Uterine injury during diestrus leads to placental and embryonic defects in future pregnancies in mice†.

Uterine injury from procedures such as Cesarean sections (C-sections) often have severe consequences on subsequent pregnancy outcomes, leading to disorders such as placenta previa, placenta accreta, and infertility. With rates of C-section at ~30% of deliveries in the USA and projected to continue to climb, a deeper understanding of the mechanisms by which these pregnancy disorders arise and opportunities for intervention are needed. Here we describe a rodent model of uterine injury on subsequent in utero outcomes. We observed three distinct phenotypes: increased rates of resorption and death, embryo spacing defects, and placenta accreta-like features of reduced decidua and expansion of invasive trophoblasts. We show that the appearance of embryo spacing defects depends entirely on the phase of estrous cycle at the time of injury. Using RNA-seq, we identified perturbations in the expression of components of the COX/prostaglandin pathway after recovery from injury, a pathway that has previously been demonstrated to play an important role in embryo spacing. Therefore, we demonstrate that uterine damage in this mouse model causes morphological and molecular changes that ultimately lead to placental and embryonic developmental defects.

Evaluation of maternal serum VEGF, TNF-alpha, IL-4, and IL-10 levels in differentiating placenta accreta spectrum from isolated placenta previa.

OBJECTIVE: Our study aimed to differentiate patients with placenta accreta spectrum (PAS) from those with placenta previa (PP) using maternal serum levels of vascular endothelial growth factor (VEGF), tumor necrosis factor-alpha (TNF-alpha), interleukin-4 (IL-4), and IL-10. METHODS: The case group consisted of 77 patients with placenta previa, and the control group consisted of 90 non-previa pregnant women. Of the pregnant women in the case group, 40 were diagnosed with PAS in addition to placenta previa and 37 had placenta previa with no invasion. The maternal serum VEGF, TNF-alpha, IL-4, and IL-10 levels were compared between the case and control groups. Then the success of these markers in differentiating between PP and PAS was evaluated. RESULTS: We found the VEGF, TNF-alpha, and IL-4 levels to be higher and the IL-10 level to be lower in the case group compared to the control group (p < 0.001). We observed a statistically significantly lower IL-10 level in the patients with PAS than those with PP (p = 0.029). In the receiver operating characteristic analysis, the optimal cut-off of IL-10 in the detection of PAS was 0.42 ng/mL). In multivariate analysis, the risk of PAS was significant for IL-10 (odds ratio (OR) 0.45, 95 % confidence interval (CI) 0.25-0.79, p = 0.006) and previous cesarean section (OR 2.50, 95 % Cl 1.34-4.66, p = 0.004). The model's diagnostic sensitivity and specificity, including previous cesarean section, preoperative hemoglobin (Hb), TNF-alpha, and IL-10 were 75 % and 72.9 %, respectively. CONCLUSION: The study showed that the IL-10 level was lower in patients with PAS than in those with PP. A statistical model combining risk factors including previous cesarean section, preoperative Hb, TNF-alpha, and IL-10 may improve clinical diagnosis of PAS in placenta previa cases. Cytokines may be used as additional biomarkers to the clinical risk factors in the diagnosis of PAS.

Two-Compartment Perfusion MR IVIM Model to Investigate Normal and Pathological Placental Tissue.

BACKGROUND: Perfusion and diffusion coexist in the placenta and can be altered by pathologies. The two-perfusion model, where f1 and, f2 are the perfusion-fraction of the fastest and slowest perfusion compartment, respectively, and D is the diffusion coefficient, may help differentiate between normal and impaired placentas. PURPOSE: Investigate the potential of the two-perfusion IVIM model in differentiating between normal and abnormal placentas. STUDY-TYPE: Retrospective, case-control. POPULATION: 43 normal pregnancy, 9 fetal-growth-restriction (FGR), 6 small-for-gestational-age (SGA), 4 accreta, 1 increta and 2 percreta placentas. FIELD STRENGTH/SEQUENCE: Diffusion-weighted-echo planar imaging sequence at 1.5 T. ASSESSMENT: Voxel-wise signal-correction and fitting-controls were used to avoid overfitting obtaining that two-perfusion model fitted the observed data better than the IVIM model (Akaike weight: 0.94). The two-perfusion parametric-maps were quantified from ROIs in the fetal and maternal placenta and in the accretion zone of accreta placentas. The diffusion coefficient D was evaluated using a b ≥ 200 sec/mm2 -mono-exponential decay fit. IVIM metrics were quantified to fix f1 + f2 = fIVIM . STATISTICAL-TESTS: ANOVA with Dunn-Sidák's post-hoc correction and Cohen's d test were used to compare parameters between groups. Spearman's coefficient was evaluated to study the correlation between variables. A P-value<0.05 indicated a statistically significant difference. RESULTS: There was a significant difference in f1 between FGR and SGA, and significant differences in f2 and fIVIM between normal and FGR. The percreta + increta group showed the highest f1 values (Cohen's d = -2.66). The f2 between normal and percreta + increta groups showed Cohen's d = 1.12. Conversely, fIVIM had a small effective size (Cohen's d = 0.32). In the accretion zone, a significant correlation was found between f2 and GA (ρ = 0.90) whereas a significant negative correlation was found between fIVIM and D (ρ = -0.37 in fetal and ρ = -0.56 in maternal side) and f2 and D (ρ = -0.38 in fetal and ρ = -0.51 in maternal side) in normal placentas. CONCLUSION: The two-perfusion model provides complementary information to IVIM parameters that may be useful in identifying placenta impairment. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY STAGE: 1.

