The study results offer parents and their newborns a better way to treat the disease, wrote a team led by Dr. Sanjiv Harpavat, PhD, an assistant professor of pediatrics-gastroenterology at Baylor College of Medicine.
"Biliary atresia is the leading indication for pediatric liver transplant, affecting [one in 8,000 to one in 18,000] infants worldwide and progressing to end-stage liver disease by 2 years of life," the team noted. "Treatment by 30 days of life has the best chance of delaying or preventing the need for transplant" (JAMA, Vol. 323:12, pp. 1141-1150).
Biliary atresia is a disease of the bile ducts that affects infants. Soon after birth, the ducts become obstructed, causing bile to remain in the liver and damage liver cells, which can lead to cirrhosis. Early treatment of the disease in newborns could delay or prevent the need for a liver transplant, but it's often difficult to detect the condition in its early stages, Harpavat and colleagues wrote. That's why finding a way to screen for the disease in newborns is crucial.
"The American Academy of Pediatrics has recommended more studies to develop strategies to help detect biliary atresia earlier. ... [One] potential strategy uses newborn direct or conjugated bilirubin measurements, which are elevated in biliary atresia starting shortly after birth," the group wrote.
To assess the diagnostic performance of this strategy, Harpavat and colleagues conducted a two-pronged study. The first aspect was a screening effort that consisted of assessing direct or conjugated bilirubin measurements of 124,385 infants born at 14 Texas hospitals between January 2015 and June 2018. The researchers also evaluated 43 infants who underwent a surgical treatment to allow for bile drainage called a Kasai portoenterostomy before screening implementation (January 2008 to June 2011) and after it (January 2015 to June 2018).
The screening arm of the study consisted of two stages:
- Stage 1: All newborns had heel-stick blood tests within 60 hours of birth. A positive screening result was determined to be bilirubin levels beyond 95th percentile reference intervals.
- Stage 2: Those infants with a positive screening result in stage 1 were retested at or before their two-week well-child visit. A positive screening result was defined as bilirubin levels greater than the stage 1 result or greater than 1 mg/dL.
Primary outcomes of the screening study were sensitivity, specificity, positive predictive value, and negative predictive value, based on participants' testing positive in both stages. The primary outcome of the pre- and postscreening part of the study was the age the children had the Kasai portoenterostomy.
Bilirubin screening identified the seven known infants with biliary atresia with a high sensitivity and specificity, the group found.
|Performance of bilirubin screening in newborns
|Positive predictive value
|Negative predictive value
Screening also identified 112 infants without biliary atresia, "resulting in a PPV that is comparable with the range of 0.5% to 6% reported for other newborn screening tests," the group noted.
Finally, the screening performance results positively affected children who underwent the surgical procedure. In the pre- and postscreening part of the study, 24 infants were treated before screening was established and 19 infants after; the infants' mean age when they underwent the Kasai portoenterostomy was significantly younger after screening was implemented (56 days versus 36 days, p = 0.004).
"One additional advantage of newborn direct or conjugated bilirubin screening is that it potentially allows infants to undergo the Kasai portoenterostomy before 30 days, the time interval correlating with the best chance of delaying or preventing the need for transplant," the group wrote. "In the pre-post study, 57.9% of infants underwent [this procedure] by 30 days after screening implementation compared with 12.5% before screening implementation."
Although it could be an effective way to identify and treat children for biliary atresia, a screening program like the one described in the study still has implementation challenges, according to an accompanying editorial written by Dr. Richard Schreiber, a professor in pediatrics at the University of British Columbia.
"Given the small number of patients with true-positive biliary atresia screened ... this study does not fully inform whether the screening test performance is acceptable," he wrote. "The lack of systematic follow-up of the infants who tested negative during screening raises the possibility that infants with biliary atresia may have been missed. Even if only one or two patients were missed, the sensitivity would be substantially lower" (Vol. 323:12, pp. 1137-1138).
Putting a biliary atresia screening program in place would take some effort, according to Schreiber.
"A national universal biliary atresia screening program with this testing approach would require a well-organized and meticulous infrastructure for implementation and execution," he wrote. "Many lines of research are still required before the program could be advocated to public health stakeholders ... and policymakers. In the meantime, biliary atresia remains a disease in need of early recognition."
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