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Objectives: To investigate the use of intravoxel incoherent motion (IVIM) to study microperfusion and microstructural characteristics of lungs, brain, and placenta in normal and small fetuses., Methods: We retrospectively enrolled 30 small fetuses and 82 normal pregnancies who underwent a 1.5-T MRI examination using an IVIM-DWI. Small fetuses were distinguished in small for gestational age (SGA) and "true" fetal growth restriction (FGR). ROIs were placed on the brain parenchyma, lungs, and fetal/maternal placental sides. Differences in perfusion fraction f, diffusion coefficient D, and pseudo-diffusion coefficient D* and their correlation with gestational age (GA) and birth weight (BW) were investigated., Results: LUNG: f showed significantly lower values (p = 2·10 -7 ) in small fetuses (SGA + FGR); f discriminates SGA and FGR from normal (p = 0.001; p = 1·10 -6 ). f increases with GA (p < 0.0001) in the control group; a positive correlation was also obtained in small fetuses, although less significant., Placenta: FGR showed lower f values than normal ones, in both the fetal (p = 1.4·10 -7 ) and maternal side (p = 0.001); f discriminates between SGA and FGR (p = 0.03). In small fetuses (SGA + FGR), f correlates positively with BW., Brain: D values in supratentorial white matter (WM) were significantly higher compared to other regions, in both normal and small fetuses. Small fetuses showed higher D values in occipital WM and pons (p = 0.041; p = 0.027) than in normal. D correlates negatively with GA in the healthy group. No correlation between D and GA was found in SGA + FGR group., Conclusions: In our study, IVIM-MRI allowed us to detect microstructural and microperfusion changes in the placenta, brain, and lung of small fetuses, noninvasively., Competing Interests: Declarations Conflict of interest Autor Robert Grimm is an employee of Siemens Healthcare GmbH. He didn’t receive any financial support for this work that could have influenced its outcome. The remaining authors declare no relationships with any companies whose products or services may be related to the subject matter of the article. Ethical approval The study was conducted in accordance with the Declaration of Helsinki. Informed consent Informed consent was obtained from all subjects involved in the study., (© 2024. Italian Society of Medical Radiology.)

Fetal liver calcifications (FLCs) are isolated or multiple areas of increased echogenicity in the fetal liver, with an estimated prevalence of 5-10 per 10 000 births. However, their clinical importance remains still unclear. Although they are often linked to infections, chromosomal disorders, thrombotic events, or tumors, isolated FLCs generally have a favorable outcome. This article aims to present a case of a 29-year-old pregnant woman with a low-risk cfDNA test, who presented for the first trimester screening scan at our hospital at 12 weeks of pregnancy. The morphology scan at 20 weeks and 5 days revealed a normal fetal size with areas of increased echogenicity in the liver. No other fetal issues were identified. The patient was monitored throughout her pregnancy at our center, receiving genetic counseling and tests for detecting cystic fibrosis, STORCH (syphilis, cytomegalovirus, herpes virus 1;2, rubella, and toxoplasma), fetal echocardiography, and MRI, all of which were normal. At 35 weeks and 6 days, the patient gave birth to a healthy male, and all subsequent postnatal examinations confirmed the baby's health. This article aims to offer comprehensive insights into the management and postnatal outcomes of isolated FLCs, based on a review of the literature., (© 2024 Wiley Periodicals LLC.)

Objective: To investigate the rate of obstetric and perinatal outcomes of premature rupture of membranes (PROM) occurring before 26 weeks in twin pregnancies., Data Source: Medline, Embase, Cinahl and Web of Science databases were searched electronically up to January 2024., Study Eligibility Criteria: The selection criteria included both prospective and retrospective studies of twin pregnancies with PROM before 26 weeks of gestation. Case reports, case series with fewer than 5 cases, review articles, letters to the editor and editorials were excluded. Studies including both singletons and twin pregnancies were also excluded., Study Appraisal and Synthesis Method: We used meta-analyses of proportions to combine data and assess the pooled proportions. We used a random-effect model to perform the pooled data analyses. The study was registered with the PROSPERO database (CRD 42022368057). Quality assessment of the included studies was performed usingthe Newcastle-Ottawa Scale for cohort studies., Results: Eight studies including 227 twin pregnancies were included in the analysis. The pooled proportion of termination of pregnancy (TOP) was 4.6 % (95 % CI 1.5-13.4), while the rate of selective TOP (sTOP) was 24.5 % (95 % CI 7.1-57.7). After the exclusion of cases of TOP, the overall rate of spontaneous miscarriage or fetal demise was 20.9 % (95 % CI 11.1-35.8), whereas the live birth rate of at least one twin was 71.6 % (95 % CI 61.2-80.1) of the ongoing pregnancies. The mean gestational age at delivery was 26.5 (95 % CI 25.1-28.0) weeks and the mean latency between PROM and delivery was 5.4 weeks (95 % CI 4.8-5.9) in all cases including those with fetal deaths. Neonatal outcomes showed that the overall neonatal mortality was 26.4 % (95 % CI 16.7-39.2). When focusing only on pregnancies undergoing sTOP, the observed livebirth rate was 87.7 %. The gestational age at rupture of membranes in these cases was 16.8 (95 % CI 14.9-18.6) weeks and the latency between PROM and delivery was significantly longer (19.9 (95 % CI 18.0-21.7) weeks) than that observed in unterminated pregnancies, with a mean gestational age at delivery nearly in the range of term (36.9 weeks)., Conclusions: PROM in twins before 26 weeks is associated with overall high rates of adverse obstetric and neonatal outcomes, and it represents a clinical challenge for both counseling and management. Larger prospective studies unified objective protocols in terms of antenatal surveillance and management are needed., 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 The Author(s). Published by Elsevier B.V. All rights reserved.)

