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| 3. |
- Hallingström, Maria, et al.
(författare)
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Proteomic Analysis of Early Mid-Trimester Amniotic Fluid Does Not Predict Spontaneous Preterm Delivery
- 2016
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 11:5
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Tidskriftsartikel (refereegranskat)abstract
- Objective The aim of this study was to identify early proteomic biomarkers of spontaneous preterm delivery (PTD) in mid-trimester amniotic fluid from asymptomatic women. This is a case-cohort study. Amniotic fluid from mid-trimester genetic amniocentesis (14-19 weeks of gestation) was collected from 2008 to 2011. The analysis was conducted in 24 healthy women with subsequent spontaneous PTD (cases) and 40 randomly selected healthy women delivering at term (controls). An exploratory phase with proteomics analysis of pooled samples was followed by a verification phase with ELISA of individual case and control samples. The median (interquartile range (IQR: 25th; 75th percentiles) gestational age at delivery was 35+5 (33+6-36+6) weeks in women with spontaneous PTD and 40+0 (39+1-40+5) weeks in women who delivered at term. In the exploratory phase, the most pronounced differences were found in C-reactive protein (CRP) levels, that were approximately two-fold higher in the pooled case samples than in the pooled control samples. However, we could not verify these differences with ELISA. The median (25th; 75th IQR) CRP level was 95.2 ng/mL (64.3; 163.5) in women with spontaneous PTD and 86.0 ng/mL (51.2; 145.8) in women delivering at term (p = 0.37; t-test). Proteomic analysis with mass spectrometry of mid-trimester amniotic fluid suggests CRP as a potential marker of spontaneous preterm delivery, but this prognostic potential was not verified with ELISA.
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- Hallingström, Maria, et al.
(författare)
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Mid-trimester amniotic fluid proteome’s association with spontaneous preterm delivery and gestational duration
- 2020
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203 .- 1932-6203. ; 15:5
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Tidskriftsartikel (refereegranskat)abstract
- Background Amniotic fluid is clinically accessible via amniocentesis and its protein composition may correspond to birth timing. Early changes in the amniotic fluid proteome could therefore be associated with the subsequent development of spontaneous preterm delivery. Objective The main objective of this study was to perform unbiased proteomics analysis of the association between mid-trimester amniotic fluid proteome and spontaneous preterm delivery and gestational duration, respectively. A secondary objective was to validate and replicate the findings by enzyme-linked immunosorbent assay using a second independent cohort. Methods Women undergoing a mid-trimester genetic amniocentesis at Sahlgrenska University Hospital/Östra between September 2008 and September 2011 were enrolled in this study, designed in three analytical stages; 1) an unbiased proteomic discovery phase using LC-MS analysis of 22 women with subsequent spontaneous preterm delivery (cases) and 37 women who delivered at term (controls), 2) a validation phase of proteins of interest identified in stage 1, and 3) a replication phase of the proteins that passed validation using a second independent cohort consisting of 20 cases and 40 matched controls. Results Nine proteins were nominally significantly associated with both spontaneous preterm delivery and gestational duration, after adjustment for gestational age at sampling, but none of the proteins were significant after correction for multiple testing. Several of these proteins have previously been described as being associated with spontaneous PTD etiology and six of them were thus validated using enzyme linked immunosorbent assay. Two of the proteins passed validation; Neutrophil gelatinase-associated lipocalin and plasminogen activator inhibitor 1, but the results could not be replicated in a second cohort. Conclusions Neutrophil gelatinase-associated lipocalin and Plasminogen activator inhibitor 1 are potential biomarkers of spontaneous preterm delivery and gestational duration but the findings could not be replicated. The negative findings are supported by the fact that none of the nine proteins from the exploratory phase were significant after correction for multiple testing.
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- Musilova, I., et al.
