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Should a Direct Bilirubin be Part of our Routine Newborn Tests?

May 5, 2022

Editor’s Note: Marium Khan is a third-year pediatrics resident at the University of Virginia. With her ever-growing interest in pediatric liver failure, congenital heart disease, and palliative care, she has found critical care to be the perfect career choice for her. She will be starting her fellowship in pediatric critical care this summer at Washington University in St Louis.

-Rachel Y. Moon, Associate Editor, Digital Media, Pediatrics

One of my first patients during pediatric residency was an infant with biliary atresia (BA) who, due to a late diagnosis, was no longer eligible for a Kasai procedure and had to be put on the list for liver transplantation.

BA is a progressive fibro-obliterative disease which can be fatal if left untreated. However, liver transplantation is not without its own risks and results in the need for lifelong immunosuppression.

The Kasai procedure helps re-establish biliary flow and increases the chances of keeping the native liver. Its success is dependent on the timing of the procedure, and success rates are highest when the procedure is performed before 30-45 days of life. Therefore, early diagnosis of BA is critical to delay or even avoid liver transplantation.

Unfortunately, the diagnosis of BA is made, upon average, after 60 days, at which point it is extremely difficult to re-establish biliary flow, and liver transplant is the only option. We need better approaches for early diagnosis.

My patient unfortunately did not survive long enough to receive a liver transplant, and I have often wondered if an earlier BA diagnosis could have changed their clinical course. I have since gravitated towards studies related to the early detection of BA, and so I was excited to see Dr. Fang-Min Liao and colleagues at National Taiwan University Children’s Hospital and Saint Paul’s Hospital, Taoyuan, Taiwan discussing the role of direct bilirubin and the risk of biliary atresia in an article being early released this week by Pediatrics (10.1542/peds.2021-053073).

In this retrospective cross-sectional study, the authors aimed to determine the sensitivities and specificities of elevated direct bilirubin and of the ratio of direct to total bilirubin (D/T ratio) for the detection of BA. They enrolled 4,468 infants aged 0-60 days old who were admitted to a tertiary care center and met criteria for direct and total bilirubin assessment. These criteria included prolonged jaundice or high risk for neonatal cholestasis (ie, prenatal concern for hepatobiliary disease, concern for an inborn error of metabolism or congenital infection, prolonged need for total parenteral nutrition, or need for hospitalization for phototherapy). They divided their population into 2 age groups, newborn and infant, and demonstrated that direct bilirubin alone can be a very effective screening tool for the detection of BA.

In the infant (3-60 days) group, a direct bilirubin of ≥ 1 mg/dL had the best sensitivity and negative predictive value.

In the newborn (<3 days of age) group, a direct bilirubin cut off level of >0.45 mg/dL had very high sensitivity for BA detection.

Prior to discharge, every newborn in our hospital undergoes a set of screening tests, including a total bilirubin. Given the need for early detection of BA, and given the high sensitivity and negative predictive value of an elevated direct bilirubin, should we include direct bilirubin in our routine newborn tests? Check out this article to decide and discuss this with your colleagues. I know that I will!

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