Derivation of pediatric within-individual biological variation by indirect sampling method: an LMS approach

Pediatric within-individual biological variation (CVi) is a challenge to derive by direct sampling due to clinical, logistical, and ethical barriers.

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.

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.

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.