Expanded Newborn Screening Using Genome Sequencing for Early Actionable Conditions.

Autor:	Ziegler A; Department of Pediatrics, Columbia University Irving Medical Center, New York, New York., Koval-Burt C; Department of Pediatrics, Columbia University Irving Medical Center, New York, New York., Kay DM; Newborn Screening Program, Wadsworth Center, New York State Department of Health, Albany., Suchy SF; GeneDx, LLC, Gaithersburg, Maryland., Begtrup A; GeneDx, LLC, Gaithersburg, Maryland., Langley KG; GeneDx, LLC, Gaithersburg, Maryland., Hernan R; Department of Pediatrics, Columbia University Irving Medical Center, New York, New York., Amendola LM; Illumina, San Diego, California., Boyd BM; Department of Pediatrics, Columbia University Irving Medical Center, New York, New York., Bradley J; Newborn Screening Program, Wadsworth Center, New York State Department of Health, Albany., Brandt T; GeneDx, LLC, Gaithersburg, Maryland., Cohen LL; NewYork-Presbyterian Weill Cornell Medical Center, New York., Coffey AJ; Illumina, San Diego, California., Devaney JM; GeneDx, LLC, Gaithersburg, Maryland., Dygulska B; NewYork-Presbyterian Brooklyn Methodist Hospital, New York., Friedman B; GeneDx, LLC, Gaithersburg, Maryland., Fuleihan RL; Division of Allergy, Immunology & Rheumatology, Columbia University Irving Medical Center, New York, New York., Gyimah A; Department of Pediatrics, Columbia University Irving Medical Center, New York, New York., Hahn S; Department of Pediatrics, Biochemical Genetics, University of Washington, Seattle Children's Hospital, Seattle., Hofherr S; GeneDx, LLC, Gaithersburg, Maryland., Hruska KS; GeneDx, LLC, Gaithersburg, Maryland., Hu Z; Department of Systems Biology, Columbia University Irving Medical Center, New York, New York., Jeanne M; Division of Genetics and Genomics, Department of Pediatrics, Boston Children's Hospital, Boston, Massachusetts., Jin G; Department of Pediatrics, Columbia University Irving Medical Center, New York, New York., Johnson DA; GeneDx, LLC, Gaithersburg, Maryland., Kavus H; Department of Pediatrics, Columbia University Irving Medical Center, New York, New York., Leibel RL; Department of Pediatrics, Columbia University Irving Medical Center, New York, New York., Lobritto SJ; Department of Pediatrics, Columbia University Irving Medical Center, New York, New York., McGee S; GeneDx, LLC, Gaithersburg, Maryland., Milner JD; Division of Allergy, Immunology & Rheumatology, Columbia University Irving Medical Center, New York, New York., McWalter K; GeneDx, LLC, Gaithersburg, Maryland., Monaghan KG; GeneDx, LLC, Gaithersburg, Maryland., Orange JS; Department of Pediatrics, Columbia University Irving Medical Center, New York, New York., Pimentel Soler N; Department of Pediatrics, Columbia University Irving Medical Center, New York, New York., Quevedo Y; Department of Pediatrics, Columbia University Irving Medical Center, New York, New York., Ratner S; Department of Pediatrics, Columbia University Irving Medical Center, New York, New York., Retterer K; GeneDx, LLC, Gaithersburg, Maryland., Shah A; Division of Pediatric Cardiology, Department of Pediatrics, Weill Cornell Medical College, New York, New York., Shapiro N; NewYork-Presbyterian Queens, Flushing., Sicko RJ; Newborn Screening Program, Wadsworth Center, New York State Department of Health, Albany., Silver ES; Division of Pediatric Cardiology, Department of Pediatrics, Columbia University Irving Medical Center, New York, New York., Strom S; Illumina, San Diego, California., Torene RI; GeneDx, LLC, Gaithersburg, Maryland., Williams O; Division of Pediatric Hematology, Oncology, and Stem Cell Transplantation, Department of Pediatrics, Columbia University Irving Medical Center, New York, New York., Ustach VD; GeneDx, LLC, Gaithersburg, Maryland., Wynn J; Department of Pediatrics, Columbia University Irving Medical Center, New York, New York., Taft RJ; Illumina, San Diego, California., Kruszka P; GeneDx, LLC, Gaithersburg, Maryland., Caggana M; Newborn Screening Program, Wadsworth Center, New York State Department of Health, Albany., Chung WK; Department of Pediatrics, Columbia University Irving Medical Center, New York, New York.; Division of Genetics and Genomics, Department of Pediatrics, Boston Children's Hospital, Boston, Massachusetts.; Harvard Medical School, Boston, Massachusetts.
Jazyk:	angličtina
Zdroj:	JAMA [JAMA] 2024 Oct 24. Date of Electronic Publication: 2024 Oct 24.
DOI:	10.1001/jama.2024.19662
Abstrakt:	Importance: The feasibility of implementing genome sequencing as an adjunct to traditional newborn screening (NBS) in newborns of different racial and ethnic groups is not well understood. Objective: To report interim results of acceptability, feasibility, and outcomes of an ongoing genomic NBS study in a diverse population in New York City within the context of the New York State Department of Health Newborn Screening Program. Design, Setting, and Participants: The Genomic Uniform-screening Against Rare Disease in All Newborns (GUARDIAN) study was a multisite, single-group, prospective, observational investigation of supplemental newborn genome screening with a planned enrollment of 100 000 participants. Parent-reported race and ethnicity were recorded at the time of recruitment. Results of the first 4000 newborns enrolled in 6 New York City hospitals between September 2022 and July 2023 are reported here as part of a prespecified interim analysis. Exposure: Sequencing of 156 early-onset genetic conditions with established interventions selected by the investigators were screened in all participants and 99 neurodevelopmental disorders associated with seizures were optional. Main Outcomes and Measures: The primary outcome was screen-positive rate. Additional outcomes included enrollment rate and successful completion of sequencing. Results: Over 11 months, 5555 families were approached and 4000 (72.0%) consented to participate. Enrolled participants reflected a diverse group by parent-reported race (American Indian or Alaska Native, 0.5%; Asian, 16.5%; Black, 25.1%; Native Hawaiian or Other Pacific Islander, 0.1%; White, 44.7%; 2 or more races, 13.0%) and ethnicity (Hispanic, 44.0%; not Hispanic, 56.0%). The majority of families consented to screening of both groups of conditions (both groups, 90.6%; disorders with established interventions only, 9.4%). Testing was successfully completed for 99.6% of cases. The screen-positive rate was 3.7%, including treatable conditions that are not currently included in NBS. Conclusions and Relevance: These interim findings demonstrate the feasibility of targeted interpretation of a predefined set of genes from genome sequencing in a population of different racial and ethnic groups. DNA sequencing offers an additional method to improve screening for conditions already included in NBS and to add those that cannot be readily screened because there is no biomarker currently detectable in dried blood spots. Additional studies are required to understand if these findings are generalizable to populations of different racial and ethnic groups and whether introduction of sequencing leads to changes in management and improved health outcomes. Trial Registration: ClinicalTrials.gov Identifier: NCT05990179.
Databáze:	MEDLINE
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