Placenta accreta spectrum disorder at single-cell resolution: a loss of boundary limits in the decidua and endothelium.

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.

Opportunities for, and barriers to, uterus-preserving surgical techniques for placenta accreta spectrum.

INTRODUCTION: Placenta accreta spectrum (PAS) can lead to major peripartum morbidity. Appropriate management approaches depend on the clinical severity, each individual's preference, and the treating team's expertise. Peripartum hysterectomy is the most frequently used treatment option. However, it can impact psychological well-being and fertility. We investigated whether conservative treatment with focal resection or leaving the placenta in situ is associated with comparable or lower maternal morbidity than hysterectomy in centers of excellence within the International Society for placenta accreta spectrum (IS-PAS). Furthermore, a survey was conducted to explore potential barriers to conservative management in antenatal counseling and intraoperative decision-making. MATERIAL AND METHODS: Confirmed PAS cases in the prospective IS-PAS database from 22 registered centers between January 2020 and June 2022 were included in the analysis. A separate online survey with 21 questions was answered by the IS-PAS center experts about indications, diagnostic criteria, patient counseling, surgical practice, changes from the preoperative treatment plan, and why conservative management may not be offered. RESULTS: A total of 234 cases were included in the analysis: 186 women received hysterectomy and 38 women were treated by focal resection, and 10 by leaving the placenta in situ. Blood loss was lower in the focal resection group and in the placenta in situ group compared to the hysterectomy group (p = 0.04). 46.4% of the women initially planned for focal resection, and 35.7% of those initially planned for leaving the placenta in situ were ultimately treated by hysterectomy. Our survey showed that the IS-PAS centers preferred hysterectomy according to a woman's wishes (64%) and when they expected less blood loss and morbidity (41%). Eighteen percent of centers did not offer focal resection at all due to a lack of experience with this technique. Reasons for not offering to leave the placenta in situ were avoidance of unexpected reoperation (36%), puerperal infection (32%), or skepticism about the method (23%). CONCLUSIONS: Uterus-preserving treatment strategies such as focal resection appear to be safe alternatives to peripartum hysterectomy. However, less than half of the IS-PAS centers perform them. Acceptance of conservative treatments could be increased by standardized criteria for their implementation and by systematic training for PAS experts.

Ultrasound scoring system for prenatal diagnosis of placenta accreta spectrum.

BACKGROUND: To develop an ultrasound scoring system for placenta accreta spectrum (PAS), evaluate its diagnostic value, and provide a practical approach to prenatal diagnosis of PAS. METHODS: A total of 532 pregnant women (n = 184 no PAS, n = 120 placenta accreta, n = 189 placenta increta, n = 39 placenta percreta) at high-risk for placenta accreta who delivered in the Third Affiliated Hospital of Zhengzhou University between January 2021 and December 2022 underwent prenatal ultrasound to evaluate placental invasion. An ultrasound scoring system that included placental and cervical morphology and history of cesarean section was created. Each feature was assigned a score of 0 ~ 2, according to severity. Thresholds for the total ultrasound score that discriminated between no PAS, placenta accreta, placenta increta, and placenta percreta were calculated. RESULTS: Univariate and multivariate regression analysis identified seven indicators of PAS that were included in the ultrasound scoring system, including placental location, placental thickness, presence/absence of the retroplacental space, thickness of the retroplacental myometrium, presence/absence of placental lacunae, retroplacental myometrial blood flow and history of cesarean section. Using the final ultrasound scoring system, no PAS is diagnosed at a total score < 5, placenta accreta or placenta increta is diagnosed at a total score 5-10, and placenta percreta is diagnosed at a total score ≥ 10. CONCLUSIONS: This study identified seven indicators of PAS and included them in an ultrasound scoring system that has good diagnostic efficacy and clinical utility. TRIAL REGISTRATION: ChiCTR2300069261 (retrospectively registered on 10/03/2023).

Efficacy of resuscitative endovascular balloon occlusion of the aorta for hemorrhage control in patients with abnormally invasive placenta: a historical cohort study.

