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The worldwide incidence of placenta accreta spectrum (PAS) is rapidly increasing, following the trend of rising cesarean delivery. PAS is an heterogeneous condition associated with a high maternal morbidity and mortality rate, presenting unique challenges in its diagnosis and management. So far, the rarity of this condition, together with the absence of high quality evidence and the lack of a standardized approach in reporting PAS cases for the ultrasound, clinical, and pathologic diagnosis, represented the main challenges for a deep understanding of this condition. The study of the available management strategies of PAS has been hampered by the heterogeneity of the available epidemiological data on this condition. The aim of this review is to provide a critical view of the current available evidence on the screening, the diagnosis, and the management options for PAS disorders, with a special focus on the challenges we foresee for the near future.

Placenta accreta spectrum (PAS) disorders are characterized by abnormal trophoblastic invasion into the myometrium, leading to significant maternal health risks. PAS includes placenta accreta (invasion < 50% of the myometrium), increta (invasion > 50%), and percreta (invasion through the entire myometrium). The condition is most associated with previous cesarean deliveries and increases in chance with the number of prior cesarians. The increasing global cesarean rates heighten the importance of early PAS diagnosis and management. This review explores genetic expression and key regulatory processes, such as apoptosis, cell proliferation, invasion, and inflammation, focusing on signaling pathways, genetic expression, biomarkers, and non-coding RNAs involved in trophoblastic invasion. It compiles the recent scientific literature (2014–2024) from the Scopus, PubMed, Google Scholar, and Web of Science databases. Identifying new biomarkers like AFP, sFlt-1, β-hCG, PlGF, and PAPP-A aids in early detection and management. Understanding genetic expression and non-coding RNAs is crucial for unraveling PAS complexities. In addition, aberrant signaling pathways like Notch, PI3K/Akt, STAT3, and TGF-β offer potential therapeutic targets to modulate trophoblastic invasion. This review underscores the need for interdisciplinary care, early diagnosis, and ongoing research into PAS biomarkers and molecular mechanisms to improve prognosis and quality of life for affected women.

Objective To evaluate the diagnostic accuracy of ultrasound and in the diagnosis of Placenta accreta spectrum (PAS). Data sources Screening of MEDLINE, CENTRAL, other bases from inception to February 2022 using the keywords related to placenta accreta, increta, percreta, morbidly adherent placenta, and preoperative ultrasound diagnosis. Study eligibility criteria All available studies- whether were prospective or retrospective- including cohort, case control and cross sectional that involved prenatal diagnosis of PAS using 2D or 3D ultrasound with subsequent pathological confirmation postnatal were included. Fifty-four studies included 5307 women fulfilled the inclusion criteria, PAS was confirmed in 2025 of them. Study appraisal and synthesis methods Extracted data included settings of the study, study type, sample size, participants characteristics and their inclusion and exclusion criteria, Type and site of placenta previa, Type and timing of imaging technique (2D, and 3D), severity of PAS, sensitivity and specificity of individual ultrasound criteria and overall sensitivity and specificity. Results The overall sensitivity was 0.8703, specificity was 0.8634 with -0.2348 negative correlation between them. The estimate of Odd ratio, negative likelihood ratio and positive likelihood ratio were 34.225, 0.155 and 4.990 respectively. The overall estimates of loss of retroplacental clear zone sensitivity and specificity were 0.820 and 0.898 respectively with 0.129 negative correlation. The overall estimates of myometrial thinning, loss of retroplacental clear zone, the presence of bridging vessels, placental lacunae, bladder wall interruption, exophytic mass, and uterovesical hypervascularity sensitivities were 0.763, 0.780, 0.659, 0.785, 0.455, 0.218 and 0.513 while specificities were 0.890, 0.884, 0.928, 0.809, 0.975, 0.865 and 0.994 respectively. Conclusions The accuracy of ultrasound in diagnosis of PAS among women with low lying or placenta previa with previous cesarean section scars is high and recommended in all suspected cases. Trial registration Number CRD42021267501.

