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Objective: To evaluate the performance of ultrasound for antenatal identification of invasive placentation in women with placenta previa in the setting of prior cesarean delivery., Study Design: This was a multicenter, retrospective, cohort study. Singleton pregnancies at risk of placenta accreta because of persistent placenta previa in the setting of prior cesarean delivery who delivered at four centers, from January 2010 to May 2020, were included in the study. For this study, pregnancies with diagnosis of accreta, increta, or percreta were considered under the umbrella term of placenta accreta. All women with placenta previa identified in the second trimester had a follow-up ultrasound at 32-34 weeks. Only those with prior cesarean delivery were considered at risk of placenta accreta. Women were considered with suspected accreta in case of suspected prenatal ultrasound. Women with suspected placenta accreta had delivery planned via cesarean hysterectomy at 34+0 - 35+6 weeks, without any attempt to remove the placenta. The primary endpoint of the study was the performance of ultrasound for antenatal identification of invasive placentation. The following ultrasound signs were evaluated: placenta lacunae; loss of clear space; increased vascularity between myometrium and placenta; intracervical lake; rail sign; uterovesical hypervascularity; increased vascularity in the inferior part of the lower uterine segment potentially extending into the parametrial region; and disruption of bladder-myometrial interface., Results: 180 singleton pregnancies with placenta previa in the setting of prior cesarean delivery were identified. Of them, 155 (86.1%) had antenatal suspected placenta accreta based on ultrasound, having at least one sign of invasive placentation. Of the 155 suspected cases, 99 had confirmed placenta accreta at the time of delivery. Among the 99 cases of confirmed placenta accreta, all of them had at least one sign of invasive placentation at ultrasound. Among the 81 cases with placenta previa, prior cesarean delivery, without placenta accreta, 25/81 (30.9%) had ultrasound scan negative for sign of invasive placentation, and 56/81 (69.1%) had at least one sign of invasive placentation). In particular, 12/81 (14.8%) had placenta lacunae, 16/81 (19.8%) had loss of clear space, 20/81 (24.7%) had increased vascularity between myometrium and placenta, 9/81 (11.1%) had intracervical lake, 14/81 (17.3%) had rail sign, 14 (17.3%) had uterovesical hypervascularity, 5/81 (6.2%) had increased vascularity in the inferior part of the lower uterine segment potentially extending into the parametrial region, 8/81 (9.9%) had disruption of bladder-myometrial interface. In the group of women with confirmed placenta accreta, the most common sign recorded was the disruption of bladder-myometrial interface, being recorded in 88/99 women. Disruption of bladder-myometrial interface had the highest sensitivity in detection placenta accreta. Women with disruption of bladder-myometrial interface at ultrasound had 73-fold increase in the risk of placenta accreta compared to those who did not., Conclusion: Prenatal ultrasound has an excellent diagnostic accuracy in identifying invasive placentation in women with placenta previa and prior cesarean delivery., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Functional studies of circular RNAs (circRNAs) began quite recently, and few data exist on their function in vivo. Here, we have generated a knockout (KO) mouse model to study circDlc1(2), a circRNA highly expressed in the prefrontal cortex and striatum. The loss of circDlc1(2) led to the upregulation of glutamatergic-response-associated genes in the striatal tissue, enhanced excitatory synaptic transmission in neuronal cultures, and hyperactivity and increased stereotypies in mice. Mechanistically, we found that circDlc1(2) physically interacts with some mRNAs, associated with glutamate receptor signaling (gluRNAs), and with miR-130b-5p, a translational regulator of these transcripts. Notably, differently from canonical microRNA (miRNA) "sponges," circDlc1(2) synergizes with miR-130b-5p to repress gluRNA expression. We found that circDlc1(2) is required to spatially control miR-130b-5p localization at synaptic regions where gluRNA is localized, indicating a different layer of regulation where circRNAs ensure robust control of gene expression via the correct subcellular compartmentalization of functionally linked interacting partners., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

MicroRNAs (miRNAs) play a crucial role in ovarian cancer (OC) pathogenesis and miRNA processing can be the object of pharmacological intervention. By exploiting our in-house quinolone library, we combined a cell-based screening with medicinal chemistry efforts, ultimately leading to derivative 33 with anti-OC activity against distinct cell lines (GI 50 values 13.52-31.04 μM) and CC 50 Wi-38 = 142.9 μM. Compound 33 retained anticancer activity against additional cancer cells and demonstrated a synergistic effect with cisplatin against cisplatin-resistant A2780 cells. Compound 33 bound TRBP by SPR ( K D = 4.09 μM) and thermal shift assays and its activity was TRBP-dependent, leading to modulation of siRNA and miRNA maturation. Derivative 33 exhibited augmented potency against OC cells and a stronger binding affinity for TRBP compared to enoxacin, the sole quinolone identified as a modulator of miRNA maturation. Consequently, 33 represents a promising template for developing novel anti-OC agents with a distinctive mechanism of action., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (This journal is © The Royal Society of Chemistry.)

Background: The aim of this study was to determine the effect of caffeine on fetal heart rate (FHR) as determined by computerized cardiotocography (cCTG) parameters., Methods: Term pregnancies that performed a fetal antepartum cCTG were included. Two physicians recorded coffee habits before the cCTG, and pregnant women were divided into two groups: the coffee group and the control group. Furthermore, cCTG' parameters were compared between the two groups., Results: One hundred thirty-four pregnant women were enrolled. Based on maternal coffee habits, 82 pregnant women were allocated to the coffee group, while 52 were in the control group. The two groups shared similar demographic and obstetric characteristics. The mean daily coffee intake was 1.4±0.6 cups. Coffee group fetuses evidenced a lower FHR baseline, 135±9.9 bpm, versus the control group, 138±8.0 bpm, (P value = 0.03). Other cCTG parameters did not show statistical differences. Multivariate analysis demonstrated no confounding factors. A subanalysis that evaluated the daily amount of coffee consumed or the half-life of caffeine found no difference in cCTG measures., Conclusions: Maternal caffeine consumption did not influence fetal cardiac reactivity after absorption.

Introduction: Placenta accreta spectrum disorders (PAS) lead to major complications in pregnancy. While the maternal morbidity associated with PAS is well known, there is less information regarding neonatal morbidity in this setting. The aim of this study is to describe the neonatal outcomes (fetal malformations, neonatal morbidity, twin births, stillbirth, and neonatal death), using an international multicenter database of PAS cases., Material and Methods: This was a prospective, multicenter cohort study based on prospectively collected cases, using the international multicenter database of the International Society for PAS, carried out between January 2020 and June 2022 by 23 centers with experience in PAS care. All PAS cases were included, regardless of whether singleton or multiple pregnancies and were managed in each center according to their own protocols. Data were collected via chart review. Local Ethical Committee approval and Data Use Agreements were obtained according to local policies., Results: There were 315 pregnancies eligible for inclusion, with 12 twin pregnancies, comprising 329 fetuses/newborns; 2 cases were excluded due to inconsistency of data regarding fetal abnormalities. For the calculation of neonatal morbidity and mortality, all elective pregnancy terminations were excluded, hence 311 pregnancies with 323 newborns were analyzed. In our cohort, 3 neonates (0.93%) were stillborn; of the 320 newborns delivered, there were 10 cases (3.13%) of neonatal death. The prevalence of major congenital malformations was 4.64% (15/323 newborns), most commonly, cardiovascular, central nervous system, and gastrointestinal tract malformations. The overall prevalence of major neonatal morbidity in pregnancies complicated by PAS was 47/311 (15.1%). There were no stillbirths, neonatal deaths, or fetal malformations in reported twin gestations., Conclusions: Although some outcomes may be too rare to detect within our cohort and data should be interpreted with caution, our observational data supports reassuring neonatal outcomes for women with PAS., (© 2024 The Author(s). Acta Obstetricia et Gynecologica Scandinavica published by John Wiley & Sons Ltd on behalf of Nordic Federation of Societies of Obstetrics and Gynecology (NFOG).)

