Maternal Serum VEGF Predicts Abnormally Invasive Placenta Better than NT-proBNP: a Multicenter Case-Control Study

Schwickert, Axel C.; Chantraine, Frédéric; Ehrlich, Laura; Henrich, Wolfgang; Muallem, Mustafa Zelal; Nonnenmacher, A; Petit, Philippe; Weizsäcker, Katharina; Braun, Thorsten

doi:10.1007/s43032-020-00319-y

Cited by 19 publications

(23 citation statements)

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“…Nowadays, the researchers try to find biochemical markers of PAS, which may be potential markers for the diagnosis of the severity of PAS. Schwickert A et al (26) found that the level of VEGF in maternal serum could predict the severity of PAS. Shainker SA et al (27) found that the soluble VEGF receptor 2, soluble Tie2, median plasminogen activator inhibitor one concentrations, and median antithrombin III concentrations in maternal plasma were associated with the severity of PAS.…”

Section: Discussionmentioning

confidence: 99%

Developing and Validating Nomogram to Predict Severe Postpartum Hemorrhage in Women With Placenta Previa Undergoing Cesarean Delivery: A Multicenter Retrospective Case-Control Study

et al. 2022

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ObjectiveDeveloping and validating nomogram to predict severe postpartum hemorrhage (SPPH) in women with placenta previa (PP) undergoing cesarean delivery.MethodsWe conducted a multicenter retrospective case-control study in five hospitals. In this study, 865 patients from January, 2018 to June, 2020 were enrolled in the development cohort, and 307 patients from July, 2020 to June, 2021 were enrolled in the validation cohort. Independent risk factors for SPPH were obtained by using the multivariate logistic regression, and preoperative nomogram and intraoperative nomogram were developed, respectively. We compared the discrimination, calibration, and net benefit of the two nomograms in the development cohort and validation cohort. Then, we tested whether the intraoperative nomogram could be used before operation.ResultsThere were 204 patients (23.58%) in development cohort and 80 patients (26.06%) in validation cohort experienced SPPH. In development cohort, the areas under the receiver operating characteristic (ROC) curve (AUC) of the preoperative nomogram and intraoperative nomogram were 0.831 (95% CI, 0.804, 0.855) and 0.880 (95% CI, 0.854, 0.905), respectively. In validation cohort, the AUC of the preoperative nomogram and intraoperative nomogram were 0.825 (95% CI, 0.772, 0.877) and 0.853 (95% CI, 0.808, 0.898), respectively. In the validation cohort, the AUC was 0.839 (95% CI, 0.789, 0.888) when the intraoperative nomogram was used before operation.ConclusionWe developed the preoperative nomogram and intraoperative nomogram to predict the risk of SPPH in women with PP undergoing cesarean delivery. By comparing the discrimination, calibration, and net benefit of the two nomograms in the development cohort and validation cohort, we think that the intraoperative nomogram performed better. Moreover, application of the intraoperative nomogram before operation can still achieve good prediction effect, which can be improved if the severity of placenta accreta spectrum (PAS) can be accurately distinguished preoperatively. We expect to conduct further prospective external validation studies on the intraoperative nomogram to evaluate its application value.

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Section: Discussionmentioning

confidence: 99%

Developing and Validating Nomogram to Predict Severe Postpartum Hemorrhage in Women With Placenta Previa Undergoing Cesarean Delivery: A Multicenter Retrospective Case-Control Study

et al. 2022

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“…Some studies demonstrated significantly higher thirdtrimester maternal serum VEGF levels in PAS cases compared to controls [33][34][35] while others had significantly lower VEGF levels in cases. 30,36 Furthermore Biberoglu et al 25 and Naghshineh and Razaghi 31 showed no significant differences in VEGF levels between both groups. After excluding studies with high risk of bias, 30,31,33,36 results demonstrated significantly higher third-trimester serum VEGF levels among PAS cases when compared to controls (SMD = 3.15, 95% confidence interval [CI] = 0.65-5.66, p = 0.01) (Figure 3b).…”

Section: Third-trimester Serum Levels Of Vegf and Pasmentioning

confidence: 90%

“…28,29 Finally, eight studies were included in this meta-analysis. 25,[30][31][32][33][34][35][36] All of them reported third trimester serum VEGF levels, 25,[30][31][32][33][34][35][36] while seven studies reported third trimester sFlt-1 levels, 25,[31][32][33][34][35][36] and only three studies explored PlGF levels. 25,32,36 The characteristics of the included studies are shown in Table 1.…”

Section: Literature Search and Study Characteristicsmentioning

confidence: 99%

“…Eight studies have evaluated the third-trimester maternal serum levels of VEGF in confirmed PAS cases and non-PAS controls. 25,[30][31][32][33][34][35][36] Analysis of these studies did not show a significant difference in the levels of VEGF between the confirmed PAS cases and non-PAS controls (SMD = 1.59, 95% confidence interval [CI] = À0.07 to 3.25, p = 0.06) (Figure 3a). Some studies demonstrated significantly higher thirdtrimester maternal serum VEGF levels in PAS cases compared to controls [33][34][35] while others had significantly lower VEGF levels in cases.…”

