Predictive Value and Limitations of the Placenta Accreta Index: A Systematic Review.

Our systematic review highlights that multiparametric PAI score assessment is a consistent tool with high sensitivity and specificity for prenatal prediction for placenta accreta spectrum (PAS) in high-risk population with anterior placenta previa or low-lying placenta and prior cesarean deliveries. A systematic search was conducted on November 1, 2022, of MEDLINE via PubMed, Scopus, Web of Science Core Collection, Cochrane Library, and Google Scholar to identify relevant studies (PROSPERO ID # CRD42022368211). A total of 11 articles met our inclusion criteria, representing the data of a total of 1,044 cases. Women with PAS had an increased mean PAI total score, compared to those without PAS. Limitations of the PAI are most studies were conducted in developing countries in high-risk population which limit the global generalizability of findings. Heterogeneity of reported data did not allow to perform meta-analysis.

A Narrative Review on the Pathophysiology of Preeclampsia.

Preeclampsia (PE) is a multifactorial pregnancy disorder characterized by hypertension and proteinuria, posing significant risks to both maternal and fetal health. Despite extensive research, its complex pathophysiology remains incompletely understood. This narrative review aims to elucidate the intricate mechanisms contributing to PE, focusing on abnormal placentation, maternal systemic response, oxidative stress, inflammation, and genetic and epigenetic factors. This review synthesizes findings from recent studies, clinical trials, and meta-analyses, highlighting key molecular and cellular pathways involved in PE. The review integrates data on oxidative stress biomarkers, angiogenic factors, immune interactions, and mitochondrial dysfunction. PE is initiated by poor placentation due to inadequate trophoblast invasion and improper spiral artery remodeling, leading to placental hypoxia. This triggers the release of anti-angiogenic factors such as soluble fms-like tyrosine kinase-1 (sFlt-1) and soluble endoglin (sEng), causing widespread endothelial dysfunction and systemic inflammation. Oxidative stress, mitochondrial abnormalities, and immune dysregulation further exacerbate the condition. Genetic and epigenetic modifications, including polymorphisms in the Fms-like tyrosine kinase 1 (FLT1) gene and altered microRNA (miRNA) expression, play critical roles. Emerging therapeutic strategies targeting oxidative stress, inflammation, angiogenesis, and specific molecular pathways like the heme oxygenase-1/carbon monoxide (HO-1/CO) and cystathionine gamma-lyase/hydrogen sulfide (CSE/H2S) pathways show promise in mitigating preeclampsia's effects. PE is a complex disorder with multifactorial origins involving abnormal placentation, endothelial dysfunction, systemic inflammation, and oxidative stress. Despite advances in understanding its pathophysiology, effective prevention and treatment strategies remain limited. Continued research is essential to develop targeted therapies that can improve outcomes for both mothers and their babies.

Customizing EV-CATCHER to Purify Placental Extracellular Vesicles from Maternal Plasma to Detect Placental Pathologies.

Placenta Accreta Spectrum (PAS) is a life-threatening condition in which placental trophoblastic cells abnormally invade the uterus, often up to the uterine serosa and, in extreme cases, tissues beyond the uterine wall. Currently, there is no clinical assay for the non-invasive detection of PAS, and only ultrasound and MRI can be used for its diagnosis. Considering the subjectivity of visual assessment, the detection of PAS necessitates a high degree of expertise and, in some instances, can lead to its misdiagnosis. In clinical practice, up to 50% of pregnancies with PAS remain undiagnosed until delivery, and it is associated with increased risk of morbidity/mortality. Although many studies have evaluated the potential of fetal biomarkers circulating in maternal blood, very few studies have evaluated the potential of circulating placental extracellular vesicles (EVs) and their miRNA contents for molecular detection of PAS. Thus, to purify placental EVs from maternal blood, we customized our robust ultra-sensitive immuno-purification assay, termed EV-CATCHER, with a monoclonal antibody targeting the membrane Placental Alkaline Phosphatase (PLAP) protein, which is unique to the placenta and present on the surface of placental EVs. Then, as a pilot evaluation, we compared the miRNA expression profiles of placental EVs purified from the maternal plasma of women diagnosed with placenta previa (controls, n = 16); placenta lying low in uterus but not invasive) to those of placental EVs purified from the plasma of women with placenta percreta (cases, n = 16), PAS with the highest level of invasiveness. Our analyses reveal that miRNA profiling of PLAP+ EVs purified from maternal plasma identified 40 differentially expressed miRNAs when comparing these two placental pathologies. Preliminary miRNA pathway enrichment and gene ontology analysis of the top 14 upregulated and top nine downregulated miRNAs in PLAP+ EVs, purified from the plasma of women diagnosed with placenta percreta versus those diagnosed with placenta previa, suggests a potential role in control of cellular invasion and motility that will require further investigation.

