Moving Beyond Direct Bilirubin in Neonatal Jaundice: Insights from a Systematic Review on Conjugated and Delta Bilirubin

Author(s): Chloe Miu MAK*, Jimmy Chi Lap WONG, Ka Chai CHEUNG, Gary Ka Chung WONG, Jacky Kwan Ho LEE, Toby Chun Hei CHAN, Koon Yuen YUET, Eric LAW, Ching Wan LAM

Introduction: Investigating neonatal jaundice are basically by plasma total bilirubin, indirect and direct bilirubin (DB). However, DB is not equivalent to conjugated bilirubin (Bc) but includes delta bilirubin (ΔB). It overestimates the degree of conjugated hyperbilirubinemia. The prolonged DB elevation is also evident during cholestasis recovery phase. Fractionated bilirubin measurements can distinguish resolving jaundice from genuine conjugated hyperbilirubinemia. This study aims to illustrate the significance of fractionated bilirubin assays in the clinical management of neonatal jaundice.

Methods: The clinical and biochemical data of 89 patients aged below six months old with plasma total bilirubin level outside the age-specific reference intervals and fractionated and DB results were analysed and compared. Five cases were presented in detail to illustrate the importance of clinical use of Bc.

Results: Among the 89 patients with hyperbilirubinemia, 56% were due to breastmilk feeding, 13% total parenteral nutrition-related, 10% no specific causes detected, 9% congenital heart diseases, 8% infection-related, 3% blood transfusion-related or ABO incompatibility and 1% biliary atresia. After comparing the DB and Bc levels and their respective percentage over total bilirubin, Bc was shown to be more specific than DB. Elevated DB has led to unnecessary investigations.

Conclusion: Bc is more specific for the diagnosis of neonatal cholestasis than DB and we recommend its routine use for every case of neonatal jaundice. Bc also drops earlier than DB in the recovery phase of resolving neonatal jaundice. The use of Bc over DB in clinical settings avoids unnecessary investigations.