Holly L. Snyder, MS, LCGC 

Illumina, a genomic sequencing company (San Diego, CA), hosted a virtual educational event for neonatal providers interested in learning more about Whole-Genome Sequencing (WGS) and sharing best practices for attendees interested in driving legislation and reimbursement in their states. The event format allowed formal presentations and open discussion through roundtable sessions. 

An estimated 30-50% of neonatal and pediatric intensive care unit (NICU/PICU) admissions are secondary to birth defects or genetic conditions, which result in death in approximately 40% of neonates. (1-4) Whole-genome sequencing (WGS) in acutely ill infants has become essential in the neonatologists’ toolkit. Over the past five years, published evidence has demonstrated the diagnostic, clinical, and economic utility of rapid WGS in the NICU setting. (5-10) The NICUSeq randomized-controlled trial, published last year, showed that a change in management is twice as likely when WGS is introduced as a first-tier test compared to infants who undergo usual care testing. (5) Genomic sequencing results that do not yield a diagnosis may also be medically actionable and add value to shared decision-making. (5-7,11 )These findings support WGS adoption and implementation in acutely ill infants. 

Even though the diagnostic yield is superior with WGS compared to standard testing in acutely ill infants, implementation as a first-tier test remains limited.(5,8-10) Several states, including California and Michigan, have worked towards legislation and Medicaid reimbursement to improve access. In addition to reimbursement limitations, there remains a gap in knowledge about WGS and comfort with clinical implementation. (12) The limited availability of geneticists and genetic counselors at many institutions may also preclude test utilization. 

Salient topics covered in this virtual event include clinical utility, management of WGS reports, result communication, economic utility, clinical implementation, and impact on precision medicine. Experts from Rady Children’s Institute of Genomic Medicine (RCIGM), Helen DeVos Children’s Hospital, HudsonAlpha Institute of Biotechnology, the University of California San Francisco (UCSF), and Illumina presented. Representatives from Project Baby programs in California, Michigan, and Minnesota shared different perspectives on their state successes. The event culminated in a discussion with a patient advocate, Amber Freed, Founder of SLC6A1 Connect, who has deep experience using her voice to raise money and drive meaningful change for rare diseases. 

[CLICK TO READ LIST OF ABSTRACTS FROM PRESENTATIONS BELOW]

References: 

1. Weiner J, Sharma J, Lantos J, Kilbride H. How infants die in the neonatal intensive care unit: trends from 1999 through 2008. Arch Pediatr Adolesc Med. 2011;165(7):630-634. 
2. Gjorgioski, S., Halliday, J., Riley, M. et al. Genetics and pediatric hospital admissions, 1985 to 2017. Genet Med 22, 1777–1785 (2020). https://doi.org/10.1038/s41436-020-0871-9 
3. Gunne, E., McGarvey, C., Hamilton, K. et al. A retrospective review of the contribution of rare diseases to paediatric mortality in Ireland. Orphanet J Rare Dis 15, 311 (2020). https://doi.org/10.1186/s13023-020-01574-7. 
4. Arth AC, Tinker SC, Simeone RM, Ailes EC, Cragan JD, Grosse SD. Inpatient Hospitalization Costs Associated with Birth Defects Among Persons of All Ages – United States, 2013. MMWR Morb Mortal Wkly Rep. 2017;66(2):41-46. 
5. Krantz et al. Effect of whole genome sequencing on the clinical management of acutely ill infants with suspected genetic disease: the NICUSeq Randomized Time-Delayed Trial. JAMA Pediatrics. 2021; 175(12):1218-1226. 
6. Dimmock D, Caylor S, Waldman B, et al. Project Baby Bear: Rapid precision care incorporating rWGS in 5 California children’s hospitals demonstrates improved clinical outcomes and reduced costs of care.. Am J Hum Genet. 2021 May 29S0002-9297(21)00192-0. doi: 10.1016/j.ajhg.2021.05.008. Epub ahead of print. PMID: 34089648. 
7. Australian Genomics Health Alliance Acute Care Flagship. Feasibility of Ultra-Rapid Exome Sequencing in Critically Ill Infants and ChilHealth Care System. JAMA. 2020;323(24):2503–2511. doi:10.1001/jama.2020.7671. 
8. Farnaes L, Hildreth A, Sweeney NM, et al. Rapid whole-genome sequencing decreases infant morbidity and cost of hospitalization. NPJ Genom Med. 2018;3:10. 
9. Petrikin JE, Cakici JA, Clark MM, et al. The NSIGHT1-randomized controlled trial: rapid whole-genome sequencing for accelerated etiologic diagnosis in critically ill infants. NPJ Genom Med. 2018 Feb 9;3:6. doi: 10.1038/s41525-018-0045-8. 
10. Willig et al. Whole genome seqeuncing for identification of Mendelian disorders in critically ill infants: a retrospective analysis of diagnostic and clinical findings. Lancet. 2015;3:377-388. 
11. Manickam, K., McClain, et al. Exome and genome sequencing for pediatric patients with congenital anomalies or intellectual disability: an evidence-based clinical guideline of the American College of Medical Genetics and Genomics (ACMG).. Genet Med (2021) https://doi.org/10.1038/s41436-021-01242-6 
12. Franck LS, Kriz RM, Rego S, Garman K, Hobbs C, Dimmock D. Implementing rapid whole-genome sequencing in critical care: A qualitative study of facilitators and barriers to new technology adoption. J. Pediatr. 2021; 237: 237–243.e2 
13. ncerti D, Xy XM, Chou JW, et al. Cost-effectiveness of genome sequencing for diagnosing patients with undiagnosed rare genetic diseases. Genet Med. 2021. doi.org/10.1016/j.gim.2021.08.015 
14. Franck LS, Scheurer-Monaghan A, Bupp CP, Fakhoury JD, Hoffmann TJ, Deshpandey M, Arenchild M, Dimmock DP. Healthcare Professionals’ Attitudes toward Rapid Whole Genome Sequencing in Pediatric Acute Care. Children (Basel). 2022 Mar 4;9(3):357. doi: 10.3390/children9030357. PMID: 35327729; PMCID: PMC8947383. 
15. East KM, Cochran ME, Kelley WV et al. Education and training of non-genetics providers on the return of genome sequencing results in a NICU setting. J Personal Med. PMID: 35330405 

Disclosures: The authors have no disclosures 

Conflict of Interest: Illumina funded the event, and all speakers were given an opportunity to accept an honorarium.