Diagnostic Yield of Newborn Screening for Biliary Atresia Using Direct or Conjugated Bilirubin Measurements

• Published in: JAMA : the journal of the American Medical Association 2020-03, Vol.323 (12), p.1141-1150
• Main Authors: Harpavat, Sanjiv, Garcia-Prats, Joseph A, Anaya, Carlos, Brandt, Mary L, Lupo, Philip J, Finegold, Milton J, Obuobi, Alice, ElHennawy, Adel A, Jarriel, William S, Shneider, Benjamin L
• Format: Article
• Language: English
• Subjects: Age; Age Factors; Biliary atresia; Biliary Atresia - blood; Biliary Atresia - diagnosis; Biliary Atresia - surgery; Bilirubin; Bilirubin - blood; Clinical outcomes; Cross-Sectional Studies; Diagnostic systems; Female; Gestational age; Health services; Hepatology; Hospitals; Humans; Infant; Infant, Newborn; Infants; Liver Transplantation; Male; Medical diagnosis; Medical screening; Neonatal Screening - methods; Neonates; Newborn babies; Original Investigation; Pediatrics; Population studies; Portoenterostomy, Hepatic - statistics & numerical data; Predictive Value of Tests; Reference Values; Sensitivity; Sensitivity and Specificity; Time-to-Treatment
• ISSN: 0098-7484; 1538-3598
• DOI: 10.1001/jama.2020.0837

IMPORTANCE: Treating biliary atresia in newborns earlier can delay or prevent the need for liver transplant; however, treatment typically occurs later because biliary atresia is difficult to detect during its early stages. OBJECTIVE: To determine the diagnostic yield of newborn screening for biliary atresia with direct or conjugated bilirubin measurements and to evaluate the association of screening implementation with clinical outcomes. DESIGN, SETTING, AND PARTICIPANTS: A cross-sectional screening study of 124 385 infants born at 14 Texas hospitals between January 2015 and June 2018; and a pre-post study of 43 infants who underwent the Kasai portoenterostomy as treatment for biliary atresia at the region’s largest pediatric hepatology center before (January 2008-June 2011) or after (January 2015-June 2018) screening implementation. Final follow-up occurred on July 15, 2019. EXPOSURES: Two-stage screening with direct or conjugated bilirubin measurements. In stage 1, all newborns were tested within the first 60 hours of life, with a positive screening result defined as bilirubin levels exceeding derived 95th percentile reference intervals. In stage 2, infants who had a positive screening result in stage 1 were retested at or before the 2-week well-child visit, with a positive screening result defined as bilirubin levels greater than the stage 1 result or greater than 1 mg/dL. MAIN OUTCOMES AND MEASURES: The primary outcomes of the screening study were sensitivity, specificity, positive predictive value, and negative predictive value based on infants testing positive in both stages. The reference standard was biliary atresia diagnosed at the region’s pediatric hepatology centers. The primary outcome of the pre-post study was the age infants underwent the Kasai portoenterostomy for treatment of biliary atresia. RESULTS: Of 124 385 newborns in the screening study, 49.2% were female, 87.6% were of term gestational age, 70.0% were white, and 48.1% were Hispanic. Screening identified the 7 known infants with biliary atresia with a sensitivity of 100% (95% CI, 56.1%-100.0%), a specificity of 99.9% (95% CI, 99.9%-99.9%), a positive predictive value of 5.9% (95% CI, 2.6%-12.2%), and a negative predictive value of 100.0% (95% CI, 100.0%-100.0%). In the pre-post study, 24 infants were treated before screening implementation and 19 infants were treated after screening implementation (including 6 of 7 from the screening study, 7 from screening at nonstudy hospitals, an