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.

Evaluation of maternal serum thiol and ischemia-modified albumin levels in cases of placenta previa: A case-control study in a tertiary center.

AIM: We aim to compare the maternal serum thiol and ischemia-modified albumin (IMA) levels between pregnant women with placenta previa and those with uncomplicated pregnancies and to determine whether changes in these levels were useful in predicting cases of abnormally invasive placenta (AIP). METHODS: Fifty-five pregnant women diagnosed with placenta previa according to the diagnostic criteria (case group) were compared to 100 women with uncomplicated pregnancies of similar demographic characteristics (control group). The patients with placenta previa were further divided into two subgroups: AIP (n = 20) and placenta previa without invasion (n = 35). The maternal serum native thiol, total thiol, disulfide, and IMA levels of the groups were evaluated. RESULTS: The native thiol, total thiol, and IMA values were significantly lower in the case group than in the control group (p < 0.001). The disulfide values were similar between the study and control groups (p = 0.488). When the AIP and placenta previa without invasion groups were compared, the levels of native thiol, total thiol, disulfide, and IMA were similar (p > 0.05). CONCLUSIONS: Maternal serum thiol and IMA levels were lower in placenta previa cases compared to the control group. However, these parameters were not useful in predicting AIP cases.

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.

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.

Peripartum hysterectomy clinical characteristics and outcomes- a hospital based retrospective audit study.

INTRODUCTION: The study aims to evaluate and report on the clinical characteristics, incidence, risk factors and associated complications of emergency and planned peripartum hysterectomy in a single training and research tertiary health care centre in Malaysia. MATERIALS AND METHODS: We conducted a 6-year retrospective cross-sectional study from the 1st January 2016 until 31st December 2021. Clinical, demographic characteristics, perioperative parameters, operative indications, blood loss, maternal/neonatal outcomes and complications were analysed. Patients were subdivided, analysed and studied in two subgroups- emergency hysterectomy (EH) and planned hysterectomy (PH). RESULTS: There were 65 cases of peripartum hysterectomy out of total 100,567 deliveries, with a prevalence rate of 0.06%. Overall, the majority of patients were multiparous (96.9%), having previous caesarean scar (73.8%) or diagnosed with placenta praevia (75.4%). More than half of the total patients (61.5%) have both previous caesarean scar and concomitant placenta praevia. EH was carried out in 39(60%) patients while 26(40%) patients underwent PH. The only indication for surgery in the PH group (100%) was abnormal placentation while the most common indication for surgery in the EH group (53.8%) was postpartum haemorrhage related to abnormal placentation. Patients who underwent EH were more likely to have massive blood loss (p=0.001), require ICU admissions (p=0.001), have DIVC cycles transfused (mean [SD] regime: 1.35 [0.95] vs 0.54 [0.99]; p=0.002), have lower postoperative haemoglobin level (mean [standard deviation, SD] haemoglobin: 9.23g/l [SD1.8] vs. 10.8 g/l [SD1.86]; p=0.001) and have higher difference between pre/post operative haemoglobin level (mean [SD] haemoglobin difference: 1.78g/l [SD6.34] vs 0.32g/l [SD1.7]; p=0.008) compared to patients with PH. Red blood cell transfusion, operating time, length of stay, weight of babies and Apgar score between two groups showed no significant differences. A significant reduction of blood loss between the first and the second half duration of the study (mean [SD] blood loss: 6978 ml [SD 4999.45] vs. 4100ml [SD2569.48]; p=0.004) was also observed. In the emergency group, 'non-placental cause' EH required significantly more red blood cell transfusion than 'placental cause' (p<0.05) while in the PH group, no significant difference was observed between the occlusive internal iliac artery 'balloon' and 'no balloon' subgroup in terms of operating time, total blood loss or blood transfusion. Overall complications showed more cases of post operative fever and relaparotomy in the EH group (18.4% vs. 7.6%) while urinary tract injuries including injuries to bladder and ureter occurred only in the PH group (9.4% vs. 0%). CONCLUSION: The majority of peripartum hysterectomy cases are due to placenta accreta spectrum disorders. Planned peripartum hysterectomies have a lower morbidity rate compared to emergency hysterectomies. Therefore, early identification of placenta accreta spectrum disorders and timely planning for elective procedures are crucial to minimise the need for emergency surgery.