BACKGROUND: Patients with abnormally invasive placenta (AIP) are at high risk of massive postpartum hemorrhage. Resuscitative endovascular balloon occlusion of the aorta (REBOA), as an adjunct therapeutic strategy for hemostasis, offers the obstetrician an alternative for treating patients with AIP. This study aimed to evaluate the role of REBOA in hemorrhage control in patients with AIP. METHODS: This was a historical cohort study with prospectively collected data between January 2014 to July 2021 at a single tertiary center. According to delivery management, 364 singleton pregnant AIP patients desiring uterus preservation were separated into two groups. The study group (balloon group, n = 278) underwent REBOA during cesarean section, whereas the reference group (n = 86) did not undergo REBOA. Surgical details and maternal outcomes were collected. The primary outcome was estimated blood loss and the rate of uterine preservation. RESULTS: A total of 278 (76.4%) participants experienced REBOA during cesarean section. The patients in the balloon group had a smaller blood loss during cesarean Sect. (1370.5 [752.0] ml vs. 3536.8 [1383.2] ml; P < .001) and had their uterus salvaged more often (264 [95.0%] vs. 23 [26.7%]; P < .001). These patients were also less likely to be admitted to the intensive care unit after delivery (168 [60.4%] vs. 67 [77.9%]; P = .003) and had a shorter operating time (96.3 [37.6] min vs. 160.6 [45.5] min; P < .001). The rate of neonatal intensive care unit admission (176 [63.3%] vs. 52 [60.4%]; P = .70) and total maternal medical costs ($4925.4 [1740.7] vs. $5083.2 [1705.1]; P = .13) did not differ between the two groups. CONCLUSIONS: As a robust hemorrhage-control technique, REBOA can reduce intraoperative hemorrhage in patients with AIP. The next step is identifying associated risk factors and defining REBOA inclusion criteria to identify the subgroups of AIP patients who may benefit more.

Placenta Accreta Spectrum Part I: anesthesia considerations based on an extended review of the literature.

"Placenta Accreta Spectrum" (PAS) describes abnormal placental adherence to the uterine wall without spontaneous separation at delivery. Though relatively rare, PAS presents a particular challenge to anesthesiologists, as it is associated with massive peripartum hemorrhage and high maternal morbidity and mortality. Standardized evidence-based PAS management strategies are currently evolving and emphasize: "PAS centers of excellence", multidisciplinary teams, novel diagnostics/pharmaceuticals (especially regarding hemostasis, hemostatic agents, point-of-care diagnostics), and novel operative/interventional approaches (expectant management, balloon occlusion, embolization). Though available data are heterogeneous, these developments affect anesthetic management and must be considered in planed anesthetic approaches. This two-part review provides a critical overview of the current evidence and offers structured evidence-based recommendations to help anesthesiologists improve outcomes for women with PAS. This first part discusses PAS management in centers of excellence, multidisciplinary care team, anesthetic approach and monitoring, surgical approaches, patient safety checklists, temperature management, interventional radiology, postoperative care and pain therapy. The diagnosis and treatment of hemostatic disturbances and preoperative prepartum anemia, blood loss, transfusion management and postpartum venous thromboembolism will be addressed in the second part of this series.

Placenta Accreta Spectrum Part II: hemostatic considerations based on an extended review of the literature.

"Placenta Accreta Spectrum" (PAS) is a rare but serious pregnancy condition where the placenta abnormally adheres to the uterine wall and fails to spontaneously release after delivery. When it occurs, PAS is associated with high maternal morbidity and mortality - as PAS management can be particularly challenging. This two-part review summarizes current evidence in PAS management, identifies its most challenging aspects, and offers evidence-based recommendations to improve management strategies and PAS outcomes. The first part of this two-part review highlighted the general anesthetic approach, surgical and interventional management strategies, specialized "centers of excellence," and multidisciplinary PAS treatment teams. The high rates of PAS morbidity and mortality are often provoked by PAS-associated coagulopathies and peripartal hemorrhage (PPH). Anesthesiologists need to be prepared for massive blood loss, transfusion, and to manage potential coagulopathies. In this second part of this two-part review, we specifically reviewed the current literature pertaining to hemostatic changes, blood loss, transfusion management, and postpartum venous thromboembolism prophylaxis in PAS patients. Taken together, the two parts of this review provide a comprehensive survey of challenging aspects in PAS management for anesthesiologists.

Role of Ultrasound and MRI in Diagnosis of Severe Placenta Accreta Spectrum Disorder: An Intraindividual Assessment With Emphasis on Placental Bulge.

