| 1. |
- Aberšek, Nina, et al.
(author)
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Characterizing of intra-amniotic inflammatory changes associated with chronic inflammation in the placenta marked by elevated amniotic fluid interferon gamma-induced protein 10 (IP-10) in pregnancies complicated by preterm prelabor rupture of membranes.
- 2024
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In: European journal of obstetrics, gynecology, and reproductive biology. - 1872-7654. ; 296, s. 292-298
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Journal article (peer-reviewed)abstract
- This study aimed to determine the occurrence of intra-amniotic inflammatory changes associated with chronic inflammation in the placenta, marked by elevated levels of interferon gamma-induced protein 10 (IP-10) (≥2200pg/mL) in the amniotic fluid of women with preterm prelabor rupture of membranes (PPROM). Specifically, the study investigated whether these intra-amniotic inflammatory changes were more common in women with microbial invasion of amniotic cavity (MIAC) and intra-amniotic inflammation (IAI), as indicated by increased amniotic fluid interleukin (IL)-6 concentration (≥3000pg/mL).A cohort of 114 women with singleton pregnancies complicated by PPROM between 24+0 and 36+6 weeks of gestation were included. Amniotic fluid samples were obtained via amniocentesis upon admission. MIAC diagnosis involved aerobic and anaerobic cultures, as well as polymerase chain reaction (PCR) analysis of the amniotic fluid. Immunoassay tests and enzyme-linked immunosorbent assay (ELISA) were used to determine IL-6 and IP-10 concentrations, respectively.Among the participants, 19.3% and 15.8% had MIAC and IAI, respectively. The occurrence of intra-amniotic inflammatory changes associated with chronic inflammation in the placenta was similar between women with and without MIAC (25% vs. 40.9%, p=0.136, adjusted p=0.213). The rate of intra-amniotic inflammatory changes associated with chronic inflammation in the placenta was significantly higher in women with IAI compared to those without, after adjusting for gestational age at sampling (55.6% vs. 22.9%, p=0.005, adjusted p=0.011).This study revealed comparable rates of intra-amniotic inflammatory changes associated with chronic inflammation in the placenta in women with and without MIAC, but a higher prevalence of intra-amniotic inflammatory changes associated with chronic inflammation in the placenta in women with IAI. These findings suggest involvement of chronic inflammation even in women with PPROM with acute intra-amniotic inflammation.
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| 2. |
- Cobo, Teresa, et al.
(author)
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A Rapid Amniotic Fluid Interleukin-6 Assessment for the Identification of Intra-Amniotic Inflammation in Women with Preterm Labor and Intact Membranes.
- 2021
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In: Fetal diagnosis and therapy. - : S. Karger AG. - 1421-9964 .- 1015-3837. ; 48:5, s. 327-332
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Journal article (peer-reviewed)abstract
- A multivariable predictive model has recently been developed with good accuracy to predict spontaneous preterm delivery within 7 days in women with preterm labor (PTL) and intact membranes. However, this model measures amniotic fluid (AF) interleukin (IL)-6 concentrations using the ELISA method, thereby limiting clinical implementation. The main objectives of this study were to validate the automated immunoassay as a quantitative method to measure AF IL-6 in women with PTL and to evaluate the diagnostic performance of AF IL-6 alone and as part of a multivariable predictive model to predict spontaneous delivery in 7 days with this automated method.This is a retrospective observational study in women with PTL below 34 weeks who underwent amniocentesis to rule out microbial invasion of the amniotic cavity. Women with clinical signs of chorioamnionitis, cervical length measurement at admission >5th centile, maternal age <18 years, and no consent to perform amniocentesis for this indication were excluded. The local Institutional Review Boards approved the study (HCB/2019/0940). Analysis of AF IL-6 Concentrations: AF IL-6 concentrations were measured using an automated Cobas e602 electrochemiluminescence immunoanalyzer and Human IL-6 Quantikine ELISA kit.Of the entire study group (n = 100), 38 women spontaneously delivered within 7 days after admission. Both laboratory methods showed good agreement (intraclass correlation coefficient: 0.937 (95% confidence interval [CI] 0.908-0.957); p < 0.001). Diagnostic performance of AF IL-6 to predict spontaneous delivery within 7 days when it was included in the multivariable predictive model showed an area under the receiver operating characteristic curve of 0.894 (95% CI 0.799-0.955), sensitivity of 97%, specificity of 74%, positive predictive value of 73%, negative predictive value of 97%, positive likelihood ratio (LR) of 3.7, and negative LR of 0.045.While both analytical methods were comparable for measuring AF IL-6 concentrations in women with PTL, the Cobas immunoanalyzer provided rapid diagnosis of intra-amniotic inflammation within minutes. The predictive model showed a good diagnostic performance to target women at high risk of spontaneous delivery within 7 days.
