Blood pH and gases in fetuses in preterm labor with and without systemic inflammatory response syndrome

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Objective Microbial invasion of the fetus due to intra-amniotic infection can lead to a systemic inflammatory response characterized by elevated concentrations of cytokines in the umbilical cord plasma/serum. Clinical chorioamnionitis represents the maternal syndrome often associated with intra-amniotic infection, although other causes of this syndrome have been recently described. The objective of this study was to characterize the umbilical cord plasma cytokine profile in neonates born to mothers with clinical chorioamnionitis at term, according to the presence or absence of bacteria and/or intra-amniotic inflammation. Materials and Methods A cross-sectional study was conducted, including patients with clinical chorioamnionitis at term (n=38; cases) and those with spontaneous term labor without clinical chorioamnionitis (n=77; controls). Women with clinical chorioamnionitis were classified according to the results of amniotic fluid culture, broad-range polymerase chain reaction coupled with electrospray ionization mass spectrometry (PCR/ESI-MS), and amniotic fluid interleukin (IL)-6 concentrations into three groups: 1) no intra-amniotic inflammation; 2) intra-amniotic inflammation without detectable microorganisms; or 3) microbial-associated intra-amniotic inflammation. Fetal inflammatory response syndrome (FIRS) was defined as an umbilical cord plasma IL-6 concentration >11 pg/mL. The umbilical cord plasma concentrations of 29 cytokines were determined with sensitive and specific V-PLEX immunoassays. Nonparametric statistical methods were used for analysis, adjusting for a false discovery rate of 5%. Results 1) Neonates born to mothers with clinical chorioamnionitis at term (considered in toto) had significantly higher median umbilical cord plasma concentrations of IL-6, IL-12p70, IL-16, IL-13, IL-4, IL-10, and IL-8, but significantly lower interferon gamma (IFN-γ) and tumor necrosis factor alpha (TNF-α) concentrations than neonates born to mothers with spontaneous term labor without clinical chorioamnionitis; 2) neonates born to mothers with clinical chorioamnionitis at term but without intra-amniotic inflammation had higher concentrations of IL-6, IL-12p70, IL-13, IL-4, IL-5, and IL-8 but lower IFN-γ than neonates not exposed to clinical chorioamnionitis, suggesting that maternal fever in the absence of intra-amniotic inflammation leads to a change in the fetal cytokine network; 3) there were significant, positive correlations between maternal and umbilical cord plasma IL-6 and IL-8 concentrations (IL-6: Spearman’s correlation=0.53; p<0.001; IL-8: Spearman’s correlation=0.42; p<0.001), consistent with placental transfer of cytokines; 4) an elevated fetal plasma IL-6 (> 11pg/mL), the diagnostic criterion for FIRS, was present in 21% of cases (8/38), and all of these neonates were born to mothers with proven intra-amniotic infection; and 5) FIRS was associated with a high concentration of umbilical cord plasma IL-8, IL-10, and monocyte chemoattractant protein (MCP)-1. Conclusions Neonates born to mothe...

Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 99%

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Clinical chorioamnionitis at term V: umbilical cord plasma cytokine profile in the context of a systemic maternal inflammatory response

Romero

Chaemsaithong

Docheva

et al. 2015

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“…FIRS was diagnosed when the umbilical cord plasma IL-6 concentration was ≥11 pg/ml [178, 187–189, 215–217]. …”

Section: Methodsmentioning

confidence: 99%

Clinical chorioamnionitis at term VI: acute chorioamnionitis and funisitis according to the presence or absence of microorganisms and inflammation in the amniotic cavity

