Dataset Information

National Rapid Genome Sequencing in Neonatal Intensive Care.

ABSTRACT:

Importance

National implementation of rapid trio genome sequencing (rtGS) in a clinical acute setting is essential to ensure advanced and equitable care for ill neonates.

Objective

To evaluate the feasibility, diagnostic efficacy, and clinical utility of rtGS in neonatal intensive care units (NICUs) throughout Israel.

Design, setting, and participants

This prospective, public health care-based, multicenter cohort study was conducted from October 2021 to December 2022 with the Community Genetics Department of the Israeli Ministry of Health and all Israeli medical genetics institutes (n = 18) and NICUs (n = 25). Critically ill neonates suspected of having a genetic etiology were offered rtGS. All sequencing, analysis, and interpretation of data were performed in a central genomics center at Tel-Aviv Sourasky Medical Center. Rapid results were expected within 10 days. A secondary analysis report, issued within 60 days, focused mainly on cases with negative rapid results and actionable secondary findings. Pathogenic, likely pathogenic, and highly suspected variants of unknown significance (VUS) were reported.

Main outcomes and measures

Diagnostic rate, including highly suspected disease-causing VUS, and turnaround time for rapid results. Clinical utility was assessed via questionnaires circulated to treating neonatologists.

Results

A total of 130 neonates across Israel (70 [54%] male; 60 [46%] female) met inclusion criteria and were recruited. Mean (SD) age at enrollment was 12 (13) days. Mean (SD) turnaround time for rapid report was 7 (3) days. Diagnostic efficacy was 50% (65 of 130) for disease-causing variants, 11% (14 of 130) for VUS suspected to be causative, and 1 novel gene candidate (1%). Disease-causing variants included 12 chromosomal and 52 monogenic disorders as well as 1 neonate with uniparental disomy. Overall, the response rate for clinical utility questionnaires was 82% (107 of 130). Among respondents, genomic testing led to a change in medical management for 24 neonates (22%). Results led to immediate precision medicine for 6 of 65 diagnosed infants (9%), an additional 2 (3%) received palliative care, and 2 (3%) were transferred to nursing homes.

Conclusions and relevance

In this national cohort study, rtGS in critically ill neonates was feasible and diagnostically beneficial in a public health care setting. This study is a prerequisite for implementation of rtGS for ill neonates into routine care and may aid in design of similar studies in other public health care systems.

SUBMITTER: Marom D

PROVIDER: S-EPMC10884880 | biostudies-literature | 2024 Feb

REPOSITORIES: biostudies-literature

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Publications

National Rapid Genome Sequencing in Neonatal Intensive Care.

Marom Daphna D Mory Adi A Reytan-Miron Sivan S Amir Yam Y Kurolap Alina A Cohen Julia Grinshpun JG Morhi Yocheved Y Smolkin Tatiana T Cohen Lior L Zangen Shmuel S Shalata Adel A Riskin Arieh A Peleg Amir A Lavie-Nevo Karen K Mandel Dror D Chervinsky Elana E Fisch Clari Felszer CF Fleisher Sheffer Vered V Falik-Zaccai Tzipora C TC Rips Jonathan J Shlomai Noa Ofek NO Friedman Smadar Eventov SE Shporen Calanit Hershkovich CH Ben-Yehoshua Sagie Josefsberg SJ Simmonds Aryeh A Yaacobi Racheli Goldfarb RG Bauer-Rusek Sofia S Omari Hussam H Weiss Karin K Hochwald Ori O Koifman Arie A Globus Omer O Batzir Nurit Assia NA Yaron Naveh N Segel Reeval R Morag Iris I Reish Orit O Eliyahu Aviva A Leibovitch Leah L Schwartz Marina Eskin ME Abramsky Ramy R Hochberg Amit A Oron Anat A Banne Ehud E Portnov Igor I Samra Nadra Nasser NN Singer Amihood A Baris Feldman Hagit H

JAMA network open 20240205 2

<h4>Importance</h4>National implementation of rapid trio genome sequencing (rtGS) in a clinical acute setting is essential to ensure advanced and equitable care for ill neonates.<h4>Objective</h4>To evaluate the feasibility, diagnostic efficacy, and clinical utility of rtGS in neonatal intensive care units (NICUs) throughout Israel.<h4>Design, setting, and participants</h4>This prospective, public health care-based, multicenter cohort study was conducted from October 2021 to December 2022 with t ...[more]

PMID: 38386321

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Project description:IntroductionRapid genomic sequencing (rGS) in critically ill infants with suspected genetic disorders has high diagnostic and clinical utility. However, rGS has primarily been available at large referral centres with the resources and expertise to offer state-of-the-art genomic care. Critically ill infants from racial and ethnic minority and/or low-income populations disproportionately receive care in safety-net and/or community settings lacking access to state-of-the-art genomic care, contributing to unacceptable health equity gaps. VIrtual GenOme CenteR is a 'proof-of-concept' implementation science study of an innovative delivery model for genomic care in safety-net neonatal intensive care units (NICUs).Methods and analysisWe developed a virtual genome centre at a referral centre to remotely support safety-net NICU sites predominantly serving racial and ethnic minority and/or low-income populations and have limited to no access to rGS. Neonatal providers at each site receive basic education about genomic medicine from the study team and identify eligible infants. The study team enrols eligible infants (goal n of 250) and their parents and follows families for 12 months. Enrolled infants receive rGS, the study team creates clinical interpretive reports to guide neonatal providers on interpreting results, and neonatal providers return results to families. Data is collected via (1) medical record abstraction, (2) surveys, interviews and focus groups with neonatal providers and (3) surveys and interviews with families. We aim to examine comprehensive implementation outcomes based on the Proctor Implementation Framework using a mixed methods approach.Ethics and disseminationThis study is approved by the institutional review board of Boston Children's Hospital (IRB-P00040496) and participating sites. Participating families are required to provide electronic written informed consent and neonatal provider consent is implied through the completion of surveys. The results will be disseminated via peer-reviewed publications and data will be made accessible per National Institutes of Health (NIH) policies.Trial registration numberNCT05205356/clinicaltrials.gov.

Dataset Information

National Rapid Genome Sequencing in Neonatal Intensive Care.

Importance

Objective

Design, setting, and participants

Main outcomes and measures

Results

Conclusions and relevance

Publications

National Rapid Genome Sequencing in Neonatal Intensive Care.

Similar Datasets

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