Authors' objectives: Carrier screening is a screening strategy designed to identify asymptomatic individuals who carry pathogenic variants for autosomal recessive and X-linked hereditary conditions. This assessment evaluated the clinical effectiveness, safety, economic, organisational, and ethical aspects of different carrier screening strategies: universal versus risk-based approaches and single-disease panels versus expanded carrier screening (ECS). The target population comprised reproductive-age individuals and pregnant women.

Authors' results and conclusions: Four systematic reviews were identified, synthesising 11 to 107 primary studies. The included systematic reviews predominantly comprised observational studies with one randomised controlled trial identified but also for example health economic evaluations, studies on ethical or organisational aspects and model studies. Clinical Effectiveness and Safety: Identified evidence indicated that carrier screening identifies at-risk couples (0-25% depending on condition and population, moderate certainty) and supports informed reproductive decision-making. Screening uptake varied substantially (4.7-99.5%) depending on strategy and setting. Among at-risk pregnancies, prenatal diagnosis uptake was 64.4% and pregnancy termination rate was 71.4% among pregnancies confirmed to be affected within the prenatal diagnosis. ECS demonstrated superior test performance compared to single-disease panels. Psychological impacts remained uncertain with very low certainty of evidence. Downstream impacts including cascade testing rates were inconsistently reported. Economic, Organisational, and Ethical Aspects: Economic evaluations were limited and context-specific to the Canadian healthcare setting; universal screening with standard panels may be cost-effective, though highly sensitive to carrier frequency and uptake. Implementation required substantial investment in genetic counselling capacity and infrastructure. Key ethical considerations included respect for autonomy, informed decision-making, and privacy protection. Guideline Recommendations: Identified guidelines recommended universal screening for Cystic Fibrosis and Spinal Muscular Atrophy, with variable recommendations for expanded panels and risk-based screening for Fragile X syndrome. Applicability of guidelines to the Austrian setting is limited.

Authors' recommendations: Evidence shows with moderate certainty that carrier screening for CF, SMA, FXS, and hemoglobinopathies identifies at-risk couples and supports informed reproductive decisions. Evidence regarding psychological impacts remains highly uncertain. International guidelines are only partially applicable to Austria due to heterogeneous strategies. While universal screening increases detection rates, it places high demands on budget and infrastructure. Expanded Carrier Screening (ECS) – including genome-wide approaches such as WES/WGS – offers more precise identification of at-risk couples but requires standardization of panel sizes and management of variants of uncertain significance (VUS). No formal carrier screening programme exists in Austria, and international guideline recommendations are not applicable to the Austrian healthcare context. Responsible implementation requires consideration of Austrian epidemiological data, ethical frameworks, substantial organisational capacity, and multidisciplinary collaboration. Prior to widespread implementation, pilot studies are recommended to evaluate feasibility, cost-effectiveness, and social impacts within the Austrian context.

Authors' methods: We employed a review-of-reviews approach to synthesise systematic reviews and health technology assessments published between June 2020 and March 2025. Systematic literature searches were conducted in five databases. International guideline recommendations were additionally identified and synthesised. Evidence was synthesised narratively.

Project Status: Completed

URL for project: https://aihta.at/page/humangenetische-untersuchungen-in-oesterreich-ein-ueberblick-ueber-massiv-parallele-sequenzierung-mps-anwendungsfelder-nutzen-und-implikationen-fuer-die-versorgung/en

Year Published: 2026

URL for published report: https://eprints.aihta.at/1603/1/HTA-Projektbericht_Nr.176b

URL for additional information: https://eprints.aihta.at/1603

English language abstract: An English language summary is available

Publication Type: Full HTA

Country: Austria

Organisation Name: Austrian Institute for Health Technology Assessment

Contact Address: Josefstaedter Strasse 39, A-1080 Vienna, Austria

Contact Name: office@aihta.at

Contact Email: office@aihta.at