Deep Learning Model Based on Multisequence MRI Images for Assessing Adverse Pregnancy Outcome in Placenta Accreta.

BACKGROUND: Preoperative assessment of adverse outcomes risk in placenta accreta spectrum (PAS) disorders is of high clinical relevance for perioperative management and prognosis. PURPOSE: To investigate the association of preoperative MRI multisequence images and adverse pregnancy outcomes by establishing a deep learning model in patients with PAS. STUDY TYPE: Retrospective. POPULATION: 323 pregnant women (age from 20 to 46, the median age is 33), suspected of PAS, underwent MRI to assess the PAS, divided into the training (N = 227) and validation datasets (N = 96). FIELD STRENGTH/SEQUENCE: 1.5T scanner/fast imaging employing steady-state acquisition sequence and single shot fast spin echo sequence. ASSESSMENT: Different deep learning models (i.e., with single MRI input sequence/two sequences/multisequence) were compared to assess the risk of adverse pregnancy outcomes, which defined as intraoperative bleeding ≥1500 mL and/or hysterectomy. Net reclassification improvement (NRI) was used for quantitative comparison of assessing adverse pregnancy outcome between different models. STATISTICAL TESTS: The AUC, sensitivity, specificity, and accuracy were used for evaluation. The Shapiro-Wilk test and t-test were used. A P value of <0.05 was considered statistically significant. RESULTS: 215 cases were invasive placenta accreta (67.44% of them with adverse outcomes) and 108 cases were non-invasive placenta accreta (9.25% of them with adverse outcomes). The model with four sequences assessed adverse pregnancy outcomes with AUC of 0.8792 (95% CI, 0.8645-0.8939), with ACC of 85.93% (95%, 84.43%-87.43%), with SEN of 86.24% (95% CI, 82.46%-90.02%), and with SPC of 85.62% (95%, 82.00%-89.23%) on the test cohort. The performance of model with four sequences improved above 0.10 comparing with that of model with two sequences and above 0.20 comparing with that of model with single sequence in terms of NRI. DATA CONCLUSION: The proposed model showed good diagnostic performance for assessing adverse pregnancy outcomes. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY: Stage 2.

A Deep Learning Pipeline Using Prior Knowledge for Automatic Evaluation of Placenta Accreta Spectrum Disorders With MRI.

BACKGROUND: The diagnosis of prenatal placenta accreta spectrum (PAS) with magnetic resonance imaging (MRI) is highly dependent on radiologists' experience. A deep learning (DL) method using the prior knowledge that PAS-related signs are generally found along the utero-placental borderline (UPB) may help radiologists, especially those with less experience, to mitigate this issue. PURPOSE: To develop a DL tool for antenatal diagnosis of PAS using T2-weighted MR images. STUDY TYPE: Retrospective. SUBJECTS: Five hundred and forty pregnant women with clinically suspected PAS disorders from two institutions, divided into training (409), internal test (103), and external test (28) datasets. FIELD STRENGTH/SEQUENCE: Sagittal T2-weighted fast spin echo sequence at 1.5 T and 3 T. ASSESSMENT: An nnU-Net was trained for placenta segmentation. The UPB straightening approach was used to extract the utero-placental boundary region. The UPB image was then fed into DenseNet-PAS for PAS diagnosis. DenseNet-PP learnt placental position information to improve the PAS diagnosis performance. Three radiologists with 8, 10, and 12 years of experience independently evaluated the images. Two radiologists marked the placenta tissue. Histopathological findings were the reference standard. STATISTICAL TESTS: Area under the curve (AUC) was used to evaluate the classification. Dice coefficient evaluated the segmentation between radiologists and the model performance. The Mann-Whitney U-test or the chi-squared test assessed the significance of differences. Decision curve analysis was used to determine clinical effectiveness. DeLong's test was used to compare AUCs. RESULTS: Of the 540 patients, 170 had PAS disorders confirmed by histopathology. The DL model using UPB images and placental position yielded the highest AUC of 0.860 and 0.897 in internal test and external test cohorts, respectively, significantly exceeding the performance of three radiologists (internal test AUC, 0.737-0.770). DATA CONCLUSION: By extracting the UPB image, this fully automatic DL pipeline achieved high accuracy and may assist radiologists in PAS diagnosis using MRI. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY: Stage 2.

Prenatal Diagnosis of Placenta Accreta Spectrum Disorders: Deep Learning Radiomics of Pelvic MRI.

