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Background: Clinical laboratories frequently encounter discordant bilirubin results, where unconjugated bilirubin (Bu) exceeds total bilirubin (TBil), particularly in neonates undergoing phototherapy. This discrepancy complicates clinical decision-making for neonatal jaundice management.
Methods: A 5-day-old female neonate with hyperbilirubinemia and cephalohematoma was analyzed. Bilirubin levels were measured using dry chemistry (Ortho 5600) and validated via wet chemistry (vanadic acid oxidation).
Results: Initial dry chemistry results showed TBil: 352.4 µmol/L, Bu: 388.1 µmol/L, and conjugated bilirubin (Bc): 13.5 µmol/L. Phototherapy-generated bilirubin photoisomers (structural and configurational isomers) interfered with assay specificity. Structural isomers were misclassified as Bc in dry chemistry but excluded from TBil assays, leading to Bu + Bc exceeding TBil. Wet chemistry confirmed TBil (355.4 µmol/L) consistency but highlighted method-dependent variability in isomer detection.
Conclusions: Methodological differences in detecting phototherapy-induced bilirubin isomers contribute to paradoxical results. Clinicians should use consistent methods for serial monitoring, and laboratories must analyze preanalytical factors, such as phototherapy timing, to ensure accurate reporting.
DOI: 10.7754/Clin.Lab.2025.250401
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