Introduction Placenta accreta spectrum (PAS) disorders occur when the definitive placenta develops within the uterus scar area. Although classically PAS develops in the anterior wall of the uterus mainly, it can also develop in the posterior uterine wall. The aim of this study was to report the risk factors, diagnostic accuracy of prenatal imaging, and surgical outcome of pregnancies complicated by posterior PAS in women with placenta previa or low‐lying. Material and Methods Secondary analysis of a multicenter prospective study involving 16 referral hospitals in Italy (ADoPAD Study). Inclusion criteria were patients with a posterior low‐lying placenta (<20 mm from the internal cervical os) or placenta previa (covering the os), aged ≥18 years undergoing ultrasound assessment at ≥26+0 weeks of gestation. The reference standard for PAS was represented by the failure of placental separation at delivery or by pathological analysis. The primary aim was to report the risk factors associated with the occurrence of posterior PAS. The secondary aims were to evaluate the ability of prenatal ultrasound in detecting posterior PAS and to report its surgical outcome compared to posterior placental previa or low‐lying with no PAS and anterior PAS, respectively, and in patients with a prenatal compared to post‐natal diagnosis. Univariate and diagnostic accuracy analyses were used to analyze the data. Results 258 patients were included in the analysis. Posterior PAS occurred in 8.1% (n = 21; 95% CI 5.4–12.1) of patients. There was a higher incidence of one or more prior CS (62% vs. 21%, p < 0.001) and myomectomy with uterine penetration (71.0% vs. 3.4%, p < 0.001) in patients with posterior PAS compared to those with no PAS. In patients with posterior PAS, placenta accreta occurred in 66.67% (14/21), increta in 23.81% (5/21), and percreta in 9.52% (2/21) of cases. Posterior PAS confirmed at birth was diagnosed prenatally by ultrasound in 62% (13/21) of cases. When comparing anterior with posterior PAS, patients with anterior PAS were more likely to have a prior CS (82% vs. 62%; p = 0.0049) and placenta percreta (54% vs. 10%; p < 0.001). Finally, the need for hysterectomy (89% vs. 48%; p < 0.001) was higher, while that of balloon tamponade insertion was lower (17% vs. 52%; p = 0.001) in patients with anterior compared to posterior PAS. Conclusions Prior uterine surgery in patients with placenta previa or low‐lying represents the commonest risk factors for posterior PAS. The diagnostic accuracy of ultrasound in detecting posterior PAS is lower in cases with posterior compared to anterior PAS. Finally, in referral centers, posterior PAS disorders were associated with a lower risk of hysterectomy compared to anterior PAS. Prenatal ultrasound has a low diagnostic accuracy in detecting posterior compared to anterior placenta accreta spectrum disorder. However, posterior placenta accreta spectrum disorders are associated with a lower risk of hysterectomy compared to cases with anterior implantation.

Introduction A peripartum hysterectomy is typically performed as a lifesaving procedure in obstetrics to manage severe postpartum hemorrhage. Severe hemorrhages that lead to peripartum hysterectomies are mainly caused by uterine atony and placenta accreta spectrum disorders. In this study, we aimed to estimate the incidence, risk factors, causes and management of severe postpartum hemorrhage resulting in peripartum hysterectomies, and to describe the complications of the hysterectomies. Material and methods Eligible women had given birth at gestational week 23+0 or later and had a postpartum hemorrhage ≥1500 mL or a blood transfusion, due to postpartum hemorrhage, at Oslo University Hospital, Norway, between 2008 and 2017. Among the eligible women, this study included those who underwent a hysterectomy within the first 42 days after delivery. The Norwegian Medical Birth Registry provided the reference group. We used Poisson regression to estimate adjusted incidence rate ratios with 95% confidence intervals to identify clinical factors associated with peripartum hysterectomy. Results The incidence of hysterectomies with severe postpartum hemorrhage was 0.44/1000 deliveries (42/96313). Among the women with severe postpartum hemorrhage, 1.6% ended up with a hysterectomy (42/2621). Maternal age ≥40, previous cesarean section, multiple pregnancy and placenta previa were associated with a significantly higher risk of hysterectomy. Placenta accreta spectrum disorders were the most frequent cause of hemorrhage that resulted in a hysterectomy (52%, 22/42) and contributed to most of the complications following the hysterectomy (11/15 women with complications). Conclusions The rate of peripartum hysterectomies at Oslo University Hospital was low, but was higher than previously reported from Norway. Risk factors included high maternal age, previous cesarean section, multiple pregnancy and placenta previa, well known risk factors for placenta accreta spectrum disorders and severe postpartum hemorrhage. Placenta accreta spectrum disorders were the largest contributor to hysterectomies and complications.