BACKGROUND: Diagnostic performance of placenta accreta spectrum (PAS) by prenatal MRI is unsatisfactory. Deep learning radiomics (DLR) has the potential to quantify the MRI features of PAS. PURPOSE: To explore whether DLR from MRI can be used to identify pregnancies with PAS. STUDY TYPE: Retrospective. POPULATION: 324 pregnant women (mean age, 33.3 years) suspected PAS (170 training and 72 validation from institution 1, 82 external validation from institution 2) with clinicopathologically proved PAS (206 PAS, 118 non-PAS). FIELD STRENGTH/SEQUENCE: 3-T, turbo spin-echo T2-weighted images. ASSESSMENT: The DLR features were extracted using the MedicalNet. An MRI-based DLR model incorporating DLR signature, clinical model (different clinical characteristics between PAS and non-PAS groups), and MRI morphologic model (radiologists' binary assessment for the PAS diagnosis) was developed. These models were constructed in the training dataset and then validated in the validation datasets. STATISTICAL TESTS: The Student t-test or Mann-Whitney U, χ2 or Fisher exact test, Kappa, dice similarity coefficient, intraclass correlation coefficients, least absolute shrinkage and selection operator logistic regression, multivariate logistic regression, receiver operating characteristic (ROC) curve, DeLong test, net reclassification improvement (NRI) and integrated discrimination improvement (IDI), calibration curve with Hosmer-Lemeshow test, decision curve analysis (DCA). P < 0.05 indicated a significant difference. RESULTS: The MRI-based DLR model had a higher area under the curve than the clinical model in three datasets (0.880 vs. 0.741, 0.861 vs. 0.772, 0.852 vs. 0.675, respectively) or MRI morphologic model in training and independent validation datasets (0.880 vs. 0.760, 0.861, vs. 0.781, respectively). The NRI and IDI were 0.123 and 0.104, respectively. The Hosmer-Lemeshow test had nonsignificant statistics (P = 0.296 to 0.590). The DCA offered a net benefit at any threshold probability. DATA CONCLUSION: An MRI-based DLR model may show better performance in diagnosing PAS than a clinical or MRI morphologic model. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY STAGE: 2.

Cesarean hysterectomy for placenta accreta spectrum: Surgeon specialty-specific assessment.

OBJECTIVE: To assess (i) clinical and pregnancy characteristics, (ii) patterns of surgical procedures, and (iii) surgical morbidity associated with cesarean hysterectomy for placenta accreta spectrum based on the specialty of the attending surgeon. METHODS: The Premier Healthcare Database was queried retrospectively to study patients with placenta accreta spectrum who underwent cesarean delivery and concurrent hysterectomy from 2016 to 2020. Surgical morbidity was assessed with propensity score inverse probability of treatment weighting based on surgeon specialty for hysterectomy: general obstetrician-gynecologists, maternal-fetal medicine specialists, and gynecologic oncologists. RESULTS: A total of 2240 cesarean hysterectomies were studies. The most common surgeon type was general obstetrician-gynecologist (n = 1534, 68.5%), followed by gynecologic oncologist (n = 532, 23.8%) and maternal-fetal medicine specialist (n = 174, 7.8%). Patients in the gynecologic oncologist group had the highest rate of placenta increta or percreta, followed by the maternal-fetal medicine specialist and general obstetrician-gynecologist groups (43.4%, 39.6%, and 30.6%, P < .001). In a propensity score-weighted model, measured surgical morbidity was similar across the three subspecialty groups, including hemorrhage / blood transfusion (59.4-63.7%), bladder injury (18.3-24.0%), ureteral injury (2.2-4.3%), shock (8.6-10.5%), and coagulopathy (3.3-7.4%) (all, P > .05). Among the cesarean hysterectomy performed by gynecologic oncologist, hemorrhage / transfusion rates remained substantial despite additional surgical procedures: tranexamic acid / ureteral stent (60.4%), tranexamic acid / endo-arterial procedure (76.2%), ureteral stent / endo-arterial procedure (51.6%), and all three procedures (55.4%). Tranexamic acid administration with ureteral stent placement was associated with decreased bladder injury (12.8% vs 23.8-32.2%, P < .001). CONCLUSION: These data suggest that patient characteristics and surgical procedures related to cesarean hysterectomy for placenta accreta spectrum differ based on surgeon specialty. Gynecologic oncologists appear to manage more severe forms of placenta accreta spectrum. Regardless of surgeon's specialty, surgical morbidity of cesarean hysterectomy for placenta accreta spectrum is significant.

A new technique to preserve the uterus in patients with placenta accreta spectrum disorders.

BACKGROUND: Placenta accreta spectrum disorders are associated with substantial maternal morbidity and mortality. Despite a preoperative diagnosis, the rate of complications remains high, and the condition is generally associated with the need for a hysterectomy. OBJECTIVE: This study aimed to evaluate the outcomes of a new uterine-preserving technique (called the combined approach, including surgical hemostasis, bilateral ligation of the descending branches of the uterine arteries, and hemostatic external supraplacental stitch with the use of the Zhukovsky double-balloon tamponade in patients with placenta accreta spectrum disorders) during cesarean delivery in women with placenta accreta spectrum disorders vs the surgical technique used until 2014. STUDY DESIGN: This retrospective cohort study included 147 patients with placenta accreta spectrum disorders who were divided into 2 groups: the study group (n=95) is to undergo cesarean delivery using the combined approach, and the control group (n=52) is to undergo the surgical technique used until 2014, which included bilateral uterine artery ligation, which is the transfusion of plasma, red blood cells, platelets, and protease inhibitors. RESULTS: The volume of blood loss was 1.5-fold lower (P=.0010), the number of blood transfusions was 5.1-fold lower (P=.026), and the rate of bladder injuries was 19-fold lower (P=.012) in the study group than that in the control group. The duration of hospital stay after delivery was 4 days lesser (P=.001) and the number of hysterectomies was 4.5-fold lower in the study group than in the control group (P=.023). The study groups did not differ in terms of placenta accreta spectrum type. CONCLUSION: The combined approach during cesarean delivery proved to be more effective than the surgical technique used until 2014 in reducing the number of hysterectomies, blood loss volume, number of blood transfusions, and duration of hospital stay in patients with placenta accreta spectrum disorders.