Background: Fetal aneuploidies, including trisomies 21, 13, and 18, represent a significant issue in prenatal care. The advent of non-invasive prenatal testing (NIPT) through the detection of cell-free DNA (cf-DNA) in maternal blood has modified screening for chromosomal abnormalities. This study evaluates NIPT adherence among pregnant of different ethnicities, addressing potential disparities in prenatal care., Methods: This was a retrospective, single-center study conducted at a tertiary care university hospital in Italy between March 31, 2021, and September 30, 2022. Participants were categorized by ethnicity (Asian/Pacific islander, Black, Latina, White, Middle Eastern). Maternal demographic characteristics and prenatal test data were recorded. Comparative analyses were executed utilizing a One-Way Analysis of Variance (ANOVA) Test, augmented by Tukey's honestly significant difference test for post-hoc evaluation. Statistical significance was denoted by a P value (P)<0.05. A multivariate analysis through a multinomial regression model was conducted for the results to detect potential bias., Results: Six hundred seventeen pregnancies were included: 418 White, 105 Asian/Pacific islander, 46 Black, 40 Latina, and 8 Middle Eastern. Maternal age showed no significant variation. Black ethnicity had higher prepregnancy Body Mass Index (BMI; mean: 27.5 kg/m 2 ±SD: 5.92, P=0.02), while Asian and White pregnancies had higher nulliparity rates (63.8% and 70.8%). Black ethnicity had no NIPT uptake (0.00%). Asian/Pacific islander and Latina pregnant had lower NIPT utilization (9.5% and 7.5%, P<0.001). White ethnicity had a higher NIPT rate (27.5%). In the NIPT group, 8.9% of White and 12.5% of Middle Eastern pregnancies chose cf-DNA without a prior first-trimester ultrasound test. Considering the first-trimester screening, 30.4% of Black pregnancies had nuchal translucency, while 17.4% combined it with beta-human chorionic gonadotrophin (β-hCG) and associated plasma protein-A (PAPP-A; P<0.001). White pregnancies had high adherence: 74.6% had nuchal translucency and 53.8% had a first-trimester combined test. Overall, 69.6% of Black pregnancies skipped both tests versus 16.5% in the White group (P<0.001)., Conclusions: Significant disparities in prenatal care and NIPT adherence were observed among pregnant women of diverse ethnic backgrounds. Lower cf-DNA adhesion and limited adherence to first-trimester screening were observed among any ethnicities. These findings highlight the critical need for targeted interventions and policies to reduce barriers and facilitate access to prenatal care for all women.

Introduction: Placenta accreta spectrum (PAS) can lead to major peripartum morbidity. Appropriate management approaches depend on the clinical severity, each individual's preference, and the treating team's expertise. Peripartum hysterectomy is the most frequently used treatment option. However, it can impact psychological well-being and fertility. We investigated whether conservative treatment with focal resection or leaving the placenta in situ is associated with comparable or lower maternal morbidity than hysterectomy in centers of excellence within the International Society for placenta accreta spectrum (IS-PAS). Furthermore, a survey was conducted to explore potential barriers to conservative management in antenatal counseling and intraoperative decision-making., Material and Methods: Confirmed PAS cases in the prospective IS-PAS database from 22 registered centers between January 2020 and June 2022 were included in the analysis. A separate online survey with 21 questions was answered by the IS-PAS center experts about indications, diagnostic criteria, patient counseling, surgical practice, changes from the preoperative treatment plan, and why conservative management may not be offered., Results: A total of 234 cases were included in the analysis: 186 women received hysterectomy and 38 women were treated by focal resection, and 10 by leaving the placenta in situ. Blood loss was lower in the focal resection group and in the placenta in situ group compared to the hysterectomy group (p = 0.04). 46.4% of the women initially planned for focal resection, and 35.7% of those initially planned for leaving the placenta in situ were ultimately treated by hysterectomy. Our survey showed that the IS-PAS centers preferred hysterectomy according to a woman's wishes (64%) and when they expected less blood loss and morbidity (41%). Eighteen percent of centers did not offer focal resection at all due to a lack of experience with this technique. Reasons for not offering to leave the placenta in situ were avoidance of unexpected reoperation (36%), puerperal infection (32%), or skepticism about the method (23%)., Conclusions: Uterus-preserving treatment strategies such as focal resection appear to be safe alternatives to peripartum hysterectomy. However, less than half of the IS-PAS centers perform them. Acceptance of conservative treatments could be increased by standardized criteria for their implementation and by systematic training for PAS experts., (© 2024 The Authors. Acta Obstetricia et Gynecologica Scandinavica published by John Wiley & Sons Ltd on behalf of Nordic Federation of Societies of Obstetrics and Gynecology (NFOG).)

Background: Preterm birth is a major cause of perinatal morbidity and mortality. It is unclear whether the introduction of a universal transvaginal ultrasound cervical length screening program in women at low risk for preterm delivery is associated with a reduction in the frequency of preterm birth., Objective: To test the hypothesis that the introduction of a midtrimester universal transvaginal ultrasound cervical length screening program in asymptomatic singleton pregnancies without prior preterm delivery would reduce the rate of preterm birth at <37 weeks of gestation., Study Design: This study was a multicenter nonblinded randomized trial of screening of asymptomatic singleton pregnancies without prior spontaneous preterm birth, who were randomized to either cervical length screening program (ie, intervention group) or no screening (ie, control group). Participants were randomized at the time of their routine anatomy scan between 18 0/7 and 23 6/7 weeks of gestation. Women randomized in the screening group received cervical length measurement. Those who were found to have cervical length ≤25 mm were offered 200 mg vaginal progesterone daily along with cervical pessary. The primary outcome was preterm birth at <37 weeks. The risk of primary outcome was quantified by the relative risk with 95% confidence interval, and was based on the intention-to-screen principle., Results: A total of 1334 asymptomatic women with singleton pregnancies and without prior preterm birth, were included in the trial. Out of the 675 women randomized in the transvaginal ultrasound cervical length screening group, 13 (1.9%) were found to have transvaginal ultrasound cervical length ≤25 mm during the screening. Preterm birth at <37 weeks of gestation occurred in 48 women in the transvaginal ultrasound cervical length screening group (7.5%), and 54 women in the control group (8.7%) (relative risk, 0.86; 95% confidence interval, 0.59-1.25). Women randomized in the transvaginal ultrasound cervical length screening group had no significant differences in the incidence of preterm birth at less than 34, 32, 30, 28, and 24 weeks of gestation., Conclusion: The introduction of a universal transvaginal ultrasound cervical length screening program at 18 0/6 to 23 6/7 weeks of gestation in singleton pregnancies without prior spontaneous preterm birth, with treatment for those with cervical length ≤25 mm, did not result in significant lower incidence of preterm delivery than the incidence without the screening program., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Cesarean scar pregnancy (CSP) rate is rising worldwide, in parallel with the rising rates of cesarean delivery. Multiple therapeutic strategies and a timely diagnosis have led to a successful management in most cases, with many women preserving fertility after treatment. Despite this, still little is known regarding pregnancy outcomes after a CSP. The main adverse outcomes reported after CSP are recurrence of CSP, miscarriage, preterm birth, placenta accreta spectrum (PAS) disorders and uterine rupture. In addition, little is known about the influence of the different treatments on subsequent pregnancy outcomes after a CSP. Being aware of the impact of the different management strategies on the fertility outcomes is highly relevant to counsel pregnant women after a CSP. The aim of this manuscript is to provide an up-to-date review of the reproductive outcomes of women with a history of CSP and of the influence of various treatments on subsequent pregnancy outcomes., Competing Interests: Declaration of competing interest The authors have no conflicts of interest., (Copyright © 2023. Published by Elsevier Ltd.)