Objective: The aim of this systematic review and meta-analysis was to assess whether early discharge from hospital after cesarean delivery (CD) affects the rate of maternal readmission., Data Source: The research was conducted using PubMed, Embase, Web of Sciences, Scopus, ClinicalTrials.gov, and the Cochrane Central Register of Controlled Trials as electronic databases, from the inception of each database to August 2023 with RCT as publication type. No restrictions for language or geographic location were applied., Study Eligibility Criteria: Selection criteria included only RCTs comparing the effect of earlier versus later hospital discharge after CD., Study Appraisal and Synthesis Methods: The primary outcome was the rate of maternal readmission. The summary measures were reported as relative risk (RR) or as mean difference (MD) with 95% confidence intervals (CI) using the random effects model of Mentel-Haenszel. I-squared (Higgins I 2 ) greater than 0% was used to identify heterogeneity. "Early" and "late" hospital discharge was first considered according to each study's definition and then a subgroup analysis was performed including only studies defining as "early" a discharge within 24-28 hours and "late" a discharge at ≥48 hours after CD. The study was registered on PROSPERO (CRD 42024529885)., Results: Seven RCTs including 4,267 individuals, of which 2,125 (49.8%) randomized in the early discharge and 2,142 (50.2%) in the late discharge group were included. There was no difference between the two groups in the rate of maternal readmission (3.6% vs. 3.4%, RR 1.10; 95% CI 0.80-1.52). There was no significant difference in both maternal complications diagnosed within 6 weeks after CD and neonatal complications. Early discharge after CD was associated with improved psychological wellbeing and was cost-effective. The subgroup analysis of the primary outcomes only in high-quality studies showed similar results: no difference in the rate of maternal readmission was observed (3.8% vs. 3.2%, RR 1.20; 95% CI 0.63-2.30) between the two groups. When focusing only on studies comparing 24-28-hour versus ≥ 48-hour hospital discharge, the rate of maternal readmission did not differ between the two groups, while the rates of neonatal readmission and neonatal jaundice were significantly higher in the early discharge group., Conclusions: There is no increase in the rate of maternal readmission following early hospital discharge at 24-28 hours as opposed to later hospital discharge after a CD. The rates of neonatal readmission and neonatal jaundice were significantly higher in the early discharge group. Patients undergoing uncomplicated CDs might be discharged from the hospital at 24-28 hours postpartum, as long as close neonatal outpatient follow-up is done in 1-2 days; if this is unfeasible, discharge at 48 hours seems to be safe and effective for both mother and baby. Early discharge after CD was associated with improved psychological wellbeing and was cost-effective., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Fetal magnetic resonance imaging (fMRI) represents a second-line imaging modality that provides multiparametric and multiplanar views that are crucial for confirming diagnoses, detecting associated pathologies, and resolving inconclusive ultrasound findings. The introduction of high-field magnets and new imaging sequences has expanded MRI's role in pregnancy management. Recent innovations in ECG-gating techniques have revolutionized the prenatal evaluation of congenital heart disease by synchronizing imaging with the fetal heartbeat, thus addressing traditional challenges in cardiac imaging. Fetal cardiac MRI (fCMR) is particularly valuable for assessing congenital heart diseases, especially when ultrasound is limited by poor imaging conditions. fCMR allows for detailed anatomical and functional evaluation of the heart and great vessels and is also useful for diagnosing additional anomalies and analyzing blood flow patterns, which can aid in understanding abnormal fetal brain growth and placental perfusion. This review emphasizes fMRI's potential in evaluating cardiac and thoracic structures, including various gating techniques like metric optimized gating, self-gating, and Doppler ultrasound gating. The review also covers the use of static and cine images for structural and functional assessments and discusses advanced techniques like 4D-flow MRI and T1 or T2 mapping for comprehensive flow quantification and tissue characterization.