Radiomics analysis of T2 -weighted images for differentiating invasive placentas in women at high risks.

PURPOSE: To develop and validate an MRI-based radiomics model for differentiating invasive placentas in patients with high risks. METHODS: A total of 181 pregnant women suspected of placenta accreta spectrum (PAS) disorders and who underwent MRI for placenta evaluation were retrospectively enrolled. The data set was randomly divided into the training (n = 125; invasive = 63, noninvasive = 62) and test (n = 56; invasive = 28, noninvasive = 28) groups. Radiomics features were extracted from half-Fourier acquisition single-shot turbo spin echo (HASTE) and sagittal true fast imaging in steady-state precession (TRUFISP) sequences independently and mainly selected based on their correlations with invasive placentas to construct two radiomics signatures including HASTE-Radscore and TRUFISP-Radscore. Then, the predictive performance of radiomic signatures, clinical features, radiographic features, and their combination were evaluated. The model with the best predictive performance was validated with its discrimination ability, calibration, and clinical usefulness. RESULTS: Five radiomics features from HASTE and three radiomics features from TRUFISP were retained, respectively, for predicting invasive placentas. The combination of radiomics signatures and clinical features including prior cesarean delivery, placenta previa, and radiographic feature, the placental thickness resulted in the best discrimination ability, with area under the curve of 0.898 (95% confidence interval [CI] 0.844-0.9522) and 0.858 (95% confidence interval 0.7514-0.9655) in the training and test cohort, respectively. The combined model showed a significantly better area under the curve performance and clinical usefulness than independent clinical or radiographic model according to DeLong test (p < .05), net reclassification improvement and integrated discrimination improvement analysis (positive improvement) and decision curve analysis (higher net benefit). CONCLUSIONS: The T2 -weighted imaging MRI radiomics model could serve as a potential prenatal diagnosis tool for identifying invasive placentas in patients with high risks.

Systemic immune-inflammation index to predict placenta accreta spectrum and its histological subtypes.

AIM: In this study, we aimed to investigate the role of systemic immune-inflammation index (SII) and other inflammatory parameters in the diagnosis of placenta accreta spectrum (PAS) and its histological subtypes. METHODS: This retrospective case-control study included patients who underwent surgery for placenta previa (PP). Case group (patients with PAS) included pregnant women diagnosed with histologically confirmed PAS, whereas control group (patients with PP) included pregnant women who underwent cesarean section with a PP diagnosis, required no additional intervention during the operation. Both groups were compared with respect to their demographic data, clinical characteristics, SII, and other laboratory parameters. Cut-off values that can predict PAS were calculated. The PAS group was separated into subgroups based on histology findings, and inflammatory parameters were compared between subgroups. RESULTS: In this study, data of 273 patients were analyzed. Of these, 68 (24.9%) were included in the PAS group and 205 (75.1%) patients were included in the PP group. Significant differences were observed in SII, platelet distribution width, mean platelet volume, neutrophil-to-lymphocyte ratio, and platelet-to-lymphocyte ratio (p = 0.000, p = 0.006, p = 0.002, p = 0.000, and p = 0.000, respectively). The best SII cut-off value was 985.02109/L (57.4% sensitivity and 72.2% specificity). There was no significant association between the histologic subtypes of PAS and inflammatory parameters. CONCLUSION: SII can be used to predict PAS in pregnant women with PP. The relationship between the histologic subtypes of PAS and inflammatory parameters should be investigated in more comprehensive studies.

The role of fetal fibronectin and plasminogen activator inhibitor 1 biomarkers in antenatal prediction of placenta accreta spectrum.