Purpose: Abnormal flow in the ductus venosus (DV) has been reported to be associated with adverse perinatal outcome, chromosomal abnormalities, and congenital heart defects (CHD). Aneuploid fetuses have increased risk of CHD, but there are discrepancies on the performance of this markers in euploid fetuses. The aim of this meta-analysis was to establish the predictive accuracy of DV for CHD., Methods: MEDLINE, EMBASE, and CINAHL were searched from inception to February 2022. No language or geographical restrictions were applied. Inclusion criteria regarded observational and randomized studies concerning first-trimester DV flow as CHD marker. Random effect meta-analyses to calculate risk ratio (RR) with 95% confidence interval (CI), hierarchical summary receiver-operating characteristics (HSROC), and bivariate models to evaluate diagnostic accuracy were used. Primary outcome was the diagnostic performance of DV in detecting prenatal CHD by means of area under the curve (AUROC). Subgroup analysis for euploid, high-risk, and normal NT fetuses was performed. Quality assessment of included papers was performed using QUADAS-2., Results: Twenty two studies, with a total of 204.829 fetuses undergoing first trimester scan with DV Doppler evaluation, fulfilled the inclusion criteria for this systematic review. Overall, abnormal DV flow at the time of first trimester screening was associated to an increased risk of CHD (RR 6.9, 95% CI 3.7-12.6; I 2  = 95.2%) as well in unselected (RR: 6.4, 95% CI 2.5-16.4; I 2  = 93.3%) and in euploid (RR: 6.45, 95% CI 3.3-12.6; I 2  = 95.8%) fetuses. The overall diagnostic accuracy of abnormal DV in detecting CHD was good in euploid fetuses with an AUROC of 0.81 (95% CI 0.78-0.84), but it was poor in the high-risk group with an AUROC of 0.66 (95% CI 0.62-0.70) and in the unselected population with an AUROC of 0.44 (95% CI 0.40-0.49)., Conclusions: Abnormal DV in the first trimester increases the risk of CHD with a moderate sensitivity for euploid fetuses. In combination with other markers (NT, TV regurgitation) could be helpful to identify fetuses otherwise considered to be at low risk for CHD. In addition to the improvement of the fetal heart examination in the first trimester, this strategy can increase the detection of major CHD at earlier stage of pregnancy., (© 2022. The Author(s).)

Background and Objectives : Endometriosis is an estrogen-dependent, inflammatory, gynecological disorder represented by the migration of endometrial tissue outside the uterus. It can manifest through gynecological and gastrointestinal (GI) signs. Given the hormonal imbalances in endometriosis and the effect of microbiota on immune dysfunction, it has been thought that the human microbiome may play a role in its pathogenesis, acting differently before and after laparotomy. The aim of this review is to establish whether there is an interaction between endometriosis and gut microbial composition. Materials and Methods : We aimed to review available literature by systematically searching five databases: PubMed, EMBASE, Scopus, Cochrane Library, and ScienceDirect. We included records describing gut microbiota in the context of endometriosis-observing PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) guidelines-to recognize the presence of disease by the expression of bacterial taxa-based on 16S ribosomal RNA gene sequencing analysis. Results : Among 10 studies selected, there were four review articles and six clinical trials. The latter identified significant differences at a genus level in increased Prevotella, Blautia, and Bifidobacterium and decreased Paraprevotella, Ruminococcus, and Lachnospira ( p < 0.05). In patients undergoing abdominal hysterectomy, Proteobacteria phylum increased from 34.36% before surgery to 54.04% after surgery ( p < 0.05). Conclusions : Although scientific literature reports different characterizations of intestinal microbiota in endometriotic patients, further evidence is needed to develop new diagnostic-therapeutic strategies, for example, administration with probiotics before surgery.

Deregulation of RNA metabolism has emerged as one of the key events leading to the degeneration of motor neurons (MNs) in Amyotrophic Lateral Sclerosis (ALS) disease. Indeed, mutations on RNA-binding proteins (RBPs) or on proteins involved in aspects of RNA metabolism account for the majority of familiar forms of ALS. In particular, the impact of the ALS-linked mutations of the RBP FUS on many aspects of RNA-related processes has been vastly investigated. FUS plays a pivotal role in splicing regulation and its mutations severely alter the exon composition of transcripts coding for proteins involved in neurogenesis, axon guidance, and synaptic activity. In this study, by using in vitro-derived human MNs, we investigate the effect of the P525L FUS mutation on non-canonical splicing events that leads to the formation of circular RNAs (circRNAs). We observed altered levels of circRNAs in FUS P525L MNs and a preferential binding of the mutant protein to introns flanking downregulated circRNAs and containing inverted Alu repeats. For a subset of circRNAs, FUS P525L also impacts their nuclear/cytoplasmic partitioning, confirming its involvement in different processes of RNA metabolism. Finally, we assess the potential of cytoplasmic circRNAs to act as miRNA sponges, with possible implications in ALS pathogenesis.

During pregnancy, SARS-CoV-2 infection is associated with several adverse outcomes, including an increased risk of pre-eclampsia, preterm delivery, hypertensive disorders, gestational diabetes, and fetal growth restriction related to the development of placenta vascular abnormalities. We analyzed human placenta from full-term, uncomplicated pregnancies with SARS-CoV-2 infection during the first, second, or third trimesters of gestation. We studied, by the immunohistochemistry technique, the expression of CD34 and podoplanin (PDPN) as markers of vasculogenesis to find any differences. As secondary outcomes, we correlated maternal symptoms with placental histological alterations, including fibrin deposits, lymphocyte infiltration in the villi, edema, and thrombi. Our results showed a PDPN expression around the villous stroma as a plexiform network around the villous nucleus of fetal vessels; significant down-regulation was observed in the villous stroma of women infected during the third trimester. CD34 showed no changes in expression levels. During SARS-CoV-2 infection, the most common maternal symptoms were fever, anosmia, ageusia and asthenia, and the majority were treated with paracetamol, corticosteroids and azithromycin. Patients that required multiple symptomatic treatments evidenced a large amount of fibrin deposition in the villi. Certainly, PDPN plays a key role in healthy placental vasculogenesis and thus in its proper physiology, and SARS-CoV-2 surely alters its normal expression. Further studies are necessary to understand what mechanisms are being altered to try to avoid possible complications for both the mother and fetus in terms of the contagions that will still occur.

Background: Protracted labor is associated with an elevated risk of maternal and fetal complications. Results of randomized controlled trials on the efficacy in labor of phloroglucinol (PHL), a pure antispasmodic drug, are uncertain., Objectives: To evaluate whether PHL is effective in shortening the first stage of labor., Search Strategy: MEDLINE, EMBASE, LILACS, Scopus, ClinicalTrials.gov, and the Cochrane Library were searched from inception to July 2020., Selection Criteria: Randomized controlled trials (RCTs) concerning women with a singleton vertex pregnancy at term who were treated with PHL., Data Collection and Analysis: Relevant data were extracted and tabulated. Review Manager 5.3 was used for data analysis. Primary outcome evaluated was the mean reduction of the first stage of labor., Main Results: Five RCTs, including 487 pregnant women, were analyzed. The first stage of labor duration was significantly shorter in the treatment arm compared to the control group [MD-113.21 min (95% CI-119.63,-106.79)]. A significant shortening of the second stage was achieved in the PHL group [MD-11.12 min (95% CI-12.64,-9.75)] while no differences were reported for the third stage., Conclusions: PHL might represent an effective treatment to shorten the duration of the first and second stage of labor., Synopsis: A meta-analysis of 5 trials found that Phloroglucinol favorably impacts on the total duration of the labor in primiparae and multiparae women with a singleton pregnancy.

