Direct bilirubin levels observed in prolonged neonatal jaundice: a retrospective cohort study

Abstract

ObjectiveProlonged neonatal jaundice is common and usually benign; however, assessment of bilirubin fractions is recommended to determine the need for further assessment for congenital liver disease, particularly biliary atresia. The direct (conjugated) bilirubin thresholds currently used are variable and poorly evidenced. Hence, we aimed to delineate direct bilirubin levels in disease-free neonates with prolonged jaundice.MethodsWe performed a retrospective cohort analysis of split bilirubin levels, and subsequent follow-up, for all neonates initially assessed in our prolonged neonatal jaundice clinic over 2 years. We plotted centile charts for total, direct and direct–total bilirubin ratio levels against age at sampling. The association was assessed using linear regression analysis.ResultsData were collected for 420 neonates (501 blood samples) across an age range of 10–70 days. No significant liver disease was found. For each day of older age, total bilirubin fell by 3.72 µmol/L (95% CI 2.46 to 5.00) and direct bilirubin fell by 0.39 µmol/L (0.18 to 0.59). The ratio between the two did not change significantly (−0.0006 to +0.0034). The 95th centile for direct bilirubin was stable at ~25 µmol/L. Direct–total bilirubin ratio was very variable with some 95th centiles >30%.ConclusionsIn a clinically relevant population of disease-free neonates with prolonged jaundice both the total and the direct bilirubin decreased with age. The absolute direct bilirubin is more useful clinically than the direct–total bilirubin ratio. Our results support National Institute for Health and Care Excellence guidance that conjugated bilirubin >25 µmol/L, or even more stringent criteria, constitutes an appropriate threshold for further investigation for neonatal liver disease.

A survey of the reactivity of in vitro diagnostic bilirubin reagents developed in Japan using artificially prepared bilirubin materials: A comparison of synthetic delta, unconjugated, and taurine-conjugated bilirubin

“…However, reason for the inversion of DB results remains unresolved. In clinical paediatrics, Hodgson et al 31 reported criteria of DB concentration as >25 mmol/L to differentiate neonatal liver disease from disease-free neonates with prolonged jaundice. Thus, reagents from EC and LSIM, both of which reacted less with UCB as DB, would be appropriate in monitoring bilirubin level in cases of neonatal jaundice.…”

A New Evolutionary Machine Learning Approach for Identifying Pyrene Induced Hepatotoxicity and Renal Dysfunction in Rats

“…There are three forms of bilirubin in plasma: unconjugated bilirubin (usually the main ingredient; reversibly bound to albumin), free conjugated bilirubin and delta bilirubin (conjugated bilirubin, also known as direct bilirubin (DBIL), normal range approximately 0.0-3.0 µmol/L; covalently bound to albumin). Hodgson et al [55] showed that, among clinically relevant population of disease-free neonates with prolonged jaundice, both the total and the direct bilirubin decrease with age. However, the absolute direct bilirubin is more clinically useful than the direct-total bilirubin ratio.…”

The Characteristics of Prolonged Neonatal Jaundice Investigated at Primary Health Clinics in Kota Bharu, Kelantan

“…Prolonged conjugated hyperbilirubinemia is often pathological; affecting 1/2500 live birth whereas the incidence of biliary atresia is 1:18000 in the general population (Hodgson et al, 2018). It may present with dark coloured urine and pale stool but normal history and physical examination in the early stage of diseases are usual (Hodgson et al, 2018). As such, late presentation and referral to tertiary centre are common resulting in delayed intervention and poor prognosis.…”