Table 1.

Principles of Newborn Screening, Adapted by the Wilson and Jungner Criteria^*

Wilson and Jungner Criteria [14]		Interpretation in the context of BA
Disease-specific	The condition sought should be an important health problem.	BA is the leading indication for pediatric LT, accounting for 60% of LTs in infants <1 year old and 30% of all LTs in children [37]. Identifying and treating infants earlier, i.e., in their latent or “preclinical” phase, can improve outcomes.
	There should be an accepted treatment for patients with recognized disease.	The KP is the only treatment proven to delay or even prevent the need for LT [38]. The KP bypasses the bile duct obstruction by connecting the liver directly to the intestines. Performing the KP earlier, i.e., before 30–45 days of life, has been associated with better outcomes [2].
	Facilities for diagnosis and treatment should be available.	BA can be diagnosed and treated in centers with pediatric specialists, including surgeons and gastroenterologists/hepatologists. These centers are available in the US and most developed countries.
	There should be a recognizable latent or early symptomatic stage.	In BA, a latent or “preclinical” phase occurs in the first weeks of life. Biliary obstruction is present, but signs such as jaundice or pale stool may not be apparent. As a result, BA is often recognized later than the ideal time for treatment [3].
	The natural history of the condition, including development from latent to declared disease, should be adequately understood.	The natural history of BA has been well-described, and includes a likely in-utero start, symptoms appearing in the first weeks of life, and end-stage liver disease and need for liver transplant by age 2 years if not treated [39,40]. BA is a neonatal disease which never starts at later time points.
	There should be an agreed policy on whom to treat as patients.	The standard of care is to treat all patients with BA surgically. Infants recognized in a timely manner receive the KP. Infants recognized too late for the KP, as well as infants who do not benefit from the KP, receive LT.
Test-specific	There should be a suitable test or examination.	Screening for BA using the physical exam, stool color cards (SCCs), fractionated bilirubin levels, and bile acid measurements have been studied.
	The test should be acceptable to the population.	Regions in Japan, Taiwan, Canada, Switzerland, Germany, and Brazil have adopted the SCC and multiple healthcare systems in the US have begun screening with fractionated bilirubin (see text for full discussion).
	The cost of case-finding (including diagnosis and treatment of patients diagnosed) should be economically balanced in relation to possible expenditure on medical care as a whole.	More studies are needed to evaluate the costs of case-finding. The cost-effectiveness of the SCC has been shown to be acceptable, and the cost-effectiveness of fractionated bilirubin measurements is still under investigation [27].
	Case-finding should be a continuing process and not a “once and for all” project.	Screening for BA is a continuous process based on the data available. For example, the SCC began in Japan has since been modified in different countries with innovations such as a phone app [11,12]. In addition, after fractionated bilirubin levels were discovered to be elevated at birth in BA, newborn screening for BA was initiated [22,26]. Both the SCC and fractionated bilirubin screening continue to be evaluated and improved, and new modalities such as bile acid screening have been proposed.

^*Does not require permission for use and reproduction.