Acute myeloid leukemia (AML) is a heterogeneous hematopoietic malignancy whose prognosis is globally poor. In more than 60% of AML patients, the PI3K/AKTs/mTOR signaling pathway is aberrantly activated because of oncogenic driver alterations and further enhanced by chemotherapy as a mechanism of drug resistance. Against this backdrop, very recently we have started a multidisciplinary research project focused on AKT1 as a pharmacological target to identify novel anti-AML agents. Indeed, the serendipitous finding of the in-house compound T187 as an AKT1 inhibitor has paved the way to the rational identification of new active small molecules, among which T126 has emerged as the most interesting compound with IC 50 = 1.99 ± 0.11 μM, ligand efficiency of 0.35, and a clear effect at low micromolar concentrations on growth inhibition and induction of apoptosis in AML cells. The collected results together with preliminary SAR data strongly indicate that the 5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3- d ]pyrimidin-4(3 H )-one derivative T126 is worthy of future biological experiments and medicinal chemistry efforts aimed at developing a novel chemical class of AKT1 inhibitors as anti-AML agents.

Circular RNAs (circRNAs) are formed in all domains of life and via different mechanisms. There has been an explosion in the number of circRNA papers in recent years; however, as a relatively young field, circRNA biology has an urgent need for common experimental standards for isolating, analyzing, expressing and depleting circRNAs. Here we propose a set of guidelines for circRNA studies based on the authors' experience. This Perspective will specifically address the major class of circRNAs in Eukarya that are generated by a spliceosome-catalyzed back-splicing event. We hope that the implementation of best practice principles for circRNA research will help move the field forward and allow a better functional understanding of this fascinating group of RNAs., (© 2022. Springer Nature America, Inc.)

Background and Objectives: Shoulder dystocia (ShD) is one of most dangerous obstetric complication. The objective of this study was to determine if the ultrasonographic fetal biacromial diameter (BA) and derived parameters could predict ShD in uncomplicated term pregnancies., Materials and Methods: We conducted a prospective observational study in a tertiary care university hospital from March 2021 to February 2022. We included all full-term pregnancies accepted for delivery that received an accurate ultrasonography (USG) scan before delivery. USG biometry and estimated fetal weight (EFW) were collected. Therefore, we evaluated the diameter of the mid-arm, the transverse thoracic diameter (TTD) and the biacromial diameter (BA). BA was estimated using Youssef's formula: TTD + 2 mid-arm diameters. The primary outcome was the evaluation of BA and its related parameters (BA/biparietal diameter (BPD), BA/head circumference (HC) and BA-BPD in fetuses with ShD versus fetuses without ShD. Diagnostic accuracy for ShD of BA, BA/BPD, BA/HC and BA-BPD was evaluated using receiver operator curve (ROC) analysis., Results: 90 women were included in the analysis, four of these had ShD and required extra maneuvers after head delivery. BA was increased in fetuses with ShD (150.4 cm; 95% CI 133.2 cm to 167.6 cm) compared to no-ShD (133.5 cm; 95% CI 130.1 cm to 137.0 cm; p = 0.04). Significant differences were also found between ShD and no-ShD groups for BA/BPD (1.66 (95% CI 1.46 to 1.86) vs. 1.44 (95% CI 1.41 to 1.48); p = 0.04), BA/HC (0.45 (95% CI 0.40 to 0.49) vs. 0.39 (95% CI 0.38 to 0.40); p = 0.01), BA-BPD (60.0 mm (95% CI 42.4 to 77.6 cm) vs. 41.4 (95% CI 38.2 to 44.6); p = 0.03), respectively. ROC analysis showed an overall good accuracy for ShD, with an AUC of 0.821 ( p = 0.001) for BA alone and 0.881 ( p = 0.001), 0.857 ( p = 0.016) and 0.867 ( p = 0.013) for BA/BPD, BA-BPD and BA/HC, respectively., Conclusions: BA alone, as well as BA/BPD, BA/HC and BA-BPD might be useful predictors of ShD in uncomplicated term pregnancies. However, such evidence needs extensive confirmation by means of additional studies with large sample sizes, especially in case of pregnancies at high risk for ShD (i.e., gestational diabetes).

Objective: Pregnant women with chronic hypertension are recommended to deliver at 36-39 6/7  weeks. The American College of Cardiology and American Heart Association in 2017 lowered the blood pressure cut-off for stage I hypertension to 130/80 mm Hg., Methods: We performed a literature review on studies comparing elective induction of labor versus expectant management in pregnant women with chronic hypertension. In addition, we reviewed fetal and maternal outcomes in pregnant women with blood pressure of 120-139/80-89 or 130-139/80-89 mm Hg., Results: We found two randomized clinical trials and one retrospective observational study comparing elective delivery of pregnant women with chronic hypertension versus expectant management. The randomized trials favored expectant management and the observational study favored induction of labor. We found 15 retrospective cohort studies analyzing maternal and fetal outcomes in pregnant women with blood pressure cut-off lower than 140/90 mm Hg. There was a consistent finding of increased risk of any hypertensive disorder of pregnancy, gestational diabetes mellitus, and small-for-gestational-age neonate., Conclusion: Randomized clinical trials are needed to assess the appropriate timing of delivery for women with stage I hypertension with a blood pressure cut-off of 130/80 mm Hg., (© 2021 International Federation of Gynecology and Obstetrics.)

Aim: To evaluate whether the first Covid-19 lockdown for Italian citizens (March to July 2021) might have altered the incidence of gestational diabetes mellitus (GDM)., Methods: A retrospective single-center study in a tertiary referral center. Primary outcome was the incidence of GDM among pregnant women. GDM incidence, from June 11, 2019 to December 4, 2020, was compared by dividing the study time as follows: from the beginning of the study to before Covid-19 lockdown (from June 11, 2019, to March 9, 2020) and lockdown period (from March 10, 2020, to December 4, 2020). GDM was diagnosed with a 75-g, 2-h oral glucose tolerance test (OGTT) at 24-28 gestational weeks., Results: Concerning 1295 women, GDM incidence increased during the lockdown period (9.3% vs. 3.4%, p < 0.001). Higher pregnancy weight gain with an increased body mass index (BMI) at the delivery was reported during the lockdown (31.3 vs. 28.4 kg/m 2 , p = 0.02 and mean weight gain of 9.3 vs. 6.6 kg, p = 0.007). There was no difference in other comorbidity incidence and OGTT values between the two groups., Conclusions: Pregnant women during the Covid-19 lockdown might have experienced higher BMI and pregnancy weight gain with increased GDM diagnoses. This may be related to physical limitations and emotional distress experienced during the lockdown. However, evidence is limited due to restricted study duration and random variations of outcomes across time. More studies are needed to understand the dietary patterns and the physical activity changes during the Covid-19 lockdown and its impact on fetal outcomes., (© 2022 The Authors. Journal of Obstetrics and Gynaecology Research published by John Wiley & Sons Australia, Ltd on behalf of Japan Society of Obstetrics and Gynecology.)