Implementation and outcomes of a uterine artery embolization and tranexamic acid protocol for placenta accreta spectrum.

BACKGROUND: Placenta accreta spectrum disorders are a continuum of placental pathologies with significant maternal morbidity and mortality. Morbidity is related to the overall degree of placental adherence, and thus patients with placenta increta or percreta represent a high-risk category of patients. Hemorrhage and transfusion of blood products represent 90% of placenta accreta spectrum morbidity. Both tranexamic acid and uterine artery embolization independently decrease obstetrical hemorrhage. OBJECTIVE: This study aimed to provide an evidence-based intraoperative protocol for placenta accreta spectrum management. STUDY DESIGN: This study was a pre- and postimplementation analysis of concomitant uterine artery embolization and tranexamic acid in cases of patients with antenatally suspected placenta increta and percreta over a 5-year period (2018-2022). For comparison, a 5-year (2013-2017) preimplementation group was used to assess the impact of the uterine artery embolization and tranexamic acid protocol for placenta accreta spectrum. Patient demographics and clinically relevant outcomes were obtained from electronic medical records. RESULTS: A total of 126 cases were managed by the placenta accreta spectrum team, of which 66 had suspected placenta increta/percreta over the 10-year time period. Two patients were excluded from the postimplementation cohort because they did not undergo both interventions. Thus, 30 (30/64; 47%) were treated after implementation of the uterine artery embolization and tranexamic acid protocol for placenta accreta spectrum, and 34 (34/64; 53%) preimplementation patients did not undergo uterine artery embolization or tranexamic acid infusion. With the uterine artery embolization and tranexamic acid protocol, operative times were longer (416 vs 187 minutes; P<.01), and patients were more likely to receive general anesthesia (80% vs 47%; P<.01). However, blood loss was reduced by 33% (2000 vs 3000 cc; P=.03), overall blood transfusion rates decreased by 51% (odds ratio, 0.05 [95% confidence interval, 0.001-0.20]; P<.01), and massive blood transfusion (>10 units transfused) was reduced 5-fold (odds ratio, 0.17 [95% confidence interval, 0.02-0.17]; P=.02). Postoperative complication rates remained unchanged (4 vs 10 events; P=.14). Neonatal outcomes were equivalent. CONCLUSION: The uterine artery embolization and tranexamic acid protocol for placenta accreta spectrum is an effective approach to the standardization of complex placenta accreta spectrum cases that results in optimal perioperative outcomes and reduced maternal morbidity.

Incidence and Clinical Implications of Placenta Accreta Spectrum after Treatment for Asherman Syndrome.

STUDY OBJECTIVE: To investigate the incidence, predictors, and clinical implications of placenta accreta spectrum (PAS) in pregnancies after hysteroscopic treatment for Asherman syndrome (AS). DESIGN: This is a retrospective cohort study, conducted through a telephone survey and chart review. SETTING: Minimally invasive gynecologic surgery center in an academic community hospital. PATIENTS: Database of 355 patients hysteroscopically treated for AS over 4 years. We identified patients who achieved pregnancy past the first trimester and evaluated the incidence and predictors for PAS as well as associated clinical implications. INTERVENTIONS: Telephone survey. MEASUREMENTS AND MAIN RESULTS: We identified 97 patients meeting the inclusion criteria. Among these patients, 23 (23.7%) patients had PAS. History of cesarean delivery was the only variable statistically significantly associated with having PAS (adjusted odds ratio 4.03, 95% confidence interval 1.31-12.39). PAS was diagnosed antenatally in 3 patients (14.3%), with patients having placenta previa more likely to be diagnosed (p <.01). Nine patients (39.13%) with PAS required cesarean hysterectomy, which is 9.3% of those with a pregnancy that progressed past the first trimester. Factors associated with cesarean hysterectomy were the etiology of AS (dilation and evacuation after the second trimester pregnancy or postpartum instrumentation, p <.01), invasive placenta (increta or percreta, p <.05), and history of morbidly adherent placenta in previous pregnancies (p <.05). Two patients with PAS (9.5%) had uterine rupture, and another 2 (9.5%) experienced uterine inversion. CONCLUSION: There is a high incidence of PAS and associated morbidity in pregnancies after hysteroscopic treatment for AS. There is a low rate of antenatal diagnosis as well as a lack of reliable clinical predictors, which both stress the importance of clinical awareness, careful counseling, and delivery planning.