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.

Society for Maternal-Fetal Medicine Special Statement: Emergency checklist, planning worksheet, and system preparedness bundle for placenta accreta spectrum.

Placenta accreta spectrum is a life-threatening complication of pregnancy that is underdiagnosed and can result in massive hemorrhage, disseminated intravascular coagulation, massive transfusion, surgical injury, multisystem organ failure, and even death. Given the rarity and complexity, most obstetrical hospitals and providers do not have comprehensive expertise in the diagnosis and management of placenta accreta spectrum. Emergency management, antenatal interdisciplinary planning, and system preparedness are key pillars of care for this life-threatening disorder. We present an updated sample checklist for emergent and unplanned cases, an antenatal planning worksheet for known or suspected cases, and a bundle of activities to improve system and team preparedness for placenta accreta spectrum.

Development and validation of MRI-based scoring models for predicting placental invasiveness in high-risk women for placenta accreta spectrum.

OBJECTIVES: To develop and validate MRI-based scoring models for predicting placenta accreta spectrum (PAS) invasiveness. MATERIALS AND METHODS: This retrospective study comprised a derivation cohort and a validation cohort. The derivation cohort came from a systematic review of published studies evaluating the diagnostic performance of MRI signs for PAS and/or placenta percreta in high-risk women. The significant signs were identified and used to develop prediction models for PAS and placenta percreta. Between 2016 and 2021, consecutive high-risk pregnant women for PAS who underwent placental MRI constituted the validation cohort. Two radiologists independently evaluated the MRI signs. The reference standard was intraoperative and pathologic findings. The predictive ability of MRI-based models was evaluated using the area under the curve (AUC). RESULTS: The derivation cohort included 26 studies involving 2568 women and the validation cohort consisted of 294 women with PAS diagnosed in 258 women (88%). Quantitative meta-analysis revealed that T2-dark bands, placental/uterine bulge, loss of T2 hypointense interface, bladder wall interruption, placental heterogeneity, and abnormal intraplacental vascularity were associated with both PAS and placenta percreta, and myometrial thinning and focal exophytic mass were exclusively associated with PAS. The PAS model was validated with an AUC of 0.90 (95% CI: 0.86, 0.93) for predicting PAS and 0.85 (95% CI: 0.79, 0.90) for adverse peripartum outcome; the placenta percreta model showed an AUC of 0.92 (95% CI: 0.86, 0.98) for predicting placenta percreta. CONCLUSION: MRI-based scoring models established based on quantitative meta-analysis can accurately predict PAS, placenta percreta, and adverse peripartum outcome. CLINICAL RELEVANCE STATEMENT: These proposed MRI-based scoring models could help accurately predict PAS invasiveness and provide evidence-based risk stratification in the management of high-risk pregnant women for PAS. KEY POINTS: • Accurately identifying placenta accreta spectrum (PAS) and assessing its invasiveness depending solely on individual MRI signs remained challenging. • MRI-based scoring models, established through quantitative meta-analysis of multiple MRI signs, offered the potential to predict PAS invasiveness in high-risk pregnant women. • These MRI-based models allowed for evidence-based risk stratification in the management of pregnancies suspected of having PAS.

Collateral Round Ligament Arterial Supply of Placenta Accreta Spectrum and Considerations for Prophylactic Balloon Occlusion Catheter Placement.

Internal iliac artery (IIA) balloon occlusion catheters have been commonly inserted to decrease the risk of postpartum hemorrhage in placenta accreta spectrum disorders; however, there has been mixed success in clinical studies. Placement of an infrarenal aortic balloon has shown more consistent effectiveness in recent studies. A possible reason for this is collateral arterial supply to the placenta from external iliac artery branches. Retrospective chart review was conducted of angiography images during prophylactic IIA balloon occlusion catheter insertion over a 7-year period. Sixty-two individual cases were identified. Digital subtraction angiography (DSA) was performed in 32 (52%) cases, and 20 (62%) showed collateral blood supply from branches of the external iliac arteries, namely the round ligament artery. In conclusion, a high proportion of placenta accreta spectrum cases have arterial blood supply from branches of the external iliac artery, which may explain the discrepancy in effectiveness seen between IIA and infrarenal aortic sites of balloon occlusion catheter placement.

Validity of ICD-10 diagnosis codes for placenta accreta spectrum disorders.

