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BioMed Research International 2022This is the first meta-analysis that assessed the association between maternal smoking and the risk of placenta accreta spectrum (PAS), so this study was aimed at... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
This is the first meta-analysis that assessed the association between maternal smoking and the risk of placenta accreta spectrum (PAS), so this study was aimed at investigating the association between maternal smoking and PAS based on observational studies. PAS is defined as a severe obstetric complication due to the abnormal invasion of the chorionic villi into the myometrium and uterine serosa.
METHODS
We searched electronic bibliographic databases including PubMed, Web of Science, Scopus, Science Direct, and Google Scholar until January 2022. The results were reported using a random effect model. The chi-square test and the statistic were used to assess heterogeneity. Egger's and Begg's tests were used to examine the probability of publication bias. All statistical analyses were performed at a significance level of 0.05 using Stata software, version 11.
RESULTS
Based on the random effect model, the estimated OR of the risk of PAS associated with smoking was 1.21 (95% CI: 1.02, 1.41; = 4.7%). Subgroup analysis was conducted based on study design, and the result showed that the association between smoking and PAS among cohort studies was significant 1.35 (95% CI: 1.15, 1.55; = 0.0%).
CONCLUSION
Our results suggested that maternal smoking is a risk factor for the PAS. There was no heterogeneity among studies that reported an association between smoking and the PAS. The Newcastle-Ottawa Scale (NOS) was used to measure study quality.
Topics: Chi-Square Distribution; Cohort Studies; Female; Humans; Observational Studies as Topic; Placenta Accreta; Pregnancy; Risk Factors; Smoking
PubMed: 35860796
DOI: 10.1155/2022/2399888 -
Placenta Feb 2020Abnormally invasive placenta (AIP, aka placenta accreta spectrum; PAS) is an increasingly common pregnancy pathology, which, despite significant morbidity risk to the...
INTRODUCTION
Abnormally invasive placenta (AIP, aka placenta accreta spectrum; PAS) is an increasingly common pregnancy pathology, which, despite significant morbidity risk to the mother, is often undiagnosed prior to delivery. We tested several potential biomarkers in plasma from PAS mothers to determine whether any were sufficiently robust for a formal, diagnostic accuracy study.
METHODS
We examined hyperglycosylated hCG (h-hCG), decorin and IL-8, based on biological plausibility and literature indications that they might be altered in PAS. These analytes were assayed by ELISA in maternal plasma from five groups, comprising (1) normal term controls, (2) placenta previa controls, and cases of (3) placenta increta/percreta without placenta previa, (4) placenta previa increta/percreta and (5) placenta previa accreta.
RESULTS
There were no differences in h-hCG, ß-hCG or the h-hCG/ß-hCG ratio between the groups. Mean decorin levels were increased in previa controls (Group 2) compared to the other groups, but there was substantial overlap between the individual values. While an initial multiplex assay showed a greater value for IL-8 in the placenta previa increta/percreta group (Group 4) compared to placenta previa controls (Group 2), the subsequent validation ELISA for IL-8 showed no differences between the groups.
DISCUSSION
We conclude that the absence of differences and the extent of overlap between cases and controls does not justify further assessment of these biomarkers.
Topics: Adult; Biomarkers; Chorionic Gonadotropin; Decorin; Female; Humans; Interleukin-8; Placenta Accreta; Placenta Previa; Pregnancy
PubMed: 32174305
DOI: 10.1016/j.placenta.2020.01.007 -
American Journal of Obstetrics and... Apr 2024Placenta accreta spectrum disorders are associated with severe maternal morbidity and mortality. Placenta accreta spectrum disorders involve excessive adherence of the...
BACKGROUND
Placenta accreta spectrum disorders are associated with severe maternal morbidity and mortality. Placenta accreta spectrum disorders involve excessive adherence of the placenta preventing separation at birth. Traditionally, this condition has been attributed to excessive trophoblast invasion; however, an alternative view is a fundamental defect in decidual biology.
OBJECTIVE
This study aimed to gain insights into the understanding of placenta accreta spectrum disorder by using single-cell and spatially resolved transcriptomics to characterize cellular heterogeneity at the maternal-fetal interface in placenta accreta spectrum disorders.