Impact of Pelvic Rest Recommendations on Follow-Up and Resolution of Placenta Previa and Low-Lying Placenta.

OBJECTIVE: To determine the rate of resolution of placenta previa and low-lying placenta (LLP) and the effect of pelvic rest recommendations on the timing of follow-up imaging. METHODS: Retrospective review of pregnancies with previa/LLP detected on mid-trimester exam at our ultrasound unit from 2019 to 2021. LLP was defined as the lower edge of placenta located within 2 cm of the internal cervical os. Previa was defined as any portion of the placenta touching with the internal os. Demographics, placental location, activity restrictions, and delivery outcomes were analyzed. Timing of follow-up imaging was stratified by individuals advised and not advised pelvic rest. RESULTS: Exactly 144 patients had previa and 266 had LLP on the mid-trimester exam with complete records. Previa resolution happened in 51.4% (74/144) of cases. Exactly 62% (46/74) of previa resolutions occurred by the 28-week ultrasound. Exactly 45% (65/144) of previa patients were advised pelvic rest. Most pelvic rest and non-pelvic rest patients had a 28-week scan. Even when clearance occurred, most patients in both groups had a repeat ultrasound at 32 weeks. Exactly 75% of LLP resolved by the 28-week scan, and the remainder by delivery. Exactly 12% (32/259) of LLP patients were advised pelvic rest. CONCLUSION: Most societies recommend follow-up imaging at 32 weeks; however, our results suggest this may be done sooner and closer to 28 weeks. Pelvic rest did not affect timing of repeat imaging or delivery.

The effect of abnormal placentation on maternal serum fetal fraction of cell-free DNA.

OBJECTIVES: Abnormal placentation may affect the maternal serum fraction of cell-free fetal DNA (fetal fraction) determined as part of non-invasive prenatal screening (NIPS). This study aimed to assess whether the fetal fraction can predict placenta accreta spectrum (PAS) with or without placenta previa (PP). We also investigated the impact of trophoblastic invasion depth on the fetal fraction. METHODS: This is a retrospective case-control study of pregnant women with and without abnormal placentation carrying a singleton and having undergone NIPS prior to 20 weeks of gestation. The eligible subjects were selected from a cohort managed at our institution for PAS suspected antenatally. We compared women with normal placentation (controls) to PAS, PP, or PAS + PP cases. Data were abstracted from electronic medical records, and PAS was confirmed histologically. RESULTS: Of the 146 patients in our cohort, 8 controls, 10 PP, 6 PAS, and 7 PAS + PP cases were eligible for the study. Among the groups, there were no significant differences in baseline demographic and clinical characteristics except the median number of prior uterine surgeries. Also, the groups did not significantly differ in their median fetal fraction. The fetal fraction did not discriminate any group when stratified according to the depth of placental invasion, i.e., no PAS, abnormally adherent, and abnormally invasive placenta. CONCLUSIONS: The maternal serum fraction of cell-free fetal DNA measured before 20 weeks of gestation is not predictive of PAS with or without concurrent PP or the depth of trophoblastic invasion.

Importance of the gynecologic oncologist in management of cesarean hysterectomy for Placenta Accreta Spectrum (PAS).

OBJECTIVE: Placenta Accreta Spectrum (PAS) is an invasive placental disorder characterized by significant maternal and fetal morbidity. Utilization of multidisciplinary teams has been shown to optimize patient outcomes. Our objective was to assess the impact of cesarean hysterectomy performed by gynecologic oncologists versus Ob/Gyn specialists in maternal morbidity. METHODS: A retrospective cohort study was performed of singleton, non-anomalous pregnancies complicated by PAS University of Texas Health San Antonio Placenta Accreta program from 2010 to 2021. Our primary outcome was a maternal morbidity composite of any of the following: estimated blood loss >2 L, ICU admission, intraoperative acidosis and post-operative length of stay >4 days. In addition, demographic and pregnancy data were obtained. Univariate and multivariate analyses were performed to identify the individual impact of variables such as general anesthesia, episodes of vaginal bleeding, uterine artery embolization, emergent delivery and placenta percreta pathology. RESULTS: 122 pregnancies complicated by PAS who underwent cesarean hysterectomy were identified from 2010 to 2021. Gynecologic oncologists were the primary surgeons for 62 (50.8%) of these cases. The involvement of gynecologic oncologists increased over the time period from 16% to 80%. Gynecologic oncologists were more like to be involved in cases with an antenatal diagnosis of placenta percreta (11.7 vs 37.1%, p = 0.001) and these cases were characterized by increased composite maternal morbidity (65 vs 83.9%, p = 0.02). These cases were also significantly longer (151 vs 271 min, p < 0.0001), involved greater usage of urinary stents (36.7 vs 66.1%, p = 0.002) and had longer post-operative lengths of stay (3 vs 4 days, p < 0.0001). PAS cesarean hysterectomies by gynecologic oncologists were less likely to be supracervical (25 vs 3.2%, p = 0.0005). Multivariate analysis controlling for placenta percreta, uterine artery embolization, vaginal bleeding and emergent delivery showed no difference in composite maternal morbidity (aOR = 0.95, 95%CI [0.35-2.52]) and lower rates of intraoperative acidosis (aOR = 0.36, 95%CI [0.14-0.93]) or post-operative length of stay >4 days (aOR = 0.37, 95%CI [0.15-0.91]). CONCLUSIONS: Gynecologic oncologists play a critical role in the surgical management of PAS cesarean hysterectomies. When compared to Ob/Gyn specialists, gynecologic oncologists are more likely to act as primary surgeons in complex cases similar morbidity and greater post-operative outcomes.

