title: Closing the gaps in pediatric laboratory reference intervals: a CALIPER database of 40 biochemical markers in a healthy and multiethnic population of children.
abstract: BACKGROUND
  Pediatric healthcare is critically dependent on the availability of accurate and precise laboratory biomarkers of pediatric disease, and on the availability of reference intervals to allow appropriate clinical interpretation. The development and growth of children profoundly influence normal circulating concentrations of biochemical markers and thus the respective reference intervals. There are currently substantial gaps in our knowledge of the influences of age, sex, and ethnicity on reference intervals. We report a comprehensive covariate-stratified reference interval database established from a healthy, nonhospitalized, and multiethnic pediatric population.
  
  
  METHODS
  Healthy children and adolescents (n = 2188, newborn to 18 years of age) were recruited from a multiethnic population with informed parental consent and were assessed from completed questionnaires and according to defined exclusion criteria. Whole-blood samples were collected for establishing age- and sex-stratified reference intervals for 40 serum biochemical markers (serum chemistry, enzymes, lipids, proteins) on the Abbott ARCHITECT c8000 analyzer.
  
  
  RESULTS
  Reference intervals were generated according to CLSI C28-A3 statistical guidelines. Caucasians, East Asians, and South Asian participants were evaluated with respect to the influence of ethnicity, and statistically significant differences were observed for 7 specific biomarkers.
  
  
  CONCLUSIONS
  The establishment of a new comprehensive database of pediatric reference intervals is part of the Canadian Laboratory Initiative in Pediatric Reference Intervals (CALIPER). It should assist laboratorians and pediatricians in interpreting test results more accurately and thereby lead to improved diagnosis of childhood diseases and reduced patient risk. The database will also be of global benefit once reference intervals are validated in transference studies with other analytical platforms and local populations, as recommended by the CLSI.
authors.affiliation: Clinical Biochemistry Division, Department of Pediatric Laboratory Medicine, The Hospital for Sick Children, Toronto, Ontario, Canada.
authors.forename: David A
authors.initials: DA
authors.lastname: Colantonio
authors.forename: Lianna
authors.initials: L
authors.lastname: Kyriakopoulou
authors.forename: Man Khun
authors.initials: MK
authors.lastname: Chan
authors.forename: Caitlin H
authors.initials: CH
authors.lastname: Daly
authors.forename: Davor
authors.initials: D
authors.lastname: Brinc
authors.forename: Allison A
authors.initials: AA
authors.lastname: Venner
authors.forename: Maria D
authors.initials: MD
authors.lastname: Pasic
authors.forename: David
authors.initials: D
authors.lastname: Armbruster
authors.forename: Khosrow
authors.initials: K
authors.lastname: Adeli
mesh_terms: D000293:Adolescent; D000367:Age Factors; D044466:Asian People; D015415:Biomarkers / Q000097:blood*; D002170:Canada; D002648:Child; D002675:Child, Preschool; D016208:Databases, Factual; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D012016:Reference Values; D012737:Sex Factors; D044465:White People
chemical_list: D015415:Biomarkers