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

Park

et al. 2022

American J Rep Immunol

Self Cite

Problem This study aimed to determine whether various novel plasma mediators of immune regulation associated with inflammation could independently predict the clinical outcome of rescue cerclage in patients with cervical insufficiency (CI). Method of study A total of 41 singleton pregnant women (17–25 weeks) who underwent rescue cerclage for CI were retrospectively evaluated. Stored plasma samples were assayed for IGFBP‐1, ‐2, ‐3, IL‐6, latexin, LBP, lipocalin‐2, M‐CSF, MIP‐1α, MMP‐8, ‐9, pentraxin 3, resistin, S100A8, S100A8/A9, thrombospondin‐2, TIMP‐1, and TNFR2 levels. The primary outcome measures were spontaneous preterm birth (SPTB) at < 28 and < 34 weeks after cerclage placement. Results Multivariate Firth's logistic regression analysis revealed that high levels of IGFBP‐3 and S100A8/A9, and low levels of MIP‐1α were significantly associated with SPTB at < 28 weeks after cerclage placement, whereas only low MIP‐1α levels were significantly associated with SPTB at < 34 weeks, even after adjustment for baseline clinical covariates (e.g., cervical dilatation). For the prediction of SPTB at < 28 weeks, the area under the curves (AUC) of IGFBP‐3, MIP‐1α, and S100A8/A9 were of .686, .691, and .693, respectively. Similarly, the AUC of MIP‐1 α was of .659 to predict SPTB at < 34 weeks. Conclusions These findings suggest that plasma IGFBP‐3, MIP‐1α, and S100A8/A9 can represent noninvasive independent biomarkers for identifying women with CI at high risk for SPTB following rescue cerclage. Nonetheless, further in large, multicenter clinical studies should be performed to confirm the clinical value of these biomarkers.

Section: Discussioncontrasting

confidence: 99%

Section: Discussionsupporting

confidence: 72%

Inflammation‐related immune proteins in maternal plasma as potential predictive biomarkers for rescue cerclage outcome in women with cervical insufficiency

Park

et al. 2022

American J Rep Immunol

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“…The patients were excluded if they had (ⅰ) prophylactic cerclage during early pregnancy; (ⅱ) preterm labor syndrome or rupture of membranes at the diagnosis; (ⅲ) multiple pregnancies; (ⅳ) clinical chorioamnionitis at presentation; and (ⅴ) major congenital anomalies. A subset of participants in the present study was included in the previous studies, which showed the value of biomarkers for cerclage failure prediction using microarray and proteomic analyses [ 6 , 13 , 15 ]. A clinical diagnosis of acute CI was made when the intact fetal membranes were visible at the level of the external os or when they protruded into the vagina, as confirmed by sterile speculum examination with mid-trimester painless cervical dilation (≥ 1 cm).…”

Section: Methodsmentioning

confidence: 99%

“…The stored AF samples were assayed using commercial ELISA kits for endoglin, endostatin, haptoglobin, IGFBP-3, -4, IL-6, kallistatin, lumican, macrophage colony-stimulating factor (M-CSF), PTX3, p-selectin, RAGE, resistin, transforming growth factor-beta-induced (TGFBI), and vitamin D-binding protein (VDBP) (DuoSet ELISA; R&D Systems, Minneapolis, MN, USA) according to the manufacturer’s instructions. 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 ].…”

Section: Methodsmentioning

confidence: 99%

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

Self Cite

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.

“…Infections considered were gonorrhea, syphilis, chlamydia, hepatitis B, hepatitis C, and GBS. The de nition of cervical insu ciency includes three criteria: painless cervical dilation of 1 cm or more, exposed or bulging fetal membranes without uterine contractions as visually determined using a sterile speculum, or cervical length equal to or less than 25mm before 24 weeks of gestation [17]. Thyroid dysfunction abnormalities was identi ed based on self-reported physician diagnosis of hyperthyroidism or hypothyroidism, or the use of antithyroid drugs.…”

Section: Predictor Variablesmentioning

confidence: 99%

Development and validation of a prediction model on spontaneous preterm birth in twin pregnancy: a retrospective cohort study

Yang,

Zong,

et al. 2023

Preprint

Background: This study was conducted to develop and validate an individualized prediction model for spontaneous preterm birth (sPTB) in twin pregnancies. Methods: This case-control study included 3,845 patients who gave birth at the Chongqing Maternal and Child Health Hospital from January 2017 to December 2022. Both univariable and multivariable logistic regression analyses were performed to find factors associated with sPTB. The associations were estimated using the odds ratio (OR) and the 95% confidence interval (CI). Model performance was estimated using sensitivity, specificity, accuracy, and area under the receiver operating characteristic curve (AUC). Results: A total of 1,313 and 564 cases were included in the training and testing sets, respectively. In the training set, univariate and multivariate logistic regression analysis indicated that age ≥ 35 years (OR, 2.28; 95% CI, 1.67-3.13), pre-pregnancy underweight (OR, 2.36; 95% CI, 1.60-3.47), pre-pregnancy overweight (OR, 1.67; 95% CI, 1.09-2.56), and obesity (OR, 10.45; 95% CI, 3.91-27.87), nulliparity (OR, 0.58; 95% CI, 0.41-0.82), pre-pregnancy diabetes (OR, 5.81; 95% CI, 3.24-10.39), pre-pregnancy hypertension (OR, 2.79; 95% CI, 1.44-5.41), and cervical incompetence (OR, 5.12; 95% CI, 3.08-8.48) are independent risk factors for sPTB in twin pregnancies. The AUC of the training and validation set was 0.71 (95% CI, 0.68-0.74) and 0.68 (95% CI, 0.64-0.73), respectively. And then we integrated those risk factors to construct the nomogram. Conclusions: The nomogram developed for predicting the risk of sPTB in pregnant women with twins demonstrated good performance. The prediction nomogram serves as a practical tool by including all necessary predictors that are readily accessible to practitioners.