Clinical chorioamnionitis at term II: the intra-amniotic inflammatory response

Abstract

Objective Recent studies indicate that clinical chorioamnionitis is a heterogeneous condition and only approximately one-half of the patients have bacteria in the amniotic cavity, which is often associated with intra-amniotic inflammation. The objective of this study is to characterize the nature of the inflammatory response within the amniotic cavity in patients with clinical chorioamnionitis at term according to the presence or absence of 1) bacteria in the amniotic cavity and 2) intra-amniotic inflammation. Materials and methods A retrospective cross-sectional case-control study was conducted to examine cytokine and chemokine concentrations in the amniotic fluid (AF). Cases consisted of women with clinical chorioamnionitis at term (n = 45). Controls were women with uncomplicated pregnancies at term who did not have intra-amniotic inflammation and were in labor (n = 24). Women with clinical chorioamnionitis were classified according to the results of AF cultures, broad-range polymerase chain reaction coupled with electrospray ionization mass spectrometry, and AF concentration of interleukin-6 (IL-6) into those: 1) without intra-amniotic inflammation, 2) with microbial-associated intra-amniotic inflammation, and 3) with intra-amniotic inflammation without detectable bacteria. The AF concentrations of 29 cytokines/chemokines were determined using sensitive and specific V-PLEX immunoassays. Results 1) The AF concentrations of pro- and anti-inflammatory cytokines/chemokines such as interferon gamma (IFN-γ), tumor necrosis factor alpha (TNF-α), interleukin-4 (IL-4), macrophage inflammatory protein-1 beta (MIP-1β), and interleukin-8 (IL-8) (except Eotaxin-3) were significantly higher in women with clinical chorioamnionitis at term than in controls (term labor without intra-amniotic inflammation); 2) patients with microbial-associated intra-amniotic inflammation, and those with intra-amniotic inflammation without detectable bacteria, had a substantially different expression of cytokines and chemokines in AF compared to patients with spontaneous labor without intra-amniotic inflammation. However, no difference could be detected in the pattern of the intra-amniotic inflammatory response between patients with intra-amniotic inflammation with and without detectable bacteria; and 3) in patients with clinical chorioamnionitis at term but without intra-amniotic inflammation, the behavior of cytokines and chemokines in the AF was similar to those in spontaneous labor at term. Conclusions Patients with clinical chorioamnionitis who had microbial-associated intra-amniotic inflammation or intra-amniotic inflammation without detectable bacteria had a substantial upregulation of the intra-amniotic inflammatory response assessed by amniotic fluid concentrations of cytokines. A subset of patients with term clinical chorioamnionitis does not have intra-amniotic infection/inflammation, as demonstrated by elevated AF concentrations of inflammation-related proteins, when compared to women in term labor with uncomplicated pregnan...

The Human Ureaplasma Species as Causative Agents of Chorioamnionitis

“…Several studies have investigated the diagnostic value of amniotic fluid and maternal serum biomarkers for the detection of chorioamnionitis in pregnant women undergoing amniocentesis. Elevated inflammatory markers such as interleukin 6 (IL-6), IL-8, matrix metalloproteinase 8 (MMP-8), MMP-9, and monocyte chemotactic proteins within amniotic fluid are positive predictors of intra-amniotic inflammation and/or clinical chorioamnionitis (15)(16)(17)(18)(19)(20)(21); however, these markers may have poor positive predictive values for the detection of subclinical, histologic chorioamnionitis and may be variably expressed within the amniotic fluid and fetal membranes during chorioamnionitis (22)(23)(24). Recently, Liu et al (25) reported that surface-enhanced laser desorption ionization-time of flight mass spectrometry (SELDI-TOF-MS) for the detection of human neutrophil defensin 1 (HNP-1) and HNP-2 and calgranulins A and C within amniotic fluid was highly accurate for the diagnosis of subclinical chorioamnionitis, but further studies with larger patient cohorts are required to validate these findings.…”

Neutrophil Extracellular Traps in the Amniotic Cavity of Women with Intra-Amniotic Infection: A New Mechanism of Host Defense

“…[11][12][13][14][15] Systemic maternal inflammation results in clinical chorioamnionitis, which refers to the presence of maternal fever associated with clinical signs (ie, foul-smelling discharge, uterine tenderness, and maternal and fetal tachycardia) as well as laboratory abnormalities such as leukocytosis. 16,17 In humans, intra-amniotic infection is associated with a local inflammatory response, 18 which is characterized by an increased amniotic fluid white blood cell (WBC) count [19][20][21][22][23] and elevated concentrations of inflammatory mediators, such as cytokines 18,24 and lipids (eg, prostaglandins). [25][26][27][28][29][30][31][32][33][34][35][36][37][38] In nonhuman primates, intra-amniotic infection also results in a local inflammatory response.…”

Twenty-four percent of patients with clinical chorioamnionitis in preterm gestations have no evidence of either culture-proven intraamniotic infection or intraamniotic inflammation

“…However, there is a paucity of studies done in the context of preterm gestation. Recent evidence derived from studies on clinical chorioamnionitis at term, as well as some early studies in preterm labor with intact membranes, suggests that a fraction of patients with this diagnosis have neither intra-amniotic infection nor intra-amniotic inflammation [45, 46]. In other words, some patients with preterm clinical chorioamnionitis appear to have a false-positive diagnosis.…”