The potential presence of infection may be indicated through non-invasive prediction of procalcitonin and C-reactive protein levels within the initial three days after cervical cerclage: a retrospective case-control study.

PURPOSE: To identify which non-invasive infection indicators could better predict post-cervical cerclage (CC) infections, and on which days after CC infection indicators should be closely monitored. METHODS: The retrospective, single-center study included 619 single-pregnancy patients from January 2021 to December 2022. Patients were categorized into infected and uninfected groups based on physicians' judgments of post-CC infections. Registered information included patient characteristics, cervical insufficiency history, gestational age at CC, surgical method (McDonald/Shirodkar), purpose of CC, mid-pregnancy miscarriage/preterm birth, infection history or risk factors, and infection indices on days 1, 3, 5, and 7 after CC. Propensity score matching (PSM) was applied to reduce patient characteristic bias. Statistical analysis of C-reactive protein (CRP), white blood cell (WBC), neutrophil count (NEU), percentage of neutrophil count (NEU_P), interleukin-6 (IL-6), and procalcitonin (PCT) in the infected group compared with the uninfected group was performed using chi-square tests and t-tests. Receiver operating characteristic (ROC) curves were used to further assess the diagnostic value of CRP, PCT, and CRP-PCT in combination. RESULTS: Among the 619 included patients, 206 patients were matched using PSM and subsequently assessed. PCT values on day 1 and day 3 after CC exhibited significant differences between the two groups in two statistical ways (P < 0.01, P < 0.05). The CRP levels on day 1 were significantly higher in the infected group compared to the uninfected group in two statistical ways (P < 0.05). On day 3, the mean CRP value was significantly elevated in the infected group compared to the uninfected group (P < 0.05). Analyses of IL-6, WBC, NEU, and NEU_P did not yield clinically significant results. The area under the ROC curves for CRP, PCT, and CRP-PCT on day 1 and day 3 were all below 0.7. In the preventive CC group, the AUC values of CRP and CRP-PCT obtained on d1 were found to be higher than 0.7, indicating moderate diagnostic accuracy. CONCLUSION: For women after CC surgery, especially of preventive aim, increased serum CRP and PCT levels from post-CC day 1 to day 3 may signal a potential postoperative infection, warranting close monitoring.

Proteomic identification of biomarkers in maternal plasma that predict the outcome of rescue cerclage for cervical insufficiency.

OBJECTIVE: We sought to identify plasma protein biomarkers that are predictive of the outcome of rescue cerclage in patients with cervical insufficiency. METHODS: This retrospective cohort study included 39 singleton pregnant women undergoing rescue cerclage for cervical insufficiency (17-25 weeks) who gave plasma samples. Three sets of pooled plasma samples from controls (cerclage success, n = 10) and cases (cerclage failure, n = 10, defined as spontaneous preterm delivery at <33 weeks) were labeled with 6-plex tandem mass tag (TMT) reagents and analyzed by liquid chromatography-tandem mass spectrometry. Differentially expressed proteins between the two groups were selected from the TMT-based quantitative analysis. Multiple reaction monitoring-mass spectrometry (MRM-MS) analysis was further used to verify the candidate proteins of interest in patients with cervical insufficiency in the final cohort (n = 39). RESULTS: From MRM-MS analysis of the 40 proteins showing statistically significant changes (P < 0.05) from the TMT-based quantitative analysis, plasma IGFBP-2, PSG4, and PGLYRP2 levels were found to be significantly increased, whereas plasma MET and LXN levels were significantly decreased in women with cerclage failure. Of these, IGFBP-2, PSG4, and LXN levels in plasma were independent of cervical dilatation. A multiple-biomarker panel was developed for the prediction of cerclage failure, using a stepwise regression procedure, which included the plasma IGFBP-2, PSG4, and LXN (area under the curve [AUC] = 0.916). The AUC for this multiple-biomarker panel was significantly greater than the AUC for any single biomarker included in the multi-biomarker model. CONCLUSIONS: Proteomic analysis identified useful and independent plasma biomarkers (IGFBP-2, PSG4, and LXN; verified by MRM) that predict poor pregnancy outcome following rescue cerclage. Their combined analysis in a multi-biomarker panel significantly improved predictability.

