Detection of microbial cell-free DNA in maternal and umbilical cord plasma in patients with chorioamnionitis using next generation sequencing

Abstract

Background Chorioamnionitis has been linked to spontaneous preterm labor and complications such as neonatal sepsis. We hypothesized that microbial cell-free (cf) DNA would be detectable in maternal plasma in patients with chorioamnionitis and could be the basis for a non-invasive method to detect fetal exposure to microorganisms. Objective The purpose of this study was to determine whether next generation sequencing could detect microbial cfDNA in maternal plasma in patients with chorioamnionitis. Study design Maternal plasma (n = 94) and umbilical cord plasma (n = 120) were collected during delivery at gestational age 28-41 weeks. cfDNA was extracted and sequenced. Umbilical cord plasma samples with evidence of contamination were excluded. The prevalence of microorganisms previously implicated in choriomanionitis, neonatal sepsis and intra-amniotic infections, as described in the literature, were examined to determine if there was enrichment of these microorganisms in this cohort. Specific microbial cfDNA associated with chorioamnionitis was first detected in umbilical cord plasma and confirmed in the matched maternal plasma samples (n = 77 matched pairs) among 14 cases of histologically confirmed

A global point prevalence survey of antimicrobial use in neonatal intensive care units: The no-more-antibiotics and resistance (NO-MAS-R) study

“…blood, urine, cerebrospinal fluid) before initiation of antibiotic therapy, obtaining sufficient quantity of blood for culture, and investigation of viral and fungal etiologies should allow comfort in discontinuation of antibiotics if cultures are sterile [49] , [50] , [51] , [52] , [53] , [54] , [55] , [56] , [57] , [58] . Ultimately, genomic methods for detection of microbial pathogens in body fluids may allow optimal identification of infected infants and more appropriate use of antimicrobial therapy [ 59 , 60 ].…”

Circulating Cell-Free Nucleic Acids: Main Characteristics and Clinical Application

“…Witt et al reported the detection of relevant microbial cf-DNA in maternal plasma of patients with chorioamnionitis. Their results may contribute to the development of a non-invasive assay for the detection of fetal exposure to microorganisms that would be useful to reduce complications from early neonatal sepsis [ 64 ]. Apart from blood, other body fluids may also contain microbial cf-DNA that may have clinical value.…”

Next-generation sequencing of microbial cell-free DNA for rapid noninvasive diagnosis of infectious diseases in immunocompromised hosts

“…Recent reports indicate that NGS measuring microbial cfDNA is useful in the diagnosis of cases of Streptococcus pneumoniae-related hemolytic uremic syndrome, Coxiella burnetii endocarditis, invasive Mycobacterium chimaera infection, Nocardia cyriacigeorgica pneumonia, Capnocytophaga canimorsus sepsis, M. tuberculosis complex and M. haemophilum infections, M. bovis aortitis; Candida spp., Aspergillus spp., non-Aspergillus molds invasive infections; Pneumocystis jirovecii pneumonia (PJP), Toxoplasma gondii infection and chorioamnionitis, among others 24,[26][27][28][29][30][31][32][33] . Among 21 patients with culture-positive infective endocarditis, cfDNA NGS identified the same organism as blood cultures in 20 patients (95% sensitivity) and additionally identified Enterococcus faecalis in one out of the three patients with definitive culture-negative endocarditis 34 .…”