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Introducing genome sequencing for newborns universally could have an immense impact on the health of our population.
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Next Generation Sequencing Will Advance Newborn Screening

Genome sequencing uncovered risks of several pediatric-onset conditions that may benefit from early intervention

Madhuri Hegde, PhD, FACMG

Madhuri Hegde, PhD, FACMG, is the SVP and chief scientific officer of Revvity Inc., responsible for setting the strategic scientific direction of the company. A medical geneticist and American Board of Medical Genetics and Genomics (ABMGG)-certified diplomat in clinical molecular genetics, Hegde heads Revvity Omics and its global network of laboratories offering innovative, omics-based services in more than 155 countries worldwide.

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Published:Dec 28, 2023
|3 min read
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Madhuri Hegde, PhD, FACMG, is the SVP and chief scientific officer of Revvity Inc., responsible for setting the strategic scientific direction of the company. She heads Revvity Omics and its global network of laboratories offering innovative, omics-based services in more than 155 countries worldwide.

The application of various sequencing technologies has dramatically increased, generating large amounts of data that have helped scientists and clinicians better understand variations in the human genome and their association to human disease. This data also helps clinicians make more informed decisions about medical management and the recommended course of treatment for patients. 

Clinicians have relied on insights from genome sequencing to make informed therapeutic decisions for critically ill newborns. But what about its utility in screening apparently healthy newborns? A team of scientists led by Madhuri Hegde, PhD, FACMG, sought to address this question in a study that appeared in JAMA Network Open

Behind the study

The objective of the study was to assess the clinical utility of genome sequencing against an exome-based gene panel for a curated set of medically actionable pediatric-onset conditions in the largest-to-date cohort of apparently healthy newborns and children tested at a single clinical laboratory. As the panel included only a limited number of genes, more findings were expected from genome analysis, which included around 6,000 disease-associated genes. However, the extent and landscape of the findings remained unknown. 

There were 562 apparently healthy children screened by genome sequencing: 46 were (8.2 percent) found to be at risk for pediatric-onset diseases, including 22 (3.9 percent) who were very likely to develop a disease. In contrast, only 2.1 percent of 606 children screened with an exome-based panel of 268 genes for well-known medically actionable pediatric conditions were found to be at risk.

Genome sequencing uncovered risks for a wide range of pediatric-onset conditions that limited gene panels would likely miss. Many of these risks involve high-penetrance pediatric conditions, often neurodevelopmental disorders that may benefit from early interventions, leading to better prognosis and clinical outcomes.

Future approach to newborn screening

The starkest difference was not so much in the percentage of children with uncovered risk (8 percent vs 2 percent), but the heterogeneity of the risks uncovered by genome sequencing—close to 50 percent of genes were associated with high penetrance conditions. Limited-number gene panels, when compared to genome sequencing, would have picked up only one-fifth of the high penetrance conditions. Discussions are underway among the medical community on what genes should be included when screening newborns using NGS, and the study provides real-world data on what can come out of this application. 

Genomic technologies have the power to revolutionize the way we detect diseases in their early stages, as demonstrated by this research. Using proactive genomic screening would enable healthcare professionals uncover a wide range of risks for pediatric-onset conditions allowing for earlier interventions and personalized treatment plans based on individual genetic make-up.

Introducing genome sequencing for newborns universally could have an immense impact on the health of our population, heralding a new era of pediatric health care. For one, beyond sequencing at birth, families can refer to recorded genomic data to look for answers to medical issues as they need it—be it for immediate care or family planning. The cost of sequencing continues to gradually decrease and soon may be more economical to implement, especially given the costs associated with delayed diagnosis of a rare disease

Looking ahead

There is no doubt that with technological advancements in the fields of genomics and precision medicine, the rate of detection and introduction of treatments for rare conditions has grown considerably. But there is more to be done. As genomic sequencing implications in diagnostics are continuously evolving, it’s important to conduct studies that expand our knowledge to better inform the development of screening programs and diagnostic tools. 

But science alone is not enough. Continued collaboration between healthcare system authorities and governments is needed to ensure real-world practices are in line with new findings as they emerge.