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Diagnostic Yield of Newborn Screening for Biliary Atresia Using Direct or Conjugated Bilirubin Measurements
Sanjiv Harpavat1, Joseph A Garcia-Prats2, Carlos Anaya3
1Division of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Baylor College of Medicine and Texas Children's Hospital, Houston.
Insights
Newborn screening using direct or conjugated bilirubin levels effectively identified all biliary atresia cases in the study. Early detection through this screening method led to significantly younger ages for the Kasai portoenterostomy procedure.
Area of Science:
- Neonatal Medicine
- Pediatric Gastroenterology
- Public Health Screening
Background:
- Biliary atresia diagnosis is often delayed, impacting treatment effectiveness and liver transplant needs.
- Early detection of biliary atresia is crucial for timely intervention and improved patient outcomes.
- Current diagnostic methods for biliary atresia present challenges in early identification.
Purpose of the Study:
- To assess the diagnostic accuracy of newborn screening using direct or conjugated bilirubin measurements for biliary atresia.
- To evaluate the impact of implementing this screening protocol on clinical outcomes, specifically the timing of surgical intervention.
- To determine the sensitivity, specificity, and predictive values of the proposed screening strategy.
Main Methods:
- A cross-sectional screening study involving 124,385 infants across 14 Texas hospitals.
- A two-stage screening process utilizing direct or conjugated bilirubin levels within the first 60 hours and by the 2-week well-child visit.
- A pre-post study comparing the age at Kasai portoenterostomy before and after screening implementation.
Main Results:
- The screening protocol demonstrated 100% sensitivity and 99.9% specificity in detecting biliary atresia.
- Infants undergoing the Kasai portoenterostomy procedure were significantly younger after screening implementation (36 days vs. 56 days).
- The screening identified all 7 known cases of biliary atresia within the study cohort.
Conclusions:
- Newborn screening with direct or conjugated bilirubin measurements is effective in identifying infants with biliary atresia.
- Early detection via bilirubin screening leads to earlier surgical treatment, potentially improving long-term outcomes.
- Further research in larger populations is recommended to refine diagnostic yield estimates and assess cost-effectiveness.
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, and 6 from referrals because of clinical symptoms). The age infants underwent the Kasai portoenterostomy was significantly younger after screening was implemented (mean age, 56 days [SD, 19 days] before screening implementation vs 36 days [SD, 22 days] after screening implementation; between-group difference, 19 days [95% CI, 7-32 days]; P = .004).
Conclusions And Relevance:
Newborn screening with direct or conjugated bilirubin measurements detected all known infants with biliary atresia in the study population, although the 95% CI around the sensitivity estimate was wide and the study design did not ensure complete ascertainment of false-negative results. Research is needed in larger populations to obtain more precise estimates of diagnostic yield and to better understand the clinical outcomes and cost-effectiveness of this screening approach.