Percreta score to differentiate between placenta accreta and placenta percreta with ultrasound and MR imaging.

INTRODUCTION: The objective of this study was to assess the performance of ultrasound and magnetic resonance imaging (MRI) features in helping to classify the type of placenta accreta spectrum (PAS; accreta/increta vs percreta), alone or combined in a predictive score. MATERIAL AND METHODS: We conducted a retrospective study in 82 pregnant women with PAS who underwent ultrasound and MRI examination of the pelvis before delivery (from an initial cohort of 185 women with PAS). We estimated the sensitivity, specificity and accuracy of MRI and ultrasound in the diagnosis of the type of PAS. We analyzed cesarean and imaging features using univariable logistic regression analysis. We constructed a nomogram to predict the risk of placenta percreta and validated it with bootstrap resampling, then used receiver operating characteristic curves to assess the performance of the model in distinguishing between placenta percreta and placenta accreta/increta. RESULTS: Among the 82 patients, 29 (35%) had placenta accreta/increta and 53 (65%) had placenta percreta. The best features to discriminate between placenta accreta/increta and placenta percreta with ultrasound were increased vascularization at the uterine serosa-bladder wall interface (odds ratio [OR] 7.93; 95% confidence interval [CI] 2.78-24.99; p < 0.01) and the number of lacunae without a hyperechogenic halo (OR 1.36; 95% CI 1.14-1.67; p = 0.012). Concerning MRI markers, heterogeneous placenta (OR 12.89; 95% CI 3.05-89.16; p = 0.002), dark intraplacental bands (OR 12.89; 95% CI 3.05-89.16; p = 0.002) and bladder wall interruption (OR 15.89; 95% CI 4.78-73.33; p < 0.001) had a higher OR in discriminating placenta accreta/increta from placenta percreta. The nomogram yielded areas under the curve of 0.841 (95% CI 0.754-0.927) and 0.856 (95% CI 0.767-0.945), after bootstrap resampling, for the accurate prediction of placenta percreta. CONCLUSIONS: The nomogram we developed to predict the risk of placenta percreta among patients with PAS had good discriminative capabilities. This performance and its impact on maternal morbidity should be confirmed by future prospective studies.

FundAl Retroflexion (FAR) Angle is a Novel Sonographic Marker Associated With Cesarean Scar Pregnancies in the First Trimester: A Case-Control Study.

OBJECTIVES: Early diagnosis of Cesarean scar pregnancies (CSP) remains difficult. This study describes a novel sonographic marker, the FundAl Retroflexion (FAR) angle, that may be used in the first trimester. The objective of the study is to compare the FAR angle between CSP and normal pregnancies. METHODS: For this case-control study, we reviewed images from our institution's database that were acquired from January 2016 to December 2019. All cases of CSP and randomly selected controls, defined as patients with history of Cesarean delivery and normal implantation, that underwent ultrasound evaluation at <14 weeks were included. The FAR angle, defined as the acute angle created between the endometrial echo and cervical canal, was measured. The mean FAR angle was then compared between the two groups and a receiver operating characteristic (ROC) curve was generated. RESULTS: We identified 15 cases of CSP during the study period and were able to measure the FAR angle in 14 of the cases. The mean FAR angle was larger in CSP than in normal control pregnancies (45° versus 27°, respectively, P < 0.001). Using an ROC curve, a FAR angle cut off of 40° maximizes the ability to distinguish between CSP from normal pregnancies. CONCLUSIONS: The FAR angle provides an easily obtainable and numerical measurement. CSP have larger FAR angle compared to normal controls with a distinguishing cut off of 40°. Larger studies are needed to determine if using the FAR angle can improve first trimester diagnosis for CSP.