The terminology and diagnostic criteria presently used by pathologists to report invasive placentation is inconsistent and does not reflect current knowledge of the pathogenesis of the disease or the needs of the clinical care team. A consensus panel was convened to recommend terminology and reporting elements unified across the spectrum of PAS specimens (i.e., delivered placenta, total or partial hysterectomy with or without extrauterine tissues, curetting for retained products of conception). The proposed nomenclature under the umbrella diagnosis of placenta accreta spectrum (PAS) replaces the traditional categorical terminology (placenta accreta, increta, percreta) with a descriptive grading system that parallels the guidelines endorsed by the International Federation of Gynaecology and Obstetrics (FIGO). In addition, the nomenclature for hysterectomy specimens is separated from that for delivered placentas. The goal for each element in the system of nomenclature was to provide diagnostic criteria and guidelines for expected use in clinical practice.

Placenta accreta spectrum (PAS) and placenta previa (PP) are severe obstetric disorders associated with high maternal and perinatal morbidity. Early diagnosis of both conditions remains challenging, particularly in cases with subtle imaging findings. This study was aimed to evaluate the diagnostic value of first-trimester maternal serum levels of pregnancy-associated plasma protein-A (PAPP-A) and free beta subunit of human chorionic gonadotropin (β-hCG) in predicting PAS and PP. In this retrospective case–control study, a total of 100 pregnant women were included: 36 with PAS, 32 with PP, and 32 healthy controls. Serum levels were measured at 11–136 weeks of gestation. Both biomarkers were significantly altered in pathological groups compared to controls: PAPP-A was lower in PP (3.04 [1.42–4.52] IU/L) and PAS (3.63 [2.51–5.39] IU/L) vs. controls (5.34 [3.72–8.41] IU/L; p < 0.001), while β-hCG was higher in PP (45.4 [40.1–54.9] IU/L) and PAS (51.4 [32.3–74.8] IU/L) vs. controls (33.5 [22.7–54.1] IU/L; p = 0.044 and p < 0.001, respectively). ROC analysis demonstrated that combined biomarker modeling improved diagnostic accuracy over single-marker use, with AUCs reaching 0.85 (sensitivity 85.2%, specificity 72%) for PAS and 0.88 (sensitivity 100%, specificity 72%) for PP. These findings support the integration of biochemical screening into first-trimester risk assessment protocols. Incorporating maternal serum biomarkers may enhance early identification of high-risk pregnancies, allow timely referral to specialized care, and reduce adverse outcomes. Further prospective studies are warranted to validate the utility of this dual-marker approach across diverse populations and clinical settings.

A well-functioning placenta is crucial for normal gestation and regulates the nutrient, gas, and waste exchanges between the maternal and fetal circulations and is an important endocrine organ producing hormones that regulate both the maternal and fetal physiologies during pregnancy. Placental insufficiency is implicated in spontaneous preterm birth (SPTB). We proposed that deficits in the capacity of the placenta to maintain bioenergetic and metabolic stability during pregnancy may ultimately result in SPTB. To explore our hypothesis, we performed a RNA-seq study in male and female placentas from women with SPTB (<36 weeks gestation) compared to normal pregnancies (≥38 weeks gestation) to assess the alterations in the gene expression profiles. We focused exclusively on Black women (cases and controls), who are at the highest risk of SPTB. Six hundred and seventy differentially expressed genes were identified in male SPTB placentas. Among them, 313 and 357 transcripts were increased and decreased, respectively. In contrast, only 61 differentially expressed genes were identified in female SPTB placenta. The ingenuity pathway analysis showed alterations in the genes and canonical pathways critical for regulating inflammation, oxidative stress, detoxification, mitochondrial function, energy metabolism, and the extracellular matrix. Many upstream regulators and master regulators important for nutrient-sensing and metabolism were also altered in SPTB placentas, including the PI3K complex, TGFB1/SMADs, SMARCA4, TP63, CDKN2A, BRCA1, and NFAT. The transcriptome was integrated with published human placental metabolome to assess the interactions of altered genes and metabolites. Collectively, significant and biologically relevant alterations in the transcriptome were identified in SPTB placentas with fetal sex disparities. Altered energy metabolism, mitochondrial function, inflammation, and detoxification may underly the mechanisms of placental dysfunction in SPTB.