[Relationship between inflammatory indexes of amniotic fluid and pregnancy outcome of women with cervical incompetence].

Objective: To investigate the relationship between the level of amniotic fluid inflammatory factor and the pregnancy outcome in patients with cervical incompetence. Methods: A retrospective case-control study was conducted. Totally 110 cases of pregnant women were diagnosed as cervical incompetence for cervical dilation at the medical examination in Sun Yat-sen Memorial Hospital of Sun Yatsen University, from January 1st, 2015 to December 31th, 2016. A total of 32 patients (29.1%, 32/110) were performed cervical cerclage. According to their neonatal outcomes, they were divided into live infant group (23 cases, 72%) and dead infant group (9 cases, 28%) . The demographic and clinical data of two groups were analyzed and compared. Results: The mean peripheral blood leucocyte counts, the median amniotic tumor necrosis factor-α (TNF-α) and the median interleukin-8 (IL-8) level of two groups were (10.5±2.8) ×10(9)/L vs (13.6±3.1) ×10(9)/L, 23.80 ng/L (14.9-85.5 ng/L) vs 379.00 ng/L (70.2-418.5 ng/L) , and 3 354 ng/L (1 020-7 500 ng/L) vs 7 500 ng/L (4 210-7 500 ng/L) respectively. The differences were statistically significant (all P<0.05) . The amniotic fluid IL-1ß, IL-2 receptor, IL-6, IL-10, C-reactive protein and procalcitonin were not significantly different (all P>0.05) between two groups. Conclusions: The peripheral blood leucocyte counts, amniotic fluid TNF-α and IL-8 level are the factors affecting the pregnancy outcome in women with cervical incompetence before cervical cerclage. When IL-8 is higher than 3 580 ng/L and TNF-α is higher than 105 ng/L, the death of perinatal infants could be predicted.

Neutrophil elastase in amniotic fluid as a predictor of preterm birth after emergent cervical cerclage.

INTRODUCTION: The aim of this study was to investigate neutrophil elastase (NE) in amniotic fluid as a potential marker for predicting pregnancy continuation. MATERIAL AND METHODS: We enrolled 34 pregnant women with bulging fetal membrane during the second trimester who underwent emergent cerclage after confirming the absence of intrauterine infection (amniotic fluid glucose ≥15 mg/dL). Amniotic fluid NE levels were compared between women who completed and did not complete 30, 34, and 36 weeks of gestation, and the optimal cut-off value for predicting pregnancy continuation was estimated. Moreover, the differences in the duration of continued pregnancy were compared between women with NE levels above and below the optimal cut-off value. RESULTS: The optimal cut-off value for NE in amniotic fluid that predicted pregnancy continuation beyond 30, 34, and 36 weeks of gestation was 180 ng/mL; this cut-off value had a sensitivity, specificity, positive predictive value, and negative predictive value of 84.0, 77.8, 91.3, and 63.7% beyond 30 weeks of gestation; 87.5, 80.0, 91.5, and 72.3% beyond 34 weeks of gestation; and 85.0, 71.4, 80.9, and 76.9% beyond 36 weeks of gestation, respectively. The duration of continued pregnancy from emergent cerclage to delivery was significantly longer in women with amniotic fluid NE <180 ng/mL (95.1 ± 5.4 days) than in women with amniotic fluid NE ≥180 ng/mL (44.8 ± 14.3 days). CONCLUSION: The NE levels in amniotic fluid may serve as a useful marker for predicting the duration of continued pregnancy after cervical cerclage.

Predicting outcomes of emergency cerclage in women with cervical insufficiency using inflammatory markers in maternal blood and amniotic fluid.

