Clinical chorioamnionitis at term X: microbiology, clinical signs, placental pathology, and neonatal bacteremia - implications for clinical care

J Perinat Med. 2021 Jan 26;49(3):275-298. doi: 10.1515/jpm-2020-0297. Print 2021 Mar 26.


Objectives: Clinical chorioamnionitis at term is considered the most common infection-related diagnosis in labor and delivery units worldwide. The syndrome affects 5-12% of all term pregnancies and is a leading cause of maternal morbidity and mortality as well as neonatal death and sepsis. The objectives of this study were to determine the (1) amniotic fluid microbiology using cultivation and molecular microbiologic techniques; (2) diagnostic accuracy of the clinical criteria used to identify patients with intra-amniotic infection; (3) relationship between acute inflammatory lesions of the placenta (maternal and fetal inflammatory responses) and amniotic fluid microbiology and inflammatory markers; and (4) frequency of neonatal bacteremia.

Methods: This retrospective cross-sectional study included 43 women with the diagnosis of clinical chorioamnionitis at term. The presence of microorganisms in the amniotic cavity was determined through the analysis of amniotic fluid samples by cultivation for aerobes, anaerobes, and genital mycoplasmas. A broad-range polymerase chain reaction coupled with electrospray ionization mass spectrometry was also used to detect bacteria, select viruses, and fungi. Intra-amniotic inflammation was defined as an elevated amniotic fluid interleukin-6 (IL-6) concentration ≥2.6 ng/mL.

Results: (1) Intra-amniotic infection (defined as the combination of microorganisms detected in amniotic fluid and an elevated IL-6 concentration) was present in 63% (27/43) of cases; (2) the most common microorganisms found in the amniotic fluid samples were Ureaplasma species, followed by Gardnerella vaginalis; (3) sterile intra-amniotic inflammation (elevated IL-6 in amniotic fluid but without detectable microorganisms) was present in 5% (2/43) of cases; (4) 26% of patients with the diagnosis of clinical chorioamnionitis had no evidence of intra-amniotic infection or intra-amniotic inflammation; (5) intra-amniotic infection was more common when the membranes were ruptured than when they were intact (78% [21/27] vs. 38% [6/16]; p=0.01); (6) the traditional criteria for the diagnosis of clinical chorioamnionitis had poor diagnostic performance in identifying proven intra-amniotic infection (overall accuracy, 40-58%); (7) neonatal bacteremia was diagnosed in 4.9% (2/41) of cases; and (8) a fetal inflammatory response defined as the presence of severe acute funisitis was observed in 33% (9/27) of cases.

Conclusions: Clinical chorioamnionitis at term, a syndrome that can result from intra-amniotic infection, was diagnosed in approximately 63% of cases and sterile intra-amniotic inflammation in 5% of cases. However, a substantial number of patients had no evidence of intra-amniotic infection or intra-amniotic inflammation. Evidence of the fetal inflammatory response syndrome was frequently present, but microorganisms were detected in only 4.9% of cases based on cultures of aerobic and anaerobic bacteria in neonatal blood.

Keywords: PCR/ESI-MS; amniotic fluid; funisitis; histologic chorioamnionitis; intra-amniotic infection; intra-amniotic inflammation; intrapartum fever; microbial invasion of the amniotic cavity (MIAC); neonatal bacteremia; sterile intra-amniotic inflammation.

MeSH terms

  • Adult
  • Amniotic Fluid* / immunology
  • Amniotic Fluid* / microbiology
  • Bacteremia* / diagnosis
  • Bacteremia* / etiology
  • Bacteremia* / microbiology
  • Bacteremia* / prevention & control
  • Biomarkers / analysis
  • Chorioamnionitis* / diagnosis
  • Chorioamnionitis* / epidemiology
  • Chorioamnionitis* / immunology
  • Chorioamnionitis* / microbiology
  • Cross-Sectional Studies
  • Female
  • Fetal Diseases / blood
  • Fetal Diseases / diagnosis
  • Gardnerella vaginalis / isolation & purification*
  • Humans
  • Infant, Newborn
  • Interleukin-6 / analysis*
  • Neonatal Sepsis / etiology
  • Neonatal Sepsis / prevention & control
  • Placenta / immunology
  • Placenta / pathology
  • Pregnancy
  • Systemic Inflammatory Response Syndrome / blood
  • Systemic Inflammatory Response Syndrome / diagnosis
  • Ureaplasma / isolation & purification*


  • Biomarkers
  • Interleukin-6