title: Derivation of pediatric within-individual biological variation by indirect sampling method: an LMS approach.
abstract: OBJECTIVE
  Pediatric within-individual biological variation (CVi) is a challenge to derive by direct sampling due to clinical, logistical, and ethical barriers.
  
  
  METHODS
  Laboratory results of 22 basic biochemistry tests performed on 9,356 children who visited primary care physicians more than once over a year were obtained from a large laboratory network in Australia. The CVi were calculated as (CVT (2) - CVa (2))(0.5), where CVT was the coefficient of variation between repeat measurements and CVa was the analytical imprecision. Smoothed 50th centile (median) CVi charts were derived using the LMS ChartMaker Light software (Medical Research Council, Cambridge, England) with L, M, and S parameters fixed at 3.0, 3.0, and 3.0 equivalent degrees of freedom, respectively.
  
  
  RESULTS
  In general, the median CVi trends for this pediatric cohort remained relatively stable with increasing age. Only aspartate aminotransferase, globulin, phosphate, urea, and creatinine had differences between the highest and lowest median CVi of more than 30%. The differences between the child and adult CVi were relatively small. Nearly all the analytes had child to adult CVi ratios of 1.0 ± 0.5.
  
  
  CONCLUSIONS
  The median CVi derived from patients with only two repeat biochemistry measurements may be considered reasonable estimates of CVi among children seeking treatment at primary care settings. The LMS approach allowed visualization of the continuous trends of CVi with age and extended the pediatric CVi estimation to younger than 4 years.
authors.affiliation: From the Department of Laboratory Medicine, National University Hospital, Singapore; tploh@hotmail.com.
authors.forename: Tze Ping
authors.initials: TP
authors.lastname: Loh
authors.affiliation: South Australian Neonatal Screening Centre and.
authors.forename: Enzo
authors.initials: E
authors.lastname: Ranieri
authors.affiliation: Division of Chemical Pathology, SA Pathology, Women's and Children's Hospital, Adelaide, Australia; and School of Paediatrics and Reproductive Health, University of Adelaide, Adelaide, Australia.
authors.forename: Michael Patrick
authors.initials: MP
authors.lastname: Metz
mesh_terms: D000293:Adolescent; D000367:Age Factors; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007206:Individuality; D008297:Male; D015588:Observer Variation; D015203:Reproducibility of Results; D012494:Sampling Studies; D015983:Selection Bias
keywords: Biological variation; Indirect sampling; LMS; Pediatric; Reference; Within-individual