Complex reference value distributions and partitioned reference intervals across the pediatric age range for 14 specialized biochemical markers in the CALIPER cohort of healthy community children and adolescents

• Pediatric reference intervals were established for endocrine/specialty biomarkers.
• Dynamic changes necessitated unique age and gender partitions.
• The reference values will aid in accurate diagnosis/monitoring of pediatric disease.

BackgroundThe CALIPER program has previously reported a comprehensive database of pediatric reference intervals for 63 biochemical and immunochemical markers. Here, covariate-stratified reference intervals were determined for a number of special assays not previously reported.MethodsA total of 1917 healthy children and adolescents were recruited and serum concentrations of 14 biochemical markers were measured using the Abbott Architect ci4100 system. Age and gender partitions were statistically determined, outliers removed and reference intervals calculated using CSLI C28-A3 guidelines.ResultsMany analytes showed dynamic changes in concentration requiring at least 3 age partitions. Unique intervals were required within the first year of life for: pancreatic amylase, C-peptide, ceruloplasmin, insulin, β-2-microglobulin, cystatin C, dehydroepiandrosterone sulfate (DHEA-S), and α-1-glycoprotein. Cholinesterase, cholinesterase–dibucaine number, and immunoglobulin E required only 2 age partitions and α-1-antitrypsin required only one. Anti-CCP and anti-TPO levels were below the detection limit of the assay. Some analytes including insulin and DHEA-S required additional gender partitions for specific age groups.ConclusionsComplex profiles were observed for endocrine and special chemistry markers, requiring establishment of age- and gender-specific reference intervals. These updated reference intervals will allow improved laboratory assessment of pediatric patients but should be validated for each analytical platform and local population as recommended by CLSI.