Patients With Biliary Atresia Have Elevated Direct/Conjugated Bilirubin Levels Shortly After Birth

Abstract

WHAT'S KNOWN ON THIS SUBJECT:Infants with biliary atresia (BA) have better outcomes if detected and treated early, typically before 8 weeks of age. Making an early diagnosis is difficult, however, because newborns appear healthy and start developing disease at an unknown time. WHAT THIS STUDY ADDS:Patients with BA have elevated direct/ conjugated bilirubin (DB/CB) levels at birth. BA could be detected earlier if: (1) all newborns have DB/CB levels measured, including those not jaundiced; and (2) all elevated DB/CB levels are followed, independent of total bilirubin measurements. abstract OBJECTIVES: Healthy infants are thought to acquire biliary atresia (BA) in the first weeks of life. Because those diagnosed earlier have better outcomes, we were interested in determining the earliest time BA could be detected. We started by examining the immediate postnatal period, hypothesizing that newborns would not yet have acquired disease and still have normal direct/conjugated bilirubin (DB/CB) levels. PATIENTS AND METHODS:Newborn DB/CB levels were obtained retrospectively from birth hospitals. Subjects with BA were born between 2007 and 2010 and cared for at Texas Children's Hospital. Those with BA splenic malformation syndrome or born prematurely were excluded. Control subjects were term newborns who later never developed neonatal liver disease. RESULTS:Of the 61 subjects with BA, 56% had newborn DB/CB levels measured. All DB/CB levels exceeded laboratory norms and rose over time. At 24 to 48 hours of life, subjects with BA had mean DB levels significantly higher than those of controls (1.4 Ϯ 0.43 vs. 0.19 Ϯ 0.075 mg/dL, P Ͻ .0001), even while their mean total bilirubin (TB) levels remained below phototherapy limits. Finally, despite the elevated DB/CB levels, the majority of patients (79%) had normal DB:TB ratios Յ0.2. CONCLUSIONS:Patients with BA have elevated DB/CB levels shortly after birth. To detect affected infants earlier and improve outcomes, the results suggest two possibilities: (1) screen all newborns for elevated DB/CB levels, rather than just those who appear jaundiced; and then (2) follow all newborns with elevated DB/CB levels, rather than just those with DB:TB ratios Ͼ0.2. Pediatrics 2011;128:e1428-e1433 Drs Harpavat, Finegold, and Karpen designed the study, analyzed and interpreted the data, revised the article, and approved the final version for publication; Dr Harpavat acquired the data and wrote the original draft; and Dr Karpen initiated the idea and provided overall supervision for the project.A companion to this article can be found on page e1598 and online at www.pediatrics.org/cgi

An Infant with Persistent Jaundice and a Normal Newborn Direct Bilirubin Measurement

“…In our experience, infants with BA have newborn direct or conjugated bilirubin concentrations that exceed their birth hospital's derived reference interval (1 ). In contrast, this infant had a reported "Neonatal Dbil" concentration of 0.5 mg/dL on DoL 1, which was within the birth hospital's reported reference interval of 0.0 -0.6 mg/dL.…”

“…For example, the main message of this report-the incorrect interpretation of "Neonatal Dbil" delaying the diagnosis of BAreinforces the conclusions of a recent landmark study published by the same group, which is casually referenced in the context of the case presentation. This notable study (1 ) documented that direct-reacting or conjugated bilirubin is increased as early as 24 -48 h after birth in most children with the perinatal form of BA, which accounts for 70%-85% of BA in infants. These findings raise the possibility that measurements of conjugated or direct bilirubin could be used as a screening tool for early detection…”

Genetic Contributors and Modifiers of Biliary Atresia

“…At present, the analysis of dried blood spots derived from the standard newborn screening card has not proven useful for biliary atresia, primarily because of the lack of a diagnostic metabolite. However, recent data suggests that measurement of direct bilirubin levels within the first 2 days of life could be used as a screening tool [6,7,13]. …”

“…This paper is focused upon highlighting the current state of discovery and knowledge regarding genes that may confer susceptibility to biliary atresia or modulate outcomes among infants after HPE. It is likely that a deeper understanding of the genetic profile of infants with biliary atresia will provide clinically substantive insights into the etiology and severity of the disease, and enable the development of more precise diagnostic methods and rational therapeutic targets to improve outcomes [2,7,8]. …”

Biliary atresia in sea lampreys. What can it tell us about the disorder in human infants?

“…Indeed, a recent study showed that over half of patients with biliary atresia have elevated direct/conjugated bilirubin levels shortly after birth. 5 The cause of biliary atresia is unknown. Several mechanisms have been proposed to account for the progressive obliteration of the extrahepatic biliary tree.…”