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| 3. |
- Kacerovsky, Marian, et al.
(author)
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Amniotic fluid glucose level in PPROM pregnancies: a glance at the old friend.
- 2020
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In: The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians. - : Informa UK Limited. - 1476-4954. ; 35:12, s. 2247-2259
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Journal article (peer-reviewed)abstract
- Introduction: To determine the amniotic fluid glucose levels in pregnancies complicated by preterm prelabor rupture of membranes (PPROM) based on the presence of microbial invasion of the amniotic cavity and/or intra-amniotic inflammation.Methods of Study: A total of 142 women with singleton pregnancies complicated by PPROM between gestational ages 24+0 and 36+6weeks were included. Amniocentesis was performed at the time of admission. The assessments of microbial invasion of the amniotic cavity (using both cultivation and non-cultivation techniques) and intra-amniotic inflammation (amniotic fluid interleukin-6 levels ≥ 3000pg/mL) were performed on all the women. Based on the presence of microbial invasion of the amniotic cavity and/or intra-amniotic inflammation, the women were further categorized into the subgroups: (i) intra-amniotic infection (the presence of both microbial invasion of the amniotic cavity and intra-amniotic inflammation); (ii) sterile intra-amniotic inflammation (the presence of intra-amniotic inflammation without microbial invasion of the amniotic cavity); (iii) colonization (the presence of microbial invasion of the amniotic cavity without intra-amniotic inflammation); and (iv) negative amniotic fluid (the absence of either microbial invasion of the amniotic cavity or intra-amniotic inflammation). Amniotic fluid glucose levels were assessed using enzymatic reference method with hexokinase.Results: There was a difference in the amniotic fluid glucose levels among the women with intra-amniotic infection, sterile intra-amniotic inflammation, colonization, and those with negative amniotic fluid (p<.0001). No difference was found in the amniotic fluid glucose levels between women with intra-amniotic infection and those with sterile intra-amniotic inflammation [infection: median 11.6mg/dL (0.7mmol/L) vs. sterile: median 6.3mg/dL (0.4mmol/L); p=.41] and between women with colonization and negative amniotic fluid [colonization: median 21.6mg/dL (1.2mmol/L) vs. negative: median 23.4mg/dL (1.3mmol/L; p=.67]. Women with intra-amniotic infection and sterile intra-amniotic inflammation had lower amniotic fluid glucose levels than women with colonization and with negative amniotic fluid in crude analysis as well as after adjustment for gestational age at sampling. Amniotic fluid glucose level of 10mg/dL (0.56mmol/L) was the optimal concentration for the identification of intra-amniotic inflammation in women with PPROM.Conclusions: The presence of intra-amniotic inflammation was associated with lower amniotic fluid glucose levels in singleton pregnancies complicated with PPROM. An amniotic fluid glucose level of 10mg/dL (0.56mmol/L) was the optimal concentration for the identification of intra-amniotic inflammation in PPROM pregnancies. In the absence of better amniotic fluid markers, amniotic glucose could be used as a marker of intra-amniotic inflammation, with very good specificity in PPROM pregnancies.
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| 4. |
- Kacerovsky, Marian, et al.
(author)
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Presence of Chlamydia trachomatis DNA in the amniotic fluid in women with preterm prelabor rupture of membranes.