(författare)
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Amniotic fluid calreticulin in pregnancies complicated by the preterm prelabor rupture of membranes
- 2016
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Ingår i: Journal of Maternal-Fetal & Neonatal Medicine. - : Informa UK Limited. - 1476-7058 .- 1476-4954. ; 29:24, s. 3921-3929
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Tidskriftsartikel (refereegranskat)abstract
- Objective: This study aimed to determine the amniotic fluid calreticulin concentrations in women with the preterm prelabor rupture of membranes (PPROM) based on the microbial invasion of the amniotic cavity (MIAC), intraamniotic inflammation (IAI) and microbial-associated IAI.Methods: One hundred sixty-eight women with singleton pregnancies were included in this study. Amniotic fluid samples were obtained by transabdominal amniocentesis and were assayed for calreticulin concentrations by ELISA. IAI was defined as an amniotic fluid interleukin-6 concentration>745pg/ml. Microbial-associated IAI was defined as the presence of both MIAC and IAI.Result: Women with MIAC (with MIAC: median 54.4ng/ml, versus without MIAC: median 32.6ng/ml; p<0.0001), IAI (with IAI: median 66.8ng/ml, versus without IAI: median 33.0ng/ml; p<0.0001) and microbial-associated IAI (with microbial-associated IAI: median 82.5ng/ml, versus without microbial-associated IAI: median 33.7ng/ml; p<0.0001) had higher concentrations of calreticulin than women without these complications. An amniotic fluid calreticulin concentration of 81.4ng/ml was found to be the best cutoff point for identifying women with microbial-associated IAI.Conclusions: The presence of microbial-associated IAI is associated with increased amniotic fluid calreticulin concentrations. Calreticulin seems to be a promising marker for the early identification of PPROM complicated by microbial-associated IAI.
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- Musilova, I., et al.
(författare)
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Maternal serum C-reactive protein concentration and intra-amniotic inflammation in women with preterm prelabor rupture of membranes
- 2017
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Ingår i: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 12:8
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Tidskriftsartikel (refereegranskat)abstract
- Objective To evaluate maternal serum C-reactive protein (CRP) concentrations in pregnancies complicated by preterm prelabor rupture of membranes (PPROM) in relation to the presence of microbial invasion of the amniotic cavity (MIAC) and/or intra-amniotic inflammation (IAI). Two hundred and eighty-seven women with singleton pregnancies complicated by PPROM between 2014 and 2016 were included in this study. Maternal blood and amniotic fluid samples were collected at the time of admission. Maternal serum CRP concentration was measured using a high-sensitivity immunoturbidimetric assay. Interleukin-6 (IL-6) concentration was measured using a point-of-care test. MIAC was diagnosed based on a positive polymerase chain reaction result for Ureaplasma species, Mycoplasma hominis, and/or Chlamydia trachomatis and for the 16S rRNA gene. IAI was characterized by an amniotic fluid IL-6 concentration of >= 745 pg/mL. Women with MIAC and IAI had higher maternal serum CRP concentrations than did women without (with MIAC: median 6.9 mg/L vs. without MIAC: median 4.9 mg/L; p = 0.02; with IAI: median 8.6 mg/L vs. without IAI: median 4.7 mg/L; p < 0.0001). When women were split into four subgroups based on the presence of MIAC and/or IAI, women with the presence of both MIAC and IAI had higher maternal serum CRP than did women with IAI alone, with MIAC alone, and women without MIAC and IAI (both MIAC and IAI: median: 13.1 mg/L; IAI alone: 6.0 mg/L; MIAC alone: 3.9 mg/L; and without MIAC and IAI: median 4.8 mg/L; p < 0.0001). The maternal serum CRP cutoff value of 17.5 mg/L was the best level to identify the presence of both MIAC and IAI, with sensitivity of 47%, specificity of 96%, positive predictive value of 42%, negative predictive value of 96%, and the positive likelihood ratio of 10.9. The presence of both MIAC and IAI was associated with the highest maternal serum CRP concentrations. Maternal serum CRP concentration in women with PPROM at the time of admission can rule out the presence of the combined condition of both MIAC and IAI, therefore, it may serve as a non-invasive screening tool to distinguish between women with PPROM who are at high or at low risk for the presence of both MIAC and IAI.
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| 7. |
- Musilova, I., et al.
