How longitudinal observational studies can guide screening strategy for rare diseases.

Area of Science:

• Medical Genetics
• Public Health
• Preventive Medicine

Background:

• Newborn screening (NBS) has evolved over 50 years, driven by technological advances like tandem mass spectrometry (MS/MS).
• Despite proven benefits, evidence on long-term clinical advantages and cost-effectiveness of expanded NBS programs remains limited.
• Current NBS programs face challenges including incomplete understanding of disease natural history, variable severity prediction, and diagnostic dilemmas.

Purpose of the Study:

• To highlight the necessity of long-term follow-up for NBS cohorts.
• To advocate for an international collaborative framework for data collection and exchange in NBS.
• To address limitations and optimize NBS strategies in the era of genetic technologies.

Main Methods:

• Review of existing NBS program benefits and limitations.
• Discussion of challenges posed by expanding screening with new technologies.
• Proposal for integrating patient registries and long-term follow-up.

Main Results:

• Formal evidence for long-term benefits and cost-effectiveness of extended NBS is scarce.
• Ambiguous screening results create diagnostic and treatment challenges.
• High-throughput genetic technologies risk exacerbating current NBS limitations.

Conclusions:

• Mandatory long-term follow-up of NBS cohorts should be a screening principle.
• An international collaborative framework is crucial for data sharing and NBS optimization.
• Integrating patient perspectives is vital for societal acceptance and program improvement.