- 2021
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In: The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians. - : Informa UK Limited. - 1476-4954. ; 34:10, s. 1586-1597
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Journal article (peer-reviewed)abstract
- Objective: The primary aim of this study was to assess the rate and load of amniotic fluid Chlamydia trachomatis DNA and their associations with intra-amniotic infection and intra-uterine inflammatory complications in women with preterm prelabor rupture of membranes (PPROM). The secondary aim was to assess the short-term morbidity of newborns from PPROM pregnancies complicated by amniotic fluid C. trachomatis DNA. Methods: A retrospective study of 788 women with singleton pregnancies complicated by PPROM between 24+0 and 36+6weeks of gestation was performed. Transabdominal amniocenteses were performed at the time of admission. C. trachomatis DNA in the amniotic fluid was assessed by real-time polymerase chain reaction using a commercial AmpliSens® C. trachomatis/Ureaplasma/Mycoplasma hominis-FRT kit, and the level of Ct DNA was quantified. Results: Amniotic fluid C. trachomatis DNA complicated 2% (16/788) of the PPROM pregnancies and was present in very low loads (median 57 copies DNA/mL). In addition to amniotic fluid C. trachomatis DNA, other bacteria were detected in 62% (10/16) of the C. trachomatis DNA-complicated PPROM pregnancies. Amniotic fluid C. trachomatis DNA was associated with intra-amniotic infection, histologic chorioamnionitis (HCA), and funisitis in 31%, 47%, and 33%, respectively. The presence of C. trachomatis DNA accompanied by Ureaplasma species in the amniotic fluid was associated with a higher rate of HCA than the presence of amniotic fluid C. trachomatis DNA alone. The composite neonatal morbidity in newborns from PPROM pregnancies with amniotic fluid C. trachomatis DNA was 31%. Conclusion: The presence of C. trachomatis DNA in the amniotic fluid is a relatively rare condition in PPROM. Amniotic fluid C. trachomatis DNA in PPROM is not related to intensive intra-amniotic and intr-auterine inflammatory responses or adverse short-term neonatal outcomes.
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| 5. |
- Kacerovsky, Marian, et al.
(author)
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Preterm prelabor rupture of membranes without microbial invasion of the amniotic cavity and intra-amniotic inflammation: a heterogeneous group with differences in adverse outcomes.
- 2022
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In: The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians. - : Informa UK Limited. - 1476-4954. ; 35:25, s. 9145-9156
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Journal article (peer-reviewed)abstract
- The absence of microbial invasion of the amniotic cavity and intra-amniotic inflammation at the time of hospital admission is the most common condition associated with preterm prelabor rupture of membranes (PPROM). Although the intensity of intra-amniotic inflammatory response does not exceed the threshold for the diagnosis of intra-amniotic inflammation in this subgroup of PPROM, whether there could be differences in outcomes concerning the intensity of intra-amniotic inflammatory response remains unclear. Therefore, the main aims of this study on PPROM without microbial invasion of the amniotic cavity and intra-amniotic inflammation were (i) to characterize the association between the intensity of intra-amniotic inflammatory response, measured according to amniotic fluid interleukin (IL)-6 concentrations, and the presence of acute histological chorioamnionitis and acute inflammation in the amnion; (ii) to characterize the association between the intensity of intra-amniotic inflammatory response and fetal inflammatory response, and (iii) to describe the short-term morbidity of infants based on the intensity of intra-amniotic inflammatory response.This retrospective study included 131 women with singleton pregnancies with PPROM without microbial invasion of the amniotic cavity and intra-amniotic inflammation between gestational ages of 24+0 and 36+6weeks and who had delivered within 72h of membrane rupture. Microbial invasion of the amniotic cavity was assessed based on a combination of cultivation and non-cultivation methods. Intra-amniotic inflammation was characterized based on the amniotic fluid IL-6 concentration. In addition, a histopathological assessment of the placenta was performed. Fetal inflammatory response syndrome was characterized according to IL-6 concentration in the umbilical cord blood of >11pg/mL. Based on the quartiles of IL-6 concentrations in the amniotic fluid, these women were divided into four subgroups (from the lowest to the highest IL-6 concentrations).IL-6 concentrations in amniotic fluid were higher in women with acute histological chorioamnionitis (median: 819pg/mL vs. 520pg/mL; p=.003) and with acute inflammation of the amnion (median: 1116pg/mL vs. 533pg/mL; p=.0002) than in women without these complications. The rates of acute histological chorioamnionitis and acute inflammation of the amnion were the highest in the subgroup with IL-6 concentrations above the 75th percentile in amniotic fluid (chorioamnionitis, p=.02; amnion, p=.0002). No differences in IL-6 concentrations in amniotic fluid were identified between women with and without a fetal inflammatory response syndrome (p=.40). The rate of fetal inflammatory response syndrome did not vary among the amniotic fluid IL-6 quartile subgroups of women. Moreover, no differences were noted in short-term neonatal outcomes among the amniotic fluid IL-6 quartile subgroups.A higher intensity of the intra-amniotic inflammatory response, measured by amniotic fluid IL-6 concentrations, is associated with a higher rate of acute inflammatory lesions in the placenta in the subset of PPROM pregnancies without microbial invasion of the amniotic cavity and intra-amniotic inflammation.