BACKGROUND. The "placental bulge" sign (focal area of myometrial-placental bulging beyond the normal uterine contour) on ultrasound (US) or MRI is postulated to represent deeper venous invasion in placenta accreta spectrum (PAS) disorder and may represent severe PAS. OBJECTIVE. The purpose of this study was to evaluate the diagnostic performance and interobserver agreement of US and MRI features for diagnosis of severe PAS, with an emphasis on the placental bulge sign. METHODS. This retrospective study included 62 pregnant women (mean age, 33.2 ± 5.5 [SD] years) with clinically suspected PAS who underwent both US and MRI. Five readers (two maternal-fetal medicine specialists for US, three abdominal radiologists for MRI) independently reviewed images for the given modality, blinded to the final diagnosis, and recorded the presence of a range of findings (nine on US, eight on MRI), including placental bulge. Intraoperative and pathologic findings were used to separate patients into those with and without severe PAS according to International Federation of Gynecology and Obstetrics classification. Diagnostic performance of US and MRI findings for severe PAS was evaluated, multivariable logistic regression was performed, and interob-server agreement was assessed. RESULTS. A total of 58.1% (36/62) of patients had severe PAS. On US, the finding with the highest accuracy for severe PAS was placental bulge (85.5%), which had a sensitivity of 91.7% and specificity of 76.9%. On MRI, the finding with highest accuracy was also placental bulge (90.3%), which had a sensitivity of 94.4% and specificity of 84.6%. In the multivariable regression analysis, placental bulge was an independent predictor of severe PAS on US (odds ratio [OR], 8.94; p = .02) and MRI (OR, 45.67; p = .003). Interobserver agreement analysis showed a kappa value for placental bulge of 0.48 for MRI and 0.40 for US. Given wide 95% CIs, differences among features for a given modality and differences between modalities were not statistically significant. CONCLUSION. The findings suggest a strong performance of placental bulge in diagnosing severe PAS on both US and MRI, with a potentially stronger performance on MRI. Nonetheless, interobserver agreement remains suboptimal for both modalities. CLINICAL IMPACT. Accurate prenatal diagnosis of severe PAS by imaging could help guide maternal counseling and selection of either hysterectomy or uterine-preserving surgery.

Effectiveness of contingent screening for placenta accreta spectrum disorders based on persistent low-lying placenta and previous uterine surgery.

