Clinical decision limits for interpretation of direct bilirubin--a CALIPER study of healthy multiethnic children and case report reviews.

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.

DESIGN AND 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%.