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| 6. |
- Musilova, Ivana, et al.
(author)
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Interleukin-6 measured using the automated electrochemiluminescence immunoassay method for the identification of intra-amniotic inflammation in preterm prelabor rupture of membranes.
- 2020
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In: The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians. - : Informa UK Limited. - 1476-4954. ; 33:11, s. 1919-1926
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Journal article (peer-reviewed)abstract
- We aimed to compare the amniotic fluid interleukin (IL)-6 concentrations measured using the automated electrochemiluminescence immunoassay method and ELISA, and to establish an IL-6 concentration cut-off value for intra-amniotic inflammation (IAI) in preterm prelabor rupture of membranes (PPROM), which can be used in the automated electrochemiluminescence immunoassay method.A total of 120 women with PPROM were included in this study. Amniotic fluid samples were obtained via transabdominal amniocentesis. IL-6 concentrations were assessed using both the automated electrochemiluminescence immunoassay method and ELISA, the current gold standard. IAI was defined as an amniotic fluid IL-6 concentration of ≥ 2600 pg/mL measured using ELISA.A correlation between both assays was found (Spearman's rho = 0.97; p < 0.0001). Based on the receiver-operating characteristic curve for the identification of IAI (area under the curve = 0.99), a cut-off value of ≥ 3000pg/mL was selected for the automated electrochemiluminescence immunoassay method with a sensitivity of 88%, specificity of 99%, positive predictive value of 97%, negative predictive value of 96%, and likelihood ratio of 76.
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| 7. |
- Musilova, Ivana, et al.
(author)
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Nicotinamide phosphoribosyltransferase and intra-amniotic inflammation in preterm prelabor rupture of fetal membranes.
