Simple lab test is abnormal early in serious bile duct disease of newborns
Biliary atresia is a rare life-threatening malformation of the ducts through which bile passes from the liver to the gut. The back pressure caused by obstruction to bile flow produces jaundice and liver damage. Morio Kasai, a Japanese surgeon, developed an operation in which a loop of gut is joined directly to the lower part of the liver where the bile emerges. When successful, it relieves back pressure and allows the baby to develop until, if necessary, liver transplantation can be carried out. Experience has shown that the Kasai operation is most successful when performed soon after birth.
A problem with diagnosing the condition early is that up to half of normal newborns have transient “physiological” jaundice from about the second to the seventh day of life, while life-threatening biliary atresia affects only one in 15,000 or so newborns. The diagnosis is suspected when jaundice persists after the seventh day of life, the stools are pale and a blood test for the yellow pigment bilirubin shows an increase of its water soluble fraction, called conjugated or direct bilirubin, which also appears in the urine. The diagnosis is confirmed by liver biopsy or by X-ray examination of the bile ducts after injecting a material opaque to X-rays during operation.
Dr Sanjiv Harpavat and colleagues from Texas Children’s Hospital, Houston, Texas wondered if they could determine the earliest time after birth that the concentration of conjugated or direct bilirubin within the blood became abnormal. They examined the records of children with biliary atresia referred from their birth hospitals to Texas Children’s Hospital for care. The results of their investigation were published in the December 2011 issue of the journal Pediatrics. Of 61 full term babies with biliary atresia born between 2007 and 2010, 34 had had conjugated or direct bilirubin measured in the first four days of life. These measurements were compared with those of 300 term babies born at a general hospital in Houston, all of whom had measurements in the first 24 to 48 hours and none of whom developed liver disease.
The results were clear cut. All the babies with biliary atresia had raised conjugated or direct bilirubin values in the first four days of life, starting as early as the first hour of life (in cord blood). During the first two days of life their total blood bilirubin concentration (conjugated plus unconjugated) were similar to those of the normal babies, so they would not have appeared distinctly jaundiced. The authors suggest that to detect affected babies earlier and avoid clinically significant liver damage, all newborns should be screened and those with raised conjugated or direct bilirubin concentrations should be referred for investigation.
The authors acknowledge that a limitation of their study is that they examined too small a number of normal babies to find out what proportion might have false-positive test results. However, the results of this study suggest that further work is needed to investigate the potential benefit of screening for biliary atresia by measurement of conjugated bilirubin.