OBJECTIVES: Maternal mortality related to placenta accreta spectrum (PAS) disorders remains substantial when diagnosed unexpectedly at delivery. The aim of this study was to evaluate the effectiveness of a routine contingent ultrasound screening program for PAS. METHODS: This was a retrospective study of data obtained between 2009 and 2019, involving two groups: a screening cohort of unselected women attending for routine mid-trimester ultrasound assessment and a diagnostic cohort consisting of women referred to the PAS diagnostic service with a suspected diagnosis of PAS. In the screening cohort, women with a low-lying placenta at the mid-trimester assessment were followed up in the third trimester, and those with a persistent low-lying placenta (i.e. placenta previa) and previous uterine surgery were referred to the PAS diagnostic service. Ultrasound assessment by the PAS diagnostic service consisted of two-dimensional grayscale and color Doppler ultrasonography, and women with a diagnosis of PAS were usually managed with conservative myometrial resection. The final diagnosis of PAS was based on a combination of intraoperative clinical findings and histopathological examination of the surgical specimen. RESULTS: In total, 57 179 women underwent routine mid-trimester fetal anatomy assessment, of whom 220 (0.4%) had a third-trimester diagnosis of placenta previa. Seventy-five of these women were referred to the PAS diagnostic service because of a history of uterine surgery, and 21 of 22 cases of PAS were diagnosed correctly (sensitivity, 95.45% (95% CI, 77.16-99.88%) and specificity, 100% (95% CI, 99.07-100%)). Univariate analysis demonstrated that parity ≥ 2 (odds ratio (OR), 35.50 (95% CI, 6.90-649.00)), two or more previous Cesarean sections (OR, 94.20 (95% CI, 22.00-656.00)) and placenta previa (OR, 20.50 (95% CI, 4.22-369.00)) were the strongest risk factors for PAS. In the diagnostic cohort, there were 173 referrals, with one false-positive and three false-negative diagnoses, resulting in a sensitivity of 96.63% (95% CI, 90.46-99.30%) and a specificity of 98.81% (95% CI, 93.54-99.97%). CONCLUSIONS: A contingent screening strategy for PAS is both feasible and effective in a routine healthcare setting. When linked to a PAS diagnostic and surgical management service, adoption of such a screening strategy has the potential to reduce the maternal morbidity and mortality associated with this condition. However, larger prospective studies are necessary before implementing this screening strategy into routine clinical practice. © 2020 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Eficacia de la detección contingente para los trastornos del espectro de la placenta acreta a partir de la placenta baja persistente y en la cirugía uterina previa OBJETIVOS: La mortalidad materna relacionada con los trastornos de la gama espectral de la placenta acreta (EPA) sigue siendo considerable cuando se diagnostica de forma inesperada en el momento del parto. El objetivo de este estudio fue evaluar la efectividad de un programa rutinario de detección contingente mediante ecografía para el EPA. MÉTODOS: Este fue un estudio retrospectivo de datos obtenidos entre 2009 y 2019, en el que participaron dos grupos: una cohorte de detección de mujeres no seleccionadas que acudieron a la evaluación ecográfica rutinaria de mitad de trimestre y una cohorte de diagnóstico, integrada por mujeres remitidas al servicio de diagnóstico del EPA con un presunto diagnóstico del EPA. En la cohorte de detección, a las mujeres con una placenta baja en la evaluación de mitad de trimestre se les hizo un seguimiento en el tercer trimestre, y a aquellas con una placenta baja persistente (es decir, placenta previa) que habían tenido cirugía uterina previa se las remitió al servicio de diagnóstico del EPA. La evaluación ecográfica por el servicio de diagnóstico del EPA consistió en una ecografía Doppler bidimensional en escala de grises y en color, y a las mujeres con diagnóstico del EPA se las trató habitualmente con una resección conservadora del miometrio. El diagnóstico final del EPA se basó en una combinación de indicadores clínicos intraoperatorios y el examen histopatológico de la muestra quirúrgica. RESULTADOS: En total, 57179 mujeres se sometieron a una evaluación rutinaria de la anatomía fetal a mitad del trimestre, de las cuales a 220 (0,4%) se les diagnosticó con placenta previa en el tercer trimestre. Setenta y cinco de estas mujeres fueron remitidas al servicio de diagnóstico del EPA, debido a su historial de cirugía uterina, y 21 de los 22 casos de EPA fueron diagnosticados correctamente (sensibilidad, 95,45% (IC 95%, 77,16-99,88%) y especificidad, 100% (IC 95%, 99,07-100%)). El análisis univariante demostró que la paridad ≥2 (razón de momios (RM), 35,50 (IC 95%, 6,90-649,00)), dos o más cesáreas previas (RM, 94,20 (IC 95%, 22,00-656,00)) y la placenta previa (RM, 20,50 (IC 95%, 4,22-369,00)) fueron los factores de riesgo más fuertes para el EPA. En la cohorte de diagnóstico, se remitió a 173 mujeres, entre las cuáles hubo un diagnóstico de falso-positivo y tres diagnósticos de falsos-negativos, lo que dio como resultado una sensibilidad del 96,63% (IC 95%, 90,46-99,30%) y una especificidad del 98,81% (IC 95%, 93,54-99,97%). CONCLUSIONES: La adopción de una estrategia de detección contingente para el EPA es tanto factible como eficaz en un entorno de atención sanitaria rutinaria. Cuando se asocia a un servicio de diagnóstico y gestión quirúrgica del EPA, la adopción de esa estrategia de detección podría reducir la morbilidad y la mortalidad maternas asociadas a esta afección. Sin embargo, se necesitan estudios prospectivos más amplios antes de aplicar esta estrategia de detección en la práctica clínica habitual. © 2020 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

When a rare condition creates a scientific society: The history of the International Society for Placenta Accreta Spectrum (IS-PAS).