(författare)
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Vaginal fluid interleukin-6 concentrations as a point-of-care test is of value in women with pretermprelabor rupture of membranes
- 2016
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Ingår i: American Journal of Obstetrics and Gynecology. - : Elsevier BV. - 0002-9378 .- 1097-6868. ; 215:5
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Tidskriftsartikel (refereegranskat)abstract
- Background Preterm prelabor rupture of membranes is frequently complicated/accompanied by infection and inflammation in the amniotic cavity. A point-of-care determination of amniotic fluid interleukin-6 has been shown to be a potentially clinically useful approach to assess inflammatory status of the amniotic cavity. Amniocentesis in preterm prelabor rupture of membranes is not broadly used in clinical practice, and therefore, a shift toward a noninvasive amniotic fluid sampling method is needed. Objective The first aim of this study was to evaluate the association between the point-of-care vaginal and amniotic fluid interleukin-6 concentrations in fresh unprocessed samples obtained simultaneously. The second goal was to determine the diagnostic indices and predictive value of the point-of-care assessment of vaginal fluid interleukin-6 concentration in the identification of microbial invasion of the amniotic cavity, intraamniotic inflammation, and microbial-associated intraamniotic inflammation in patients with preterm prelabor rupture of membranes. Study Design A prospective cohort study was conducted in women with singleton gestation complicated by preterm prelabor rupture of membranes at between 24+0 and 36+6 weeks. A total of 153 women with singleton pregnancies were included in this study. Vaginal fluid was obtained from the posterior vaginal fornix by aspiration with a sterile urine sample tube with a suction tip. Amniotic fluid was obtained by transabdominal amniocentesis. Interleukin-6 concentrations were assessed with a lateral flow immunoassay in both fluids immediately after sampling. Microbial invasion of the amniotic cavity was determined based on a positive polymerase chain reaction analysis. Intraamniotic inflammation was defined as an amniotic fluid point-of-care interleukin-6 concentration ≥745 pg/mL. Results Several results were obtained in this study. First, it was possible to perform the point-of-care assessment of interleukin-6 in vaginal fluid in 92% of the women (141 of 153), and only those women were included in the analyses. Second, the rate of microbial invasion of the amniotic cavity and intraamniotic inflammation was 26% (36 of 141) and 19% (27 of 141), respectively. Microbial-associated intraamniotic inflammation was identified in 12% of the women (17 of 141). Third, a strong positive correlation was found between the interleukin-6 concentrations in vaginal and amniotic fluids (Spearman rho 0.68; P <.0001). Fourth, the presence of microbial invasion of the amniotic cavity, intraamniotic inflammation, or microbial-associated intraamniotic inflammation was associated with higher vaginal fluid interleukin-6 concentrations in both crude and adjusted analyses. Fifth, a vaginal fluid interleukin-6 concentration of 2500 pg/mL was determined to be the best cutoff value for the identification of microbial invasion of the amniotic cavity (sensitivity of 53% [19 of 36], specificity of 89% [93 of 104], positive predictive value of 63% [19 of 30], negative predictive value of 85% [93 of 110], positive likelihood ratio of 5.0 [95% confidence interval, 2.5–9.5], and negative likelihood ratio of 0.5 [95% confidence interval, 0.4–0.8]); intraamniotic inflammation (sensitivity of 74% [20/27], specificity of 91% [104/114], positive predictive value of 67% [20 of 30], negative predictive value of 94% [104 of 111], positive likelihood ratio of 8.4 [95% confidence interval, 4.5–15.9], and negative likelihood ratio of 0.3 [95% confidence interval, 0.2–0.5]); and microbial-associated intraamniotic inflammation (sensitivity of 100% [17 of 17], specificity of 90% [111 of 124), positive predictive value of 57% [17 of 30], negative predictive value of 100% [111 of 111], positive likelihood ratio of 9.5 [95% confidence interval, 5.7–16.0], and negative likelihood ratio of 0). Conclusion The point-of-care assessment of interleukin-6 in vaginal fluid is an easy, rapid, noninvasive, and inexpensive method for the identification of intraamniotic inflammation and microbial-associated intraamniotic inflammati n in preterm prelabor rupture of membranes pregnancies, showing good specificity and negative predictive value. © 2016 Elsevier Inc.
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| 8. |
- Stepan, M., et al.
(författare)
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Maternal Serum C-Reactive Protein in Women with Preterm Prelabor Rupture of Membranes
- 2016
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Ingår i: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 11:3
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Tidskriftsartikel (refereegranskat)abstract
- Objective This study evaluated maternal C-reactive protein (CRP) as a predictor of microbial invasion of the amniotic cavity (MIAC) and histological chorioamnionitis (HCA) in women with pre-term prelabor rupture of the membranes (PPROM) before and after 32 weeks of gestation. This study was a prospective observational cohort study of 386 women. Maternal serum CRP concentrations were evaluated, and amniotic fluid samples were obtained via transabdominal amniocentesis at the time of admission. Placentas underwent histopathological examination after delivery. MIAC was defined based on a positive PCR for Ureaplasma species, Mycoplasma hominis and Chlamydia trachomatis and/or positive 16S rRNA gene amplification. HCA was defined based on the Salafia classification. Maternal CRP was significantly higher in women with MIAC and HCA (median 9.0 mg/l) than in women with HCA alone (median 6.9 mg/l), MIAC alone (median 7.4 mg/l) and without MIAC or HCA (median 4.5 mg/l) (p<0.0001). CRP was a weak predictor of the occurrence of MIAC and HCA before and after 32 weeks of gestation. Only the 95th percentile of CRP and PPROM before 32 weeks exhibited a false-positive rate of 1%, a positive predictive value of 90% and a positive likelihood ratio of 13.2 to predict MIAC and HCA. However, the low sensitivity of 15% limits the clinical utility of this detection. CRP is a poor predictor of the occurrence of MIAC and HCA, even at early gestational ages.
