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

Alissa M D'Gama; Maya C Del Rosario; Mairead A Bresnahan; Timothy W Yu; Monica H Wojcik; Pankaj B Agrawal

doi:10.1038/s41525-022-00326-9

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

NPJ Genom Med. 2022 Sep 5;7(1):51. doi: 10.1038/s41525-022-00326-9.

Authors

Alissa M D'Gama^{1

2

3

4

5

6}, Maya C Del Rosario³, Mairead A Bresnahan¹, Timothy W Yu^{3

4

5

6}, Monica H Wojcik^#^{7

8

9

10

11}, Pankaj B Agrawal^#^{12

13

14

15

16}

Affiliations

¹ Neonatal Genomics Program, Division of Newborn Medicine, Boston Children's Hospital, Boston, MA, USA.
² Epilepsy Genetics Program, Division of Epilepsy and Neurophysiology, Department of Neurology, Boston Children's Hospital, Boston, MA, USA.
³ Division of Genetics and Genomics, Boston Children's Hospital, Boston, MA, USA.
⁴ Department of Pediatrics, Harvard Medical School, Boston, MA, USA.
⁵ Broad Institute of MIT and Harvard, Cambridge, MA, USA.
⁶ The Manton Center for Orphan Disease Research, Boston Children's Hospital, Boston, MA, USA.
⁷ Neonatal Genomics Program, Division of Newborn Medicine, Boston Children's Hospital, Boston, MA, USA. monica.wojcik@childrens.harvard.edu.
⁸ Division of Genetics and Genomics, Boston Children's Hospital, Boston, MA, USA. monica.wojcik@childrens.harvard.edu.
⁹ Department of Pediatrics, Harvard Medical School, Boston, MA, USA. monica.wojcik@childrens.harvard.edu.
¹⁰ Broad Institute of MIT and Harvard, Cambridge, MA, USA. monica.wojcik@childrens.harvard.edu.
¹¹ The Manton Center for Orphan Disease Research, Boston Children's Hospital, Boston, MA, USA. monica.wojcik@childrens.harvard.edu.
¹² Neonatal Genomics Program, Division of Newborn Medicine, Boston Children's Hospital, Boston, MA, USA. pankaj.agrawal@enders.tch.harvard.edu.
¹³ Division of Genetics and Genomics, Boston Children's Hospital, Boston, MA, USA. pankaj.agrawal@enders.tch.harvard.edu.
¹⁴ Department of Pediatrics, Harvard Medical School, Boston, MA, USA. pankaj.agrawal@enders.tch.harvard.edu.
¹⁵ Broad Institute of MIT and Harvard, Cambridge, MA, USA. pankaj.agrawal@enders.tch.harvard.edu.
¹⁶ The Manton Center for Orphan Disease Research, Boston Children's Hospital, Boston, MA, USA. pankaj.agrawal@enders.tch.harvard.edu.

^# Contributed equally.

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.

Abstract

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