BACKGROUND: The 10th revision of the International Classification of Diseases, Clinical Modification (ICD-10) includes diagnosis codes for placenta accreta spectrum for the first time. These codes could enable valuable research and surveillance of placenta accreta spectrum, a life-threatening pregnancy complication that is increasing in incidence. OBJECTIVE: We sought to evaluate the validity of placenta accreta spectrum diagnosis codes that were introduced in ICD-10 and assess contributing factors to incorrect code assignments. METHODS: We calculated sensitivity, specificity, positive predictive value and negative predictive value of the ICD-10 placenta accreta spectrum code assignments after reviewing medical records from October 2015 to March 2020 at a quaternary obstetric centre. Histopathologic diagnosis was considered the gold standard. RESULTS: Among 22,345 patients, 104 (0.46%) had an ICD-10 code for placenta accreta spectrum and 51 (0.23%) had a histopathologic diagnosis. ICD-10 codes had a sensitivity of 0.71 (95% CI 0.56, 0.83), specificity of 0.98 (95% CI 0.93, 1.00), positive predictive value of 0.61 (95% CI 0.48, 0.72) and negative predictive value of 1.00 (95% CI 0.96, 1.00). The sensitivities of the ICD-10 codes for placenta accreta spectrum subtypes- accreta, increta and percreta-were 0.55 (95% CI 0.31, 0.78), 0.33 (95% CI 0.12, 0.62) and 0.56 (95% CI 0.31, 0.78), respectively. Cases with incorrect code assignment were less morbid than cases with correct code assignment, with a lower incidence of hysterectomy at delivery (17% vs 100%), blood transfusion (26% vs 75%) and admission to the intensive care unit (0% vs 53%). Primary reasons for code misassignment included code assigned to cases of occult placenta accreta (35%) or to cases with clinical evidence of placental adherence without histopatholic diagnostic (35%) features. CONCLUSION: These findings from a quaternary obstetric centre suggest that ICD-10 codes may be useful for research and surveillance of placenta accreta spectrum, but researchers should be aware of likely substantial false positive cases.

Placental lakes vs lacunae: spot the differences.

Sonographic sonolucencies are anechoic areas surrounded by tissue of normal echogenicity, commonly found in the placental parenchyma during the second and third trimesters of pregnancy. The ultrasound appearance of lakes and lacunae derives from the low echogenicity of villous-free areas within the placental parenchyma, filled with maternal blood of varying velocities. In normal placentation, lakes usually start appearing as soon as maternal blood begins to flow freely within the intervillous space at the end of the first trimester, whereas, in accreta placentation, lacunae develop progressively during the second trimester. Larger lakes are found mainly in areas of lower villous density under the fetal plate or in the marginal areas, but can also be found in the center of a lobule above the entry of a spiral artery. Lakes of variable size, position and shape are of no clinical significance, except if they transform into echogenic cystic lesions, which have been associated with poor fetal growth and placental malperfusion. Lacunae are formed by the distortion of one or more placental lobules developing inside a uterine scar, resulting from high-volume, high-velocity flows from the radial/arcuate arteries, and are associated with a high probability of placenta accreta spectrum at birth. They often present with ultrasound signs of uterine remodeling following scarring. Lakes and lacunae can coexist within the same placenta and both will change in size and shape as pregnancy advances. Better understanding of the etiopathology of placental sonolucent spaces and associated morphological changes is necessary to identify patients at risk of subsequent complications during pregnancy and/or at delivery. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Trimester-specific diagnostic accuracy of ultrasound for detection of placenta accreta spectrum: systematic review and meta-analysis.

OBJECTIVE: To assess the diagnostic accuracy of ultrasound for detecting placenta accreta spectrum (PAS) during the first trimester of pregnancy and compare it with the accuracy of second- and third-trimester ultrasound examination in pregnancies at risk for PAS. METHODS: PubMed, EMBASE and Web of Science databases were searched to identify relevant studies published from inception until 10 March 2023. Inclusion criteria were cohort, case-control or cross-sectional studies that evaluated the accuracy of ultrasound examination performed at < 14 weeks of gestation (first trimester) or ≥ 14 weeks of gestation (second/third trimester) for the diagnosis of PAS in pregnancies with clinical risk factors. The primary outcome was the diagnostic accuracy of sonography in detecting PAS in the first trimester, compared with the accuracy of ultrasound examination in the second and third trimesters. The secondary outcome was the diagnostic accuracy of each sonographic marker individually across the trimesters of pregnancy. The reference standard was PAS confirmed at pathological or surgical examination. The potential of ultrasound and different ultrasound signs to detect PAS was assessed by computing summary estimates of sensitivity, specificity, diagnostic odds ratio and positive and negative likelihood ratios. RESULTS: A total of 37 studies, including 5764 pregnancies at risk of PAS, with 1348 cases of confirmed PAS, were included in our analysis. The meta-analysis demonstrated that ultrasound had a sensitivity of 86% (95% CI, 78-92%) and specificity of 63% (95% CI, 55-70%) during the first trimester, and a sensitivity of 88% (95% CI, 84-91%) and specificity of 92% (95% CI, 85-96%) during the second/third trimester. Regarding sonographic markers examined in the first trimester, lower uterine hypervascularity exhibited the highest sensitivity (97% (95% CI, 19-100%)), and uterovesical interface irregularity demonstrated the highest specificity (99% (95% CI, 96-100%)). In the second/third trimester, loss of clear zone had the highest sensitivity (80% (95% CI, 72-86%)), and uterovesical interface irregularity exhibited the highest specificity (99% (95% CI, 97-100%)). CONCLUSIONS: First-trimester ultrasound examination has similar accuracy to second- and third-trimester ultrasound examinations for the diagnosis of PAS. Routine first-trimester ultrasound screening for patients at high risk of PAS may improve detection rates and allow earlier referral to tertiary care centers for pregnancy management. © 2024 International Society of Ultrasound in Obstetrics and Gynecology.