Almost 10 years ago, clinicians at multiple locations all over Europe observed an increased number of antenatally undiagnosed cases of placenta accreta spectrum (PAS) resulting in significant morbidity and the occasional maternal death. Even with an improvement in antenatal imaging, the management of severe PAS remains challenging. One solution to improve understanding in rare but potentially lethal conditions is international collaboration. Consequently, a European working group was formed, which over the next few years grew into an international society, the IS-PAS. The collective goals are to develop a large shared database of cases, generate high-quality research into all aspects of PAS, and improve education of both healthcare professionals and patients. The first results of this collaboration are presented within this supplement.

The relation between maternal obesity and placenta accreta spectrum: A multinational database study.

INTRODUCTION: It has been suggested that women with obesity have increased risk of developing placenta accreta spectrum (PAS). It is unclear if this is independent of the increased risk of cesarean delivery seen with obesity itself. The aim of this study was to explore the association between maternal obesity and PAS, particularly severe PAS (percreta). MATERIAL AND METHODS: This is a cohort study based on cases recorded in the International Society for Placenta Accreta Spectrum (IS-PAS) database between April 2008 and May 2019. Multivariable logistic regression was used to explore the effect of maternal obesity on severity of PAS; this model was adjusted for other known risk factors including previous cesarean deliveries, maternal age, and placenta previa. The estimated rate of obesity in a hypothetical cohort with similar characteristics (previous cesarean delivery and same parity) was calculated and compared with the observed rate of obesity in the women of the PAS cohort (one sample test of proportions). RESULTS: Of the 386 included women with PAS, 227 (58.8%) had severe disease (percreta). In univariable analysis, maternal obesity initially appeared to be associated with increased odds of developing the most severe type of PAS, percreta (odds ratio [OR] 1.87; 95% CI 1.14-3.09); however, this association was lost after adjustment for other risk factors including previous cesarean delivery (OR 1.44; 95% CI 0.85-2.44). There was no difference in the observed rate of obesity and the rate estimated based on the risk of cesarean delivery from obesity alone (31.3% vs 36.8%, respectively; P = .07). CONCLUSIONS: Obesity does not seem to be an independent risk factor for PAS or severity for PAS. These findings are relevant for clinicians to provide accurate counseling to women with obesity regarding increased risks related to pregnancy.

Developing a database for multicenter evaluation of placenta accreta spectrum.

Studies of rare, but complex clinical conditions require multicenter cooperation. The International Society for Placenta accreta spectrum (IS-PAS) have established a secure web-based database to analyze pregnancies complicated by PAS. By repeated in-person meetings of the IS-PAS, a core dataset was established. Then, a custom-made, secure online database, capable of receiving strictly anonymized patient-related textual and imaging data and allowing statistical queries was designed, tested, amended and implemented. Between 2008 and 2019, 14 IS-PAS centers across Europe and one center in the USA contributed data for all their PAS cases, containing pregnancy data for a total of 442 pregnant women. Data were analyzed by a designated data analysis sub-group of the IS-PAS. Center characteristics are presented. Based on experiences with previous versions, our new online database now allows an all-encompassing data collection. It has shown its usefulness in the current analysis project.

Maternal and neonatal outcomes in planned versus emergency cesarean delivery for placenta accreta spectrum: A multinational database study.

INTRODUCTION: Placenta accreta spectrum (PAS) is a condition often resulting in severe maternal morbidity. Scheduled delivery by an experienced team has been shown to improve maternal outcomes; however, the benefits must be weighed against the risk of iatrogenic prematurity. The aim of this study is to investigate the rates of emergency delivery seen for antenatally suspected PAS and compare the resulting outcomes in the 15 referral centers of the International Society for PAS (IS-PAS). MATERIAL AND METHODS: Fifteen centers provided cases between 2008 and 2019. The women included were divided into two groups according to whether they had a planned or an emergency cesarean delivery. Delivery was defined as "planned" when performed at a time and date to suit the team. All the remaining cases were classified as "emergency". Maternal characteristics and neonatal outcomes were compared between the two groups according to gestation at delivery. RESULTS: In all, 356 women were included. Of these, 239 (67%) underwent a planned delivery and 117 (33%) an emergency delivery. Vaginal bleeding was the indication for emergency delivery in 41 of the 117 women (41%). There were no significant differences in terms of blood loss, transfusion rates or major maternal morbidity between planned and emergency deliveries. However, the rate of maternal intensive therapy unit admission was increased with emergency delivery (45% vs 33%, P = .02). Antepartum hemorrhage was the only independent predictor of emergency delivery (aOR: 4.3, 95% confidence interval 2.4-7.7). Emergency delivery due to vaginal bleeding was more frequent with false-positive cases (antenatally suspected but not confirmed as PAS at delivery) and the milder grades of PAS (accreta/increta). The rate of infants experiencing any major neonatal morbidity was 25% at 34+1 to 36+0  weeks and 19% at >36+0  weeks. CONCLUSIONS: Emergency delivery in centers of excellence did not increase blood loss, transfusion rates or maternal morbidity. The single greatest risk factor for emergency delivery was antenatal hemorrhage. When adequate expertise and resources are available, to defer delivery in women with no significant antenatal bleeding and no risk factors for pre-term birth until >36+0  weeks can be considered to improve fetal outcomes. Further studies are needed to investigate this fully.