STUDY DESIGN
To assess cellular heterogeneity and the function of cell types, single-cell RNA sequencing and spatially resolved transcriptomics were used. A total of 12 placentas were included, 6 placentas with placenta accreta spectrum disorder and 6 controls. For each placenta with placenta accreta spectrum disorder, multiple biopsies were taken at the following sites: placenta accreta spectrum adherent and nonadherent sites in the same placenta. Of note, 2 platforms were used to generate libraries: the 10× Chromium and NanoString GeoMX Digital Spatial Profiler for single-cell and spatially resolved transcriptomes, respectively. Differential gene expression analysis was performed using a suite of bioinformatic tools (Seurat and GeoMxTools R packages). Correction for multiple testing was performed using Clipper. In situ hybridization was performed with RNAscope, and immunohistochemistry was used to assess protein expression.
RESULTS
In creating a placenta accreta cell atlas, there were dramatic difference in the transcriptional profile by site of biopsy between placenta accreta spectrum and controls. Most of the differences were noted at the site of adherence; however, differences existed within the placenta between the adherent and nonadherent site of the same placenta in placenta accreta. Among all cell types, the endothelial-stromal populations exhibited the greatest difference in gene expression, driven by changes in collagen genes, namely collagen type III alpha 1 chain (COL3A1), growth factors, epidermal growth factor-like protein 6 (EGFL6), and hepatocyte growth factor (HGF), and angiogenesis-related genes, namely delta-like noncanonical Notch ligand 1 (DLK1) and platelet endothelial cell adhesion molecule-1 (PECAM1). Intraplacental tropism (adherent versus non-adherent sites in the same placenta) was driven by differences in endothelial-stromal cells with notable differences in bone morphogenic protein 5 (BMP5) and osteopontin (SPP1) in the adherent vs nonadherent site of placenta accreta spectrum.
CONCLUSION
Placenta accreta spectrum disorders were characterized at single-cell resolution to gain insight into the pathophysiology of the disease. An atlas of the placenta at single cell resolution in accreta allows for understanding in the biology of the intimate maternal and fetal interaction. The contributions of stromal and endothelial cells were demonstrated through alterations in the extracellular matrix, growth factors, and angiogenesis. Transcriptional and protein changes in the stroma of placenta accreta spectrum shift the etiologic explanation away from "invasive trophoblast" to "loss of boundary limits" in the decidua. Gene targets identified in this study may be used to refine diagnostic assays in early pregnancy, track disease progression over time, and inform therapeutic discoveries.
Topics: Pregnancy; Female; Infant, Newborn; Humans; Placenta Accreta; Endothelial Cells; Placenta; Placenta Diseases; Abruptio Placentae; Intercellular Signaling Peptides and Proteins; Decidua; Endothelium
PubMed: 38296740
DOI: 10.1016/j.ajog.2023.10.001 -
Placenta Dec 2020The invasion of the uterine wall by extravillous trophoblast is acknowledged as a crucial component of the establishment of pregnancy however, the only part of this... (Review)
Review
The invasion of the uterine wall by extravillous trophoblast is acknowledged as a crucial component of the establishment of pregnancy however, the only part of this process that has been clearly identified is the differentiation of cytotrophoblast (CTB) into the invasive extravillous trophoblast (EVT). The control of invasion, both initiation and termination, have yet to be elucidated and even the mechanism of differentiation is unclear. This review describes our studies which are designed to characterize the intracellular mechanisms that drive differentiation. We have used the over-invasion observed in abnormally invasive placenta (AIP; placenta accreta) to further interrogate this mechanism. Our results show that first trimester CTB to EVT differentiation is accomplished via an epithelial-mesenchymal transition (EMT), with EVT displaying a metastable, mesenchymal phenotype. In the third trimester, while the invasiveness of the EVT is lost, these cells still demonstrate signs of the EMT, albeit diminished. EVT isolated from AIP pregnancies do not however, show the same degree of reduction in EMT shown by normal third trimester cells. They exhibit a more mesenchymal phenotype, consistent with a legacy of greater invasiveness. The master regulatory transcription factor controlling the EMT appears, from the observational data, to be ZEB2 (zinc finger E-box binding protein 2). We verified this by overexpressing ZEB2 in the BeWo and JEG3 trophoblast cell lines and showing that they became more stellate in shape, up-regulated the expression of EMT-associated genes and demonstrated a substantially increased degree of invasiveness. The identification of the differentiation mechanism will enable us to identify the factors controlling invasion and those aberrant processes which generate the abnormal invasion seen in pathologies such as AIP and preeclampsia.