Determinants of emergency Cesarean delivery in pregnancies complicated by placenta previa with or without placenta accreta spectrum disorder: analysis of ADoPAD cohort.

OBJECTIVES: To investigate the rate and outcome of emergency Cesarean delivery (CD) in women with placenta previa with or without placenta accreta spectrum disorders (PAS) and to elucidate the diagnostic accuracy of ultrasound in predicting emergency CD. METHODS: This was a secondary analysis of a multicenter prospective study involving 16 referral hospitals in Italy (ADoPAD study). Inclusion criteria were women with placenta previa minor (< 20 mm from the internal cervical os) or placenta previa major (covering the os), aged ≥ 18 years, who underwent transabdominal and transvaginal ultrasound assessment at ≥ 26 + 0 weeks of gestation. The primary outcome was the occurrence of emergency CD, defined as the need for immediate surgical intervention performed for emergency maternal or fetal indication, including active labor, cumulative maternal bleeding > 500 mL, severe and persistent vaginal bleeding such that maternal hemodynamic stability could not be achieved or maintained, or category-III fetal heart rate tracing unresponsive to resuscitative measures. The primary outcome was reported separately in the population of women with placenta previa and no PAS confirmed after birth and in those with PAS. The secondary aim was to report on the strength of association and to test the diagnostic accuracy of ultrasound in predicting emergency CD. Univariate, multivariate and diagnostic accuracy analyses were used to analyze the data. RESULTS: A total of 450 women, including 97 women with placenta previa and PAS and 353 with placenta previa only, were analyzed. In women with placenta previa and PAS, emergency CD was required in 20.6% (95% CI, 14-30%), and 60.0% (12/20) delivered before 34 weeks of gestation. The mean gestational age at delivery was 32.3 ± 2.7 weeks in women undergoing emergency CD and 34.9 ± 1.8 weeks in those undergoing elective CD (P < 0.001). Women undergoing emergency CD had a higher median estimated blood loss (2500 (interquartile range (IQR), 1350-4500) vs 1100 (IQR, 625-2500) mL; P = 0.012), mean units of blood transfused (7.3 ± 8.8 vs 2.5 ± 3.4; P = 0.02) and more frequent placement of a mechanical balloon (50.0% vs 16.9%; P = 0.002) compared with those undergoing elective CD. On univariate analysis, the presence of interrupted retroplacental space, interrupted bladder line and placental lacunae was more common in women not experiencing emergency CD. No comprehensive multivariate analysis could be performed in this subgroup of women. Ultrasound signs of PAS, including presence of interrupted retroplacental space, interrupted bladder line and placental lacunae, were not predictive of emergency CD. In women with placenta previa but no PAS, emergency CD was required in 31.2% (95% CI, 26.6-36.2%), and 32.7% (36/110) delivered before 34 weeks of gestation. The mean gestational age at delivery was lower in women undergoing emergency CD compared with those undergoing elective CD (34.2 ± 2.9 vs 36.7 ± 1.6 weeks; P < 0.001). Pregnancies complicated by emergency CD were associated with a lower birth weight (2330 ± 620 vs 2800 ± 480 g; P < 0.001) and had a higher risk of need for blood transfusion (22.7% vs 10.7%; P = 0.003) compared with those who underwent elective CD. On multivariate analysis, only placental thickness (odds ratio (OR), 1.02 (95% CI, 1.00-1.03); P = 0.046) and cervical length < 25 mm (OR, 3.89 (95% CI, 1.33-11.33); P = 0.01) were associated with emergency CD. However, a short cervical length showed low diagnostic accuracy for predicting emergency CD in these women. CONCLUSION: Emergency CD occurred in about 20% of women with placenta previa and PAS and 30% of those with placenta previa only and was associated with worse maternal outcome compared with elective intervention. Prenatal ultrasound is not predictive of the risk of emergency CD in women with these disorders. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.

Evaluation of preoperative ultrasound signs associated with bladder injury during complex Cesarean delivery: case-control study.

