference intervals;
- Body mass index;
- CALIPER reference intervals;
- CLSI guidelines;
- Reference intervals;
- Canadian Laboratory Initiative;
- Pediatric laboratory medicine;
- Population-specific reference intervals;
- Outpatient pediatric population;
- Pediatric outpatient population;
- Blood urea nitrogen;
- Years of age;
- EP28-A3c;
- Pediatric population;
- Mass index;
- Outpatient data;
- CLSI;
- U.S. population;
- Alanine aminotransferase;
- Outpatient population;
- Interpretation of laboratory results;
- Urea nitrogen