Topics: Animals; Cell Differentiation; Cesarean Section; Epithelial-Mesenchymal Transition; Female; Humans; Placenta Accreta; Placenta Previa; Pregnancy; Pregnancy Trimester, Third; Trophoblasts
PubMed: 33218581
DOI: 10.1016/j.placenta.2020.01.004 -
European Journal of Radiology Nov 2023To build and validate a predictive model of placental accreta spectrum (PAS) in patients with placenta previa (PP) combining clinical risk factors (CRF) with US and MRI...
PURPOSE
To build and validate a predictive model of placental accreta spectrum (PAS) in patients with placenta previa (PP) combining clinical risk factors (CRF) with US and MRI signs.
METHOD
Our retrospective study included patients with PP from two institutions. All patients underwent US and MRI examinations for suspicion of PAS. CRF consisting of maternal age, cesarean section number, smoking and hypertension were retrieved. US and MRI signs suggestive of PAS were evaluated. Logistic regression analysis was performed to identify CRF and/or US and MRI signs associated with PAS considering histology as the reference standard. A nomogram was created using significant CRF and imaging signs at multivariate analysis, and its diagnostic accuracy was measured using the area under the binomial ROC curve (AUC), and the cut-off point was determined by Youden's J statistic.
RESULTS
A total of 171 patients were enrolled from two institutions. Independent predictors of PAS included in the nomogram were: 1) smoking and number of previous CS among CRF; 2) loss of the retroplacental clear space at US; 3) intraplacental dark bands, focal interruption of the myometrial border and placental bulging at MRI. A PAS-prediction nomogram was built including these parameters and an optimal cut-off of 14.5 points was identified, showing the highest sensitivity (91%) and specificity (88%) with an AUC value of 0.95 (AUC of 0.80 in the external validation cohort).
CONCLUSION
A nomogram-based model combining CRF with US and MRI signs might help to predict PAS in PP patients, with MRI contributing more than US as imaging evaluation.
Topics: Pregnancy; Humans; Female; Placenta Accreta; Placenta Previa; Placenta; Retrospective Studies; Cesarean Section; Magnetic Resonance Imaging
PubMed: 37801998
DOI: 10.1016/j.ejrad.2023.111116 -
The Journal of Maternal-fetal &... Dec 2023To demonstrate the surgical and morbidity differences between upper and lower parametrial placenta invasion (PPI).
OBJECTIVE
To demonstrate the surgical and morbidity differences between upper and lower parametrial placenta invasion (PPI).
MATERIALS AND METHODS
Forty patients with placenta accreta spectrum (PAS) into the parametrium underwent surgery between 2015 and 2020. Based on the peritoneal reflection, the study compared two types of parametrial placental invasion (PPI), upper or lower. Surgical approach to PAS follows a conservative-resective method. Before delivery, surgical staging by pelvic fascia dissection established a final diagnosis of placental invasion. In upper PPI cases, the team attempted to repair the uterus after resecting all invaded tissues or performing a hysterectomy. In cases of lower PPI, experts performed a hysterectomy in all cases. The team only used proximal vascular (aortic occlusion) control in cases of lower PPI. Surgical dissection for lower PPI started finding the ureter in the pararectal space, ligating all the tissues (placenta and newly formed vessels) to create a tunnel to release the ureter from the placenta and placenta suppletory vessels. Overall, at least three pieces of the invaded area were sent for histological analysis.