Background: Glucose-6-phosphate dehydrogenase (G6PD) deficiency is an X-linked recessive disorder that predisposes individuals to hemolysis due to an inborn error of metabolism. We performed a systematic literature review to evaluate G6PD deficiency as a possible etiology of nonimmune hydrops fetalis (NIHF) and severe fetal anemia., Methods: PubMed, OVID Medline, Scopus, and clinicaltrials.gov were queried from inception until 31 April 2023 for all published cases of NIHF and severe fetal anemia caused by G6PD deficiency. Keywords included "fetal edema," "hydrops fetalis," "glucose 6 phosphate dehydrogenase deficiency," and "fetal anemia." Cases with workup presuming G6PD deficiency as an etiology for NIHF and severe fetal anemia were included. PRISMA guidelines were followed., Results: Five cases of G6PD-related NIHF and one case of severe fetal anemia were identified. Four fetuses (4/6, 66.7%) were male and two fetuses (2/6, 33.3%) were female. Mean gestational age at diagnosis of NIHF/anemia and delivery was 32.2 ± 4.9 and 35.7 ± 2.4 weeks, respectively. Four cases (66.7%) required a cordocentesis for fetal transfusion, and two cases (33.3%) received blood transfusions immediately following delivery. Among the four multigravida cases, two (50%) noted previous pregnancies complicated by neonatal anemia. When reported, the maternal cases included two G6PD deficiency carrier patients and two G6PD-deficient patients. Exposures to substances known to cause G6PD deficiency-related hemolysis occurred in 3/6 (50%) cases., Conclusion: Six cases of NIHF/severe fetal anemia were associated with G6PD deficiency. While G6PD deficiency is an X-linked recessive condition, female fetuses can be affected. Fetal G6PD deficiency testing can be considered if parental history indicates, particularly if the standard workup for NIHF is negative., (© 2024 The Author(s). Molecular Genetics & Genomic Medicine published by Wiley Periodicals LLC.)

The aim of this systematic review is to report the normal cortical development of different fetal cerebral fissures on ultrasound, describe associated anomalies in fetuses with cortical malformations, and evaluate the quality of published charts of cortical fissures. The inclusion criteria were studies reporting development, anomalies, and reference charts of fetal cortical structures on ultrasound. The outcomes observed were the timing of the appearance of different cortical fissures according to different gestational age windows, associated central nervous system (CNS) and extra-CNS anomalies detected at ultrasound in fetuses with cortical malformation, and rate of fetuses with isolated anomaly. Furthermore, we performed a critical evaluation of the published reference charts for cortical development on ultrasound. Random-effect meta-analyses of proportions were used to combine the data. Twenty-seven studies (6875 fetuses) were included. Sylvian fissure was visualized on ultrasound in 97.69% (95% CI 92.0-100) of cases at 18-19, 98.17% (95% CI 94.8-99.8) at 20-21, 98.94% (95% CI 97.0-99.9) at 22-23, and in all cases from 24 weeks of gestation. Parieto-occipital fissure was visualized in 81.56% (95% CI 48.4-99.3) of cases at 18-19, 96.59% (95% CI 83.2-99.8) at 20-21, 96.85% (95% CI 88.8-100) at 22-23, and in all cases from 24 weeks of gestation, while the corresponding figures for calcarine fissure were 37.27% (95% CI 0.5-89.6), 80.42% (95% CI 50.2-98.2), 89.18% (95% CI 74.0-98.2), and 96.02% (95% CI 96.9-100). Malformations of cortical development were diagnosed as an isolated finding at ultrasound in 6.21% (95% CI 2.9-10.9) of cases, while they were associated with additional CNS anomalies in 93.79% (95% CI 89.1-97.2) of cases. These findings highlight the need for large studies specifically looking at the timing of the appearance of the different brain sulci. Standardized algorithms for prenatal assessment of fetuses at high risk of malformations of cortical development are also warranted.

Background: As resources into gynecological surgical simulation training increase, research showing an association with improved clinical outcomes is needed., Objective: To evaluate the association between surgical simulation training for total laparoscopic hysterectomy (TLH) and rates of intraoperative vascular/visceral injury (primary outcome) and operative time., Search Strategy: We searched Medline OVID, Embase, Web of Science, Cochrane, and CINAHL databases from the inception of each database to April 5, 2022. Selection Critera: Randomized controlled trials (RCTs) or cohort studies of any size published in English prior to April 4, 2022., Data Collection and Analysis: The summary measures were reported as relative risks (RR) or as mean differences (MD) with 95% confidence intervals using the random effects model of DerSimonian and Laird. A Higgins I2 >0% was used to identify heterogeneity. We assessed risk of bias using the Cochrane Risk of Bias tool 2.0 (for RCTs) and the Newcastle Ottawa Scale (for cohort studies)., Main Results: The primary outcome of this systematic review and meta-analysis was to evaluate the impact of simulation training on the rates of vessel/visceral injury in patients undergoing TLH. Of 989 studies screened 3 (2 cohort studies, 1 randomized controlled trial) met the eligibility criteria for analysis. There was no difference in vessel/visceral injury (OR 1.73, 95% CI 0.53-5.69, p=0.36) and operative time (MD 13.28, 95% CI -6.26 to 32.82, p=0.18) when comparing before and after simulation training., Conclusion: There is limited evidence that simulation improves clinical outcomes for patients undergoing TLH.