Association of peripartum management and high maternal blood loss at cesarean delivery for placenta accreta spectrum (PAS): A multinational database study.

INTRODUCTION: Placenta accreta spectrum (PAS) carries a high burden of adverse maternal outcomes, especially significant blood loss, which can be life-threatening. Different management strategies have been proposed but the association of clinical risk factors and surgical management options during cesarean delivery with high blood loss is not clear. MATERIAL AND METHODS: In this international multicenter study, 338 women with PAS undergoing cesarean delivery were included. Fourteen European and one non-European center (USA) provided cases treated retrospectively between 2008 and 2014 and prospectively from 2014 to 2019. Peripartum blood loss was estimated visually and/or by weighing and measuring of volume. Participants were grouped based on blood loss above or below the 75th percentile (>3500 ml) and the 90th percentile (>5500 ml). RESULTS: Placenta percreta was found in 58% of cases. Median blood loss was 2000 ml (range: 150-20 000 ml). Unplanned hysterectomy was associated with an increased risk of blood loss >3500 ml when compared with planned hysterectomy (adjusted OR [aOR] 3.7 [1.5-9.4], p = 0.01). Focal resection was associated with blood loss comparable to that of planned hysterectomy (crude OR 0.7 [0.2-2.1], p = 0.49). Blood loss >3500 ml was less common in patients undergoing successful conservative management (placenta left in situ, aOR 0.1 [0.0-0.6], p = 0.02) but was more common in patients who required delayed hysterectomy (aOR 6.5 [1.7-24.4], p = 0.001). Arterial occlusion methods (uterine or iliac artery ligation, embolization or intravascular balloons), application of uterotonic medication or tranexamic acid showed no significant effect on blood loss >3500 ml. Patients delivered by surgeons without experience in PAS were more likely to experience blood loss >3500 ml (aOR 3.0 [1.4-6.4], p = 0.01). CONCLUSIONS: In pregnant women with PAS, the likelihood of blood loss >3500 ml was reduced in planned vs unplanned cesarean delivery, and when the surgery was performed by a specialist experienced in the management of PAS. This reinforces the necessity of delivery by an expert team. Conservative management was also associated with less blood loss, but only if successful. Therefore, careful patient selection is of great importance. Our study showed no consistent benefit of other adjunct measures such as arterial occlusion techniques, uterotonics or tranexamic acid.

Online survey on uterotomy closure techniques in caesarean section.

OBJECTIVES: Uterine closure technique in caesarean section (CS) influences the rate of late complications in subsequent pregnancies. As no common recommendation on suture techniques exists, we developed a questionnaire to determine the techniques currently used and the frequencies of late complications. METHODS: The online questionnaire consisted of 13 questions and was sent to 648 obstetric hospitals (level I-IV) in Germany. Number of CS, rate of vaginal birth after caesarean section (VBAC), the type of uterus suturing technique and the frequency of uterine dehiscences, ruptures and placenta accreta spectrum (PAS) were queried. The answers were anonymous, and results were evaluated descriptively. RESULTS: The response rate was 24.7%. The mean CS rate was 27.3% (±6.2), the repeat CS rate 33.2% (±18.1). After CS, 46.2% (±20.2) women delivered vaginally. To close the uterotomy, 74.4% of hospitals used single layer continuous sutures, 16.3% single layer locked sutures, 3.8% interrupted sutures, 3.1% double layer continuous sutures and 2.5% used other suture techniques. The percentages of observed uterine dehiscences did not differ significantly between the different levels of care nor did the uterotomy suture techniques. CONCLUSIONS: There is no uniform suturing technique in Germany. A detailed description of suture technique in surgery reports is required to evaluate complications in subsequent pregnancies. National online surveys on obstetric topics are feasible and facilitate the discussion on the need to define a standardized uterine closure technique for CS.