In this study, we aimed to assess the determining role of foetal fibronectin (FFN) and plasminogen activator inhibitor type (PAI-1) levels in the antenatal prediction of placenta accreta spectrum in cases with risk factors for placenta accreta spectrum. Singleton live pregnancies with placenta previa or low-lying placenta within 32-34 weeks of gestation were included in the study. The cases were divided into two groups after delivery as those with PAS and those with normal placentation. 54 cases diagnosed with placenta previa or low-lying placenta were included in the study. 17 of the cases underwent peripartum hysterectomy due to placenta accreta spectrum. 37 cases with normal placentation underwent caesarean delivery. Foetal fibronectin (p:.03) and PAI-1 (p:.02) levels were determined to be significantly different between cases with placenta accreta spectrum and cases with normal placentation. AUC for foetal FFN was calculated to be 0.69, while the AUC for, PAI-1was 0.66. Results for both FFN and PAI-1 were not found useful enough for the diagnosis of PAS. IMPACT STATEMENTWhat is already known on this subject? We lack biomarkers which can identify placenta accreta spectrum.What do the results of this study add? Maternal plasma levels of FFN and PAI-1 significantly altered in PASWhat are the implications of these findings for clinical practice and/or future research? If multiple of median values of FFN and PAI-1 levels in maternal blood are determined in future studies, it can be used in the antenatal diagnosis of PAS cases.

Predictive value of vascular endothelial growth factor and placenta growth factor for placenta accreta spectrum.

This study aimed to assess the maternal features, Vascular Endothelial Growth Factor (VEGF) and Placenta Growth Factor (PLGF) in the Placenta Accreta Spectrum (PAS); then, to determine a predictive value of VEGF and PLGF in the PAS. This prospective case-control study was conducted on 90 pregnant women including 45 PAS, and 45 Normal Placenta (NP). Maternal age, gravidity, C/S, and serum levels of VEGF and PLGF were assessed between NP and PAS, and among NP and PAS sub-groups, including Placenta Accreta (PA), Placenta Increta (PI), and Placenta Percreta (PP). The Multi-gravidity, previous C/S, maternal age, and serum level of PLGF were significantly higher in the PAS group compared to the NP group OR = 42, 8.1, 1.17, and 1.002 (p-value <.05 for all); however, there was no difference regarding serum level of VEGF (p-value >.05). The same differences were seen among NP with PA, PI, and PP sub-groups (p-value <.05 for all, but p-value >.05 for VEGF). Placenta Previa was uniformly distributed across the PAS sub-groups (p-value >.05), also the VEGF and PLGF serum levels did not differ between PAS with Previa and PAS without Previa groups (p-value >.05). A valid cut-off point for PLGF was reported at 63.55. A predictive value of PLGF for the PAS patients is presented enjoying high accuracy and generalisability for the study population.Impact statementWhat is already known on this subject? The Placenta Accreta Spectrum (PAS), in which the placenta grows too deep in the uterine wall, is responsible for maternal-foetal morbidity and mortality worldwide; so, the antenatal diagnosis of PAS is an important key to improve maternal-foetal health. Normal placental implantation requires a fine balance among the levels of angiogenic and anti-angiogenic factors, such as the Placenta Growth Factor (PLGF), the Vascular Endothelial Growth Factor (VEGF), and soluble Fms-like tyrosine kinase-1. However, there is still controversy regarding The PLGF and VEGF level changes in PAS patients.What do the results of this study add? Despite traditional measuring the levels of PLGF and VEGF from the placenta at the time of delivery; in this study including 90 participants (28-34 weeks of gestation) the maternal serum levels of PLGF and VEGF were measured in advance (temporality causation), resulted in presenting a more valid cut-off point for PLGF in PAS group. In addition, the serum level of PLGF was significantly higher in the PAS and PAS sub-groups compared to the Normal Placenta group. Also, the Previa status of PAS patients did not affect the VEGF and PLGF serum levels.What are the implications of these findings for clinical practice and/or further research? PLGF cut-off point derived from the maternal serum level could predict PAS validly and, if used as a screening test in an earlier pregnancy, the maternal-foetal morbidity and mortality would decrease.

Can the Cell-free DNA Test Predict Placenta Accreta Spectrum or Placenta Previa Totalis?

