Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2022 Sep 5;7(1):51.
doi: 10.1038/s41525-022-00326-9.

Integrating rapid exome sequencing into NICU clinical care after a pilot research study

Alissa M D'Gama  1   2   3   4   5   6 , Maya C Del Rosario  3 , Mairead A Bresnahan  1 , Timothy W Yu  3   4   5   6 , Monica H Wojcik #  7   8   9   10   11 , Pankaj B Agrawal #  12   13   14   15   16
Affiliations

Integrating rapid exome sequencing into NICU clinical care after a pilot research study

Alissa M D'Gama et al. NPJ Genom Med. .

Abstract

Genomic sequencing is a powerful diagnostic tool in critically ill infants, but performing exome or genome sequencing (ES/GS) in the context of a research study is different from implementing these tests clinically. We investigated the integration of rapid ES into routine clinical care after a pilot research study in a Level IV Neonatal Intensive Care Unit (NICU). We performed a retrospective cohort analysis of infants admitted with suspected genetic disorders to the NICU from December 1, 2018 to March 31, 2021 and compared results to those obtained from a previous research study cohort (March 1, 2017 to November 30, 2018). Clinical rapid ES was performed in 80/230 infants (35%) with a suspected genetic disorder and identified a genetic diagnosis in 22/80 infants (28%). The majority of diagnoses acutely impacted clinical management (14/22 (64%)). Compared to the previous research study, clinically integrated rapid ES had a significantly lower diagnostic yield and increased time from NICU admission and genetics consult to ES report, but identified four genetic diagnoses that may have been missed by the research study selection criteria. Compared to other genetic tests, rapid ES had similar or higher diagnostic yield and similar or decreased time to result. Overall, rapid ES was utilized in the NICU after the pilot research study, often as the first-tier sequencing test, and could identify the majority of disease-causing variants, shorten the diagnostic odyssey, and impact clinical care. Based on our experience, we have identified strategies to optimize the clinical implementation of rapid ES in the NICU.

PubMed Disclaimer

Conflict of interest statement

Dr. Agrawal is a member of the Scientific Advisory Board of GeneDx and Illumina Inc. No other authors declare any competing interests.

Figures

Fig. 1
Fig. 1. Genetic testing and genetic diagnoses in the NICU.
Flowchart of the infants analyzed in Phase II and genetic diagnoses made.
Fig. 2
Fig. 2. Comparison of the NICU rapid ES workflow in Phase 1 versus Phase II.
Details of the rapid ES workflow in the pilot research study (Phase I) and subsequent integration into routine clinical care (Phase II) in the NICU. Potential strategies for optimizing implementation in routine NICU clinical care based on our experience are highlighted for each stage of the workflow.
Fig. 3
Fig. 3. Utilization of rapid ES in the NICU.
Number of rapid ES tests sent per month in our institution’s NICU during Phase I and Phase II.
See this image and copyright information in PMC

References

    1. Swaggart KA, et al. Making a Genetic Diagnosis in a Level IV Neonatal Intensive Care Unit Population: Who, When, How, and at What Cost. J. Pediatr. 2019;213:211–217e214. doi: 10.1016/j.jpeds.2019.05.054. - DOI - PubMed
    1. Wojcik MH, et al. Genetic disorders and mortality in infancy and early childhood: delayed diagnoses and missed opportunities. Genet Med. 2018;20:1396–1404. doi: 10.1038/gim.2018.17. - DOI - PMC - PubMed
    1. Australian Genomics Health Alliance Acute Care, F. et al. Feasibility of Ultra-Rapid Exome Sequencing in Critically Ill Infants and Children With Suspected Monogenic Conditions in the Australian Public Health Care System. JAMA. 2020;323:2503–2511. doi: 10.1001/jama.2020.7671. - DOI - PMC - PubMed
    1. Dimmock D, 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;108:1231–1238. doi: 10.1016/j.ajhg.2021.05.008. - DOI - PMC - PubMed
    1. Dimmock DP, et al. An RCT of Rapid Genomic Sequencing among Seriously Ill Infants Results in High Clinical Utility, Changes in Management, and Low Perceived Harm. Am. J. Hum. Genet. 2020;107:942–952. doi: 10.1016/j.ajhg.2020.10.003. - DOI - PMC - PubMed