Objective: Counseling of pregnancies complicated by pre- and periviable premature rupture of membranes to reach shared decision-making is challenging, and the current limited evidence hampers the robustness of the information provided. This study aimed to elucidate the rate of obstetrical and neonatal outcomes after expectant management for premature rupture of membranes occurring before or at the limit of viability., Data Sources: Medline, Embase, CINAHL, and Web of Science databases were searched electronically up to September 2023., Study Eligibility Criteria: Our study included both prospective and retrospective studies of singleton pregnancies with premature rupture of membranes before and at the limit of viability (ie, occurring between 14 0/7 and 24 6/7 weeks of gestation)., Methods: Quality assessment of the included studies was performed using the Newcastle-Ottawa Scale for cohort studies. Moreover, our study used meta-analyses of proportions to combine data and reported pooled proportions. Given the clinical heterogeneity, a random-effects model was used to compute the pooled data analyses. This study was registered with the International Prospective Register of Systematic Reviews database (registration number: CRD42022368029)., Results: The pooled proportion of termination of pregnancy was 32.3%. After the exclusion of cases of termination of pregnancy, the rate of spontaneous miscarriage or fetal demise was 20.1%, whereas the rate of live birth was 65.9%. The mean gestational age at delivery among the live-born cases was 27.3 weeks, and the mean latency between premature rupture of membranes and delivery was 39.4 days. The pooled proportion of cesarean deliveries was 47.9% of the live-born cases. Oligohydramnios occurred in 47.1% of cases. Chorioamnionitis occurred in 33.4% of cases, endometritis in 7.0%, placental abruption in 9.2%, and postpartum hemorrhage in 5.3%. Hysterectomy was necessary in 1.2% of cases. Maternal sepsis occurred in 1.5% of cases, whereas no maternal death was reported in the included studies. When focusing on neonatal outcomes, the mean birthweight was 1022.8 g in live-born cases. The neonatal intensive care unit admission rate was 86.3%, respiratory distress syndrome was diagnosed in 66.5% of cases, pulmonary hypoplasia or dysplasia was diagnosed in 24.0% of cases, and persistent pulmonary hypertension was diagnosed in 40.9% of cases. Of the surviving neonates, the other neonatal complications included necrotizing enterocolitis in 11.1%, retinopathy of prematurity in 27.1%, and intraventricular hemorrhage in 17.5%. Neonatal sepsis occurred in 30.2% of cases, and the overall neonatal mortality was 23.9%. The long-term follow-up at 2 to 4 years was normal in 74.1% of the available cases., Conclusion: Premature rupture of membranes before or at the limit of viability was associated with a great burden of both obstetrical and neonatal complications, with an impaired long-term follow-up at 2 to 4 years in almost 30% of cases, representing a clinical challenge for both counseling and management. Our data are useful when initially approaching such patients to offer the most comprehensive possible scenario on short- and long-term outcomes of this condition and to help parents in shared decision-making. El resumen está disponible en Español al final del artículo., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: To report the outcome of fetuses with a prenatal diagnosis of congenital lung malformation (CLM) diagnosed on ultrasound by performing a comprehensive assessment of these outcomes through a systematic review and meta-analysis., Content: CLMs are a heterogeneous group of anomalies that involve the lung parenchyma and its bronchovascular structures. Their presentation and evolution are variable, from entirely asymptomatic lesions with sonographic regression in utero to hydropic fetuses requiring fetal therapy, intrauterine death or neonatal morbidity. A systematic review was conducted in Medline, Embase and Cochrane databases including studies on fetuses with CLM diagnosed prenatally in order to report the in-utero natural history of these lesions. Thirty-nine studies (2,638 fetuses) were included in the final review., Summary: Regression/reduction in size of the lung lesion during pregnancy was reported in 31 % of cases, while its increase in 8.5 % of cases. Intra-uterine death complicated 1.5 % of pregnancies with fetal CLM, while neonatal and perinatal death were 2.2 and 3 %, respectively. Neonatal morbidity occurred in 20.6 % of newborns with CLM; 46 % had surgery, mainly elective. In fetuses with CLM and hydrops, fetal/perinatal loss occurred in 42 %. Assessment of the role of fetal therapy in improving the outcomes of pregnancies complicated by CLM was hampered by the small number of included cases and heterogeneity of type of interventions., Outlook: Fetuses with CLM prenatally diagnosed have a generally favorable outcome. Conversely, there is a low quality of evidence on the actual role of fetal therapy in improving the outcome of fetuses presenting with these anomalies., (© 2024 Walter de Gruyter GmbH, Berlin/Boston.)