OBJECTIVE: To identify inflammatory markers in maternal blood and amniotic fluid that can predict outcomes of emergency cerclage in women with cervical insufficiency. METHODS: This retrospective cohort study included patients at 18-24 weeks of pregnancy who underwent amniocentesis before receiving emergency cerclage for cervical insufficiency between August 2004 and August 2013 at a university teaching hospital in South Korea. Total and differential white blood cell counts were measured during amniocentesis. Amniotic fluid was cultured and analyzed for the presence of interleukin (IL)-6 and IL-8. The primary outcome measure was spontaneous preterm delivery (SPTD) at less than 32weeks of pregnancy following cerclage placement. RESULTS: Of 37 patients, 18 (49%) experienced SPTD at less than 32weeks of pregnancy. These patients were found to have significantly more advanced cervical dilatation at presentation, as well as higher mean neutrophil-lymphocyte ratios (NLRs) and higher IL-6 and IL-8 levels in amniotic fluid in comparison with those who did not experience SPTD at less than 32weeks of pregnancy. In a multivariable analysis, a high NLR and high amniotic fluid IL-8 levels showed a significant correlation with the occurrence of SPTD at less than 32weeks of pregnancy (P=0.032). CONCLUSION: Pre-operative NLR and amniotic fluid IL-8 levels may be important markers for predicting emergency cerclage outcomes in women with cervical insufficiency.

Pregnancy-associated diseases are characterized by the composition of the systemic regulatory T cell (Treg) pool with distinct subsets of Tregs.

Dysregulations concerning the composition and function of regulatory T cells (T(regs)) are assumed to be involved in the pathophysiology of complicated pregnancies. We used six-colour flow cytometric analysis to demonstrate that the total CD4(+) CD127(low+/-) CD25(+) forkhead box protein 3 (FoxP3)(+) T(reg) cell pool contains four distinct T(reg) subsets: DR(high+) CD45RA(-), DR(low+) CD45RA(-), DR(-) CD45RA(-) T(regs) and naive DR(-) CD45RA(+) T(regs). During the normal course of pregnancy, the most prominent changes in the composition of the total T(reg) cell pool were observed between the 10th and 20th weeks of gestation, with a clear decrease in the percentage of DR(high+) CD45RA(-) and DR(low+) CD45RA(-) T(regs) and a clear increase in the percentage of naive DR(-) CD45RA(+) T(regs). After that time, the composition of the total T(reg) cell pool did not change significantly. Its suppressive activity remained stable during normally progressing pregnancy, but decreased significantly at term. Compared to healthy pregnancies the composition of the total T(reg) cell pool changed in the way that its percentage of naive DR(-) CD45RA(+) T(regs) was reduced significantly in the presence of pre-eclampsia and in the presence of preterm labour necessitating preterm delivery (PL). Interestingly, its percentage of DR(high+) CD45RA(-) and DR(low+) CD45RA(-) T(regs) was increased significantly in pregnancies affected by pre-eclampsia, while PL was accompanied by a significantly increased percentage of DR(-) CD45RA(-) and DR(low+) CD45RA(-) T(regs). The suppressive activity of the total T(reg) cell pool was diminished in both patient collectives. Hence, our findings propose that pre-eclampsia and PL are characterized by homeostatic changes in the composition of the total T(reg) pool with distinct T(reg) subsets that were accompanied by a significant decrease of its suppressive activity.

Free fetal DNA levels in patients at risk of preterm labour.

OBJECTIVES: Our main goals were to evaluate the capability of ffDNA to increase the accuracy in prediction of preterm labour by cervical length and to explore potential mechanisms of disease associated with this pathology. METHODS: Fifty-six women, with male fetus, with cervical length assessment at between 22 and 24 weeks were included in the study and divided in 1) Short cervix (<15 mm) delivered at term (T = 20); 2) Short cervix delivered before 37 weeks (PT = 14); and 3) Patients who delivered at term with normal cervical length (N = 22). Maternal plasma samples were collected between 22 and 24 weeks of gestational age. PCR using primers against DYS14 gene were used to quantified ffDNA in plasma samples. Statistical analysis was done using ANOVA test and spearman´s correlation. RESULTS: The median gestational age at delivery for short cervix groups was 26 + 1 for PT and 39 + 3 for T. The control group delivered at a median gestational age of 39 + 6 weeks. ffDNA was detectable in all cases. There was no significant difference between the 3 groups. Similarly, no significant correlation was observed between ffDNA and gestational age at delivery (r = -0.23; p = 0.07). CONCLUSIONS: ffDNA does not increase the accuracy of short cervix at between 22 and 24 weeks for the prediction of preterm labour.

C-reactive protein levels at pre-/post-indicated cervical cerclage predict very preterm birth.

