Screening for biliary atresia: it’s in the cards

Problem of late referral

The most important prognostic factor for a successful KP is the age of the infant at the time of the procedure. The best outcomes are achieved when the KP is performed at or before 30 days of age.² In a large Canadian cohort study (N = 349), the worst outcomes were in patients who underwent KP at older than 90 days of age, with a high likelihood of KP failure and need for liver transplant. Only 14% of BA cases who received the operation after 90 days of age still had native liver survival by 4 years of age.² Late referral, delayed diagnosis, and untimely surgery for BA are worldwide problems.² In Canada, the median age at BA referral to a tertiary centre was 59 days, and about 20% of Canadian BA patients were identified after 90 days of age (late referral).²

Many factors contribute to late referral and delayed KP.³ The cardinal clinical features of BA are jaundice and pale stools. However, jaundice in neonates is often considered inconsequential and no further investigations are pursued. Moreover, the assessment of stool colour is not routine to “well-baby” care, and monitoring for pale stools, especially in infants with jaundice, is not standard practice for health care providers or parents. In general, there is a poor understanding among health care providers of the importance of early identification of BA. Although the Canadian Paediatric Society recommends total and conjugated (direct) bilirubin testing in all neonates with jaundice beyond 2 weeks of age, this is rarely done. In most jurisdictions, ordering a test for total bilirubin does not automatically trigger a test for conjugated bilirubin. Therefore, any physician managing a newborn with prolonged jaundice who requisitions a serum total bilirubin test or uses transcutaneous bilirubin measurement will not identify BA cases with conjugated hyperbilirubinemia. Additionally, the well-baby visit schedule in Canada is not uniform across jurisdictions and often infants are seen at 2 and then 8 weeks of age, at which time the “window of opportunity” for early BA case identification has nearly passed.

Screening for BA using infant stool colour cards

Efforts have been made worldwide to facilitate earlier diagnosis and more timely KP in order to improve outcomes.^4,5 Attempts to develop a BA diagnostic biochemical test have been hampered by the lack of a known disease-specific serum or urine biomarker. Recently, Taiwan introduced a universal infant stool colour card screening program for BA, with proven success.^6,7 The rate of KP surgery at earlier than 60 days increased from 47% to 74%, and no case underwent KP at later than 90 days.⁶ Since the introduction of the screening program, there has been a remarkable increase in the success of the KP (61%), and the 3-year native liver survival rate is 62%.⁷ This is well above the current Canadian 4-year native liver survival rate of 39%.²

A recent project funded by the Canadian Institutes of Health Research involving more than 9000 families showed that, in Canada, introduction of a BA stool colour card screening program would be feasible and highly cost effective, and that such a program would be used by families.^8,9 Based on these studies, a BA home screening program was implemented throughout British Columbia (BC) in July 2014. The program is managed by Perinatal Services BC and is designed such that the parents of each newborn are issued a stool colour card when they are discharged from the maternity ward, or at home by their midwives, with instructions to monitor their infant’s stool colour every day for the first month of life. The stool card has 6 pictures depicting shades of abnormal (pale) stool colour and 3 pictures depicting shades of normal stool colour. If parents notice an abnormal stool colour, they are instructed to call the screening centre using a toll-free number. Perinatal Services BC expedites telephone follow-up with a pediatric hepatologist who then decides whether any further evaluation is required.

Additionally, in BC and Alberta, a policy has been implemented that requires all laboratories to automatically test for both total and fractionated (conjugated or direct) bilirubin whenever a serum bilirubin test is requisitioned for a child between 7 days and 1 year of age. If the result finds the conjugated bilirubin fraction is above 20% of the total bilirubin, the following flagged message will appear: “Conjugated hyperbilirubinemia in infants is considered pathologic when conjugated bilirubin is greater than 20 percent of total bilirubin. Prompt evaluation is necessary, especially to assess biliary atresia.”

How can you help?

If parents present to your office with concern that their infant’s stool colour is pale, or the infant has prolonged jaundice beyond 2 weeks of age, it is recommended that a serum total and conjugated bilirubin test is requisitioned. For further information about the home BA screening program, please go to www.perinatalservicesbc.ca and click on the screening programs link.

Biliary atresia is the most important and serious pediatric liver disease. Early diagnosis before 2 months of age yields the best outcomes. Careful assessment of newborn infants for persistent jaundice and pale stool colour in the first month of life is key to timely case identification. A test for serum bilirubin including the conjugated fraction is recommended should there be any concern. More information about the new BA home screening program introduced in BC using infant stool colour cards is available from www.perinatalservicesbc.ca.