Towards Next-Generation Sequencing (NGS)-Based Newborn Screening: A Technical Study to Prepare for the Challenges...

Area of Science:

• Genomics
• Biochemistry
• Public Health

Background:

• Newborn screening (NBS) currently uses a biochemistry-first approach, primarily for inherited metabolic disorders (IMD).
• Next-generation sequencing (NGS) presents potential advantages, including detecting IMDs without clear biochemical markers.

Purpose of the Study:

• To explore the use of next-generation sequencing (NGS) as a first-tier approach in newborn screening (NBS).
• To design and set up the NGS-first for NBS (NGSf4NBS) project.
• To prepare for the integration of an NGS-based workflow into the Dutch NBS program.

Main Methods:

• Step 1: Identify treatable IMDs suitable for NGS-first testing.
• Step 2: Investigate technical NGS approaches, limitations, and analysis workflows for NBS, aiming for a rapid workflow.
• Step 3: Develop protocols for incorporating NGS into the Dutch NBS program and for post-positive test referral.

Main Results:

• The study outlines a three-step technical approach to evaluate NGS for NBS.
• It aims to establish the feasibility and comparability of different NGS methods and workflows.
• Results will inform the potential addition of an NGS analytical route to NBS.

Conclusions:

• The NGSf4NBS project will provide a basis for a new analytical route in NBS.
• This study will assess the applicability of NGS in NBS, considering ethical, legal, financial, and social implications.
• The findings will support the potential incorporation of rapid NGS workflows into national newborn screening programs.