Although the clinical work-up of CMV in pregnancy has gradually become more accurate, counseling for CMV is still challenging. Despite the potential feasibility of universal prenatal serological screening, its introduction in prenatal diagnosis continues to raise concerns related to its real cost-effectiveness. Contextually, anticipating the confirmation of fetal infection earlier in pregnancy is one of the most pressing issues to reduce the parental psychological burden. Amniocentesis is still the gold standard and recent data have demonstrated that it could be performed before 20 weeks of gestation, provided that at least 8 weeks have elapsed from the presumed date of maternal seroconversion. New approaches, such as chorionic villus sampling (CVS) and virome DNA, even if not yet validated as confirmation of fetal infection, have been studied alternatively to amniocentesis to reduce the time-interval from maternal seroconversion and the amniocentesis results. Risk stratification for sensorineural hearing loss (SNHL) and long-term sequelae should be provided according to the prognostic predictors. Nevertheless, in the era of valacyclovir, maternal high-dose therapy, mainly for first trimester infections, can reduce the risk of vertical transmission and increase the likelihood of asymptomatic newborns, but it is still unclear whether valacyclovir continues to exert a beneficial effect on fetuses with positive amniocentesis. This review provides updated evidence-based key counseling points with GRADE recommendations., 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 The Author(s). Published by Elsevier B.V. All rights reserved.)

