Wilson and Jungner Revisited: Are Screening Criteria Fit for the 21st Century?

Abstract

Driven by technological innovations, newborn screening (NBS) panels have been expanded and the development of genomic NBS pilot programs is rapidly progressing. Decisions on disease selection for NBS are still based on the Wilson and Jungner (WJ) criteria published in 1968. Despite this uniform reference, interpretation of the WJ criteria and actual disease selection for NBS programs are highly variable. A systematic literature search [PubMED search "Wilson" AND "Jungner"; last search 16.07.22] was performed to evaluate the applicability of the WJ criteria for current and future NBS programs and the need for adaptation. By at least two reviewers, 105 publications (systematic literature search, N = 77; manual search, N = 28) were screened for relevant content and, finally, 38 publications were evaluated. Limited by the study design of qualitative text analysis, no statistical evaluation was performed, but a structured collection of reported aspects of criticism and proposed improvements was instead collated. This revealed a set of general limitations of the WJ criteria, such as imprecise terminology, lack of measurability and objectivity, missing pediatric focus, and absent guidance on program management. Furthermore, it unraveled specific aspects of criticism on clinical, diagnostic, therapeutic, and economical aspects. A major obstacle was found to be the incompletely understood natural history and phenotypic diversity of rare diseases prior to NBS implementation, resulting in uncertainty about case definition, risk stratification, and indications for treatment. This gap could be closed through the systematic collection and evaluation of real-world evidence on the quality, safety, and (cost-)effectiveness of NBS, as well as the long-term benefits experienced by screened individuals. An integrated NBS public health program that is designed to continuously learn would fulfil these requirements, and a multi-dimensional framework for future NBS programs integrating medical, ethical, legal, and societal perspectives is overdue.

Keywords: genomic newborn screening; neonatal screening; newborn screening; newborn sequencing; phenotypic diversity; public health program; screening criteria.

Figure 1

PRISMA diagram of the literature search [38].

Figure 2

Revising the screening criteria. Principles and Practice of Screening for Disease, as published by Wilson and Jungner in 1968 [32], includes 10 specific criteria which have been the basis of all NBS programs worldwide for more than 50 years (left). In subsequent studies, these criteria have been commonly re-arranged in four different sub-categories (middle). The systematic literature review not only identified relevant shortcomings of single WJ criteria, but also highlighted their missing focus on complex aspects of program management and the insufficient systematic consideration of ethical, legal, and societal implications (ELSI), which should form the basis of all NBS programs (right). A multi-dimensional framework integrating all relevant perspectives would be an excellent opportunity to revise the original WJ criteria and to make them fit for the demands and further developments of NBS programs. Figure was created with draw.io (https://drawio-app.com/, accessed on 17 July 2024).

Figure 3

Extension of the phenotypic spectrum of an NBS target disease after NBS implementation. Introduction to NBS expands the phenotypic spectrum towards attenuated disease variants. While severe and attenuated variants are usually easy to distinguish, the exact differentiation between healthy and attenuated forms can be challenging, requiring risk-stratified and individualized treatment indications.