Rapid diagnosis of intra-amniotic infection using nanopore-based sequencing

J Perinat Med. 2022 Dec 13;51(6):769-774. doi: 10.1515/jpm-2022-0504. Print 2023 Jul 26.

Abstract

Objectives: Early diagnosis and treatment of intra-amniotic infection is crucial. Rapid pathogen identification allows for a definite diagnosis and enables proper management. We determined whether the 16S amplicon sequencing performed by a nanopore sequencing technique make possible rapid bacterial identification at the species level in intra-amniotic infection.

Methods: Five cases of confirmed intra-amniotic infection, determined by either cultivation or 16S rDNA polymerase chain reaction (PCR) Sanger sequencing, and 10 cases of women who underwent mid-trimester genetic amniocentesis were included. DNA was extracted from amniotic fluid and PCR was performed on the full-length 16S rDNA. Nanopore sequencing was performed. The results derived from nanopore sequencing were compared with those derived from cultivation and Sanger sequencing methods.

Results: Bacteria were successfully detected from amniotic fluid using nanopore sequencing in all cases of intra-amniotic infection. Nanopore sequencing identified additional bacterial species and polymicrobial infections. All patients who underwent a mid-trimester amniocentesis had negative cultures, negative 16S PCR Sanger sequencing and nanopore sequencing. Identification of the microorganisms using nanopore sequencing technique at the bacterial species level was achieved within 5-9 h from DNA extraction.

Conclusions: This is the first study demonstrating that the nanopore sequencing technique is capable of rapid diagnosis of intra-amniotic infection using fresh amniotic fluid samples.

Keywords: 16S rDNA; Sanger sequencing; amniocentesis; amniotic fluid; bacteria; infection; intra-amniotic inflammation; long-read sequencing; microorganism; preterm labor.

MeSH terms

  • Amniocentesis
  • Amniotic Fluid / microbiology
  • Bacteria
  • Chorioamnionitis* / diagnosis
  • Chorioamnionitis* / microbiology
  • Female
  • Humans
  • Nanopore Sequencing*
  • Nanopores*
  • Pregnancy