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

Area of Science:

• Clinical Laboratory Medicine
• Pediatric Reference Interval Development
• Biostatistics in Healthcare

Background:

• Accurate pediatric reference intervals (RIs) are crucial for interpreting lab results but face challenges like physiological variation and limited sample sizes.
• This study assesses the applicability of Canadian Laboratory Initiative on Pediatric Reference Intervals (CALIPER) RIs in a diverse US pediatric outpatient setting.
• Two methods, RefineR inverse modeling and Clinical and Laboratory Standards Institute (CLSI) EP28-A3c, were used for evaluation.

Purpose of the Study:

• To evaluate the applicability of existing Canadian Laboratory Initiative on Pediatric Reference Intervals (CALIPER) to a US pediatric outpatient population.
• To compare the performance of the RefineR inverse modeling approach versus the CLSI EP28-A3c recommended approach for deriving pediatric reference intervals.
• To assess the accuracy and practicality of RefineR for developing population-specific pediatric reference intervals.

Main Methods:

• Collected outpatient laboratory data from 51,863 pediatric patients (under 19 years) between January 2023 and December 2024.
• Derived reference intervals (RIs) for nine common chemistry analytes using both RefineR and CLSI guidelines with bootstrap resampling.
• Compared derived RIs to CALIPER RIs using a flagging system based on 95% confidence intervals and total allowable error (TAE).

Main Results:

• RefineR-derived RIs aligned with CALIPER RIs in 86 out of 88 age- and gender-specific analyte groups.
• CLSI-derived RIs showed alignment in 77 out of 88 groups, indicating lower concordance.
• Discrepancies were noted for specific analytes (e.g., ALT, AST, ALP, BUN), influenced by factors like sample type, BMI, and hydration status.

Conclusions:

• RefineR demonstrated superior alignment with CALIPER RIs compared to CLSI guidelines in a US pediatric outpatient cohort.
• RefineR is a robust and practical method for deriving population-specific pediatric reference intervals, handling mixed data and skewed distributions effectively.
• The RefineR approach aids in verifying the implementation of external RIs, such as CALIPER, in diverse pediatric populations.