Development of placental abnormalities in location and anatomy.

Low-lying placentas, placenta previa and abnormally invasive placentas are the most frequently occurring placental abnormalities in location and anatomy. These conditions can have serious consequences for mother and fetus mainly due to excessive blood loss before, during or after delivery. The incidence of such abnormalities is increasing, but treatment options and preventive strategies are limited. Therefore, it is crucial to understand the etiology of placental abnormalities in location and anatomy. Placental formation already starts at implantation and therefore disorders during implantation may cause these abnormalities. Understanding of the normal placental structure and development is essential to comprehend the etiology of placental abnormalities in location and anatomy, to diagnose the affected women and to guide future research for treatment and preventive strategies. We reviewed the literature on the structure and development of the normal placenta and the placental development resulting in low-lying placentas, placenta previa and abnormally invasive placentas.

Recurrence of post-partum hemorrhage in women with a history of uterine artery embolization.

AIM: To evaluate pregnancy outcome and complications in subsequent pregnancies after severe post-partum hemorrhage (PPH) between women with and without a history of uterine artery embolization (UAE). METHODS: Women who had a history of severe PPH, and delivered newborns at ≥22 gestational weeks in subsequent pregnancies were enrolled. Severe PPH was defined as blood loss volume of more than 2000 mL. RESULTS: The blood loss volume (median 1581 mL) in women with UAE (n = 14) was significantly more than that in women without UAE (median 1021 mL, n = 32, P < 0.01), and the recurrence rate of severe PPH in women with UAE (n = 5, 35.7%) was significantly higher than that in women without UAE (n = 3, 9.4%, P < 0.05). There were no significant differences in frequencies of premature delivery, hypertensive disorders of pregnancy, fetal growth restriction, or placenta previa/low lying placenta. Of 14 women with UAE, 7 (50.0%) had abnormally invasive placenta, whereas of 32 women without UAE, none had abnormally invasive placenta. CONCLUSION: Subsequent pregnancies after UAE for severe PPH had high risks for recurrence of severe PPH.

The role of ultrasound in prediction of intra-operative blood loss in cases of placenta accreta spectrum disorders.

PURPOSE: To assess the value of various grey-scale ultrasound, 2D color Doppler, and 3D power Doppler sonographic markers in predicting major intraoperative blood loss during planned cesarean hysterectomy for cases diagnosed with placenta accreta spectrum (PAS) disorders. METHODS: 50 women diagnosed with PAS were scanned the day before planned delivery and hysterectomy for various sonographic markers indicative of placental invasion. These women were then later divided according to blood loss in two groups: group A (minor hemorrhage, < 2500 ml), and group B (major hemorrhage, > 2500 ml), and the data were analyzed. RESULTS: The odds ratio (OR) for major hemorrhage was as follows for the following sonographic markers: 'number of lacunae > 4' OR 3.8 95% CI (1.0-13.8) (p = 0.047); 'subplacental hypervascularity' OR 10.8 95% CI (1.2-98.0) (p = 0.035); 'tortuous vascularity with 'chaotic branching' OR 10.8 95%CI (1.2-98.0) (p = 0.035); 'numerous coherent vessels involving the serosa-bladder interface OR 14.6 95% CI (2.7-80.5) (p = 0.002); and 'presence of bridging vessels OR 2.9 95% CI (1.4-6.9) (p = 0.005). Only the presence of numerous coherent vessels involving the bladder-serosal interface (p = 0.002) was proven to be independent predictor of major hemorrhage during hysterectomy. CONCLUSION: The use of 2D color Doppler and 3D power Doppler can help predict massive hemorrhage in cases of PAS disorders.

Intra-operative uterine artery embolization with caesarean delivery in an adjoining operating theatre and catheter lab (OT/CL) complex vs. conventional management in patients with abnormally invasive placenta: a retrospective case control study.

