TCH researchers push for universal newborn biliary atresia screening

 

Texas Children’s pediatric gastroenterologist Dr. Sanjiv Harpavat is working to ensure every newborn is screened for biliary atresia, a rare but deadly liver disease affecting 1 in 10,000 births in the U.S.  It’s the number one reason for liver transplants in infants.

Biliary atresia occurs when the bile duct connecting the liver to the small intestine is blocked. The buildup of bile in the liver scars the tissue so rapidly that most infants need a liver transplant to survive.

“Infants with biliary atresia have more scarring after the first few months of life than a chronic alcoholic’s liver,” said Harpavat. “An important way to improve their outcomes is by detecting and treating the disease early before symptoms appear.”

Just like a hearing screen is a standard test for all newborns in the U.S., Harpavat hopes to implement a newborn screening program nationwide for biliary atresia. While this may seem like an uphill battle, it’s notif you’re armed with compelling data and research.

In a retrospective study published in the journal Pediatrics, Harpavat, along with a team including Department of Pathology Chairman Emeritus Milton Finegold, examined lab records of 61 children with biliary atresia referred from their birth hospitals to Texas Children’s for care. Unlike healthy infants, all newborns with biliary atresia had persistently high levels of conjugated bilirubin (CB) in their blood, which indicates a problem with liver function.

“While the total bilirubin levels of newborns are routinely checked after birth, most pediatricians are trained to look for the unconjugated bilirubin that determines the severity of jaundice in newborns,” Harpavat said. “The other type of bilirubin – direct or conjugated bilirubin – is recorded but often ignored.”

In collaboration with neonatologists at Texas Children’s Newborn Center, Ben Taub Hospital, St. Luke’s Episcopal Hospital in The Woodlands and St. Luke’s Vintage Hospital, Harpavat is leading a large, multicenter prospective screening study to validate a blood screening tool that measures CB levels in newborns shortly after birth and retests newborns with high CB levels at their 2-week pediatrician checkup to confirm biliary atresia. “The rescreen eliminates false positives since many healthy newborns have slightly high CB levels at birth while their liver is going through a critical transition period,” Harpavat said.

Of the 11,500 newborns screened in this ongoing study, 121 had high CB levels. After repeat testing, 12 babies had high CB levels and two were diagnosed with biliary atresia. This disease can only be treated with a liver transplant or the Kasai procedure, which removes the abnormal bile duct and connects the liver to the small intestine to create a new duct.

“Preliminary data suggests infants who undergo Kasai before 30 days of life have a better outcome and may have less chance of needing a liver transplant,” said Texas Children’s pediatric surgeon Dr. Mary Brandt, who performs roughly 10 to 12 Kasai operations a year at Texas Children’s. “Waiting until there is significant scarring in the liver increases the chance of needing a liver transplant.”

 

Texas Children’s Neonatologist Dr. Joseph Garcia-Prats, who helped implement a screening program for biliary atresia at Texas Children’s and Ben Taub General Hospital based on Harpavat’s research, says biliary atresia screening should be a standard of care for all newborns. “Unlike a stool color card test, the newborn CB screening test diagnoses the disease before infants get sick and it is inexpensive.”

To mobilize statewide support, Harpavat has collaborated with longtime newborn screening advocate and Texas Children’s Neonatologist Dr. Charleta Guillory to encourage Texas and other states to add biliary atresia to their newborn screening panel.

Harpavat has presented his findings to the Texas Medical Association, the Texas Pediatric Society’s  Fetus and Newborn Committee, the March of Dimes, and the State Newborn Screening Advisory Committee that Guillory co-chairs.  Harpavat also is promoting his research at pediatric conferences around the country.

“The more compelling statistics we present in the state of Texas, the more credibility we’ll have in pushing forth this newborn biliary atresia screening test on a national level,” said Guillory.

Harpavat’s goal is to screen 70,000 newborns in his study before presenting his findings to national health screening panels, like the National Screening Advisory Committee.