Integrating the Genomic Revolution into Newborn Screening: Current Challenges and Future Perspectives

Area of Science:

• Genetics
• Biotechnology
• Public Health

Background:

• Tandem mass spectrometry (MS/MS) and next-generation sequencing (NGS) have revolutionized genetic disease diagnosis, offering faster, cheaper, and less invasive methods.
• Neonatal screening programs, initially driven by MS/MS, are increasingly exploring NGS, particularly in pilot projects and private initiatives.
• Traditional screening criteria are expanding to include equity and access considerations due to technological advancements.

Purpose of the Study:

• To review the global status of metabolic screening panels and ongoing genomic screening projects.
• To outline current models for integrating metabolomic and genomic screening systems in newborn screening (NBS).
• To discuss the potential of multi-omics approaches, AI, and machine learning in enhancing NBS.

Main Methods:

• Review of global NBS programs and technological integration models.
• Analysis of country-specific differences in screening panels and adoption of new technologies.
• Examination of emerging evidence from integrated multi-omics approaches in NBS.

Main Results:

• Significant international variation exists in the scope of national NBS programs.
• Italy showcases a comprehensive metabolic screening panel, with ongoing initiatives to incorporate genomic technologies.
• No country currently mandates NGS as a first-tier NBS test, unlike established metabolomic programs.

Conclusions:

• Integrating metabolomic and genomic screening, potentially with AI, is crucial for reducing false positives/negatives and improving equitable access.
• A transitional phase focusing on rigorous improvements is necessary before widespread adoption of integrated genomic technologies in NBS.
• Future NBS conceptualization should prioritize equitable access, faster diagnosis, and timely treatment through optimized screening systems.