Romero¹,

Chaemsaithong²,

Docheva³

et al. 2015

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Objective Neonates born to mothers with clinical chorioamnionitis at term are at an increased risk of infection. Acute subchorionitis, chorioamnionitis, and funisitis are considered placental histologic features consistent with acute inflammation according to the Society for Pediatric Pathology. The objectives of this study were to examine the performance of placental histologic features in the identification of: 1) microbial-associated intra-amniotic inflammation (intra-amniotic infection); and 2) a fetal inflammatory response syndrome (FIRS). Methods and Materials This retrospective cohort study included women with the diagnosis of clinical chorioamnionitis at term (n=45), who underwent an amniocentesis to determine: 1) the presence of microorganisms using both cultivation and molecular biologic techniques [polymerase chain reaction (PCR) with broad range primers]; and 2) interleukin (IL)-6 concentrations by enzyme-linked immunosorbent assay (ELISA). The diagnostic performance (sensitivity, specificity, accuracy, and likelihood ratios) of placental histologic features consistent with acute inflammation was determined for the identification of microbial-associated intra-amniotic inflammation and FIRS. Results 1) The presence of acute histologic chorioamnionitis and funisitis was associated with the presence of proven intra-amniotic infection assessed by amniotic fluid analysis; 2) funisitis was also associated with the presence of FIRS; 3) the negative predictive value of acute funisitis ≥ stage 2 for the identification of neonates born to mothers with intra-amniotic infection was less than 50%, and therefore, suboptimal to exclude fetal exposure to bacteria in the amniotic cavity; and 4) acute funisitis ≥ stage 2 had a negative predictive value of 86.8% for the identification of FIRS in a population with a prevalence of 20%. Conclusion Acute histologic chorioamnionitis and funisitis are associated with intra-amniotic infection and the presence of FIRS. However, current pathologic methods have limitations in the identification of the fetus exposed to microorganisms present in the amniotic cavity. Further studies are required to determine whether molecular markers can enhance the performance of placental pathology in the identification of neonates at risk for neonatal sepsis.

“…Microorganisms and their products can initiate an inflammatory response by the engagement of pattern recognition receptors [163,172,186–200] and the production of cytokines [112,122,151,201–224], chemokines [213,215,216,219,223,225–244], prostaglandins [245–261] and proteases [142,145,262–277]. If microorganisms in the amniotic cavity reach the fetus, this can result in a fetal systemic inflammatory response [278,279], which is associated with multi-organ involvement [141,278,280–289], and preterm delivery [290]. …”

Section: Discussionmentioning

confidence: 99%

Clinical chorioamnionitis at term IV: the maternal plasma cytokine profile

Romero¹,

Chaemsaithong²,

Docheva³

et al. 2015

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Introduction Fever is a major criterion for clinical chorioamnionitis; yet, many patients with intrapartum fever do not have demonstrable intra-amniotic infection. Some cytokines, such as interleukin (IL)-1, IL-6, interferon-gamma (IFN-γ) and tumor necrosis factor-alpha (TNF-α) can induce a fever. The objective of this study was to determine whether maternal plasma concentrations of cytokines could be of value in the identification of patients with the diagnosis of clinical chorioamnionitis at term who have microbial-associated intra-amniotic inflammation. Methods A retrospective cross-sectional study was conducted, including patients with clinical chorioamnionitis at term (n=41; cases) and women in spontaneous labor at term without clinical chorioamnionitis (n=77; controls). Women with clinical chorioamnionitis were classified into three groups according to the results of amniotic fluid cultures, broad-range polymerase chain reaction coupled with electrospray ionization mass spectrometry (PCR/ESI-MS), and amniotic fluid IL-6 concentrations: 1) no intra-amniotic inflammation; 2) intra-amniotic inflammation without detectable microorganisms; or 3) microbial-associated intra-amniotic inflammation. The maternal plasma concentrations of 29 cytokines were determined with sensitive and specific V-PLEX immunoassays. Nonparametric statistical methods were used for analysis, adjusting for a false discovery rate of 5%. Results 1) The maternal plasma concentrations of pyrogenic cytokines (IL-1β, IL-2, IL-6, IFN-γ and TNF-α) were significantly higher in patients with clinical chorioamnionitis at term than in those with spontaneous term labor without clinical chorioamnionitis; 2) the maternal plasma concentrations of cytokines were not significantly different among the three subgroups of patients with clinical chorioamnionitis (intra-amniotic inflammation with and without detectable bacteria and those without intra-amniotic inflammation); and 3) among women with the diagnosis of clinical chorioamnionitis, but without evidence of intra-amniotic inflammation, the maternal plasma concentrations of pyrogenic cytokines were significantly higher than in patients with spontaneous labor at term. These observations suggest that the fever can be mediated by increased circulating concentrations of these cytokines, despite the absence of a local intra-amniotic inflammatory response. Conclusions 1) The maternal plasma concentrations of pyrogenic cytokines (e.g. IL-1β, IL-2, IL-6, IFN-γ and TNF-α) are higher in patients with intra-partum fever and the diagnosis of clinical chorioamnionitis at term than in those in spontaneous labor at term without a fever; and 2) maternal plasma cytokine concentrations have limited value in the identification of patients with bacteria in the amniotic cavity. Accurate assessment of the presence of intra-amniotic infection requires amniotic fluid analysis.