Effect of anesthesia selection on neonatal outcomes in cesarean hysterectomies for placenta accreta spectrum (PAS).

OBJECTIVES: Optimal treatment for placenta accreta spectrum (PAS) is late-preterm cesarean hysterectomy to minimize maternal morbidity. This study aims to assess the impact of surgical planning during this gestational age on neonates as a key part of the pregnancy dyad. METHODS: A retrospective cohort analysis was performed of 115 singleton, non-anomalous pregnancies complicated by PAS at the University of Texas Health San Antonio Placenta Accreta program from 2005 to 2020. Univariate and multivariate analyses were performed to identify the individual impact of variables such as anesthesia selection, advancing gestational age and operative characteristics. RESULTS: With regards to neonatal intubation, on multivariate analysis, neuraxial anesthesia (OR=0.09, [95% CI 0.02, 0.37]) and advancing gestational age (OR=0.49 [95% CI 0.34, 0.71]) were independent protective factors. In addition, NICU length of stay was directly impacted by neuraxial anesthesia (IRR=0.73, [95% CI 0.55, 0.97]) and advancing gestational age (IRR=0.80 [95% CI 0.76, 0.84]), resulting in shorter NICU admissions. CONCLUSIONS: As gestational age at delivery may not be modifiable in cases of PAS, the utilization of neuraxial anesthesia (as oppose to general anesthesia) presents a modifiable intervention which may optimize neonatal outcomes from cesarean hysterectomy.

Retrospective evaluation of peripartum hysterectomy patients: 8 years' experience of tertiary health care.

Background: Peripartum hysterectomy (PPH), which means surgical removal of the uterus during pregnancy or postpartum period, is a life-saving procedure performed as a last resort to stop obstetric serious bleeding. Aim: Evaluation of the prevalence, risk factors, indications, associated complications, and neonatal outcomes of PPH performed in our clinic. Patients and Methods: A total of 35 patients who underwent PPH in our clinic between 2013 and 2020 were analyzed retrospectively. Clinical and demographic characteristics of patients, age, gestational week, delivery type, type of hysterectomy performed, length of hospital stay, PPH indications, additional procedures and complications during PPH, maternal and fetal mortality, neonatal characteristics, intensive care unit (ICU) need after PPH, and blood transfusion amount and time were recorded. Patients with PPH were subdivided and studied in subgroups: Emergency - elective surgery, total - subtotal hysterectomy. Results: PPH was performed in 35 (3.2/1000) patients who gave birth during the study period. The most common indication for hysterectomy was placental invasion anomaly (57.1%, n = 20), and the most performed operation was total hysterectomy (68.6%, n = 24). Bilateral hypogastric artery ligation (14.3%, n = 5) was the most common alternative procedure performed before hysterectomy, and the most common complication was bladder injury (22.9%, n = 8). Blood transfusion was performed in 94.3% (n = 33) of the patients due to acute blood loss. The mean newborn weight was 2788.79 ± 913.37 g, and the 1st and 5th-minute APGAR scores were 6.71 ± 2.25 and 7.56 ± 2.35, respectively. Conclusion: Before PPH, uterine integrity should be preserved using medical and surgical methods, but if success is not achieved, hysterectomy is the last life-saving step. It should be kept in mind that in patients with anemia and increased gravidity, the risk of bleeding may be high in the first 24 h after birth and therefore PPH may be required. It would be more appropriate for patients with placentation anomalies to be operated in experienced centers due to possible complications, increased blood transfusion, and intensive care requirement.

Vasa previa: when antenatal diagnosis can change fetal prognosis.