RESULTS
Forty patients with PPI were included, 13 in the upper parametrium and 27 in the lower parametrium. MRI indicated PPI in 33/40 patients; in three, the diagnosis was presumed by ultrasound or medical background. The intrasurgical staging categorizes 13 cases of PPI performed and finds diagnosis in seven undetected cases. The expertise team completed a total hysterectomy in 2/13 upper PPI cases and all lower PPI cases (27/27). Hysterectomies in the upper PPI group were performed by extensive damage of the lateral uterine wall or with a tube compromise. Ureteral injury ensued in six cases, corresponding to cases without catheterization or incomplete ureteral identification. All aortic vascular proximal control (aortic balloon, internal aortic compression, or aortic loop) was efficient for controlling bleeding; in contrast, ligature of the internal iliac artery resulted in a useless procedure, resulting in uncontrollable bleeding and maternal death (2/27). All patients had antecedents of placental removal, abortion, curettage after a cesarean section, or repeated D&C.
CONCLUSIONS
Lower PAS parametrial involvement is uncommon but associated with elevated maternal morbidity. Upper and lower PPI has different surgical risks and technical approaches; consequently, an accurate diagnosis is needed. The clinical background of manual placental removal, abortion, and curettage after a cesarean or repeated D&C could be ideally studied to diagnose a possible PPI. For patients with high-risk antecedents or unsure ultrasound, a T2 weight MRI is always recommended. Performing comprehensive surgical staging in PAS allows the efficient diagnosis of PPI before using some procedures.
Topics: Pregnancy; Humans; Female; Placenta Accreta; Cesarean Section; Peritoneum; Placenta; Hysterectomy; Retrospective Studies; Morbidity
PubMed: 36966802
DOI: 10.1080/14767058.2023.2183764 -
International Journal of Molecular... May 2022Placenta accreta spectrum (PAS) accounts for 7% of maternal mortality and is associated with intraoperative and postoperative morbidity caused by massive blood loss,...
Placenta accreta spectrum (PAS) accounts for 7% of maternal mortality and is associated with intraoperative and postoperative morbidity caused by massive blood loss, infection, and adjacent organ damage. The aims of this study were to identify the protein biomarkers of PAS and to further explore their pathogenetic roles in PAS. For this purpose, we collected five placentas from pregnant subjects with PAS complications and another five placentas from normal pregnancy (NP) cases. Then, we enriched protein samples by specifically isolating the trophoblast villous, deeply invading into the uterine muscle layer in the PAS patients. Next, fluorescence-based two-dimensional difference gel electrophoresis (2D-DIGE) and MALDI-TOF/MS were used to identify the proteins differentially abundant between PAS and NP placenta tissues. As a result, nineteen spots were determined as differentially abundant proteins, ten and nine of which were more abundant in PAS and NP placenta tissues, respectively. Then, specific validation with western blot assay and immunohisto/cytochemistry (IHC) assay confirmed that heat shock 70 kDa protein 4 (HSPA4) and chorionic somatomammotropin hormone (CSH) were PAS protein biomarkers. Further tube formation assays demonstrated that HSPA4 promoted the in vitro angiogenesis ability of vessel endothelial cells, which is consistent with the in vivo scenario of PAS complications. In this study, we not only identified PAS protein biomarkers but also connected the promoted angiogenesis with placenta invasion, investigating the pathogenetic mechanism of PAS.
Topics: Biomarkers; Cesarean Section; Endothelial Cells; Female; HSP110 Heat-Shock Proteins; Humans; Placenta; Placenta Accreta; Pregnancy
PubMed: 35628491
DOI: 10.3390/ijms23105682 -
American Journal of Perinatology Jan 2019To investigate the association between the intraoperative diagnosis of placenta accreta at the time of cesarean hysterectomy and pathological diagnosis.
OBJECTIVE
To investigate the association between the intraoperative diagnosis of placenta accreta at the time of cesarean hysterectomy and pathological diagnosis.
STUDY DESIGN
This is a retrospective cohort study of all patients undergoing cesarean hysterectomy for suspected placenta accreta from 2000 to 2016 at Barnes-Jewish Hospital. The primary outcome was the presence of invasive placentation on the pathology report. We estimated predictive characteristics of clinical diagnosis of placenta accreta using pathological diagnosis as the correct diagnosis.