To estimate the correlation between the maternal perception of Braxton-Hicks contractions (BHC) and foetal wellbeing throughout antepartum computerised cardiotocography (cCTG) parameters, we performed a prospective observational study between April 2019 and March 2020. Non-labouring women with a term pregnancy were recruited. We collected data regarding maternal perception of BHC in the last two weeks before delivery. For each patient, an external computerised cardiotocography (cCTG) was registered. Women were subdivided in accordance with perception or non-perception of BHC. Fifty women were recruited. Women who felt BHC showed higher foetal heart rate (135 bpm vs 128 bpm, p  = .008), lower long-term variability (47.2 ms vs 57.7 ms, p  = .02) and reduced number of accelerations (7.8 vs 11.4, p  = .04). In conclusion, the absence of mother's perception of BHC showed lower baseline foetal heart rate, increased number of accelerations and higher long-term variability related to mothers who perceived BHC.IMPACT STATEMENT What is already known on this subject? BHC are common painful contractions that start in the third trimester. They are random spots of uterine action that happen in the absence of sufficient gap-junction connectivity. BHC have a significant impact on foetal wellbeing. What do the results of this study add? BHC are associated with reduced long-term variability during cCTG examination. Moreover, baseline foetal heart rate seems lower, and accelerations are less frequent when BHC are felt by pregnant women. What are the implications of these findings for clinical practice and/or further research? These findings could be related to a cumulative effect on the uterine flow mediated by BHC. Further researches are needed to state the impact of BHC on the foetal wellbeing.

Aberrant right subclavian artery (ARSA) is the most common embryologic abnormality of the aortic arch. The presence of ARSA has been previously associated with an increased risk of Down syndrome. ARSA at birth may be associated with dysphagia, respiratory distress and stridor and there is no clear evidence-based management. The aim of this study was to describe the associations with chromosomal abnormalities and the postnatal outcome of fetuses diagnosed with ARSA. We analysed fetuses diagnosed antenatally with ARSA between January 2013 and September 2019 in the fetal echocardiography unit of the Hospital Monaldi, University 'Vanvitelli' of Naples, Italy. The results showed fifty fetuses diagnosed with ARSA, all confirmed after birth. The ARSA was an isolated finding in 46 fetuses (92%), while in 4 fetuses the ARSA was associated with other cardiac and/or extra-cardiac anomalies. Only one fetus was diagnosed with trisomy 21 (2%). In this fetus the ARSA was the only ultrasound anomaly identified. There were no cases necessitating referral due to the presence of compression symptoms at birth. The presence of ARSA was associated with trisomy 21 in the 2% of cases in our series and there were no neonatal complications due to airway compression at birth.IMPACT STATEMENT What is already known on this subject? Aberrant right subclavian artery (ARSA) is the most common embryologic abnormality of the aortich arch. ARSA at birth could be associated with dysphagia, respiratory distress and stridor and no evidence-based management of these fetuses has been described yet. The presence of ARSA has been previously associated with an increased risk of Down syndrome. What do the results of this study add? This study confirms known data on association with chromosomal defects and provides some original data on the absence of symptomatology due to tracheal compression with a postnatal follow-up up to three years of age. What are the implications of these findings for clinical practice and/or further research? Our findings suggest that in cases with adequate prenatal assessment performed by experienced clinicians, delivery can safely take place at local hospitals, with no need of referral soon after birth. The use of transthoracic echocardiography to confirm the diagnoses of ARSA after birth and to plan the next follow-up appointments can be supported.

Objectives: The main goal of our research was to explore correlations between a history of uterine myomectomy and maternal-fetal outcomes, throughout a comparison between vaginal deliveries in patients with or without a history of uterine myoma excision., Materials and Methods: A prospective study was carried out at two tertiary care hospitals between January 2019 and January 2020. Women were assigned into two groups according to the history of laparoscopic or laparotomic myomectomy (Group 1) or without myomectomy (Group 2)., Results: 80 women successfully delivered after myomectomy. Pregnancies with previous laparoscopic or laparotomic myomectomy were associated with a minor rate of spontaneous labor onset (RR 1.17; 95% CI 1.04 - 1.31) and with an increased rate of emergency cesarean section (RR 1.22; 95% CI 1.09 - 1.36). Moreover, myomectomy group had a significant number of indications to emergency cesarean section correlated to suspected uterine rupture (RR 1.19; 95% CI 1.02-1.39). There were no uterine ruptures or neonatal deaths recorded. First stage of labor was longer in the myomectomy group (316 vs 204 mins, p = 0.01). No differences in the rates of the prolonged first and second stage of labor, postpartum hemorrhage and vaginal laceration, and no neonatal adverse outcomes were found between groups., Conclusions: Pregnancies after myomectomy might be associated with an elevated rate of emergency cesarean section only due to a higher percentage of suspected uterine rupture, without a real hazard of adverse obstetric or neonatal outcomes.

Microbiota composition is progressively being connected to different physiologic effects, such as glucose metabolism, and also to different pathologies, such as gestational diabetes mellitus (GDM). GDM is a public health concern that affects an important percentage of pregnancies and is correlated with many adverse maternal and neonatal outcomes. An increasing number of studies are showing some connections between specific microbial composition of the gut microbiota and development of GDM and adverse outcomes in mothers and neonates. The aim of this review is to analyze the available data on microbial changes that characterize healthy pregnancies and pregnancies complicated by GDM and to understand the correlation of these changes with adverse maternal outcomes; this review will also discuss the consequences of these maternal gut microbiome alterations on neonatal microbiota composition and neonatal long-term outcomes., Competing Interests: The authors declare no conflict of interest., (Copyright © 2021 Caterina Neri et al.)

CircRNAs belong to a family of RNA molecules which are conserved in evolution, have tissue-specific expression, and are abundant in neuronal cells. Here, we define several features of circ-Hdgfrp3 and describe interesting alterations occurring in motor neurons (MNs) carrying ALS-associated FUS mutations. Through a highly sensitive in situ approach we describe that circ-Hdgfrp3 traffics along neurites, while upon oxidative stress it is retained in the perinuclear region. While in wild-type stressed MNs, circ-Hdgfrp3 localizes in stress granules (SGs), in MNs carrying mutant FUS, a higher proportion of circ-Hdgfrp3 was trapped into cytoplasmic aggregates. Upon stress removal, circ-Hdgfrp3 was easily freed from SGs whereas it was less efficiently released from FUS-aggregates. We found that the human circ-Hdgfrp3 counterpart was also similarly associated to mutant FUS-aggregates in stressed neuronal cells. Overall, the alteration of circ-Hdgfrp3 trafficking adds a further layer of complexity to the role of FUS-aggregates in ALS disease., (© 2021 The Authors.)

Background: Diabetes in pregnancy is associated with an increased risk to the woman and to the developing fetus. Currently, there is no consensus on the optimal management strategies for the follow-up and the timing of delivery of pregnancies affected by gestational and pregestational diabetes, with different international guidelines suggesting different management options., Materials and Methods: We conducted a retrospective cohort study from January 2017 to January 2021, to compare maternal and neonatal outcomes of pregnancies complicated by gestational and pregestational diabetes, followed-up and delivered in a third level referral center before and after the introduction of a standardized multidisciplinary management protocol including diagnostic, screening, and management criteria., Results: Of the 131 women included, 55 were managed before the introduction of the multidisciplinary management protocol and included in group 1 (preprotocol), while 76 were managed according to the newly introduced multidisciplinary protocol and included in group 2 (after protocol). We observed an increase in the rates of vaginal delivery, rising from 32.7% to 64.5% (<0.001), and the rate of successful induction of labor improved from 28.6% to 86.2% ( P < 0.001). No differences were found in neonatal outcomes, and the only significant difference was demonstrated for the rates of fetal macrosomia (20% versus 5.3%, P : 0.012). Therefore, the improvements observed in the maternal outcomes did not impact negatively on fetal and neonatal outcomes., Conclusion: The introduction of a standardized multidisciplinary management protocol led to an improvement in the rates of vaginal delivery and in the rate of successful induction of labor in our center. A strong cooperation between obstetricians, diabetologists, and neonatologists is crucial to obtain a successful outcome in women with diabetes in pregnancy., Competing Interests: All the authors declare no conflicts of interest., (Copyright © 2021 Maddalena Morlando et al.)