Section: Third-trimester Serum Levels Of Vegf and Pasmentioning

confidence: 99%

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Association between placenta accreta spectrum and third‐trimester serum levels of vascular endothelial growth factor, placental growth factor, and soluble Fms‐like tyrosine kinase‐1: A meta‐analysis

Alzoubi

Maaita

Madain

et al. 2022

J of Obstet and Gynaecol

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Aim Antenatal suspicion of placenta accreta spectrum (PAS) currently relies on ultrasonographic findings, color doppler, and MRI, which have rendered it operator and expertise‐dependent. No serum markers for PAS have been integrated into clinical practice yet. The aim of this meta‐analysis was to identify potential serum markers for PAS by investigating third‐trimester serum levels of vascular endothelial growth factor (VEFG), placental growth factor (PIGF), and soluble Fms‐like tyrosine kinase‐1 (sFlt‐1) among PAS‐cases and controls. Methods PubMed, Scopus, EBSCO, Web of Science, and CNKI databases were systematically searched for relevant articles. Random‐effects model was applied to calculate the overall standardized mean difference (SMD) for each marker. Subgroup analysis and meta‐regression were performed to assess for potential covariates. Results Eight studies involving 366 PAS‐cases and 518 controls were included. Third trimester sFlt‐1 levels were significantly lower in PAS‐cases when compared to controls (SMD = −7.76, 95%CI = −10.42 to −5.10). This was, to a certain extent, consistent among studies though they differed in their extent of significance. Levels of VEGF (SMD = 1.59, 95%CI = −0.07 to 3.25) and PlGF (SMD = −0.49, 95%CI = −1.66 to 0.67) were not significantly different between PAS cases and controls, in which studies demonstrated conflicting results. Conclusions Third trimester sFlt‐1 levels may be useful to predict PAS. Nonetheless, further studies are recommended to better understand conflicting results before adopting either VEGF or PlGF.

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“…Placental tissue can be seen invading through the myometrium and serosa, sometimes even into the urinary bladder, parametria, or even the colon [4][5][6]. In addition to excessive extravillous trophoblastic invasion, abnormal maternal vascular remodeling (i.e., neoangiogenesis) is one of the driving factors of increased placental invasiveness [7][8][9][10]. Angiogenic growth factors, such as vascular endothelial growth factor and angiopoietin-2, are upregulated in PAS lysates.…”

Section: Introductionmentioning

confidence: 99%

Placenta Percreta Presents with Neoangiogenesis of Arteries with Von Willebrand Factor-Negative Endothelium

et al. 2021

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In placenta percreta cases, large vessels are present on the precrete surface area. As these vessels are not found in normal placentation, we examined their histological structure for features that might explain the pathogenesis of neoangiogenesis induced by placenta accreta spectrum disorders (PAS). In two patients with placenta percreta (FIGO grade 3a) of the anterior uterine wall, one strikingly large vessel of 2 cm length was excised. The samples were formalin fixed and paraffin-embedded. Gomori trichrome staining was used to evaluate the muscular layers and Weigert-Van Gieson staining for elastic fibers. Immunohistochemical staining of the vessel endothelium was performed for Von Willebrand factor (VWF), platelet endothelial cell adhesion molecule (CD31), Ephrin B2, and EPH receptor B4. The structure of the vessel walls appeared artery-like. The vessel of patient one further exhibited an unorderly muscular layer and a lack of elastic laminae, whereas these features appeared normal in the vessel of the other patient. The endothelium of both vessels stained VWF-negative and CD31-positive. In conclusion, this study showed VWF-negative vessel endothelia of epiplacental arteries in placenta accreta spectrum. VWF is known to regulate artery formation, as the absence of VWF has been shown to cause enhanced vascularization. Therefore, we suppose that PAS provokes increased vascularization through suppression of VWF. This process might be associated with the immature vessel architecture as found in one of the vessels and Ephrin B2 and EPH receptor B4 negativity of both artery-like vessels. The underlying pathomechanism needs to be evaluated in a greater set of patients.

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Maternal Serum VEGF Predicts Abnormally Invasive Placenta Better than NT-proBNP: a Multicenter Case-Control Study

Cited by 19 publications

References 50 publications

Developing and Validating Nomogram to Predict Severe Postpartum Hemorrhage in Women With Placenta Previa Undergoing Cesarean Delivery: A Multicenter Retrospective Case-Control Study

Developing and Validating Nomogram to Predict Severe Postpartum Hemorrhage in Women With Placenta Previa Undergoing Cesarean Delivery: A Multicenter Retrospective Case-Control Study

Association between placenta accreta spectrum and third‐trimester serum levels of vascular endothelial growth factor, placental growth factor, and soluble Fms‐like tyrosine kinase‐1: A meta‐analysis

Placenta Percreta Presents with Neoangiogenesis of Arteries with Von Willebrand Factor-Negative Endothelium

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