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| 9. |
- Aberšek, Nina, et al.
(författare)
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Calprotectin levels in amniotic fluid in relation to intra-amniotic inflammation and infection in women with preterm labor with intact membranes: A retrospective cohort study
- 2022
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Ingår i: European Journal of Obstetrics & Gynecology and Reproductive Biology. - : Elsevier BV. - 1872-7654 .- 0301-2115. ; 272, s. 24-29
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To evaluate the concentrations of calprotectin in amniotic fluid with respect to intra-amniotic inflammation and infection and to assess the presence or absence of bacteria in the amnio-chorionic niche with respect to presence or absence of intra-amniotic inflammation. Study design: Seventy-nine women with singleton pregnancies and preterm labor with intact membranes (PTL) were included in the study. Amniotic fluid was collected at the time of admission by amniocentesis and calprotectin levels were analyzed from frozen/thawed samples using ELISA. Interleukin (IL)-6 concentration was measured by point-of-care test. Samples from amniotic fluid and the amnio-chorionic niche (space between amniotic and chorionic membranes) were microbiologically analyzed. Microbial invasion of the amniotic cavity (MIAC) was diagnosed based on a positive PCR result for Ureaplasma species, Mycoplasma hominis, 16S rRNA or positive culture. Intra-amniotic inflammation (IAI) was defined as amniotic fluid point-of-care IL-6 concentration ≥ 745 pg/mL. The cohort of included women was divided into 4 subgroups based on the presence or absence of IAI/MIAC; i) intra-amniotic infection, ii) sterile IAI, iii) intra-amniotic colonization and iv) neither MIAC nor IAI. Results: Women with intra-amniotic infection had a significantly higher intra-amniotic calprotectin concentration (median; 101.6 µg/mL) compared with women with sterile IAI (median; 9.2 µg/mL), women with intra-amniotic colonization (median; 2.6 µg/mL) and women with neither MIAC nor IAI (median 4.6 µg/mL) (p = 0.001). Moreover, significantly higher amniotic fluid calprotectin concentration was seen in women who delivered within 7 days (p = 0.003). A significant negative correlation was found between amniotic fluid calprotectin and gestational age at delivery (rho = 0.32, p = 0.003). Relatively more bacteria in the amnio-chorionic niche were found in the sterile IAI group compared with the other groups. Conclusions: Calprotectin concentrations in amniotic fluid were significantly higher in the intra-amniotic infection group compared with the other groups. Moreover, the bacterial presence in the amnio-chorionic niche was higher in IAI group.
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- Cobo, Teresa, et al.
(författare)
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A prediction model of histological chorioamnionitis and funisitis in preterm prelabor rupture of membranes: analyses of multiple proteins in the amniotic fluid.
- 2012
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Ingår i: 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.
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To determine the best prediction model of histological chorioamnionitis and funisitis in preterm prelabor rupture of membranes (PPROM) using selected candidate proteins in the amniotic fluid (AF). Material and methods: Prospective cohort study. Twenty-six AF proteins were assayed by a multiple immunoassay from 107 women with membranes rupture from 23+0 to 36+6 weeks. The Czech Republic policy is active management, and the majority of women were delivered within 72 h after the rupture of membranes, except for women with PPROM <28+0 weeks who were managed conservatively. The best predictive models to diagnose histological chorioamnionitis and funisitis were calculated by logistic regression depending on the gestational age (GA) at membrane rupture. Results: Both IL-6 and a combination of IL-10, and migration inhibiting factor (MIF) were the best predictive models of histological chorioamnionitis and funisitis, respectively, with sensitivity, specificity, positive and negative predictive values and positive likelihood ratio (LR+) of 62, 83, 37, 93 and 3.6 and of 63, 91, 53, 94 and 7.0, respectively. Depending on whether GA at membrane rupture was <32 or ≥ 32 weeks, IL-10, alone or in combination with MIF and triggering receptor expressed on myeloid cells-1, was the strongest inflammatory biomarker for funisitis (LR+10.6 and 36.6, respectively). Conclusion: Regardless of the GA at membrane rupture, IL-6 from the AF was the best predictor of histological chorioamnionitis. Amniotic fluid IL-10 was notably accurate in the prediction of funisitis.
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