OBJECTIVE: Intraoperative hemorrhage and peripartum hysterectomy are the main complications in patients presenting with a low-lying placenta or placenta previa undergoing repeat Cesarean delivery (CD). Patients with a high probability of placenta accreta spectrum (PAS) at birth also have a higher risk of intraoperative urologic injury. The aim of this study was to evaluate the ultrasound signs and intraoperative features associated with these injuries. METHODS: This was a retrospective case-control study of consecutive singleton pregnancies included in a prospective cohort of patients with a history of at least one prior CD and diagnosed prenatally with an anterior low-lying placenta or placenta previa at 32-36 weeks' gestation. All patients underwent investigational preoperative transabdominal and transvaginal ultrasound examination within 48 h prior to delivery. Ultrasound anomalies of uterine contour and uteroplacental vascularity, and gross anomalies of the lower uterine segment (LUS) and surrounding pelvic tissue at delivery, were recorded using a standardized protocol, which included evaluation of the extent of uterine contour anomalies. The diagnosis of PAS was established when one or more placental lobules could not be separated digitally from the uterine wall at delivery or during the gross examination of the hysterectomy or partial myometrial resection specimens, and was confirmed by histopathology. Data were compared between cases complicated by intraoperative bladder injury and controls from the same cohort matched at a 1:3 ratio by parity and the number of prior CDs using conditional logistic regression. RESULTS: There were 16 (9.4%) patients with an intraoperative bladder injury in a cohort of 170 managed by the same multidisciplinary team during the study period. There were no patients diagnosed with ureteric or bladder trigone damage. There were 14 (87.5%) patients with a bladder injury that had histopathologic evidence of PAS at birth, including 11 (68.8%) cases described on microscopic examination as placenta increta and three (18.8%) as placenta creta. There was a significant (P = 0.03) difference between cases and controls in the distribution of intraoperative LUS vascularity, whereby the higher the number of enlarged vessels, the higher the odds of bladder injury. Multivariable regression analysis revealed that both gestational age at delivery and LUS remodeling on transabdominal ultrasound were associated with bladder injury. A higher gestational age was associated with a lower risk of injury. A higher LUS remodeling grade on transabdominal ultrasound was associated with an increased risk of bladder injury. Patients with Grade-3 remodeling (involving > 50% of the LUS) had 9-times higher odds of a bladder injury compared to patients with Grade-1 remodeling (involving < 30% of the LUS). CONCLUSIONS: Preoperative ultrasound examination is useful in the evaluation of the risk of intraoperative bladder injury in patients with a history of prior CD presenting with a low-lying placenta or placenta previa. The larger the remodeling of the LUS on transabdominal ultrasound, the higher the risk of adverse urologic events. © 2024 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Neonatal outcomes in the surgical management of placenta accreta spectrum disorders: a retrospective single-center observational study from 468 Vietnamese pregnancies beyond 28 weeks of gestation.

BACKGROUND: Placenta accreta spectrum disorders (PASDs) increase the mortality rate for mothers and newborns over a decade. Thus, the purpose of the study is to evaluate the neonatal outcomes in emergency cesarean section (CS) and planned surgery as well as in Cesarean hysterectomy and the modified one-step conservative uterine surgery (MOSCUS). The secondary aim is to reveal the factors relating to poor neonatal outcomes. METHODS: This was a single-center retrospective study conducted between 2019 and 2020 at Tu Du Hospital, in the southern region of Vietnam. A total of 497 pregnant women involved in PASDs beyond 28 weeks of gestation were enrolled. The clinical outcomes concerning gestational age, birth weight, APGAR score, neonatal intervention, neonatal intensive care unit (NICU) admission, and NICU length of stay (LOS) were compared between emergency and planned surgery, between the Cesarean hysterectomy and the MOSCUS. The univariate and multivariable logistic regression were used to assess the adverse neonatal outcomes. RESULTS: Among 468 intraoperatively diagnosed PASD cases who underwent CS under general anesthesia, neonatal outcomes in the emergency CS (n = 65) were significantly poorer than in planned delivery (n = 403). Emergency CS increased the odds ratio (OR) for earlier gestational age, lower birthweight, lower APGAR score at 5 min, higher rate of neonatal intervention, NICU admission, and longer NICU LOS ≥ 7 days with OR, 95% confidence interval (CI) were 10.743 (5.675-20.338), 3.823 (2.197-6.651), 5.215 (2.277-11.942), 2.256 (1.318-3.861), 2.177 (1.262-3.756), 3.613 (2.052-6.363), and 2.298 (1.140-4.630), respectively, p < 0.05. Conversely, there was no statistically significant difference between the neonatal outcomes in Cesarean hysterectomy (n = 79) and the MOSCUS method (n = 217). Using the multivariable logistic regression, factors independently associated with the 5-min-APGAR score of less than 7 points were time duration from the skin incision to fetal delivery (min) and gestational age (week). One minute-decreased time duration from skin incision to fetal delivery contributed to reduce the risk of adverse neonatal outcome by 2.2% with adjusted OR, 95% CI: 0.978 (0.962-0.993), p = 0.006. Meanwhile, one week-decreased gestational age increased approximately two fold odds of the adverse neonatal outcome with adjusted OR, 95% CI: 1.983 (1.600-2.456), p < 0.0001. CONCLUSIONS: Among pregnancies with PASDs, the neonatal outcomes are worse in the emergency group compared to planned group of cesarean section. Additionally, the neonatal comorbidities in the conservative surgery using the MOSCUS method are similar to Cesarean hysterectomy. Time duration from the skin incision to fetal delivery and gestational age may be considered in PASD surgery. Further data is required to strengthen these findings.

Incidence, risk factors and maternal outcomes of unsuspected placenta accreta spectrum disorders: a retrospective cohort study.

