Groundbreaking GUARDIAN Study Shows Benefits of Adding Genome Sequencing to Newborn Screening; Augments and Improves Standard Newborn Screening
GeneDx announced the publication of peer-reviewed research from the GUARDIAN study in JAMA, examining the use of whole genome sequencing (WGS) for newborn screening. The study, aiming to enroll 100,000 newborns, found that 3.7% of 4,000 enrolled newborns had positive screenings, with 92% of true positive findings being conditions not included in traditional newborn screening. The study screened for 255 early-onset genetic conditions, including 156 with established treatments. Notable findings included conditions like Long QT syndrome, severe combined immunodeficiencies, and Wilson disease. The study showed high acceptance rates, with 72% of families consenting to participate and 90.6% opting for additional neurodevelopmental disorder screening.
GeneDx ha annunciato la pubblicazione di una ricerca sottoposta a revisione paritaria dallo studio GUARDIAN su JAMA, esaminando l'uso del sequenziamento dell'intero genoma (WGS) per lo screening neonatale. Lo studio, che mira ad arruolare 100.000 neonati, ha rivelato che il 3,7% dei 4.000 neonati arruolati ha avuto risultati positivi, con il 92% delle scoperte vere positive che riguardano condizioni non incluse nello screening neonatale tradizionale. Lo studio ha esaminato 255 condizioni genetiche ad esordio precoce, includendo 156 con trattamenti consolidati. Tra le scoperte significative ci sono condizioni come la sindrome del QT lungo, gravi immunodeficienze combinate e la malattia di Wilson. Lo studio ha mostrato alti tassi di accettazione, con il 72% delle famiglie che hanno acconsentito a partecipare e il 90,6% che hanno optato per uno screening aggiuntivo dei disturbi neurodevelopmentali.
GeneDx anunció la publicación de una investigación revisada por pares del estudio GUARDIAN en JAMA, examinando el uso de la secuenciación del genoma completo (WGS) para el tamizaje neonatal. El estudio, que busca inscribir a 100,000 recién nacidos, encontró que el 3.7% de los 4,000 recién nacidos inscritos tuvieron resultados positivos, con el 92% de los hallazgos verdaderamente positivos siendo condiciones no incluidas en el tamizaje neonatal tradicional. El estudio examinó 255 condiciones genéticas de inicio temprano, incluyendo 156 con tratamientos establecidos. Entre los hallazgos notable están condiciones como el síndrome de QT largo, inmunodeficiencias combinadas severas y la enfermedad de Wilson. El estudio mostró altas tasas de aceptación, con el 72% de las familias dando su consentimiento para participar y el 90.6% optando por un tamizaje adicional de trastornos del neurodesarrollo.
GeneDx는 신생아 검진을 위한 전체 유전체 시퀀싱(WGS)의 사용을 조사한 GUARDIAN 연구의 동료 검토 연구 결과를 JAMA에 발표했습니다. 100,000명의 신생아를 등록할 목표를 가진 이 연구에서, 등록된 4,000명의 신생아 중 3.7%이 긍정적인 검진 결과를 나타냈으며, 진짜 긍정적인 발견의 92%는 전통적인 신생아 선별에 포함되지 않은 질환이었습니다. 이 연구는 255개의 조기 발병 유전 질환을 검토했으며, 이 중 156개는 확립된 치료법을 가지고 있습니다. 주요 발견으로는 긴 QT 증후군, 심각한 복합 면역 결핍 및 윌슨병과 같은 질환이 포함되었습니다. 연구는 72%의 가족이 참여를 동의하고 90.6%가 추가적인 신경발달 장애 검진을 선택하는 등 높은 수용율을 보여줬습니다.
GeneDx a annoncé la publication d'une recherche revue par des pairs de l'
GeneDx hat die Veröffentlichung einer peer-reviewed Forschung aus der GUARDIAN-Studie in JAMA angekündigt, die den Einsatz von Whole Genome Sequencing (WGS) für das Neugeborenen-Screening untersucht. Die Studie, die 100.000 Neugeborene einschreiben möchte, ergab, dass 3,7% der 4.000 eingeschriebenen Neugeborenen positive Ergebnisse hatten, wobei 92% der wahren positiven Befunde Bedingungen waren, die nicht im traditionellen Neugeborenen-Screening enthalten sind. In der Studie wurden 255 genetische Erkrankungen mit frühem Beginn untersucht, darunter 156 mit bestehenden Behandlungen. Zu den bemerkenswerten Befunden gehörten Erkrankungen wie das Long-QT-Syndrom, schwere kombinierte Immunodeficienzen und die Wilson-Krankheit. Die Studie zeigte hohe Akzeptanzraten, da 72% der Familien der Teilnahme zustimmten und 90,6% sich für ein zusätzliches Screening von neurodevelopmentalen Störungen entschieden.
