Next-Generation Sequencing Could Enhance Early Disease Detection in Newborns

Routine newborn screening (NBS) is a cornerstone of preventive pediatric care, enabling early detection of inherited disorders before symptoms appear. However, traditional NBS programs rely primarily on biochemical markers, limiting the number of conditions that can be identified at birth. Many genetic diseases do not produce detectable metabolic signals in newborns, allowing disease progression to begin before diagnosis. Now, a new review examines how next-generation sequencing (NGS) could complement existing screening methods and enable broader, genome-enabled detection of inherited conditions from birth.

The review, conducted by researchers from the Children’s Hospital of Fudan University (CHFU, Shanghai, China) and Guangzhou Women and Children’s Medical Center (GWCMC, Guangzhou, China), explored how NGS could reshape newborn screening by shifting from single-disease biochemical assays to genome-enabled, multi-disease approaches. NGS-based newborn screening, also referred to as genomic newborn screening (gNBS), analyzes DNA extracted from the same dried blood spots already collected in routine screening programs.

Image: Genomic analysis of dried blood spots could expand newborn screening beyond biochemical tests (Photo courtesy of 123RF)

Genomic approaches include targeted gene panels, whole-exome sequencing, and whole-genome sequencing, allowing simultaneous assessment of multiple genes linked to inherited disorders. This strategy enables the detection of conditions that remain invisible to conventional biochemical screening during the neonatal period. By directly identifying disease-causing genetic variants, gNBS has the potential to uncover risks for early-onset disorders before irreversible damage occurs, significantly expanding the scope of current newborn screening programs.

The review, published in Pediatric Investigation, highlights both the promise and the limitations of genomic newborn screening. While gNBS can identify a broader range of genetic conditions, it also introduces challenges such as interpreting variants of uncertain significance and determining which findings should be reported in a population-wide screening context. The authors emphasize that careful selection of clinically actionable genes and variants is essential to minimize unnecessary anxiety and ethical concerns for families.

Another key limitation discussed is turnaround time. Traditional biochemical screening delivers results within days, whereas genomic sequencing may take weeks, reducing its utility for conditions requiring immediate intervention. Ongoing research aims to shorten sequencing timelines through rapid whole-genome approaches that are already being tested in critically ill infants. The authors suggest that, rather than replacing existing methods, gNBS could initially be used alongside conventional assays to clarify ambiguous results and extend detection beyond biochemical limits.

“Driven by lower costs, technological advances, and supportive policy frameworks, gNBS is expected to gradually integrate with or even evolve into a standardized tool for newborn healthcare management,” said Dr. Wenhao Zhou, co-author of the review.