title: Marked biological variance in endocrine and biochemical markers in childhood: establishment of pediatric reference intervals using healthy community children from the CALIPER cohort.
abstract: BACKGROUND
  Reference intervals are indispensable in evaluating laboratory test results; however, appropriately partitioned pediatric reference values are not readily available. The Canadian Laboratory Initiative for Pediatric Reference Intervals (CALIPER) program is aimed at establishing the influence of age, sex, ethnicity, and body mass index on biochemical markers and developing a comprehensive database of pediatric reference intervals using an a posteriori approach.
  
  
  METHODS
  A total of 1482 samples were collected from ethnically diverse healthy children ages 2 days to 18 years and analyzed on the Abbott ARCHITECT i2000. Following the CLSI C28-A3 guidelines, age- and sex-specific partitioning was determined for each analyte. Nonparametric and robust methods were used to establish the 2.5th and 97.5th percentiles for the reference intervals as well as the 90% CIs.
  
  
  RESULTS
  New pediatric reference intervals were generated for 14 biomarkers, including α-fetoprotein, cobalamin (vitamin B12), folate, homocysteine, ferritin, cortisol, troponin I, 25(OH)-vitamin D [25(OH)D], intact parathyroid hormone (iPTH), thyroid-stimulating hormone, total thyroxine (TT4), total triiodothyronine (TT3), free thyroxine (FT4), and free triiodothyronine. The influence of ethnicity on reference values was also examined, and statistically significant differences were found between ethnic groups for FT4, TT3, TT4, cobalamin, ferritin, iPTH, and 25(OH)D.
  
  
  CONCLUSIONS
  This study establishes comprehensive pediatric reference intervals for several common endocrine and immunochemical biomarkers obtained in a large cohort of healthy children. The new database will be of global benefit, ensuring appropriate interpretation of pediatric disease biomarkers, but will need further validation for specific immunoassay platforms and in local populations as recommended by the CLSI.
authors: CALIPER Program, Department of Pediatric Laboratory Medicine, Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada.
authors: Dana
authors: D
authors: Bailey
authors: David
authors: D
authors: Colantonio
authors: Lianna
authors: L
authors: Kyriakopoulou
authors: Ashley H
authors: AH
authors: Cohen
authors: Man Khun
authors: MK
authors: Chan
authors: David
authors: D
authors: Armbruster
authors: Khosrow
authors: K
authors: Adeli
mesh_terms: D000293:Adolescent; D000367:Age Factors; D015415:Biomarkers / Q000097:blood*; D001774:Blood Chemical Analysis / Q000592:standards*; D015992:Body Mass Index; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D012016:Reference Values; D012737:Sex Factors
chemical_list: D015415:Biomarkers