Introduction: Cesarean section affects subsequent spontaneous pregnancies because of implantation issues. However, its impact on post-embryo transfer pregnancies is still debated. This review aimed to evaluate the impact of a previous cesarean section on fertility and pregnancy outcomes of women undergoing fresh or frozen embryo transfer., Material and Methods: MEDLINE, Scopus, ClinicalTrials.gov, Scielo, EMBASE, Cochrane Library at the CENTRAL, and LILACS were searched from inception to February 2021. Studies were included if they evaluated reproductive or pregnancy outcomes after fresh or frozen embryo transfer in infertile women with a previous cesarean section relative to women with a previous vaginal delivery. Random-effect meta-analyses to calculate risk ratio (RR) or mean differences with 95% confidence intervals (CI) followed by subgroup analysis for fresh and frozen embryo transfer were performed. Risk of bias and quality assessment were conducted using Newcastle-Ottawa scale and GRADE criteria. The review was registered in the International Prospective Register of Systematic Reviews (CRD42021226297)., Results: Ten studies, with data provided for 13 696 participants, were eligible. For embryo transfers after cesarean section, compared with vaginal delivery, there was a significant reduction of the live birth rate (RR 0.88, 95% CI 0.79-0.99) and biochemical pregnancy rate (RR 0.89, 95% CI 0.82-0.96). No statistically significant differences were found for clinical pregnancy rate (RR 0.92, 95% CI 0.84-1.02), ectopic pregnancies (RR 1.00, 95% CI 0.68-1.46), pregnancy loss (RR 1.05, 95% CI 0.94-1.18), multiple pregnancies (RR 0.80, 95% CI 0.63-1.02), stillbirths (RR 0.86, 95% CI 0.27-2.69), birth defects (RR 1.71, 95% CI 0.49-5.96) or birthweight (mean difference 46.82, 95% CI -40.16 to 133.80). Subgroup analysis revealed an increased risk for preterm birth in post-cesarean section fresh embryo transfer pregnancies (RR 1.59, 95% CI 1.16-2.19)., Conclusions: Low-grade evidence shows that post-embryo transfer pregnancies in infertile women who had a previous cesarean delivery result in reduced biochemical pregnancy and live birth rates relative to women with a previous vaginal delivery. An increased risk for preterm birth is notable in post-fresh embryo transfer pregnancies., (© 2021 The Authors. Acta Obstetricia et Gynecologica Scandinavica published by John Wiley & Sons Ltd on behalf of Nordic Federation of Societies of Obstetrics and Gynecology (NFOG).)

Mutations in the RNA-binding protein (RBP) FUS have been genetically associated with the motoneuron disease amyotrophic lateral sclerosis (ALS). Using both human induced pluripotent stem cells and mouse models, we found that FUS-ALS causative mutations affect the activity of two relevant RBPs with important roles in neuronal RNA metabolism: HuD/ELAVL4 and FMRP. Mechanistically, mutant FUS leads to upregulation of HuD protein levels through competition with FMRP for HuD mRNA 3'UTR binding. In turn, increased HuD levels overly stabilize the transcript levels of its targets, NRN1 and GAP43. As a consequence, mutant FUS motoneurons show increased axon branching and growth upon injury, which could be rescued by dampening NRN1 levels. Since similar phenotypes have been previously described in SOD1 and TDP-43 mutant models, increased axonal growth and branching might represent broad early events in the pathogenesis of ALS., (© 2021. The Author(s).)

Background: Besides reducing the quality of obstetric care, the direct impact of COVID-19 on pregnancy and postpartum is uncertain., Objective: To evaluate the characteristics of pregnant women who died due to COVID-19., Search Strategy: Cochrane Library, Embase, MEDLINE, Scopus, and Google Scholar were searched from inception to February 2021., Selection Criteria: Studies that compared deceased and survived pregnant women with COVID-19., Data Collection and Analysis: Relevant data were extracted and tabulated. The primary outcome was maternal co-morbidity., Main Results: Thirteen studies with 154 deceased patients were included. Obesity doubled the risk of death (relative risk [RR] 2.48, 95% confidence interval [CI] 1.41-4.36, I 2  = 0%). No differences were found for gestational diabetes (RR 5.71; 95% CI 0.77-42.44, I 2  = 94%) or asthma (RR 2.05, 95% CI 0.81-5.15, I 2  = 0%). Overall, at least one severe co-morbidity showed a twofold increased risk of death (RR 2.26, 95% CI 1.77-2.89, I 2  = 76%). Admission to intensive care was related to a fivefold increased risk of death (RR 5.09, 95% CI 2.00-12.98, I 2  = 56%), with no difference in need for respiratory support (RR 0.53, 95% CI 0.23-1.48, I 2  = 95%) or mechanical ventilation (RR 4.34, 95% CI 0.96-19.60, I 2  = 58%)., Conclusion: COVID-19 with at least one co-morbidity increases risk of intensive care and mortality., (© 2021 International Federation of Gynecology and Obstetrics.)

Background: It has still to be ascertained whether severe acute respiratory syndrome coronavirus 2 infection in pregnancy is associated with worse maternal and fetal outcomes compared to low risk gestations., Objective: This study aimed to evaluate maternal and perinatal outcomes in high- and low-risk pregnancies complicated by severe acute respiratory syndrome coronavirus 2 infection., Study Design: This was a multinational retrospective cohort study involving women with laboratory-confirmed severe acute respiratory syndrome coronavirus 2 infection from 76 centers from 25 countries in Europe, the United States, South America, Asia, and Australia from April 4, 2020, to October 28, 2020. The primary outcome was a composite measure of maternal mortality and morbidity, including admission to the intensive care unit, use of mechanical ventilation, or death. The secondary outcome was a composite measure of adverse perinatal outcome, including miscarriage, fetal loss, neonatal and perinatal death, and admission to the neonatal intensive care unit. All outcomes were assessed in high- and low-risk pregnancies. Pregnancies were considered high risk in case of either preexisting chronic medical conditions in pregnancy or obstetrical disorders occurring in pregnancy. The Fisher exact test and logistic regression analysis were used to analyze the data., Results: A total of 887 singleton pregnancies who tested positive for severe acute respiratory syndrome coronavirus 2 infection using reverse transcription-polymerase chain reaction of nasal and pharyngeal swab specimens were included in the study. The risk of composite adverse maternal outcomes was higher in high-risk pregnancies than in low-risk pregnancies (odds ratio, 1.52; 95% confidence interval, 1.03-2.24; P=.035). In addition, women carrying high-risk pregnancies were at higher risk of hospital admission (odds ratio, 1.48; 95% confidence interval, 1.07-2.04; P=.002), presence of severe respiratory symptoms (odds ratio, 2.13; 95% confidence interval, 0.41-3.21; P=.001), admission to the intensive care unit (odds ratio, 2.63; 95% confidence interval, 1.42-4.88), and invasive mechanical ventilation (odds ratio, 2.65; 95% confidence interval, 1.19-5.94; P=.002). When exploring perinatal outcomes, high-risk pregnancies were at high risk of adverse perinatal outcomes (odds ratio, 1.78; 95% confidence interval, 0.15-2.72; P=.009). However, such association was mainly because of the higher incidence of miscarriage in high-risk pregnancies compared with that in low-risk pregnancies (5.3% vs 1.6%, P=.008); furthermore, there was no difference in other explored outcomes between the 2 study groups. At logistic regression analysis, maternal age (odds ratio, 1.12; 95% confidence interval, 1.02-1.22; P=.023) and high-risk pregnancy (odds ratio, 4.21; 95% confidence interval, 3.90-5.11; P<.001) were independently associated with adverse maternal outcomes., Conclusion: High-risk pregnancies complicated by severe acute respiratory syndrome coronavirus 2 infection were at higher risk of adverse maternal outcomes than low-risk pregnancies complicated by severe acute respiratory syndrome coronavirus 2 infection., (Copyright © 2021. Published by Elsevier Inc.)