- 2021
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In: The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians. - : Informa UK Limited. - 1476-4954. ; 34:5, s. 736-746
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Journal article (peer-reviewed)abstract
- The amniotic fluid nicotinamide phosphoribosyltransferase (NAMPT) levels have not been compared among women with preterm prelabor rupture of membranes (PPROM) comorbid with intra-amniotic infection, sterile intra-amniotic inflammation (IAI), colonization, or without IAI and microbial invasion of the amniotic cavity (MIAC). Therefore, the main aim was to quantify the amniotic fluid NAMPT in women with PPROM complicated by intra-amniotic infection, sterile IAI, or colonization. The second aim was to characterize the diagnostic indices of NAMPT to reveal IAI. The third aim was to determine whether the cervical fluid and maternal serum NAMPT quantitation might be of value in the identification of intra-amniotic inflammatory complications in PPROM.NAMPT levels in amniotic fluid, cervical fluid, and maternal serum were assessed in three independent cohorts of women with singleton pregnancies complicated by PPROM between 24+0 and 36+6 weeks of gestation consisting of 88, 121, and 88 women, respectively. Amniotic fluid samples were obtained by transabdominal amniocentesis, cervical fluid samples were obtained using a Dacron polyester swab, and maternal blood was obtained by venipuncture of the cubital vein. The NAMPT levels were measured by an enzyme linked immunosorbent assay. Testing for MIAC and IAI was performed on all women, who were then categorized into four subgroups: intra-amniotic infection (MIAC and IAI), sterile IAI (IAI alone), colonization (MIAC alone), and without MIAC and IAI.Women with intra-amniotic infection and women with sterile IAI had higher NAMPT levels than did women with colonization and women without MIAC and IAI (intra-amniotic infection: median 73.6ng/mL, sterile IAI: median 55.5ng/mL, colonization: median 12.1ng/mL, without MIAC and IAI: 10.6ng/mL; p < 0.0001). An amniotic fluid NAMPT level of 37ng/mL was the best value for the detection of intra-amniotic infection in women with PPROM. Cervical fluid (p = 0.51) and maternal serum (p = 0.50) NAMPT levels did not reflect intra-amniotic inflammatory complications in women with PPROM.Intra-amniotic infection and sterile IAI are associated with higher NAMPT levels in amniotic fluid but not in cervical fluid or maternal serum in women with PPROM. Amniotic fluid NAMPT might be a marker for invasive identification of IAI in PPROM.
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| 8. |
- Stranik, Jaroslav, et al.
(author)
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Development of a Rat Model of Intra-Amniotic Inflammation via Ultrasound-Guided Administration of a Triggering Agent in the Gestational Sac to Enable Analysis of Individual Amniotic Fluid Samples.
- 2022
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In: Frontiers in pharmacology. - : Frontiers Media SA. - 1663-9812. ; 13
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Journal article (peer-reviewed)abstract
- Objectives: To develop a rat model of intra-amniotic inflammation, characterized by the concentration of interleukin-6 in the amniotic fluid, induced by an ultrasound-guided transabdominal administration of lipopolysaccharide into individual gestational sacs. Methods: An ultrasound-guided transabdominal intra-amniotic administration of lipopolysaccharide or phosphate-buffered saline (PBS) as control was performed in rats on embryonic day 18. Only accessible gestational sacs with precise recording of their positions were injected. Twenty-four hours later, individual amniotic fluid samples were collected from the gestational sacs of laparotomized animals. The gestational sacs were divided into four subgroups: (i) with lipopolysaccharide: injected gestational sacs from rats undergoing lipopolysaccharide administration; (ii) without lipopolysaccharide: non-injected gestational sacs from rats undergoing lipopolysaccharide administration; (iii) with PBS: injected gestational sacs from rats undergoing PBS administration; and (iv) without PBS: non-injected gestational sacs from rats undergoing PBS administration. The concentration of interleukin-6 in individual amniotic fluid samples was assessed using ELISA. Results: In the group of five animals receiving lipopolysaccharide, 24 (33%) and 48 (77%) gestational sacs were and were not injected, respectively. The amniotic fluid was obtained from 21 (88%) injected and 46 (95%) non-injected sacs. In the control group of five animals receiving phosphate-buffered saline, 28 (35%) and 52 (75%) gestational sacs were and were not injected, respectively. The amniotic fluid was obtained from 18 (64%) injected and 50 (96%) non-injected sacs. No labor occurred, and only one fetal death was observed in a gestational sac injected with lipopolysaccharide. Differences in concentrations of interleukin-6 in the amniotic fluid were found among the subgroups of the gestational sacs (with lipopolysaccharide: median 762pg/ml; without lipopolysaccharide: median 35.6pg/ml; with PBS: median 35.6pg/ml; and without PBS: median 35.6pg/ml; p < 0.0001). Concentrations of interleukin-6 in the amniotic fluid from the gestational sacs with lipopolysaccharide were significantly higher than those in the three remaining subgroups (p < 0.0001). No differences in concentrations of interleukin-6 in the amniotic fluid were identified between the three remaining subgroups. Conclusion: The ultrasound-guided transabdominal intra-amniotic administration of lipopolysaccharide with a subsequent collection and analysis of amniotic fluid samples is feasible in rats. The intra-amniotic administration of lipopolysaccharide led to the development of intra-amniotic inflammation without leading to fetal mortality or induction of labor.