OBJECTIVES: Evaluate ultrasound diagnostic accuracy, maternal-fetal characteristics and outcomes in case of vasa previa diagnosed antenatally, postnatally or with spontaneous resolution before delivery. METHODS: Monocentric retrospective study enrolling women with antenatal or postnatal diagnosis of vasa previa at Sant'Anna Hospital in Turin from 2007 to 2018. Vasa previa were defined as fetal vessels that lay 2 cm within the uterine internal os using 2D and Color Doppler transvaginal ultrasound. Diagnosis was confirmed at delivery and on histopathological exam. Vasa previa with spontaneous resolutions were defined as fetal vessels that migrate >2 cm from uterine internal os during scheduled ultrasound follow-ups in pregnancy. RESULTS: We enrolled 29 patients (incidence of 0.03%). Ultrasound antenatally diagnosed 25 vasa previa (five had a spontaneous resolution) while four were diagnosed postnatally, with an overall sensitivity of 96.2%, specificity of 100%, positive predictive value of 96.2%, and negative predictive value of 100%. Early gestational age at diagnosis is significally associate with spontaneously resolution (p 0.023; aOR 1.63; 95% IC 1.18-2.89). Nearly 93% of our patient had a risk factor for vasa previa: placenta previa at second trimester or low-lying placenta, bilobated placenta, succenturiate cotyledon, velametous cord insertion or assisted reproduction technologies. CONCLUSIONS: Maternal and fetal outcomes in case of vasa previa antenatally diagnosed are significally improved. Our data support the evaluation of umbilical cord insertion during routine second trimester ultrasound and a targeted screening for vasa previa in women with risk factor: it allows identification of fetus at high risk, reducing fetal mortality in otherwise healthy newborns.

Fishbone double-layer barbed suture in cesarean section: a help in preventing long-term obstetric sequelae?

Due to the high number of cesarean sections over the last two decades, there has been a growing awareness of the post-surgical obstetric long-term sequelae (i.e., uterine scar defects and abnormal placentation) following this surgical procedure. Knotless barbed suture is an absorbable bidirectional and unidirectional monofilament, characterized by the presence of "barbs" along its length. After being introduced in gynecology, the favorable features of the knotless barbed suture, such as the uniform distribution of tensile force, provide the rationale for studying its benefits in obstetric surgery. Recently, our research group has investigated a double-layer barbed suture ("fishbone" suture) for closing the uterine wall during cesarean section by a case-control study, reporting a low incidence of uterine scar defects and a reduced size of defects in women who had developed them (NCT04825821). In the near future, large prospective studies are strongly awaited to investigate reproductive outcomes and long-term sequelae after cesarean section performed with knotless barbed suture.

BHLHE40 plays a pathological role in pre-eclampsia through upregulating SNX16 by transcriptional inhibition of miR-196a-5p.

Pre-eclampsia (PE), which results from abnormal placentation, is a primary cause of maternal and neonatal morbidity and mortality. However, the causes of abnormal development of the placenta remain poorly understood. BHLHE40 is a transcriptional repressor in response to hypoxia. Bioinformatics analysis demonstrated that BHLHE40 negatively regulates miR-196a-5p expression, which may decrease miR-196a-5p to target SNX16. Since SNX16 exerts an inhibitory effect on cell migration, it may disrupt trophoblast cell migration in placentation. Therefore, the objective of this study was to explore a possible role of the BHLHE40/miR-196a-5p/SNX16 axis in PE pathogenesis. BHLHE40, miR-196a-5p and SNX16 mRNA and/or protein levels were detected in PE and normal placenta tissues. PE models in vitro and in vivo were constructed by culturing trophoblasts under hypoxia and reducing the uterine perfusion pressure in pregnant C57/BL6N mice, respectively. BHLHE40 and SNX16 were upregulated in PE placenta, while miR-196a-5p was downregulated. Knockdown of BHLHE40 reversed miR-196a-5p expression in trophoblasts under hypoxia, and upregulation of miR-196a-5p inhibited SNX16 expression. As indicated by ChIP assay, BHLHE40 bound to the promoter of the miR-196a-5p gene; luciferase reporter analysis showed that miR-196a-5p could bind to the 3'-untranslated region of SNX16 mRNA. Knockdown of either BHLHE40 or SNX16, or an increase in miR-196a-5p, restored cell viability, migration, invasion and matrix metalloprotein (MMP)-2 and MMP-9 expression under hypoxia. BHLHE40 knockdown also alleviated PE symptoms in pregnant C57/BL6N mice. This study supports involvement of the BHLHE40/miR-196a-5p/SNX16 axis in PE pathogenesis; Proper adjustment of the BHLHE40/miR-196a-5p/SNX16 axis is able to attenuate PE symptoms.

Emergency peripartum hysterectomy at Jordan University hospital - a teaching hospital experience.

