GENOMICS
currently covered by standard screening programmes. It can reveal pathogenic variants associated with rare diseases such as metabolic, neurological, and cardiac disorders – many of which present without clear early symptoms. Moreover, WGS offers a single-
platform solution, reducing the need for multiple sequential tests. A single WGS assay can generate data that replaces several traditional tests, including chromosomal microarray analysis, gene panel testing, exome sequencing, and the identification of repeat expansion disorders. Additionally, screening newborns at birth using a WGS approach enables earlier detection - before disease manifestation – potentially reducing the demand for neonatal intensive care unit (NICU) resources. Early diagnosis directly influences clinical decision-making, helping to alter disease progression and guide timely treatment.
Large-scale newborn sequencing initiatives can accelerate the discovery of novel therapies and improve the classification of rare diseases; further bridging the gap between diagnostics and therapeutics.
considerations that come with this paradigm shift and policy frameworks needed to ensure responsible implementation.
Evolution of NBS
Since its inception in the 1960s, NBS has been grounded in the detection of a limited set of metabolic and endocrine disorders using DBS samples. The expansion of national NBS panels over the decades has largely depended on the availability of biochemical markers, disease prevalence, and cost-effective testing. While the current approach has had measurable success, it is limited in its capacity to detect conditions without known metabolic signatures or those that require more complex genetic interpretation. The introduction of next-generation sequencing (NGS) technologies in clinical diagnostics has opened a new frontier for NBS. By reading the entirety of an individual’s genetic code, WGS
can identify thousands of variants – some associated with well-understood conditions and others with diseases still under investigation.2
For newborns,
this means a single genomic test could detect actionable conditions far earlier than traditional biochemical assays, including disorders with no biochemical marker.
In this context, WGS-based screening has the potential to complement current biochemical screening, offering a multi- OMICS comprehensive, efficient, and future-proof strategy for safeguarding child health.
Genomic advantage The central promise of genomics in NBS lies in its ability to provide a comprehensive genetic profile from birth. Unlike targeted genetic panels or biochemical assays, WGS reads an individual’s entire genome, enabling clinicians to detect a much wider range of conditions, including those not
New model for early diagnostics Across Europe and North America, pilot programmes are examining how genomics can be effectively integrated into routine NBS. In the UK, the Newborn Genomes Programme, led by Genomics England, is a major national initiative evaluating the clinical utility and acceptability of WGS for newborns. The programme plans to sequence up to 100,000 genomes to identify more than 200 rare but actionable genetic conditions.3
Delivering genomic screening at this
scale relies on high-throughput, clinical- grade laboratory infrastructure capable of end-to-end workflow integration, from sample intake and DNA extraction to sequencing, bioinformatics, variant interpretation and clinical reporting.1 Such systems are essential to ensure both diagnostic accuracy and timely turnaround, making population-level implementation of WGS-based screening feasible.
Timely and targeted interventions
Long-term data storage and reanalysis policies also need ethical scrutiny. While genomic data could offer lifelong clinical utility, they also require robust safeguards
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One of the most compelling arguments for genomic NBS is the ability to initiate timely, life-altering interventions. Many rare diseases are progressive and irreversible, with treatment windows limited to the first weeks or months of life. For example, spinal muscular atrophy (SMA), if untreated, leads to severe neuromuscular decline; but early therapy can preserve mobility and life expectancy.4
Similarly, conditions like
X-linked adrenoleukodystrophy (X-ALD) and severe combined immunodeficiency
SEPTEMBER 2025
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