Intra-Amniotic Infection and Sterile Intra-Amniotic Inflammation in Cervical Insufficiency with Prolapsed Fetal Membranes: Clinical Implications

Chalupska, Martina; Kacerovský, Marian; Stráník, Jaroslav; Gregor, Miroslav; Malý, Jan; Jacobsson, Bo; Musilová, Ivana

doi:10.1159/000512102

Cited by 31 publications

(52 citation statements)

References 75 publications

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“…In women with cervical insufficiency, subclinical intra-amniotic infection/inflammation has been consistently reported as a prognostic factor for outcome of rescue cerclage [7,12,17,18]. This is in agreement with the current study wherein elevated levels of inflammatory markers (IL-8, MIP-1α, and S100 A8/A9) in AF are observed.…”

Section: Discussionsupporting

confidence: 92%

Antibody microarray analysis of the amniotic fluid proteome for predicting the outcome of rescue cerclage in patients with cervical insufficiency

et al. 2021

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Little is known about the biomarkers that can identify patient candidates suitable for rescue cerclage procedure. The purpose of the study was to identify novel biomarkers in amniotic fluid (AF) that can predict the outcome of rescue cerclage in patients with cervical insufficiency by using an antibody microarray. This case-control study was conducted using AF samples collected from singleton pregnant women who underwent rescue cerclage following a diagnosis of cervical insufficiency (19–25 weeks). Patients were divided into case (n=20) and control (n=20) groups based on the occurrence of spontaneous preterm delivery (SPTD) at <34 weeks of gestation after cerclage placement. The AF proteomes were analyzed using an antibody microarray for biomarker discovery work. Ten candidate biomarkers of interest were validated by ELISA. Thirty-one of the molecules studied showed significant intergroup differences (≥ 2-fold change in signal intensity). Validation by ELISA confirmed significantly higher levels of APRIL, S100 A8/A9, TIMP-1, MIP-1α, and IL-8 in women who had SPTD at <34 weeks. Of these, AF S100 A8/A9 and TIMP-1 levels were independent of other potentially confounding factors (e.g., cervical dilatation). S100 A8/A9 had the highest area under the curve at 0.857. Using protein–antibody microarray technology, we identified differentially expressed proteins and several novel biomarkers (APRIL, IL-8, MIP-1α, S100 A8/A9, and TIMP-1) in AF from women who had SPTB at <34 weeks after cerclage for cervical insufficiency. These data can provide an insight into the molecular mechanisms underlying SPTD after rescue cerclage in patients with cervical insufficiency.

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Section: Discussionsupporting

confidence: 92%

Antibody microarray analysis of the amniotic fluid proteome for predicting the outcome of rescue cerclage in patients with cervical insufficiency

et al. 2021

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“…IAI and/or MIAC, as well as advanced cervical dilation at presentation, have been consistently reported as the most important risk factors for poor pregnancy outcomes of emergency cerclage for CI [ 4 – 6 , 14 , 39 – 42 ]. In particular, sterile IAI is a common phenotype of IAI observed in pregnancies with CI with protruding fetal membranes [ 4 , 7 ]. It is found in over 50% of these pregnancies and is associated with worse outcomes in this context [ 4 , 7 , 35 , 43 ].…”

Section: Discussionmentioning

confidence: 99%

“…These proteins were chosen for the study because they are important regulators of inflammation, angiogenesis, and extracellular matrix–related and immune responses ( https://www.uniprot.org/ ); they are potential AF biomarkers for identifying patients with acute CI at high risk of SPTD after emergency cerclage based on our previous studies and other reports [ 13 , 21 , 28 – 34 ]; little information is currently available regarding their altered expression in AF associated with poor pregnancy outcomes after emergency cerclage; and an appropriate ELISA kit was commercially available. IL-6 levels were assayed in the AF for comparison with potential biomarkers assessed in this study, as it is a prototype marker for rescue cerclage failure [ 4 , 6 , 17 , 35 ]. The AF dilutions used and the working range for each ELISA kit are described in detail in the Supplementary information.…”

Section: Methodsmentioning

confidence: 99%

“…Acute CI is frequently associated with subclinical microbial invasion of the amniotic cavity (MIAC)/intra-amniotic inflammation (IAI), which is observed in more than half of such cases [ 4 – 7 ]. In particular, an emergency cervical cerclage has not been traditionally considered helpful in women with acute CI who were exposed to MIAC/IAI, since such patients demonstrate spontaneous preterm labor (PTL), premature ruptured membranes, or clinical chorioamnionitis [ 5 , 7 – 10 ].…”