Introduction: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has been a major global health problem since December 2019. This work aimed to investigate whether pregnant women's mild and moderate SARS-CoV-2 infection was associated with microstructural and vascular changes in the placenta observable in vivo by Intravoxel Incoherent Motion (IVIM) at different gestational ages (GA)., Methods: This was a retrospective, nested case-control of pregnant women during the SARS-CoV-2 pandemic (COVID-19 group, n = 14) compared to pre-pandemic healthy controls (n = 19). MRI IVIM protocol at 1.5T was constituted of diffusion-weighted (DW) images with TR/TE = 3100/76 ms and 10 b-values (0,10,30,50,75,100,200,400,700,1000s/mm2). Differences between IVIM parameters D (diffusion), and f (fractional perfusion) quantified in the two groups were evaluated using the ANOVA test with Bonferroni correction and linear correlation between IVIM metrics and GA, COVID-19 duration, the delay time between a positive SARS-CoV-2 test and MRI examination (delay-time exam+) was studied by Pearson-test., Results: D was significantly higher in the COVID-19 placentas compared to that of the age-matched healthy group (p < 0.04 in fetal and p < 0.007 in maternal site). No significant difference between f values was found in the two groups suggesting no-specific microstructural damage with no perfusion alteration (potentially quantified by f) in mild/moderate SARS-Cov-2 placentas. A significant negative correlation was found between D and GA in the COVID-19 placentas whereas no significant correlation was found in the control placentas reflecting a possible accelerated senescence process due to COVID-19., Discussion: We report impaired microstructural placental development during pregnancy and the absence of perfusion-IVIM parameter changes that may indicate no perfusion changing through microvessels and microvilli in the placentas of pregnancies with mild/moderate SARS-Cov-2 after reaching negativity., 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 article., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective: There are over 145 million births worldwide, with over 30 million cesarean deliveries yearly. There are limited data comparing the perinatal and maternal outcomes between planned cesarean delivery and planned vaginal delivery. This study aimed to evaluate perinatal and maternal morbidity and mortality by meta-analysis of randomized controlled trials that randomly assigned patients to either planned cesarean delivery or planned vaginal delivery., Data Sources: Scopus, PubMed, CINAHL, Cochrane Library, and the World Health Organization clinical trial databases were searched from inception through August 2022., Study Eligibility Criteria: Randomized controlled trials that compared planned cesarean delivery with planned vaginal delivery at any gestational age and for any delivery indication were included., Methods: Two authors independently extracted data. PRISMA guidelines were used for data extraction and quality assessment. The primary outcome was perinatal mortality. The summary measures were reported as relative risks or as mean differences with 95% confidence intervals. Pooled odds ratios and 95% confidence intervals were calculated using Mantel-Haenszel random-effects models for outcomes., Results: In 15 primary randomized controlled trials, 3265 patients were randomized to planned cesarean delivery and 3353 to planned vaginal delivery. The incidence of perinatal deaths was not different (1.3% vs 1.3%; relative risk, 0.71; 95% confidence interval, 0.33-1.52). Planned cesarean delivery was associated with lower neonatal incidences of low umbilical artery pH (0.3% vs 2.4%; relative risk, 0.18; 95% confidence interval, 0.05-0.67), birth trauma (0.3% vs 0.7%; relative risk, 0.46; 95% confidence interval, 0.22-0.96), tube feeding requirement (2.5% vs 7.1%; relative risk, 0.36; 95% confidence interval, 0.19-0.66), and hypotonia (0.4% vs 3.5%; relative risk, 0.11; 95% confidence interval, 0.03-0.47), compared to planned vaginal delivery. Chorioamnionitis was less frequent in the planned cesarean delivery group (0.3% vs 1.0%; relative risk, 0.27; 95% confidence interval, 0.08-0.98). Wound infection was more common in the planned cesarean delivery group (1.9% vs 1.1%; relative risk, 1.61; 95% confidence interval, 1.04-2.52). Lower rates were observed in the planned cesarean delivery group for urinary incontinence at both ≤3 months (8.7% vs 12.2%; relative risk, 0.71; 95% confidence interval, 0.59-0.85) and 1 to 2 years (16.9% vs 22%; relative risk, 0.77; 95% confidence interval, 0.67-0.88) and for a painful perineum at 2 years (4% vs 6.2%; relative risk, 0.64; 95% confidence interval, 0.47-0.87) compared to planned vaginal delivery. Among singleton pregnancies, planned cesarean delivery was associated with a lower rate of perinatal death (0.69% vs 1.81%; relative risk, 0.45; 95% confident interval, 0.21-0.93)., Conclusion: Planned cesarean delivery and planned vaginal delivery were associated with similar rates of perinatal and maternal mortality in this meta-analysis of randomized controlled trials. Planned cesarean delivery was associated with significant decreases in adverse neonatal outcomes such as low umbilical artery pH, birth trauma, tube feeding requirement, and hypotonia, and significant decreases in chorioamnionitis, urinary incontinence, and painful perineum. Planned vaginal delivery was associated with significant decreases in need for general anesthesia and wound infection. Further randomized trials are needed to assess the risks and benefits of planned cesarean delivery vs planned vaginal delivery in lower-risk patients and in the general population., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objectives: The primary objective was to evaluate the effects of fetal sex on fetal cortical development in low-risk pregnancies. Secondary objective was the evaluate the impact of gestational age., Methods: This was a secondary analysis of a prospective cross-sectional study on low-risk fetuses undergoing fetal neurosonography between 19 and 34 weeks of gestation. The depth of Sylvian Fissure (SF), Parieto Occipital Fissure (POF) and Calcarine Fissure (CF) were evaluated and related to fetal sex. Neurosonographic variables were normalized for fetal head circumference and expressed as multiple of the median (MoM)., Results: A total of 344 fetuses were considered (173 male, 171 female). The baseline characteristic of the two groups were similar except a higher birthweight present in male fetuses (p=0.044). The depth SF (p=0.023) CF (p=0.014) and POF (p=0.046) showed significantly higher values in male fetuses when all the gestational age range was considered. However, when data were controlled for gestational age, these differences resulted significant only after 28 weeks., Conclusions: Differences in cortical development related to gender occur after 28 weeks of gestation with an increase depth of SF, POF and CF in male fetuses., (© 2023 Walter de Gruyter GmbH, Berlin/Boston.)