- High study participation rate of 72% demonstrates strong market acceptance
- 92% of positive findings were conditions not detected by traditional screening, proving superior detection capability
- Study expanded to cover 446 genes and over 460 conditions, showing significant scalability
- Early diagnosis can reduce healthcare costs by avoiding average $10,000 in diagnostic expenses
- 3.7% positive screening rate may indicate high false positive potential
- Implementation costs and infrastructure requirements not addressed
- Study to NewYork-Presbyterian hospitals, showing geographic reach
Insights
The GUARDIAN study represents a significant breakthrough in newborn screening, with 3.7% of 4,000 tested newborns showing positive screenings. Critically, 92% of true positive findings were for conditions not included in traditional newborn screening (NBS), demonstrating substantial market expansion potential for GeneDx's genomic testing services.
The study's high consent rate of 72% and 90.6% opt-in for additional neurodevelopmental screening indicates strong market acceptance. This positions GeneDx favorably in the expanding genomic screening market, particularly as healthcare systems seek to reduce the typical
The expansion to 446 genes and 460 conditions, including high-profile conditions like Dravet syndrome and Duchenne muscular dystrophy, significantly broadens the addressable market. With 13,000 newborns enrolled to date and growing, this validates the scalability of GeneDx's technology platform.
Findings published today in JAMA (Journal of the American Medical Association) reveal limitations of current screening methods and showcase the promise of advanced genomic technology to deliver equitable health care for all children
The ongoing GUARDIAN study is a collaboration between GeneDx, Columbia University Irving Medical Center, NewYork-Presbyterian, the
GUARDIAN’s principal investigator, Wendy Chung, M.D., Ph.D., a clinical and molecular geneticist and the Chief of Pediatrics at Boston Children’s Hospital and Harvard Medical School, launched the study in 2022 at Columbia University Irving Medical Center and NewYork-Presbyterian. “Our study signifies a major advance in children’s health: the successful integration of genome sequencing into routine care accessible to all newborns,” said Dr. Chung. “By providing early diagnoses and enabling prompt treatment, we are not only proving the feasibility of this innovative approach but also advancing health equity. This milestone reflects our commitment to leveraging cutting-edge science to deliver better, faster care starting at birth.”
Findings from the study:
Over an 11-month period, 4,000 newborns were enrolled and 3.7 percent of newborns had positive screenings. The majority of those positive screens would not have been picked up by traditional NBS today. Of the 120 newborns with true positive findings,
Genetic conditions detected in newborns by GUARDIAN with known actions and treatments that are not screened with standard NBS include:
- Long QT syndrome, a rare heart condition that may cause Sudden Infant Death Syndrome (SIDS) and can be treated with beta-blockers
- Severe combined immunodeficiencies, which can be managed through stem cell transplant or gene-therapy and although included on traditional NBS, milder variants can be missed 1
- Wilson disease, which can be treated with liver transplant, as well as early zinc supplementation and a low-copper diet 2
Additionally, the study highlights the wide acceptance of more advanced and modernized NBS, with
Diagnosing these rare genetic conditions can be a lengthy and challenging process, often taking 5 years or longer if they are ever diagnosed. 3,4 During this period, pediatric patients typically undergo an average of five uninformative medical tests and accumulate around
“Today we have scalable genomic technology that provides tremendous benefits to children, families and health systems right at our fingertips. We have an opportunity to end the diagnostic odyssey by delivering actionable diagnoses to children at birth,” said Paul Kruszka, MD, FACMG, Chief Medical Officer at GeneDx. “GUARDIAN is proof of principle that we can apply medicine’s most advanced technology in an accurate, actionable and responsible way to ensure that more children have access to an early diagnosis to prevent disease progression.”
There continues to be increasing support from rare genetic disease advocates, parents, and public health professionals to expand NBS to enable timely access to new, and often precise, rare disease therapies.8,9 GUARDIAN’s panel has expanded to cover 446 genes and over 460 conditions, including a number of genes associated with conditions like epilepsy, including developmental and epileptic encephalopathy, Dravet syndrome, Rett syndrome, Angelman syndrome and Duchenne muscular dystrophy. The GUARDIAN study is ongoing, with more than 13,000 newborns enrolled to date. The study is open to all babies born at one of the NewYork-Presbyterian hospitals in
“While work remains to ensure equitable access to testing and follow-up care, studies such as GUARDIAN provide strong evidence that whole genome sequencing of newborns can enable timely access to rare disease therapies, as well as support and resources for parents and caregivers,” said Swaroop Aradhya, PhD, Vice President for Medical and Clinical Affairs at Illumina.
About GeneDx:
GeneDx (Nasdaq: WGS) delivers personalized and actionable health insights to inform diagnosis, direct treatment, and improve drug discovery. The company is uniquely positioned to accelerate the use of genomic and large-scale clinical information to enable precision medicine as the standard of care. GeneDx is at the forefront of transforming healthcare through its industry-leading exome and genome testing and interpretation services, fueled by the world’s largest, rare disease data sets. For more information, please visit www.genedx.com and connect with us on LinkedIn, Facebook, and Instagram.
About GUARDIAN
GUARDIAN (Genomic Uniform-screening Against Rare Diseases In All Newborns) is a research study conducted at
References
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