Patients of abnormally invasive placenta (AIP) undergoing caesarean delivery are at increased risk of haemorrhage. Conventional management includes piecemeal removal of placenta or placenta left in situ. However, they often require hysterectomy after delivery. Post-delivery prophylactic uterine artery embolisation (UAE) can help reduce morbidity and preserve fertility. We created an adjoining operating theatre and catheter lab (OT/CL complex). This is a retrospective case control study in which 37 patients of AIP were evaluated. Sixteen subjects (cases) had UAE immediately after caesarean delivery, and 21 subjects (controls) had usual care with traditional methods of controlling postpartum haemorrhage and hysterectomy where required. The hysterectomy rate (18.7% vs. 85.7%), mean duration of hospital stay (6.8 ± 2.6 vs. 13.9 ± 8.1) and number of units of blood transfusion required were significantly less in the case group as compared with controls. UAE is an effective conservative treatment along with caesarean delivery in patients with AIP.Impact statementWhat is already known? AIP is associated with high rates of PPH, maternal morbidity and mortality and need for hysterectomy after delivery. UAE has been advocated to preserve fertility and reduce PPH in these patients along with caesarean delivery.What does the study add? We created an adjoining operating theatre and catheter lab (OT/CL complex) in a tertiary care centre and managed these patients with prompt UAE after caesarean delivery with team approach. We have shown significant reduction in morbidity and hospital stay with this coordinated management.What are the implications for clinical practice and/or further research? UAE with caesarean delivery is a preferred mode of delivery for patients of AIP. These patients should be diagnosed and referred to tertiary care centres with such facilities electively so as to provide optimal care to these patients. Cooperation between interventionist and obstetrician and adjoining availability of OT and catheter lab can further help in reducing the time to embolisation after delivery. A hybrid operating theatre with digital subtraction angiography (DSA) facilities would be ideal for the management of such patients.

Prolongated pregnancy: unusual case.

OBJECTIVE: To present a patient with prolongated postterm pregnancy. DESIGN: Case study. SETTING: Department of Obstetrics and Gynecology, Vyškov Hospital. CASE REPORT: According to the literature, pregnancy that exceeds 42+0 weeks is considered to be a postterm pregnancy. We present a case of a 21-year-old primigravid women with extremely prolongated postterm pregnancy and associated complications. The patient repeatedly rejects the proposed prostaglandin induction of labor or iterative cesarean section. Pregnancy was terminated by cesarean section at 43+3 due to multiple unsuccessful attempts to induce labor in postterm pregnancy. During the surgery abnormally invasive placenta was found with massive blood loss and necessity of subsequent ligation of aa. iliacae internae. CONCLUSION: Pregnant women with postterm pregnancy should be offered the possibility of induction of labor. We should educate pregnant women in detail about the risks of postterm pregnancy.

Evidence-based guidelines for the management of abnormally invasive placenta: recommendations from the International Society for Abnormally Invasive Placenta.

The worldwide incidence of abnormally invasive placenta is rapidly rising, following the trend of increasing cesarean delivery. It is a heterogeneous condition and has a high maternal morbidity and mortality rate, presenting specific intrapartum challenges. Its rarity makes developing individual expertise difficult for the majority of clinicians. The International Society for Abnormally Invasive Placenta aims to improve clinicians' understanding and skills in managing this difficult condition. By pooling knowledge, experience, and expertise gained within a variety of different healthcare systems, the Society seeks to improve the outcomes for women with abnormally invasive placenta globally. The recommendations presented herewith were reached using a modified Delphi technique and are based on the best available evidence. The evidence base for each is presented using a formal grading system. The topics chosen address the most pertinent questions regarding intrapartum management of abnormally invasive placenta with respect to clinically relevant outcomes, including the following: definition of a center of excellence; requirement for antenatal hospitalization; antenatal optimization of hemoglobin; gestational age for delivery; antenatal corticosteroid administration; use of preoperative cystoscopy, ureteric stents, and prophylactic pelvic arterial balloon catheters; maternal position for surgery; type of skin incision; position of the uterine incision; use of interoperative ultrasound; prophylactic administration of oxytocin; optimal method for intraoperative diagnosis; use of expectant management; adjuvant therapies for expectant management; use of local surgical resection; type of hysterectomy; use of delayed hysterectomy; intraoperative measures to treat life-threatening hemorrhage; and fertility after conservative management.