Background: Transversus abdominis plane (TAP) block and wound infiltration (WI) with local anesthetics are used for postoperative analgesia after cesarean section (CS), reducing the need for administration of opioids., Objective: To compare the analgesic effect of TAP block related to WI., Search Strategy: MEDLINE, Scopus, ClinicalTrials.gov, EMBASE, Cochrane Library, and CINAHL were searched from inception until April 2020., Selection Criteria: Randomized controlled trials (RCTs) about women who underwent TAP block or WI after CS., Data Collection and Analysis: Relevant data were extracted and tabulated. Review Manager 5.3 was used for data analysis. Primary outcome was cumulative opioid consumption (COC) 24 and 48 h after CS., Main Results: Five RCTs, enrolling 268 women, were included. There were no significant differences between the interventions regarding COC at 24 (mean difference [MD] -1.68, 95% confidence interval [CI] -6.29 to 2.93) and 48 hours (MD 1.28, 95% CI -10.44 to 13.00). Adverse effects (relative risk [RR] 0.93, 95% CI 0.75-1.16), gastrointestinal reactions (RR 1.30, 95% CI 0.46-3.68), or mild-moderate sedation (RR 1.12, 95% CI 0.72-1.74), pain scores, satisfaction of women, and withdrawals were similar between groups., Conclusions: There might be no significant advantages selecting TAP block over WI for post-CS analgesia., (© 2020 International Federation of Gynecology and Obstetrics.)

Gestational diabetes mellitus (GDM) represents a challenging pregnancy complication in which women present a state of glucose intolerance. GDM has been associated with various obstetric complications, such as polyhydramnios, preterm delivery, and increased cesarean delivery rate. Moreover, the fetus could suffer from congenital malformation, macrosomia, neonatal respiratory distress syndrome, and intrauterine death. It has been speculated that inflammatory markers such as tumor necrosis factor-alpha (TNF-α), interleukin (IL) 6, and C-reactive protein (CRP) impact on endothelium dysfunction and insulin resistance and contribute to the pathogenesis of GDM. Nutritional patterns enriched with plant-derived foods, such as a low glycemic or Mediterranean diet, might favorably impact on the incidence of GDM. A high intake of vegetables, fibers, and fruits seems to decrease inflammation by enhancing antioxidant compounds. This aspect contributes to improving insulin efficacy and metabolic control and could provide maternal and neonatal health benefits. Our review aims to deepen the understanding of the impact of a plant-based diet on oxidative stress in GDM.

Introduction: Breech/transverse presentation is responsible for about 30-50 % of cesarean sections in the world. Cesarean section carries a five-fold greater morbidity than vaginal delivery, deeply impacting on women's health. External Cephalic Version (ECV) is an external manipulation used to convert a non-cephalic to a cephalic presentation. The use of tocolysis might facilitate this procedure; however, it is still controversial which drug should be considered as first choice., Objective: To assess the effectiveness of tocolysis with atosiban, a competitive oxytocin receptor antagonist, in order to increase the rate of successful ECV., Study Design: Nine databases (including MEDLINE, CINAHL, LILACS, EMBASE, Scopus, ClinicalTrials.gov, Scielo, PROSPERO, Cochrane at CENTRAL) were searched from the inception to August 2020 using a combination of MeSH terms and keywords regarding "atosiban" and "external cephalic version". We included trials of women with a singleton pregnancy who reached at least 36 weeks of gestation and were scheduled to ECV and tocolysis with atosiban (intervention group) compared to beta-agonists or other drugs (control group). The primary outcome was the incidence of successful ECV. Summary measures were reported as relative risk (RR) with 95 % confidence interval (CI)., Data Collection and Analysis: Four studies (1534 women) were eligible for analysis. ECV success rate was significantly lower in women randomized to atosiban (36.7 % vs 45.3 %; RR 0.78 [95 % CI 0.6 to 0.98]). Cesarean section and vaginal delivery rates did not differ between intervention and control group ((59.8 % vs 52.6 %; RR 1.17 [0.98-1.38] and (38.6 % vs 45.0 %; RR 0.83 [95 % CI 0.69-1.01] respectively). Cephalic (36.9 % vs 44.6 %; RR 0.81 [95 % CI 0.65 to 1.01], or breech/transverse presentation at labor (63.4 % vs 55.1 %; RR 1.18 [95 % CI 0.99-1.40]), APGAR score less than 7 at 5 min (1.6 % vs 2.0 %; RR 1.14 [95 % CI 0.27-4.73], NICU admissions (44.2 % vs 48.1 %; RR 0.92 [95 % CI 0.58-1.46] and Umbilical cord pH were similar in both groups. Drug-related side effects were lower in women randomized to atosiban, compared with control group (16.0 % vs 42.9 %; RR 0.38 [95 % CI 0.31 to 0.47]., Conclusion: The use of atosiban for tocolysis does not improve the rate of successful ECVs when compared to beta-agonists. However, atosiban was associated with a significantly lower incidence of side effects and comparable cesarean section rates., Competing Interests: Declaration of Competing Interest The authors have no conflict of interest to disclose., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Studies of rare, but complex clinical conditions require multicenter cooperation. The International Society for Placenta accreta spectrum (IS-PAS) have established a secure web-based database to analyze pregnancies complicated by PAS. By repeated in-person meetings of the IS-PAS, a core dataset was established. Then, a custom-made, secure online database, capable of receiving strictly anonymized patient-related textual and imaging data and allowing statistical queries was designed, tested, amended and implemented. Between 2008 and 2019, 14 IS-PAS centers across Europe and one center in the USA contributed data for all their PAS cases, containing pregnancy data for a total of 442 pregnant women. Data were analyzed by a designated data analysis sub-group of the IS-PAS. Center characteristics are presented. Based on experiences with previous versions, our new online database now allows an all-encompassing data collection. It has shown its usefulness in the current analysis project., (© 2021 The Authors. Acta Obstetricia et Gynecologica Scandinavica published by John Wiley & Sons Ltd on behalf of Nordic Federation of Societies of Obstetrics and Gynecology (NFOG).)

