Application of Full-Spectrum Rapid Clinical Genome Sequencing Improves Diagnostic Rate and Clinical Outcomes in Critically Ill Infants in the China Neonatal Genomes Project.
Journal
Critical care medicine
ISSN: 1530-0293
Titre abrégé: Crit Care Med
Pays: United States
ID NLM: 0355501
Informations de publication
Date de publication:
01 10 2021
01 10 2021
Historique:
pubmed:
4
5
2021
medline:
5
10
2021
entrez:
3
5
2021
Statut:
ppublish
Résumé
To determine the diagnostic and clinical utility of trio-rapid genome sequencing in critically ill infants. In this prospective study, samples from critically ill infants were analyzed using both proband-only clinical exome sequencing and trio-rapid genome sequencing (proband and biological parents). The study occurred between April 2019 and December 2019. Thirteen member hospitals of the China Neonatal Genomes Project spanning 10 provinces were involved. Critically ill infants (n = 202), from birth up until 13 months of life were enrolled based on eligibility criteria (e.g., CNS anomaly, complex congenital heart disease, evidence of metabolic disease, recurrent severe infection, suspected immune deficiency, and multiple malformations). None. Of the 202 participants, neuromuscular (45%), respiratory (22%), and immunologic/infectious (18%) were the most commonly observed phenotypes. The diagnostic yield of trio-rapid genome sequencing was higher than that of proband-only clinical exome sequencing (36.6% [95% CI, 30.1-43.7%] vs 20.3% [95% CI, 15.1-26.6%], respectively; p = 0.0004), and the average turnaround time for trio-rapid genome sequencing (median: 7 d) was faster than that of proband-only clinical exome sequencing (median: 20 d) (p < 2.2 × 10-16). The metagenomic analysis identified pathogenic or likely pathogenic microbes in six infants with symptoms of sepsis, and these results guided the antibiotic treatment strategy. Sixteen infants (21.6%) experienced a change in clinical management following trio-rapid genome sequencing diagnosis, and 24 infants (32.4%) were referred to a new subspecialist. Trio-rapid genome sequencing provided higher diagnostic yield in a shorter period of time in this cohort of critically ill infants compared with proband-only clinical exome sequencing. Precise and fast molecular diagnosis can alter medical management and positively impact patient outcomes.
Identifiants
pubmed: 33935161
doi: 10.1097/CCM.0000000000005052
pii: 00003246-202110000-00007
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1674-1683Commentaires et corrections
Type : CommentIn
Informations de copyright
Copyright © 2021 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.
Déclaration de conflit d'intérêts
The authors have disclosed that they do not have any potential conflicts of interest.
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