Neonatal and carrier screening for rare diseases: how innovation challenges screening criteria worldwide

Abstract

Screening for rare diseases first began more than 50 years ago with neonatal bloodspot screening (NBS) for phenylketonuria, and carrier screening for Tay-Sachs disease, sickle cell anaemia and β-thalassaemia. NBS’s primary aim is health gain for children, while carrier screening enables autonomous reproductive choice. While screening can be beneficial, it also has the potential to cause harm and thus decisions are needed on whether a specific screening is worthwhile. These decisions are usually based on screening principles and criteria. Technological developments, both treatment driven and test driven, have led to expansions in neonatal screening and carrier screening. This article demonstrates how the dynamics and expansions in NBS and carrier screening have challenged four well-known screening criteria (treatment, test, target population and programme evaluation), and the decision-making based on them. We show that shifting perspectives on screening criteria for NBS as well as carrier screening lead to converging debates in these separate fields. For example, the child is traditionally considered to be the beneficiary in NBS, but the family and society can also benefit. Vice versa, carrier screening may be driven by disease prevention, rather than reproductive autonomy, raising cross-disciplinary questions regarding potential beneficiaries and which diseases to include. In addition, the stakeholders from these separate fields vary: Globally NBS is often governed as a public health programme while carrier screening is usually available via medical professionals. The article concludes with a call for an exchange of vision and knowledge among all stakeholders of both fields to attune the dynamics of screening.

Evaluating genetic and genomic tests for heritable conditions in Australia: lessons learnt from health technology assessments

“…The challenges included different views held by different clinical specialities; established use of biochemical methods with acceptable accuracy and cost; established uptake of genomic testing in the private sector; and different funding responsibilities between the federal and state governments. Similar challenges have been discussed by Cornel et al (2021), who describe how innovations in sequencing technology are challenging established principles for screening.…”

Current Status of Genetic Counselling for Rare Diseases in Spain

“…These disease-causing genetic changes might be passed from one generation to the next, although for rare disorders they also might occur de novo, with the patient being the first affected person in the family [ 15 , 16 , 17 ]. Inheritance of these variants increases the risk of passing the disease to the next generation, and thus, some relatives who might be carriers will need support, help and guidance to manage and plan a future pregnancy trying to reduce risks of having an affected child [ 18 , 19 ]. However, there are still challenges for the application of cascade genetic testing, such as cost, cultural and social issues, communication (including reduced access to genetic counsellors) and logistic issues (including lack of genetic specialists or the geographical location).…”

Expanding Neonatal Bloodspot Screening: A Multi-Stakeholder Perspective

“…Technological developments in screening, diagnostics and treatment have led to an ongoing expansion of the number of disorders included in these NBS programs. However, the screening principles for inclusion of conditions are interpreted and applied differently worldwide as reflected by differences in the scope of NBS between countries (2). Besides, the possibility to simultaneously test for a much wider range of disorders than those fitting within the original aim of NBS, has given new impetus to the debate about whether other benefits than health gains for the child might legitimate inclusion of disorders in NBS programs (1,2).…”

“…However, the screening principles for inclusion of conditions are interpreted and applied differently worldwide as reflected by differences in the scope of NBS between countries (2). Besides, the possibility to simultaneously test for a much wider range of disorders than those fitting within the original aim of NBS, has given new impetus to the debate about whether other benefits than health gains for the child might legitimate inclusion of disorders in NBS programs (1,2). In 2015, the Health Council of the Netherlands advised that NBS be expanded to include an additional 14 disorders, resulting in a program targeting 31 disorders in total (3).…”