title: Clinical decision limits for interpretation of direct bilirubin--a CALIPER study of healthy multiethnic children and case report reviews.
abstract: OBJECTIVE
  Measurement of total and direct bilirubin is routinely performed for the differential diagnosis of hyperbilirubinemias. The diagnostic efficiency of a test is dependent on the chosen clinical decision limit. This study is designed to address the clinical decision limits for direct bilirubin.
  
  
  METHODS
  Routine laboratory method was used to measure total and direct bilirubin in children up to the age of 18years. Case study data and serum from a group of healthy children were analyzed and statistical exercise was performed to establish decision limits.
  
  
  RESULTS
  The reference interval for total bilirubin was 1-12μmol/L and for direct bilirubin 1-9μmol/L with the median direct bilirubin of 3μmol/L. In 17% of children with non-pathological jaundice, median total bilirubin was 173μmol/L, median direct bilirubin was 8μmol/L and median direct bilirubin percent was 49%. From birth direct bilirubin percentage decreased until total bilirubin was 41μmol/L, then it remained at ≤10%. Albumin increased with age, and was on average 2.4g/L higher when measured using bromocresol-green compared with bromocresol-purple. An increased amount of direct bilirubin was observed when albumin (detected using the bromocresol-purple method) was >35g/L.
  
  
  CONCLUSIONS
  Direct bilirubin concentration of ≥10μmol/L should be used to consider the presence of conjugated hyperbilirubinemia provided that total bilirubin is also above the reference interval. A high direct bilirubin percentage is unlikely to offer any clinical value when total bilirubin is not increased. It is, however, a useful diagnostic tool when there is a persistence of hyperbilirubinemia or when total bilirubin increases during times of stress with direct bilirubin >10%.
authors.affiliation: Clinical Laboratories, Department of Biochemistry, NHS Lanarkshire, Wishaw General Hospital, 50 Netherton Street, Wishaw ML2 0DP, Scotland, UK. Electronic address: manjit.devgun@lanarkshire.scot.nhs.uk.
authors.forename: Manjit S
authors.initials: MS
authors.lastname: Devgun
authors.affiliation: Clinical Biochemistry Division, Department of Pediatric Laboratory Medicine, the Hospital for Sick Children, Toronto, Ontario, Canada.
authors.forename: Man Khun
authors.initials: MK
authors.lastname: Chan
authors.affiliation: Department of Medicine and Gastroenterology, NHS Lanarkshire, Wishaw General Hospital, 50 Netherton Street, Wishaw ML2 0DP, Scotland, UK.
authors.forename: Adil M
authors.initials: AM
authors.lastname: El-Nujumi
authors.affiliation: Department of Paediatrics and Neonatology, NHS Lanarkshire, Wishaw General Hospital, 50 Netherton Street, Wishaw ML2 0DP, Scotland, UK.
authors.forename: Rosemary
authors.initials: R
authors.lastname: Abara
authors.affiliation: Abbott Diagnostics, Abbott Park, IL, USA.
authors.forename: David
authors.initials: D
authors.lastname: Armbruster
authors.affiliation: Clinical Biochemistry Division, Department of Pediatric Laboratory Medicine, the Hospital for Sick Children, Toronto, Ontario, Canada; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Khosrow
authors.initials: K
authors.lastname: Adeli
mesh_terms: D001663:Bilirubin / Q000097:blood*; D002675:Child, Preschool; D020000:Decision Support Systems, Clinical; D005006:Ethnicity; D005260:Female; D006262:Health; D006801:Humans; D008297:Male; D012016:Reference Values
chemical_list: D001663:Bilirubin
keywords: Clinical decision limit; Conjugated bilirubin; Direct bilirubin; Hyperbilirubinemia; Inherited hyperbilirubinemia; Reference interval