Reference intervals for plasma total bilirubin in children

Plasma total bilirubin is a commonly requested biochemical test in children used for assessment of hyperbilirubinemia. Physiological adaptations in newborns challenge the interpretation, and more evidence is needed to substantiate the dynamics of plasma total bilirubin throughout childhood and across routinely used analyzers to support the choice of reference interval (RI) in clinical laboratories. This was a retrospective study in the North Denmark Region utilizing routine laboratory results of plasma total bilirubin for establishment of RI in children aged 0-18 years with an indirect approach. Plasma total bilirubin had been measured on routinely used analyzers (method 1: Alinity, Abbott Laboratories, method 2: Atellica, Siemens Healthineers, method 3: Cobas 8000, Roche Diagnostics), and RIs were established non-parametrically as the 2.5th and 97.5th percentile. Plasma total bilirubin from a total of 29,195 children aged 0-18 years (51.0% girls) were evaluated. The established upper RI limit for plasma total bilirubin differed by child's age: 0-1 days (method 1: 62 µmol/L, method 2: 81 µmol/L, and method 3: 73 µmol/L), 6-7 days (method 1: 350 µmol/L, method 2: 384 µmol/L, and method 3: 346 µmol/L), 7-30 days (method 1: 297 µmol/L, method 2: 300 µmol/L, and method 3: 282 µmol/L), 1 month-18 years (method 1: 17 µmol/L, method 2: 17 µmol/L, and method 3: 15 µmol/L). Plasma total bilirubin levels were dynamic within the first month of life and thereafter stable low throughout childhood and adolescence. The dynamics were consistent across routinely used methods, and results provided age-dependent RIs for implementation in clinical laboratories.