RESULTS
There were 50 cesarean hysterectomies performed for suspected abnormal placentation from 2000 to 2016. Of these, 34 (68%) had a diagnosis of accreta preoperatively and 16 (32%) were diagnosed intraoperatively at the time of cesarean delivery. Two patients had no pathological evidence of invasion, corresponding to a false-positive rate of 4% (95% confidence interval [CI]: 0.5%, 13.8%) and a positive predictive value of 96% (95% CI: 86.3%, 99.5%). There were no differences in complications among patients diagnosed intraoperatively compared with those diagnosed preoperatively.
CONCLUSION
Most patients undergoing cesarean hysterectomy for placenta accreta do have this diagnosis confirmed on pathology. However, since the diagnosis of placenta accreta was made intraoperatively in nearly a third of cesarean hysterectomies, intraoperative vigilance is required as the need for cesarean hysterectomy may not be anticipated preoperatively.
Topics: Adult; Cesarean Section; False Positive Reactions; Female; Humans; Hysterectomy; Intraoperative Period; Placenta; Placenta Accreta; Placentation; Pregnancy; Retrospective Studies; Uterus
PubMed: 30193384
DOI: 10.1055/s-0038-1670635 -
Ultrasound in Obstetrics & Gynecology :... Apr 2022To perform a systematic review and meta-analysis of the diagnostic test accuracy of ultrasound and magnetic resonance imaging (MRI) and compare the performance of the... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
To perform a systematic review and meta-analysis of the diagnostic test accuracy of ultrasound and magnetic resonance imaging (MRI) and compare the performance of the two modalities in the diagnosis of placenta accreta spectrum (PAS).
METHODS
This was a systematic review conducted following the Cochrane Diagnostic Test Accuracy Reviews guideline. A literature search was performed in five databases: PubMed, EMBASE, PMC, The Cochrane Library and BVS-Bireme between 27 July and 4 August 2020. The search was updated on 18 August 2021. We included observational studies evaluating diagnostic accuracy in women with risk factors for PAS who had undergone both ultrasound and MRI examinations, published in English between 2011 and 2021. Quality Assessment of Diagnostic Accuracy Studies-2 was used to evaluate the quality of the studies. Forest plots for sensitivity and specificity with 95% CIs and receiver-operating-characteristics curves for ultrasound and MRI were constructed.
RESULTS
The literature search identified 266 studies. After reviewing the titles and abstracts of the articles, 51 were selected for full-text review and 17 studies including 1301 women with MRI and ultrasound data available were selected for the meta-analysis. The study population included 457 cases with PAS diagnosed using the gold standard method (intraoperative or histopathological analysis). The overall quality of the evaluated studies was considered satisfactory according to QUADAS-2. The meta-analysis revealed a sensitivity of 0.833 (95% CI, 0.776-0.878) and specificity of 0.834 (95% CI, 0.746-0.897) for ultrasound. For MRI, sensitivity was 0.838 (95% CI, 0.786-0.879) and specificity was 0.831 (95% CI, 0.770-0.878). There was no statistically significant difference between the two modalities. The Cochran's Q values indicated a high level of heterogeneity of sensitivity and specificity of ultrasound and MRI across studies.
CONCLUSIONS
Ultrasound and MRI have similar accuracy in the diagnosis of PAS. These results suggest that, in a setting with a high prevalence of risk factors, the choice of imaging modality for initial screening for PAS should depend on the availability of equipment and the examiner's expertise. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.
Topics: Female; Humans; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Placenta Accreta; Pregnancy; Sensitivity and Specificity; Ultrasonography
PubMed: 35041250
DOI: 10.1002/uog.24861 -
Revista Brasileira de Ginecologia E... Sep 2021
Topics: Cesarean Section; Female; Humans; Hysterectomy; Placenta; Placenta Accreta; Pregnancy; Retrospective Studies
PubMed: 34670307
DOI: 10.1055/s-0041-1736371