Clinical impact of plasma cell-free DNA metagenomic next-generation sequencing testing in neonatal and infant populations.

Objective: Plasma cell-free DNA metagenomic next-generation sequencing (cf-mNGS) tests offer the ability to detect microbial DNA from a single blood sample; however, its clinical utility in infants remains incompletely characterized. This study aims to evaluate the real-world clinical impact of plasma cf-mNGS testing in the neonatal and infant population. Design: Retrospective cohort study. Setting: A large academic medical center in Los Angeles, California. Patients: 95 hospitalized neonates and infants (≤12 months of age). Methods: Clinical impact was adjudicated using predefined criteria. Results: We reviewed 95 unique plasma cf-mNGS testing episodes performed between February 2018 and August 2024. The mean age at testing was 4.2 months (SD, 3.8). All patients were hospitalized in the intensive care unit at the time of testing. Tests were most frequently performed for evaluation of "culture-negative sepsis" (30.5%), unexplained hospital-onset fevers (25.3%), and multiorgan failure (21.1%). Plasma cf-mNGS testing did not influence clinical management in the majority of cases (86.3%; 95% CI, 78.0%-91.8%). Positive clinical impact occurred in 5/95 cases (5.3%; 95% CI, 2.3%-11.7%), where plasma mNGS results assisting in antimicrobial de-escalation/discontinuation or earlier/new diagnoses. Negative clinical impact occurred in 4/95 cases (4.2%; 95% CI, 1.6%-10.3%), with plasma cf-mNGS results prompting unnecessary investigations or treatment. Conclusions: Our findings do not support the routine use of plasma cf-mNGS testing for indications including "culture-negative sepsis" in neonatal and infant populations.