Section: Introductionmentioning

confidence: 99%

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Prediction of emergency cerclage outcomes in women with cervical insufficiency: The role of inflammatory, angiogenic, and extracellular matrix-related proteins in amniotic fluid

et al. 2022

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Objective We aimed to determine whether various novel inflammatory, angiogenic, and extracellular matrix-related mediators in amniotic fluid (AF) can independently predict emergency cerclage outcomes in women with acute cervical insufficiency (CI). Methods This was a retrospective cohort study conducted among 50 singleton pregnant women (18–25 weeks) who underwent emergency cerclage for CI and were subjected to amniocentesis. The AF samples were assayed for endoglin, endostatin, haptoglobin, insulin-like growth factor-binding protein (IGFBP)-3, -4, kallistatin, lumican, macrophage colony-stimulating factor (M-CSF), pentraxin 3, p-selectin, receptor for advanced glycation end products (RAGE), resistin, transforming growth factor beta-induced (TGFBI), and vitamin D-binding protein (VDBP) levels. Interleukin (IL)-6 levels in the AF were also measured for comparison with potential biomarkers assessed in this study. The primary endpoint was spontaneous preterm delivery (SPTD) at <34 weeks following emergency cerclage. Results The AF levels of pentraxin 3, RAGE, and resistin were significantly higher in women who had SPTD at <34 weeks after cerclage placement (pentraxin-3: P = 0.003; RAGE: P = 0.041; and resistin; P = 0.002). In multivariate analysis, elevated AF levels of pentraxin 3 (P = 0.007) and resistin (P = 0.006), but not those of RAGE (P = 0.069), were independently associated with the occurrence of SPTD at <34 weeks after cerclage, following adjustment for baseline clinical variables (e.g., cervical dilation). The area under the curve (AUC) values of AF pentraxin 3, RAGE, and resistin for the prediction of SPTD at <34 weeks were 0.749, 0.669, and 0.770, respectively, which were similar to those of AF IL-6. However, in univariate analyses, no differences in the AF levels of endoglin, endostatin, haptoglobin, IGFBP-3, IGFBP-4, kallistatin, lumican, p-selectin, TGFBI, and VDBP were found to be associated with SPTD at <34 weeks after cerclage placement. Conclusions In women with acute CI, the AF levels of pentraxin 3, RAGE, and resistin could be useful novel biomarkers for predicting SPTD following emergency cerclage. However, the clinical utility of these new biomarkers should be validated in larger multicenter studies.

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“…Data regarding short-term neonatal morbidity were reviewed for all the newborns. Definitions of selected aspects of short-term neonatal morbidity have been described in our previous publications 20 , 45 .…”

Section: Methodsmentioning

confidence: 99%

Clinical characteristics of colonization of the amniotic cavity in women with preterm prelabor rupture of membranes, a retrospective study

Kacerovský

Stráník

Matulova

et al. 2022

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To determine the main clinical characteristics of preterm prelabor rupture of membranes (PPROM) complicated by colonization of the amniotic cavity (microbial invasion of the amniotic cavity without intra-amniotic inflammation). A total of 302 women with PPROM were included. Transabdominal amniocentesis was performed and amniotic fluid was assessed. Based of microbial invasion of the amniotic cavity and intra-amniotic inflammation (interleukin-6 ≥ 3000 pg/mL), the women were divided into following groups: intra-amniotic infection, sterile intra-amniotic inflammation, colonization of the amniotic cavity, and negative amniotic fluid. Colonization was found in 11% (32/302) of the women. The most common bacteria identified in the amniotic fluid were Ureaplasma spp. with a lower burden than those with intra-amniotic infection (p = 0.03). The intensity of intra-amniotic inflammatory response measured by interleukin-6 was higher in women with colonization than in those with negative amniotic fluid (medians: 961 pg/mL vs. 616 pg/mL; p = 0.04). Women with colonization had higher rates of acute inflammatory placental lesions than those with negative amniotic fluid. In PPROM, colonization, caused mainly by microorganisms from the lower genital tract, might represent an early stage of microbial invasion of the amniotic cavity with a weak intra-amniotic inflammatory response.

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Intra-Amniotic Infection and Sterile Intra-Amniotic Inflammation in Cervical Insufficiency with Prolapsed Fetal Membranes: Clinical Implications

Cited by 31 publications

References 75 publications

Antibody microarray analysis of the amniotic fluid proteome for predicting the outcome of rescue cerclage in patients with cervical insufficiency

Antibody microarray analysis of the amniotic fluid proteome for predicting the outcome of rescue cerclage in patients with cervical insufficiency

Prediction of emergency cerclage outcomes in women with cervical insufficiency: The role of inflammatory, angiogenic, and extracellular matrix-related proteins in amniotic fluid

Clinical characteristics of colonization of the amniotic cavity in women with preterm prelabor rupture of membranes, a retrospective study

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