BACKGROUND: Following the discovery that fetal DNA originates from the trophoblastic cells of the placenta, the contribution of the cell-free DNA test in placenta-related obstetric complications has begun to be investigated. Compared to uncomplicated pregnancies, higher fetal fractions were detected in placenta accreta spectrum and placenta previa, which are among placenta-related obstetric complications. However, this data applies only to advanced gestational weeks. AIM: To investigate the possible predictive value of fetal fraction in cell-free DNA tests in pregnancies with placenta previa and placenta accreta spectrum in early gestational ages. MATERIALS AND METHODS: This study was conducted in women who were screened via cell-free DNA tests for common aneuploidies in the first and second trimester and subsequently diagnosed with placenta previa or placenta accreta spectrum. After the diagnosis was confirmed with a C-section, fetal fractions were retrospectively compared to a control group with a history of an uncomplicated C-section who were also previously screened by cell-free DNA test. RESULTS: The median and interquartile range (IQR) of fetal fractions for placenta previa (n=19), placenta accreta spectrum (n=7), and control groups (n=85) were 8.1 (6-10), 6.8 (6.7-10.7), and 7.1 (4.7-9.65), respectively. No statistically significant difference was observed among the three groups in terms of fetal fractions (p=0.587). CONCLUSIONS: According to our data, we did not observe any relationship between placental invasion abnormalities vs. control group or placenta previa vs. control group using the fetal fractions of the cell-free DNA test. Furthermore, we could not confirm a predictive role and/or any additional clinical contribution. We believe that future studies focusing on placental mRNA might be more helpful than cell-free fetal DNA testing.

Introducing an efficient model for the prediction of placenta accreta spectrum using the MCP regression approach based on sonography indexes: how efficient is sonography in diagnosing accreta?

BACKGROUND: For the first time, we aimed to introduce a model for prediction of placenta accreta spectrum (PAS), using existing sonography indices. METHODS: Women with a history of Cesarean sections were included. Participants were categorized "high risk" for PAS if the placenta was previa or low-lying. Sonography indices including abnormal placental lacuna, loss of clear zone, bladder wall interruption, myometrial thinning, placental bulging, exophytic mass, utero-vesical hypervascularity, subplacental hypervascularity, existence of bridging vessels, and lacunar flow, were registered. To investigate simultaneous effects of 15 variables on PAS, Minimax Concave Penalty (MCP) was used. RESULTS: Among 259 participants, 74 (28.5%) were high risk and 43 individuals had PASs. All sonography indices were higher among patient with PAS (p < 0.001) in the high risk group. Our model showed that utero-vesical hypervascularity, bladder interruption and new lacunae have significant contribution in PAS. Optimal cut off point was p = 0.51 in ROC analysis. Probability of PAS for women with lacunae was between 96 and 100% and probability of PAS for women without lacunae was between 0 to 7%, therefore accuracy of the proposed model was equal to 100%. CONCLUSIONS: Using the introduced model based on three factors of abnormal lacuna structures (grades 2 and 3), bladder wall interruption and utero-vesical vascularity, 100% of all cases of PASs are diagnosable. If supported by future studies our model eliminates the need for other imaging assessments for diagnosis of invasive placentation among high risk women with previous history of Cesarean sections.

The use of magnetic resonance imaging to predict placenta previa with placenta accreta spectrum.