Objective: This study aimed to evaluate the rate of adverse neonatal or maternal outcomes in parturients with fetal heart rate tracings categorized as I, II or, III within the last 30 to 120 minutes of delivery., Data Sources: The MEDLINE Ovid, Scopus, Embase, CINAHL, and Clinicaltrials.gov databases were searched electronically up to May 2022, using combinations of the relevant medical subject heading terms, keywords, and word variants that were considered suitable for the topic., Study Eligibility Criteria: Only observational studies of term infants reporting outcomes of interest with category I, II, or III fetal heart rate tracings were included., Study Appraisal and Synthesis Methods: The coprimary outcome was the rate of either Apgar score <7 at 5 minutes or umbilical artery pH <7.00. Secondary outcomes were divided into neonatal and maternal adverse outcomes. Quality assessment of the included studies was performed using the Newcastle-Ottawa Scale. Random-effect meta-analyses of proportions were used to estimate the pooled rates of each categorical outcome in fetal heart rate tracing category I, II, and III patterns, and random-effect head-to-head meta-analyses were used to directly compare fetal heart rate tracings category I vs II and fetal heart rate tracing category II vs III, expressing the results as summary odds ratio or as mean differences with relative 95% confidence intervals., Results: Of the 671 articles reviewed, 3 publications met the inclusion criteria. Among them were 47,648 singletons at ≥37 weeks' gestation. Fetal heart rate tracings in the last 30 to 120 minutes before delivery were characterized in the following manner: 27.0% of deliveries had category I tracings, 72.9% had category II tracings, and 0.1% had category III tracings. A single study, which was rated to be of poor quality, contributed 82.1% of the data and it did not provide any data for category III fetal heart rate tracings. When compared with category I fetal heart rate tracings (0.74%), the incidence of an Apgar score <7 at 5 minutes were significantly higher among deliveries with category II fetal heart rate tracings (1.51%) (odds ratio, 1.56; 95% confidence interval, 1.23-1.99) and among those with category III tracings (14.63%) (odds ratio, 14.46; 95% confidence interval, 2.77-75.39). When compared with category II tracings, category III tracings also had a significantly higher likelihood of a low Apgar score at 5 minutes (odds ratio, 14.46; 95% confidence interval, 2.77-75.39). The incidence of an umbilical artery pH <7.00 were similar among those with category I and those with category II tracings (0.08% vs 0.24%; odds ratio, 2.85; 95% confidence interval, 0.41-19.55). When compared with category I tracings, the incidence of an umbilical artery pH <7.00 was significantly more common among those with category III tracings (31.04%; odds ratio, 161.56; 95% confidence interval, 25.18-1036.42); likewise, when compared with those with category II tracings, those with category III tracings had a significantly higher likelihood of having an umbilical artery pH <7.00 (odds ratio, 42.29; 95% confidence interval, 14.29-125.10). Hypoxic-ischemic encephalopathy occurred with similar frequency among those with categories I and those with category II tracings (0 vs 0.81%; odds ratio, 5.86; 95% confidence interval, 0.75-45.89) but was significantly more common among those with category III tracings (0 vs 18.97%; odds ratio, 61.43; 95% confidence interval, 7.49-503.50). Cesarean delivery occurred with similar frequency among those with category I (13.41%) and those with category II tracings (11.92%) (odds ratio, 0.87; 95% confidence interval, 0.72-1.05) but was significantly more common among those with with category III tracings (14.28%) (odds ratio, 3.97; 95% confidence interval, 1.62-9.75). When compared with those with category II tracings, cesarean delivery was more common among those with category III tracings (odds ratio, 4.55; 95% confidence interval, 1.88-11.01)., Conclusion: Although the incidence of an Apgar score <7 at 5 minutes and umbilical artery pH <7.00 increased significantly with increasing fetal heart rate tracing category, about 98% of newborns with category II tracings do not have these adverse outcomes. The 3-tiered fetal heart rate tracing interpretation system provides an approximate but imprecise measurement of neonatal prognosis., (Copyright © 2023 Elsevier Inc. All rights reserved.)

To evaluate obstetrical outcomes for women having late amniocentesis (on or after 24 weeks). Electronic databases were searched from inception to January 1st, 2023. The obstetrical outcomes evaluated were gestational age at delivery, preterm birth (PTB) < 37 weeks, PTB within 1 week from amniocentesis, premature prelabor rupture of membranes (pPROM), chorionamnionitis, placental abruption, intrauterine fetal demise (IUFD) and termination of pregnancy (TOP). The incidence of PTB <37 weeks was 4.85% (95% CI 3.48-6.56), while the incidence of PTB within 1 week was 1.42% (95% CI 0.66-2.45). The rate of pPROM was 2.85% (95% CI 1.21-3.32). The incidence of placental abruption was 0.91% (95% CI 0.16-2.25), while the rate of IUFD was 3.66% (95% CI 0.00-14.04). The rate of women who underwent TOP was 6.37% (95%CI 1.05-15.72). When comparing amniocentesis performed before or after 32 weeks, the incidence of PTB within 1 week was 1.48% (95% CI 0.42-3.19) and 2.38% (95% CI 0.40-5.95). Amniocentesis performed late after 24 weeks of gestation is an acceptable option for patients needing prenatal diagnosis in later gestation., (© 2023 John Wiley & Sons Ltd.)

Objective: To evaluate maternal and perinatal outcomes of removal versus retention of cervical cerclage after premature preterm rupture of membranes (pPROM)., Study Design: Medline, Embase and Cochrane databases were searched electronically on February 2023 utilizing combinations of the relevant medical subject heading (MeSH) terms, keywords, and word variants that were considered suitable for the topic. Either prospective or retrospective trials were considered suitable for the inclusion. The coprimary outcome of this study were pregnancy latency >7 days from pPROM and pregnancy latency >48 h from pPROM. Random effect head to-head meta-analyses were performed to directly compare each outcome, expressing the results as summary odds ratio (OR) for dichotomous outcomes and as mean difference (MD) for continuous outcomes, plus relative 95% confidence interval (CI). Quality assessment of the included studies was performed using the Newcastle-Ottawa Scale., Results: Six studies involving a total of 377 women (169 in the "removal" and 208 in the "retention" group) were included. The rate of pregnancy prolongation >48 h was significantly lower in the removal compared to retention group (OR 0.15, 95% CI 0.07-0.31; p < 0.0001), as well as the rate of pregnancy prolongation >7 days (OR 0.30 95% CI 0.11-0.83; p = 0.02) and pregnancy latency expressed in days (MD -2.84 days, 95% CI -5.40 to -0.29; p = 0.03). The rate of chorioamnionitis was significantly lower in the removal compared to the retention group (OR 0.57 95% CI 0.34-0.96p = 0.03) as was the rate of Apgar score < 7 at 5 min (OR 0.22 95% CI 0.08-0.56; p = 0.002). There was no difference between removal and retention groups for all the other maternal and perinatal outcomes., Conclusions: The decision whether to remove or retain cerclage in case of pPROM should balance the prematurity-related risks with that of infectious complications, thus highlighting the need for tailored management based on gestational age at occurrence of pPROM., 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 © 2023 Elsevier B.V. All rights reserved.)