BACKGROUND: To identify incidence and underlying risk factors for unsuspected placenta accreta spectrum (PAS) and compare the maternal outcomes between suspected and unsuspected cases in three large academic referral centers. METHODS: A retrospective cohort study was conducted in three university-based tertiary referral centers from Jan 1st, 2013, to Dec 31st, 2022. All cases of PAS confirmed by pathology were included in the study. Unsuspected PAS cases were diagnosed at the time of delivery, while suspected cases served as the control group. Potential risk factors were compared between the two groups. Multivariable regression model was also performed to identify risk factors. Maternal outcomes were also evaluated. RESULTS: A total of 339 pathology-confirmed PAS cases were included in the study out of 415,470 deliveries, of which 35.4% (n = 120) were unsuspected cases. Unsuspected PAS cases were 7.9 times more likely to have a history of intrauterine adhesions (adjusted odds ratio [aOR] 7.93; 95% confidence interval [CI] 2.35-26.81), 7.0 times more likely to have a history of clinically confirmed PAS (aOR, 6.99; 95% CI 2.85-17.18), 6.3 times more likely to have a posterior placenta (aOR, 6.30; 95% CI 3.48-11.40), and 3.4 times more likely to have a history of placenta previa (aOR, 3.41; 95% CI 1.18-9.82). On the other hand, cases with gravidity > 3, placenta previa, and/or a history of previous cesarean delivery were more likely to be diagnosed antenatally (aOR 0.40, 0.19, 0.36; 95% CI 0.22-0.74, 0.09-0.40, 0.19-0.70). Although the suspected PAS group had a higher proportion of invasive cases and abdominal and pelvic organ injuries (74.4% vs. 25.8%, p < 0.001; 6.8% vs. 1.7%, p = 0.037), the maternal outcomes were more favorable in the sPAS group, with a lower median volume of 24-hour blood loss and blood product transfusion (estimated blood loss in 24 h, 1000 [800-2000] vs. 2000 [1400-2400], p < 0.001; RBC unit transfusion, 0 [0-800] vs. 800 [600-1000], p < 0.001; fresh-frozen plasma transfusion, 0 [0-450] vs. 600 [400-800], p < 0.001). CONCLUSIONS: Our findings indicate that 35% of patients with PAS were unsuspected prior to delivery. Factors associated with PAS being unsuspected prior to delivery include a history of intrauterine adhesions, a history of clinically confirmed PAS, a posterior placenta, and a history of placenta previa. Additionally, gravidity > 3, a history of previous cesarean delivery, and placenta previa increase the likelihood of antenatal diagnosis.

Transabdominal and transvaginal ultrasound findings help to guide the clinical management of placenta accreta spectrum cases.

INTRODUCTION: The clinical management of placenta accreta spectrum (PAS) depends on placental topography and vascular involvement. Our aim was to determine whether transabdominal and transvaginal ultrasound signs can predict PAS management. MATERIAL AND METHODS: We conducted a retrospective cohort study of consecutive prenatally suspected PAS cases in a single tertiary-care PAS center between January 2021 and July 2022. When PAS was confirmed during surgery, abdominal and transvaginal ultrasound scans were analyzed in relation to PAS management. The preferred surgical approach of PAS was one-step conservative surgery (OSCS). Massive blood loss and PAS topography in the lower bladder trigone necessitated cesarean hysterectomy. Transvaginal ultrasound-diagnosed intracervical hypervascularity was split into three categories based on their quantity. Anatomically, the internal cervical os is located at the level of the bladder trigone and was used as landmark for upper and lower bladder trigone PAS. RESULTS: Ninety-one women underwent OSCS and 35 women underwent cesarean hysterectomy (total 126 women with PAS). Abdominal and transvaginal ultrasound features differed significantly between women that underwent OSCS and cesarean hysterectomy: decreased myometrial thickness (<1 mm), 82.4% vs. 100%, p = 0.006; placental bulge, 51.6% vs. 94.3%, p < 0.001; bladder wall interruption, 62.6% vs. 97.1%, p < 0.001; abnormal placental lacunae, 75.8% vs. 100%, p < 0.001; hypervascularity (large lacunae feeding vessels, 57.8% vs. 94.6%, p < 0.001; parametrial hypervascularity, 15.4% vs. 60%, p < 0.001; the rail sign, 6.6% vs. 28.6%, p = 0.003; three-dimensional Doppler intra-placental hypervascularity, 81.3% vs. 100%, p < 0.001; intracervical hypervascularity 60.4% vs. 94.3%, p < 0.001); and cervical length 2.5 ± 0.94 vs. 2.2 ± 0.73, p = 0.038. Other ultrasound signs were not significantly different. The results of multivariable logistic regression showed placental bulge (odds ratio [OR] 9.3; 95% CI 1.9-44.3; p = 0.005), parametrial hypervascularity (OR 4.1; 95% CI 1.541-11.085; p = 0.005), and intracervical hypervascularity (OR 9.2; 95% CI 1.905-44.056; p = 0.006) were weak predictors of OSCS. Intracervical hypervascularity Grade 1 (vascularity <50% of cervical tissue) was more present in OSCS than higher gradings two and three (91% vs. 27.6% vs. 14.3%; p < 0.001). CONCLUSIONS: Cesarean hysterectomy is associated with the PAS signs of placental bulge and Grade 2 and 3 intracervical hypervascularity. OSCS is associated with intracervical hypervascularity Grade 1 on transvaginal ultrasound. Prospective validation is required to formulate predictors for PAS management.