INTRODUCTION: Massive hemorrhage due to placenta previa with placenta accreta spectrum is associated with high maternal mortality and morbidity. Therefore, accurate prediction of placenta previa with placenta accreta spectrum is essential; magnetic resonance imaging (MRI) is a useful tool for this purpose. This study investigated novel predictors of anterior and posterior placenta previa with placenta accreta spectrum using MRI. MATERIAL AND METHODS: This was a retrospective study at a tertiary obstetrics hospital in Japan. The singleton patients with placenta previa who were scanned with MRI prenatally and had a cesarean section at our institution between 2007 and 2018 were included. The prediction of anterior and posterior placenta previa with placenta accreta spectrum was evaluated using four MRI findings: heterogeneous signals in the placenta, dark T2-weighted intraplacental bands, myometrial thinning or interruption, and focal uterine bulging. The prediction of posterior placenta previa with placenta accreta spectrum was performed using the quantification of cervical varicosities, which were defined as the ratio of the distance between the minimum distance from the most dorsal cervical varicosities (a) to the deciduous and amniotic placenta (b) on a sagittal image. RESULTS: Among 202 patients, 14 (6.9%) patients were pathologically diagnosed as having placenta accreta spectrum. Further, 38 (18.8%) patients had anterior placenta previa and 164 (81.2%) patients had posterior placenta previa. When anterior placenta previa with placenta accreta spectrum was predicted using at least one of the four MRI findings, the sensitivity and specificity of the anterior placenta previa with placenta accreta spectrum were 87.5% and 86.7%, respectively. In contrast, the sensitivity and specificity of posterior placenta previa with placenta accreta spectrum were 42.9% and 96.2%, respectively. But when the A/B ratio was set at 0.20, the sensitivity and specificity of the prediction for posterior placenta previa with placenta accreta spectrum using cervical varicosities were 100.0% and 89.2%, respectively. CONCLUSIONS: The findings of MRI to predict the anterior placenta previa with placenta accreta spectrum were different from posterior placenta previa. The cervical varicosities may be useful in predicting posterior placenta previa with placenta accreta spectrum.

Assisted reproductive technologies (ART) and placental abnormalities.

Objectives Assisted reproductive technologies (ART) may be associated with placental abnormalities including placenta previa, umbilical cord abnormalities, and placental abruption. Our study evaluates the relationship between ART and placental abnormalities compared with spontaneously conceived controls. Methods An IRB-approved cohort study was conducted including women who delivered between January 2013 and December 2018. We excluded delivery prior to 23 weeks and known fetal anomalies. Patients were matched with controls (2:1) for parity, age, and mode of delivery. Controls were women who had spontaneously conceived and delivered immediately preceding and following the index delivery. The primary outcome was placental abnormalities found on both antenatal ultrasound and pathology in ART gestations compared with spontaneously conceived gestations. Results There were 120 ART pregnancies and 240 matched control pregnancies identified. The groups were similar for parity, BMI, comorbidities, number of multiples, mode of delivery, and female newborns. The ART group had a higher maternal age (37.1±5 y vs. 30.0±5 y; p<0.001), greater preterm birth (29 vs. 6%; p<0.001), and lower BW (2,928±803 g vs. 3,273±586 g; p<0.001). The ART group had a higher incidence of placenta previa on ultrasound (4.0 vs. 0.4%, p=0.01), adherent placentas at delivery (3 vs. 0% p=0.014), placental abruption (2 vs. 0%; p=0.04), as well as an increased rate of velamentous cord insertion (12 vs. 3%, p<0.001) and marginal cord insertion (28 vs. 15%, p=0.002). ART demonstrated a two-fold likelihood of abnormal placental pathology. Conclusions ART is associated with increased rate of placental abnormalities, including abnormal umbilical cord insertion and increased rates of adherent placentation. This information may be beneficial in planning and surveillance in patients with ART pregnancies.

Uterine artery Doppler velocimetry at mid-term gestation as a potential predictive factor for the resolution of placenta previa at the end of third trimester of pregnancy.

AIM: The incidence of placenta previa before the third trimester is high. But many cases resolve as pregnancy progresses. Our study was to evaluate the efficacy of uterine artery Doppler velocimetry at mid-term gestation for predicting placenta previa resolution in third trimester. METHODS: A single-center retrospective study was done. A study cohort of 504 subjects with placenta-cervix os distance measured both at 22-24 weeks and after 36 weeks of gestation and uterine artery Doppler velocimetry measured at 22-24 weeks of gestation were selected. The subjects were assigned to control group (n = 351), resolving group (n = 89) and placenta previa group (n = 64) according to their diagnosis of placenta previa at mid-term and the end of the third trimester. The averages of the bilateral ratio of uterine artery systolic to end-diastolic maximum blood flow velocity (S/D ratio), pulsatility index (PI) and resistance index (RI) were used for analysis. RESULTS: The means of S/D ratio, PI and RI of uterine arteries in the placenta previa group were significantly lower than that in either control group or resolving group. No differences were observed between control group and resolving group. The areas under the receiver operating characteristic curve were 0.7632, 0.7579 and 0.7644 for the means of S/D ratio, PI and RI, respectively (P < 0.0001). CONCLUSION: The means of S/D ratio, PI and RI of the uterine arteries at mid-term gestation are reduced in patients with persistent placenta previa, indicating unique pathogenic changes at mid-term gestation, and have the potential to be a predictive factor on placenta previa resolution.