INTRODUCTION: Emergency peripartum hysterectomy (EPH) is a foremost operation and is perpetually implemented in the presence of life intimidating hemorrhage during or immediately after abdominal or vaginal deliveries. The aim of this study was to review cases managed at the Department of Gynecology and Obstetrics at Jordan University Hospital (JUH). MATERIAL AND METHODS: All women who underwent EPH due to any cause in the period from January 2010, to December 2017 were included in the study. Data were collected retrospectively using the patients' files namelessly. Main measures: age, gravidity, parity, number of previous cesarean sections, previous uterine surgeries, indication for hysterectomy, complications, antepartum bleeding and the need for blood transfusion. RESULTS: In total, 74 cases of EPH were managed during the study period. The incidence of EPH ranged from 0.24 to 8.7 per 1000 deliveries. EPH was found to be more common following cesarean sections than vaginal deliveries. The prime indication was abnormal placentation, uterine atony, and uterine rupture. The risk factors included previous cesarean sections, scarred uteruses, multiparity, older age group. Maternal morbidity ranged from 26.5 to 31.5% and mortality from 0 to 12.5% with a mean of 4.8%. CONCLUSIONS: EPH is the most demanding obstetric surgery performed in very tiresome circumstances of life threatening hemorrhage. The indication for EPH in recent years has changed from outdated uterine atony to abnormal placentation. Antenatal eagerness of the risk factors, engrossment of proficient obstetricians at an early stage of management and a prompt hysterectomy after adequate resuscitation would go a long way in tumbling morbidity and mortality.

Histological Features of Shallow Placental Implantation Unify Early-Onset and Late-Onset Preeclampsia.

Preeclampsia is distinguishable from other hypertensive conditions of pregnancy by its high rates of decidual arteriopathy, the uterine type of chronic hypoxic placental injury, the occurrence of villous infarctions, and clusters of multinucleate trophoblasts in the maternal floor. To retrospectively study the clinical and placental phenotypes of 230 women with early-onset preeclampsia, 261 women with late-onset preeclampsia, and 5059 women without hypertension in pregnancy (comparative group), 24 clinical and 46 placental phenotypes were statistically compared (analysis of variance, χ2 with Bonferroni correction). The frequency of decidual arteriopathy (both hypertrophic and atherosis), patterns of chronic hypoxic placental injury, villous infarction, membrane laminar necrosis, membrane microscopic chorionic pseudocysts, clusters of maternal floor multinucleated trophoblasts, excessive number of extravillous trophoblasts, and intervillous thrombi was strikingly higher in both late-onset preeclampsia and early-onset preeclampsia than in the comparative group without hypertension in pregnancy. All 3 patterns of chronic hypoxic placental injury were 2- to 3-fold more common in preeclampsia. Although the preuterine pattern was as common in early-onset preeclampsia as it was in late-onset preeclampsia, the postuterine pattern was 2-fold more common in early-onset preeclampsia, and chronic villitis of unknown etiology was more common in late-onset preeclampsia than in the other 2 groups. Features of shallow placental implantation occurred at the same frequency in early-onset preeclampsia as in late-onset preeclampsia, which reflects an underlying common pathological mechanism in both subgroups of preeclampsia, while hypoxic lesions and patterns of placental injury were more common in early-onset preeclampsia than in late-onset preeclampsia, which correlates with more severe clinical outcomes of the former.

Emergency peripartal hysterectomy - a single-center analysis of the last 13 years at a tertiary perinatal care unit.

Background Peripartal hysterectomy (PH) is a challenging surgical procedure with elevated maternal morbidity. Methods From 2004 to 2016, 41 emergency PHs were performed at the tertiary care center of the Department of Gynecology and Obstetrics at University Hospital Ulm. In our retrospective analysis, the incidence of PH in our hospital was 12.8 per 10,000 deliveries with a maternal mortality of 2.4%. PH followed in 80.5% after cesarean section (c-section). Underlying causes/indications for PH were abnormal placentation (53.7%; n=22), uterine atony (26.8%; n=11), uterine lacerations (14.6%; n=6) and in rare cases uterine infection (4.9%; n=2). The median number of transfused products was 11 packed red blood cells (range 0-55 products), 10 fresh frozen plasma units (range 1-43) and two platelet concentrates (0-16). Results Loss of blood as estimated by surgeons was significantly correlated with actual transfused blood volume (P<0.001). Clinically relevant intra- and/or postoperative complications occurred in 53.7% of patients (n=22). Abnormal placentation was the leading cause for PH with an increased incidence during the last 10 years presumptively representing the elevated rate of c-sections. Conclusion PH goes along with increased rates of blood product transfusions independently of indication for surgery and has a high morbidity with a major complication rate of more than 50%. Prepartal assessment of risk factors like abnormal invasive placenta are crucial for reducing maternal morbidity.