Objective: The association between the most severe types of placenta accreta spectrum disorders and caesarean scar pregnancy (CSP) poses the question of whether early diagnosis may impact the clinical outcome of these anomalies. The aim of this study is to report the outcome of cesarean scar pregnancy (CSP) diagnosed in the early (≤9 weeks) versus late (>9 weeks) first trimester of pregnancy., Study Design: Medline, Embase and Clinicaltrail.gov databases were searched. Studies including cases of CSP with an early (≤9 weeks of gestation) compared to a late (>9 weeks) first trimester diagnosis of CSP, followed by immediate treatment, were included in this systematic review. The primary outcome was a composite measure of severe maternal morbidity including either severe first trimester bleeding, need for blood transfusion, uterine rupture or emergency hysterectomy. The secondary outcomes were the individual components of the primary outcome. Random-effect meta-analyses were used to combine data., Results: Thirty-six studies (724 women with CSP) were included. Overall, composite adverse outcome complicated 5.9 % (95 % CI 3.5-9.0) of CSP diagnosed ≤9 weeks and 32.4 % (95 % CI 15.7-51.8) of those diagnosed >9 weeks. Massive hemorrhage occurred in 4.3 % (95 % CI 2.3-7.0) of women with early and in 28.0 % (95 % CI 14.1-44.5) of those with late first trimester diagnosis of CSP, while the corresponding figures for the need for blood transfusion were 1.5 % (95 % CI 0.6-2.8) and 15.8 % (95 % CI 5.5-30.2) respectively. Uterine rupture occurred in 2.5 % (95 % CI 1.2-4.1) of women with a prenatal diagnosis of CSP ≤ 9 weeks and in 7.5 % (95 % CI 2.5-14.9) of those with CSP > 9 weeks, while an emergency intervention involving hysterectomy was required in 3.7 % (95 % CI 2.2-5.4) and 16.3 % (95 % CI5.9-30.6) respectively. When computing the risk, early diagnosis of CSP was associated with a significantly lower risk of composite adverse outcome, (OR: 0.14; 95 % CI 0.1-0.4 p < 0.001)., Conclusions: Early first trimester diagnosis of CSP is associated with a significantly lower risk of maternal complications, thus supporting a policy of universal screening for these anomalies in women with a prior cesarean delivery although the cost-effectiveness of such policy should be tested in future studies., (Copyright © 2020. Published by Elsevier B.V.)

Introduction: Placenta accreta spectrum (PAS) is a condition often resulting in severe maternal morbidity. Scheduled delivery by an experienced team has been shown to improve maternal outcomes; however, the benefits must be weighed against the risk of iatrogenic prematurity. The aim of this study is to investigate the rates of emergency delivery seen for antenatally suspected PAS and compare the resulting outcomes in the 15 referral centers of the International Society for PAS (IS-PAS)., Material and Methods: Fifteen centers provided cases between 2008 and 2019. The women included were divided into two groups according to whether they had a planned or an emergency cesarean delivery. Delivery was defined as "planned" when performed at a time and date to suit the team. All the remaining cases were classified as "emergency". Maternal characteristics and neonatal outcomes were compared between the two groups according to gestation at delivery., Results: In all, 356 women were included. Of these, 239 (67%) underwent a planned delivery and 117 (33%) an emergency delivery. Vaginal bleeding was the indication for emergency delivery in 41 of the 117 women (41%). There were no significant differences in terms of blood loss, transfusion rates or major maternal morbidity between planned and emergency deliveries. However, the rate of maternal intensive therapy unit admission was increased with emergency delivery (45% vs 33%, P = .02). Antepartum hemorrhage was the only independent predictor of emergency delivery (aOR: 4.3, 95% confidence interval 2.4-7.7). Emergency delivery due to vaginal bleeding was more frequent with false-positive cases (antenatally suspected but not confirmed as PAS at delivery) and the milder grades of PAS (accreta/increta). The rate of infants experiencing any major neonatal morbidity was 25% at 34 +1 to 36 +0  weeks and 19% at >36 +0  weeks., Conclusions: Emergency delivery in centers of excellence did not increase blood loss, transfusion rates or maternal morbidity. The single greatest risk factor for emergency delivery was antenatal hemorrhage. When adequate expertise and resources are available, to defer delivery in women with no significant antenatal bleeding and no risk factors for pre-term birth until >36 +0  weeks can be considered to improve fetal outcomes. Further studies are needed to investigate this fully., (© 2021 The Authors. Acta Obstetricia et Gynecologica Scandinavica published by John Wiley & Sons Ltd on behalf of Nordic Federation of Societies of Obstetrics and Gynecology (NFOG).)

Objective: To evaluate benefits of use of ureteral stents in association with cesarean hysterectomy in case of placenta accreta. Methods: This was a single center, cohort study. Clinical records of singleton pregnancies with placenta accreta who underwent cesarean hysterectomy were included in the study. For this study, pregnancies with diagnoses of placenta accreta, increta, or percreta were considered under the umbrella term of placenta accreta. For all women with placenta accreta, delivery was planned via cesarean hysterectomy at 34 0 -35 6 weeks, without any attempt to remove the placenta. Reasons for earlier delivery included vaginal bleeding and spontaneous onset of labor. The primary outcome was the incidence of unintentional urinary tract injury. Outcomes were compared in a cohort of women who had planned the placement of ureteral stents and in those who did not. Results: Forty-four singleton gestations with confirmed placenta accreta at the time of cesarean hysterectomy were included in the study. Twenty-four (54.5%) of the included women had the placing of ureteral stents prior to cesarean, while 20 (45.5%) did not. At histological confirmation, most of them had placenta accreta (17/44, 38.6%), 14 placenta increta (31.8%), and 13 placenta percreta (29.6%). Urinary tract injuries occurred in eight cases (18.2%), six in the ureteral stents and two in the non-ureteral stents group (25 versus 10%; p  = .21). All the injuries were bladder injuries, while no cases of ureteral injury were recorded. All injuries were recognized intraoperatively. Conclusion: In case of placenta accreta, the use of ureteral stents in association with cesarean hysterectomy does not reduce the risk of urinary tract injury.

The aim of this review is to highlight the influence of the Mediterranean Diet (MedDiet) on Gestational Diabetes Mellitus (GDM) and Gestational Weight Gain (GWG) during the COVID-19 pandemic era and the specific role of interleukin (IL)-6 in diabesity. It is known that diabetes, high body mass index, high glycated hemoglobin and raised serum IL-6 levels are predictive of poor outcomes in coronavirus disease 2019 (COVID-19). The immunopathological mechanisms of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection include rising levels of several cytokines and in particular IL-6. The latter is associated with hyperglycemia and insulin resistance and could be useful for predicting the development of GDM. Rich in omega-3 polyunsaturated fatty acids, vitamins, and minerals, MedDiet improves the immune system and could modulate IL-6, C reactive protein and Nuclear Factor (NF)-κB. Moreover, polyphenols could modulate microbiota composition, inhibit the NF-κB pathway, lower IL-6, and upregulate antioxidant enzymes. Finally, adhering to the MedDiet prior to and during pregnancy could have a protective effect, reducing GWG and the risk of GDM, as well as improving the immune response to viral infections such as COVID-19.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease associated with motor neuron degeneration, muscle atrophy and paralysis. To date, multiple panels of biomarkers have been described in ALS patients and murine models. Nevertheless, none of them has sufficient specificity and thus the molecular signature for ALS prognosis and progression remains to be elucidated. Here we overcome this limitation through a longitudinal study, analyzing serum levels of circulating miRNAs, stable molecules that are recently used as promising biomarkers for many types of human disorders, in ALS patients during the progression of the pathology. We performed next-generation sequencing (NGS) analysis and absolute RT quantification of serum samples of ALS patients and healthy controls. The expression levels of five selected miRNAs were quantitatively analyzed during disease progression in each patient and we demonstrated that high levels of miR-206, miR-133a and miR-151a-5p can predict a slower clinical decline of patient functionality. In particular, we found that miR-206 and miR-151a-5p serum levels were significantly up-regulated at the mild stage of ALS pathology, to decrease in the following moderate and severe stages, whereas the expression levels of miR-133a and miR-199a-5p remained low throughout the course of the disease, showing a diagnostic significance in moderate and severe stages for miR-133a and in mild and terminal ones for miR-199a-5p. Moreover, we found that miR-423-3p and 151a-5p were significantly downregulated respectively in mild and terminal stages of the disease. These data suggest that these miRNAs represent potential prognostic markers for ALS disease.