Perinatal and maternal outcome after vitrification of blastocysts: a Nordic study in singletons from the CoNARTaS group.

STUDY QUESTION: Is transfer of vitrified blastocysts associated with higher perinatal and maternal risks compared with slow-frozen cleavage stage embryos and fresh blastocysts? SUMMARY ANSWER: Transfer of vitrified blastocysts is associated with a higher risk of preterm birth (PTB) when compared with slow-frozen cleavage stage embryos and with a higher risk of a large baby, hypertensive disorders in pregnancy (HDPs) and postpartum hemorrhage (PPH) but a lower risk of placenta previa when compared with fresh blastocysts. WHAT IS KNOWN ALREADY: Transfer of frozen-thawed embryos (FETs) plays a central role in modern fertility treatment, limiting the risk of ovarian hyperstimulation syndrome and multiple pregnancies. Following FET, several studies report a lower risk of PTB, low birth weight (LBW) and small for gestational age (SGA) yet a higher risk of fetal macrosomia and large for gestational age (LGA) compared with fresh embryos. In recent years, the introduction of new freezing techniques has increased treatment success. The slow-freeze technique combined with cleavage stage transfer has been replaced by vitrification and blastocyst transfer. Only few studies have compared perinatal and maternal outcomes after vitrification and slow-freeze and mainly in cleavage stage embryos, with most studies indicating similar outcomes in the two groups. Studies on perinatal and maternal outcomes following vitrified blastocysts are limited. STUDY DESIGN, SIZE, DURATION: This registry-based cohort study includes singletons born after frozen-thawed and fresh transfers following the introduction of vitrification in Sweden and Denmark, in 2002 and 2009, respectively. The study includes 3650 children born after transfer of vitrified blastocysts, 8123 children born after transfer of slow-frozen cleavage stage embryos and 4469 children born after transfer of fresh blastocysts during 2002-2015. Perinatal and maternal outcomes in singletons born after vitrified blastocyst transfer were compared with singletons born after slow-frozen cleavage stage transfer and singletons born after fresh blastocyst transfer. Main outcomes included PTB, LBW, macrosomia, HDP and placenta previa. PARTICIPANTS/MATERIALS, SETTING, METHODS: Data were obtained from the CoNARTaS (Committee of Nordic ART and Safety) group. Based on national registries in Sweden, Finland, Denmark and Norway, the CoNARTaS cohort includes all children born after ART treatment in public and private clinics 1984-2015. Outcomes were assessed with logistic multivariable regression analysis, adjusting for the country and year of birth, maternal age, body mass index, parity, smoking, parental educational level, fertilisation method (IVF/ICSI), single embryo transfer, number of gestational sacs and the child's sex. MAIN RESULTS AND THE ROLE OF CHANCE: A higher risk of PTB (<37 weeks) was noted in the vitrified blastocyst group compared with the slow-frozen cleavage stage group (adjusted odds ratio, aOR [95% CI], 1.33 [1.09-1.62]). No significant differences were observed for LBW (<2500 g), SGA, macrosomia (≥4500 g) and LGA when comparing the vitrified blastocyst with the slow-frozen cleavage stage group. For maternal outcomes, no significant difference was seen in the risk of HDP, placenta previa, placental abruption and PPH in the vitrified blastocyst versus the slow frozen cleavage stage group, although the precision was limited.When comparing vitrified and fresh blastocysts, we found higher risks of macrosomia (≥4500 g) aOR 1.77 [1.35-2.31] and LGA aOR 1.48 [1.18-1.84]. Further, the risks of HDP aOR 1.47 [1.19-1.81] and PPH aOR 1.68 [1.39-2.03] were higher in singletons born after vitrified compared with fresh blastocyst transfer while the risks of SGA aOR 0.58 [0.44-0.78] and placenta previa aOR 0.35 [0.25-0.48] were lower. LIMITATIONS, REASONS FOR CAUTION: Since vitrification was introduced simultaneously with blastocyst transfer in Sweden and Denmark, it was not possible to explore the effect of vitrification per se in this study. WIDER IMPLICATIONS OF THE FINDINGS: The results from the change of strategy to vitrification of blastocysts are reassuring, indicating that the freezing technique per se has no major influence on the perinatal and maternal outcomes. The higher risk of PTB may be related to the extended embryo culture rather than vitrification. STUDY FUNDING/COMPETING INTEREST(S): The study is part of the ReproUnion Collaborative study, co-financed by the European Union, Interreg V ÖKS. The study was also financed by grants from the Swedish state under the agreement between the Swedish government and the county councils, the ALF agreement (LUA/ALF 70940), Hjalmar Svensson Research Foundation and NordForsk (project 71 450). There are no conflicts of interest to declare. TRIAL REGISTRATION NUMBER: ISRCTN11780826.