Magnetic resonance imaging is often misleading when used as an adjunct to ultrasound in the management of placenta accreta spectrum disorders.

BACKGROUND: Magnetic resonance imaging is reported to have good sensitivity and specificity in the diagnosis of placenta accreta spectrum disorders, and is often used as an adjunct to ultrasound. But the additional utility of obtaining magnetic resonance imaging to assist in the clinical management of patients with placenta accreta spectrum disorders, above and beyond the information provided by ultrasound, is unknown. OBJECTIVE: We aimed to determine whether magnetic resonance imaging provides data that may inform clinical management by changing the sonographic diagnosis of placenta accreta spectrum disorders. STUDY DESIGN: In all, 78 patients with sonographic evidence or clinical suspicion of placenta accreta spectrum underwent magnetic resonance imaging of the abdomen and pelvis in orthogonal planes through the uterus utilizing T1- and T2-weighted imaging sequences at the University of Utah and the University of Colorado from 1997 through 2017. The magnetic resonance imaging was interpreted by radiologists with expertise in diagnosis of placenta accreta spectrum who had knowledge of the sonographic interpretation and clinical risk factors for placenta accreta spectrum disorders. The primary outcome was a change in diagnosis from sonographic interpretation that could alter clinical management, which was defined a priori. Diagnostic accuracy was verified by surgical and histopathologic diagnosis at the time of delivery. RESULTS: A change in diagnosis that could potentially alter clinical management occurred in 28 (36%) cases. Magnetic resonance imaging correctly changed the diagnosis in 15 (19%), and correctly confirmed the diagnosis in 34 (44%), but resulted in an incorrect change in diagnosis in 13 (17%), and an incorrect confirmation of ultrasound diagnosis in 15 (21%). Magnetic resonance imaging was not more likely to change a diagnosis in the 24 cases of posterior and lateral placental location compared to anterior location (33% vs 37%, P = .84). Magnetic resonance imaging resulted in overdiagnosis in 23% and in underdiagnosis in 14% of all cases. When ultrasound suspected severe disease (percreta) in 14 cases, magnetic resonance imaging changed the diagnosis in only 2 cases. Lastly, the proportion of accurate diagnosis with magnetic resonance imaging did not improve over time (61-65%, P = .96 for trend) despite increasing volume and increasing numbers of changed diagnoses. CONCLUSION: Magnetic resonance imaging resulted in a change in diagnosis that could alter clinical management of placenta accreta spectrum disorders in more than one third of cases, but when changed, the diagnosis was often incorrect. Given its high cost and limited clinical value, magnetic resonance imaging should not be used routinely as an adjunct to ultrasound in the diagnosis of placenta accreta spectrum until evidence for utility is clearly demonstrated by more definitive prospective studies.

MRI Features Predictive of Invasive Placenta With Extrauterine Spread in High-Risk Gravid Patients: A Prospective Evaluation.

OBJECTIVE: The objective of our study was to evaluate MRI diagnostic ability in predicting invasive placenta with extrauterine spread in high-risk gravid patients. SUBJECTS AND METHODS: Between March 2016 and June 2017, 49 patients (mean age, 35.7 years; mean gestational age, 32.5 weeks) with sonographically confirmed placenta previa underwent dedicated MRI. All MRI examinations were reviewed by two experienced radiologists prospectively. Intraoperative and pathologic findings were the standard of reference. Kappa values were calculated to assess the agreement between MRI findings and histologic results as well as interrater reliability. ROC curve analysis was used to test the discriminative ability of MRI features for invasive placenta with extrauterine spread. Stepwise multiple logistic regression analysis was performed to identify any MRI findings predictive of invasive placenta and of bladder and parametrial involvement. RESULTS: MRI exhibited significant overall accuracy (AUC = 0.77, p = 0.006) in identifying invasive placenta with 100% sensitivity and negative predictive values; it was highly specific (100%) in identifying placental extension to both bladder and parametrial tissues. Lumpy tapering of the placental edges, intraplacental dark T2 bands, prominent intraplacental vascularity, and serosal hypervascularity were independently associated with an increased risk for invasive placenta. Serosal hypervascularity and vesicouterine space hypervascularity were independent predictors of bladder invasion; abnormal vascularization within the parametrial fat was significant for parametrial invasion. CONCLUSION: MRI is highly accurate in depicting placental extrauterine spread. The presence of abnormal vessels at the uterine serosa was the most important MRI feature for identifying invasive placenta. An abnormal vascular network within the vesicouterine space or parametrium was the most reliable MRI sign for detecting bladder or parametrial involvement.