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| 9. |
- Stranik, Jaroslav, et al.
(author)
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IgGFc-binding protein in pregnancies complicated by spontaneous preterm delivery: a retrospective cohort study.
- 2021
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In: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 11:1
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Journal article (peer-reviewed)abstract
- To determine the IgGFc-binding protein (FcgammaBP) concentration in amniotic and cervical fluids in preterm prelabor rupture of membranes (PPROM) and preterm labor with intact membranes (PTL) and to assess the diagnostic indices of FcgammaBP to predict intra-amniotic infection (the presence of both microbial invasion of the amniotic cavity and intra-amniotic inflammation). In this study, we included 170 and 79 women with PPROM and PTL, respectively. Paired cervical and amniotic fluid samples were obtained using a Dacron polyester swab and transabdominal amniocentesis, respectively. The FcgammaBP concentrations in the samples were assessed using an enzyme-linked immunosorbent assay. The presence of intra-amniotic infection was associated with elevated FcgammaBP concentrations in pregnancies with PPROM and PTL [PPROM-presence: 86ng/mL vs. absence: 13ng/mL, p<0.0001, area under receiver operating characteristic curve (AUC)=0.94; PTL-presence: 140ng/mL vs. absence: 22ng/mL, p<0.0001, AUC=0.86]. In cervical fluid, the concentrations of FcgammaBP were elevated in the presence of intra-amniotic infection in pregnancies with PPROM only (presence: 345ng/mL vs. absence: 60ng/mL, p<0.0001, AUC=0.93). FcgammaBP in amniotic fluid might be a marker of intra-amniotic infection in women with both PPROM and PTL However, in cervical fluid, it is only observed in women with PPROM.
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| 10. |
- Stranik, Jaroslav, et al.
(author)
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Intra-amniotic infection and sterile intra-amniotic inflammation are associated with elevated concentrations of cervical fluid interleukin-6 in women with spontaneous preterm labor with intact membranes.
- 2022
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In: The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians. - : Informa UK Limited. - 1476-4954. ; 35:25, s. 4861-4869
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Journal article (peer-reviewed)abstract
- To determine the concentration of interleukin-6 (IL-6) in the cervical fluid in women with spontaneous preterm labor with intact fetal membranes (PTL) complicated by intra-amniotic infection (the presence of both microbial invasion of the amniotic cavity and intra-amniotic inflammation), or sterile intra-amniotic inflammation (the presence of intra-amniotic inflammation alone).Eighty women with singleton pregnancies complicated by PTL between gestational ages 22+0 and 34+6weeks were included in this retrospective cohort study. Samples of amniotic and cervical fluids were collected at the time of admission. Amniotic fluid samples were obtained via transabdominal amniocentesis, and cervical fluid was obtained using a Dacron polyester swab. Microbial invasion of the amniotic cavity was diagnosed based on the combination of culture and molecular biology methods. The concentration of IL-6 in the amniotic and cervical fluids were measured using an automated electrochemiluminescence immunoassay method. Intra-amniotic inflammation was defined as an amniotic fluid IL-6 concentration ≥3000pg/mL.The presence of intra-amniotic infection and sterile inflammation was identified in 15% (12/80) and 26% (21/80) of the women, respectively. Women with intra-amniotic infection (median: 587pg/mL; p=.01) and with sterile intra-amniotic inflammation (median: 590pg/mL; p=.005) had higher concentrations of IL-6 in the cervical fluid than those without intra-amniotic inflammation (intra-amniotic infection: median 587pg/mL vs. without inflammation, median: 136pg/mL; p=.01; sterile intra-amniotic inflammation, median: 590pg/mL vs. without inflammation, p=.005). No differences were found in the concentrations of IL-6 in the cervical fluid between women with intra-amniotic infection and sterile intra-amniotic inflammation (p=.81).In pregnancies with PTL, both forms of intra-amniotic inflammation are associated with elevated concentrations of IL-6 in the cervical fluid.
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