Identification of suspicious invasive placentation based on clinical MRI data using textural features and automated machine learning.

OBJECTIVE: The aim of this study was to investigate whether intraplacental texture features from routine placental MRI can objectively and accurately predict invasive placentation. MATERIAL AND METHODS: This retrospective study includes 99 pregnant women with pathologically confirmed placental invasion and 56 pregnant women with simple placenta previa. All participants underwent magnetic resonance imaging after 24 gestational weeks. The placenta was segmented in sagittal images from both turbo spin echo (TSE) and balanced turbo field echo (bTFE) sequences. Textural features were extracted from the both original and Laplacian of Gaussian (LoG)-filtered MRI images. An automated machine learning algorithm was applied to the extracted feature sets to obtain the optimal preprocessing steps, classification algorithm, and corresponding hyper-parameters. RESULTS: A gradient boosting classifier using all textual features from original and LoG-filtered TSE images and bTFE images identified by the automated machine learning algorithm achieved the optimal performance with sensitivity, specificity, accuracy, and area under ROC curve (AUC) of 100%, 88.5%, 95.2%, and 0.98 in the prediction of placental invasion. In addition, textural features that contributed to the prediction of placental invasion differ from the features significantly affected by normal placenta maturation. CONCLUSIONS: Quantifying intraplacental heterogeneity using LoG filtration and texture analysis highlights the different heterogeneous appearance caused by abnormal placentation relative to normal maturation. The predictive model derived from automated machine learning yielded good performance, indicating the proposed radiomic analysis pipeline can accurately predict placental invasion and facilitate clinical decision-making for pregnant women with suspicious placental invasion. KEY POINTS: • The intraplacental texture features have high efficiency in prediction of invasive placentation after 24 gestational weeks. • The features with dominated predictive power did not overlap with the features significantly affected by gestational age.

Human placental lactogen mRNA in maternal plasma play a role in prenatal diagnosis of abnormally invasive placenta: yes or no?

Objective: To determine whether maternal plasma human placental lactogen (hPL) mRNA levels can predict abnormally invasive placenta. Study design: Sixty-eight singleton pregnant women with prior Cesarean deliveries were classified into three groups: 35 with normal placentation (control group); 21 with placenta previa alone (placenta previa group); 12 with placenta previa and placenta accreta (placenta accreta group). Maternal plasma hPL mRNA concentrations were measured by real-time reverse-transcription polymerase chain reaction Result: The multiple of the median (median, range) for hPL mRNA was significantly higher for the placenta accreta group (2.78, 1.09-4.56) than the control (1.00, 0.29-2.98) or placenta previa (1.12, 0.33-3.25) groups (Steel-Dwass test, p < .001 and p = .005, respectively), was not significantly different between the women with placenta accreta who underwent hysterectomies (2.96, 1.38-4.56) and the women whose deliveries did not result in hysterectomy (2.36, 1.09-3.25) in the placenta accreta group (Mann-Whitney U test, p = .372). Conclusion: hPL mRNA in maternal plasma may indicate abnormally invasive placenta but cannot predict whether abnormally invasive placenta will result in hysterectomy.