Backgrounds Pregnancy termination during the second trimester in patients with placenta previa and placenta accreta spectrum (PAS) is a complex and challenging clinical problem. Based on our literature review, there has been a relative increase in the number of such cases being treated by hysterotomy and/or local uterine lesion resection and repair. In the present study, a retrospective analysis was conducted to compare the clinical outcomes when different management strategies were used to terminate pregnancy in the patients with placenta previa and PAS. Methods A total of 51 patients who underwent pregnancy termination in the second trimester in Beijing Obstetrics and Gynecology Hospital between June 2013 and December 2018 were retrospectively analyzed in this study. All patients having previous caesarean delivery (CD) were diagnosed with placenta previa status and PAS. Results ① Among the 51 patients, 16 cases received mifepristone and misoprostol medical termination, 15 cases received mifepristone and Rivanol medical termination, but 1 of them was transferred to hysterotomy due to failed labor induction, another 20 cases were performed planned hysterotomy. There was no placenta percreta cases and uterine artery embolization (UAE) was all performed before surgery.② There were 31 cases who underwent medical termination and 30 cases were vaginal delivery. Dilation and evacuation (D&E) were used in 20 cases of medical abortion failure and in all 30 cases of difficult manual removal of placental tissue. ③ A statistically significant difference was found among the three different strategies in terms of gestational weeks, the type of placenta previa status, main operative success rate and β-HCG regression time ( P  < 0.05). ④ There were 4(7.8%) cases who were taken up for hysterectomy because of life-threatening bleeding or severe bacteremia during or after delivery and hysterotomy. The uterus was preserved with the implanted placenta partly or completely left in situ in 47(92.2%) cases. Combined medical and/or surgical management were used for the residual placenta and the time of menstrual recovery was 52(range: 33 to 86) days after pregnancy termination. Conclusions Terminating a pregnancy by vaginal delivery through medical induction of labor may be feasible if clinicians have an overall understanding of gestational age, the type of placenta previa status, the type of placenta accreta, and patients concerns about preserving fertility. A collaborative team effort in tertiary medical centers with a very experience MDT and combined application of multiple methods is required to optimize patient outcomes.

Placenta accreta spectrum (PAS) refers to excessive placental invasion into the maternal uterus and it is associated with high risk of obstetric haemorrhage and adverse maternal-neonatal outcomes. Currently, no specific circulating biomarkers of PAS have been identified. Given that in PAS disorders, the depth and the extension of placental invasion into the uterus are expected to be increased, in this study, we analysed plasma levels of syncytiotrophoblast-derived extracellular vesicles (STBEVs) in women with placenta previa (PP), at a high risk of PAS disorders, and pregnant women with normal placentation. Venous blood samples were collected from 35 women with ultrasonographic diagnosis of PP and 35 women with normal placentation, matched for gestational age. Plasma samples were ultracentrifuged at 120.000 g to collect extracellular vesicles (EVs). To identify and quantify plasma placenta–derived EVs (or STBEVs), EVs were analysed by flow cytometry using a monoclonal antibody against placental alkaline phosphatase (PLAP). Plasma levels of STBEVs were significantly higher in PP patients compared to controls. Plasma levels of STBEVs in women with PP and PAS showed a trend to a higher concentration compared to women with PP without PAS, although not reaching a statistical significance. Circulating STBEVs are potential candidates as biological markers to be integrated to ultrasonography in the antenatal screening programme for PAS. More studies are needed to confirm our observation in a larger cohort of patients and to analyse a possible association between high circulating levels of STBEVs and PAS.