AIMS: To investigate the relation between serum levels of C-reactive protein (CRP) at pre-/post-cerclage points and preterm birth at <33 weeks of gestation in women with indicated cervical cerclage (CC). METHODS: Fifty-eight women with CC indicated for a short or soft cervix, but no visible or protruding fetal membranes into the vagina, between 17 and 26 weeks of gestation, were reviewed. Serum CRP levels were examined three times: just before cerclage, and on day 1 and day 2 post-cerclage. RESULTS: Serum CRP levels on day 1 and day 2, but not just before cerclage, predicted the occurrence of very preterm birth. In women with cervical dilatation of <3.0 cm, serum CRP levels on post-cerclage day 1 were associated with the increase of very preterm birth [CRP ≥1.5 mg/dL vs. <1.5 mg/dL: 4/5 (80%) vs. 8/31 (26%), P=0.033]. In women with cervical dilatation of <3.0 cm, serum CRP ≥3.0 mg/dL on post-cerclage day 2 was also associated with the increase of very preterm birth. CONCLUSION: In women with indicated CC between 17 and 26 weeks of gestation, increased levels of serum CRP on post-cerclage day 1 or 2 might be ominous signs for very preterm birth.

[Levels of fetal and plasma fibronectin in patients with cervical incompetence]. / Poziom fibronektyny plodowej i osoczowej u pacjentek z objawami niewydolnosci ciesniowo-szyjkowej.

In 45 gravidae (below 24 weeks) fetal fibronectin (fF) was measured in cervico-vaginal discharge and plasma fibronectin (pF) was evaluated in venous blood. Twenty women had cervical incompetence (CI) diagnosed and 25 healthy gravidae served as a control. The fF level in patients with CI (0.073 +/- 0.014 mg/ml) was significantly (p < 0.01) higher than that found in the control group (0.058 +/- 0.011 mg/ml). The same was true for pF (p < 0.001). A diagnostic value of fibronectin levels in patients suspected of cervical incompetence is suggested.

Plasma oxytocin but not prostaglandin F2 alpha metabolite levels at cerclage may predict preterm delivery.

Plasma oxytocin and prostaglandin F2 alpha metabolite (PGFM) concentrations were measured in 45 patients admitted for cerclage during the second trimester. Samples were collected before, 3 hours after, and 3 days after the Shirodkar procedure. Uterine activity was recorded by external tocography twice daily for 30 minutes. Twenty-eight women with uncomplicated pregnancy and commensurate gestational age served as controls. Cervical length, measured by ultrasonography, was significantly shorter before cerclage (36 +/- 2 mm) than after cerclage (43 +/- 2 mm) or compared with controls (48 +/- 1 mm). Bishop scores ranged from 3-6 (median 4) in the cerclage group and 0-1 (median 0) in controls. Fifteen cerclage patients and one control delivered preterm 5-22 weeks after the procedure. Initial plasma PGFM levels were significantly higher in cerclage patients than in controls. The cerclage procedure caused an immediate rise in plasma PGFM and a subsequent fall below initial levels to control values. Neither the initial levels of PGFM nor the increments 3 hours after cerclage correlated with the outcome of pregnancy. By contrast, plasma oxytocin levels before cerclage were significantly higher in patients who subsequently delivered preterm than in those who delivered at term. Cerclage resulted in a significant fall in plasma oxytocin at 3 hours in patients with preterm delivery, but after 3 days the oxytocin levels had returned to the precerclage values. Patients who had increased uterine contractions had significantly higher plasma oxytocin levels but lower PGFM levels than those without contractions.(ABSTRACT TRUNCATED AT 250 WORDS)

Plasma prostaglandin concentrations after cerclage in early pregnancy.

A prospective, randomized controlled study was made to measure the circulating levels of 13, 14-dihydro-15-keto-prostaglandin F (PGFM) in two groups of women having cervical cerclage early in the second trimester of pregnancy. One group of patients was given omnopon by intramuscular injection for 24 hours after operation and the other salbutamol by intravenous infusion. A significant rise in circulating PGFM was found in both groups after cervical cerclage and the magnitude of the rise was similar in the two groups; levels of PGFM in both groups had returned to the preoperative levels within 24 hours of operation. The levels of PGFM before and after operation showed no relation to the eventual outcome of the pregnancy, which was successful in 80 percent of patients.