Clinical and Ultrasound Predictors of Placenta Accreta in Pregnant Women with Antepartum Diagnosis of Placenta Previa: A Multicenter Study.

BACKGROUND/AIMS: Abnormally invasive placenta (AIP) includes placenta accreta, increta, and percreta and represents major complications of pregnancy. This study was designed to assess the role of ultrasonography in the identification of AIP among pregnant women with antepartum diagnosis of placenta previa. METHODS: A cross-sectional study was performed between May 2015 and April 2016 in 11 centers, including 242 women with antepartum diagnosis of placenta previa. RESULTS: Ninety-eight out of 242 (40.49%) women had a histological diagnosis of placenta accreta. A higher number of caesarean deliveries (p = 0.001) and curettages (p = 0.027) and older age of the woman at the delivery (p = 0.031) were identified as risk factors for placenta accreta. The presence of irregularly shaped placental lacunae (vascular spaces) within the placenta (p = 0.008), protrusion of the placenta into the bladder (p < 0.0001), and turbulent blood flow through the lacunae on Doppler ultrasonography (p = 0.008) were predictors of placenta accreta. CONCLUSIONS: Women with a prior delivery by caesarean section have a high incidence of placenta accreta among women with antepartum diagnosis of placenta previa.

Bleeding control using intrauterine continuous running suture during cesarean section in pregnant women with placenta previa.

PURPOSE: The purpose of this study was to evaluate the effectiveness of intrauterine continuous running suture during cesarean section in pregnant women with placenta previa. METHODS: We enrolled 277 women and medical records were retrospectively reviewed. Pregnant women were grouped according to uterine bleeding control methods as follows: Group A, using intrauterine continuous running suture and Group B (control group) using figure-of-eight suture. RESULTS: Intrauterine continuous running sutures were used in 104 pregnant women. Mean total blood loss in Group A was significantly less than that in Group B (1332.70 ± 152.92 mL vs 1861.56 ± 157.74 mL, P = 0.029). Mean total transfusion unit of Group A was significantly less than that in Group B (1.74 ± 0.41 vs 3.52 ± 0.75, P = 0.037). CONCLUSIONS: Intrauterine continuous running sutures can significantly reduce postpartum blood loss and transfusion units during cesarean section in pregnant women with placenta previa.

The Jellyfish Sign: A New Sonographic Cervical Marker to Predict Maternal Morbidity in Abnormally Invasive Placenta Previa.

PURPOSE: To investigate the value of a new cervical sonographic sign, called the jellyfish sign (JS), for predicting the risk of maternal morbidity in cases of abnormally invasive placenta (AIP) previa totalis. MATERIALS AND METHODS: Retrospective evaluation of transvaginal (TV) and transabdominal (TA) scans performed in all singleton pregnancies with placenta previa totalis. JS, i. e. the absence of the normal linear demarcation between the placenta previa and the cervix, was evaluated by TV scans. The presence/severity of AIP and outcomes of maternal morbidity were related to this sign. RESULTS: JS was noted in 8/39 (20.5 %) patients. The two analyzed groups, i. e. with and without JS, were similar. The specificity of JS in AIP diagnosis, histological findings of accreta/increta/percreta, need for caesarean hysterectomy or blood loss > 2000 ml ranges between 92 % and 96.2 %, with the PPV and NPV ranging between 71.4 % and 85.7 % and 61.3 % and 80.6 %, respectively. The JS group had a significant increase in blood loss (ml) (p = 0.003), transfusions (%) (p = 0.016), red blood cells (p = 0.002) and plasma (p = 0.002), admission to an postoperative intensive care unit (ICU) (%) (p = 0.002), hospitalization length (p < 0.001) and the need of cesarean hysterectomy (%) (p < 0.001). JS was independently correlated to cesarean hysterectomy (OR 25.6; 95 % CI 2.0:322.3, p = 0.012) and blood loss > 2000 ml (OR 16.6; 95 % CI 1.5:180.1, p = 0.021) also in a logistic regression model. CONCLUSION: JS is useful in predicting the increase in maternal morbidity: massive transfusion, admission to the ICU and cesarean hysterectomy related to intraoperative bleeding in patients with a previa AIP.