Echogenic fetal bowel (EB) is a prenatal ultrasound finding (0.2%-1.4% of all pregnancies) defined as bowel of similar or greater echogenicity than surrounding bone. In fact, the ultrasound assessment is strongly subjective with inter-observer variability. The pathophysiology depends on the underlying condition, apparently related with meconium stasis and hypercellularity. It is often an isolated finding, with possible association with other structural anomalies. About the origin, it was observed in fetuses with cystic fibrosis, congenital infections, thalassemia, intraamniotic bleeding, fetal growth restriction. Fetuses with EB are at increased risk of adverse perinatal outcome, such as intrauterine growth restriction, placental dysfunction and perinatal death, highlighting the need for a thorough antenatal management and post-natal follow-up. It seems to be associated with a plenty of conditions, such as a poor fetal outcome, fetal growth restriction and placental dysfunction. Therefore management requires a multidisciplinary approach with different specialties' involvement and the prognosis is influenced by the underlying pathophysiology. In this complex scenario, the present review aims to define the clinical pathway which should be offered to pregnant women in case of finding of fetal EB ultrasound marker, to rule out any suspected pathological cause., (© 2023 The Authors. Journal of Clinical Ultrasound published by Wiley Periodicals LLC.)

Objectives: To develop charts for fetal brain cortical structures following a proposed standardized methodology and using quantile regression., Methods: Prospective cross-sectional study including 344 low-risk singleton pregnancies between 19 and 34 weeks of gestation. The depth of Sylvian (SF), Parieto-occipital (POF) and Calcarine fissures (CF) were measured on ultrasound images using a standardized technique and their changes were evaluated by quantile regression as a function of gestational age (GA) interval or head circumference (HC)., Results: The measurements of SF, POF and CF depth significantly increased with gestation. Linear models better described the changes of cortical variables with GA and HC. When the fit of sulci depth with GA and HC were compared, a close relationship was highlighted for the latter variable., Conclusions: We provided prospective charts of fetal cortical development using quantile regression and following a strict standardized methodology These new charts may help in better identifying cases at higher risk of abnormal cortical neurodevelopment., (© 2023 Walter de Gruyter GmbH, Berlin/Boston.)

In the setting of postpartum care after vaginal delivery, rooming-in is associated with a higher rate of exclusive breastfeeding rate at hospital discharge, but there is insufficient evidence to support or refute rooming-in to increase breastfeeding at 6 months. Education and support for breastfeeding are valuable interventions to promote initiation of breastfeeding whether it is offered by a healthcare professional, nonhealthcare professional, or peer. A combined intervention, a professional provider-led intervention, having a protocol available for the provider training program, and implementation during both the prenatal and postnatal periods increased the rate of exclusive breastfeeding for 6 months. There is no single effective treatment for breast engorgement. Breast massage, continuing breastfeeding, and pain relief are recommended by national guidelines. Nonsteroidal anti-inflammatory drugs and acetaminophen are better than placebo for relief of pain caused by uterine cramping and perineal trauma; acetaminophen is effective in breastfeeding individuals who underwent episiotomy; and local cooling pain relievers have been shown to reduce perineal pain for 24 to 72 hours, compared with no treatment. There is insufficient evidence to assess the safety and efficacy of postpartum routine universal thromboprophylaxis after vaginal delivery. Anti-D immune globulin administration is recommended in Rhesus-negative individuals who have given birth to a Rhesus-positive infant. There is very low-quality evidence that a universal complete blood count is useful in reducing the risk of receiving blood products. In the absence of any postpartum complication, there is insufficient evidence to recommend a routine postpartum ultrasound. Measles, mumps, and rubella combination; varicella; human papillomavirus; and tetanus, diphtheria, and pertussis vaccines should be administered in nonimmune individuals in the postpartum period. Smallpox and yellow fever vaccines should be avoided. Individuals undergoing postplacental placement are more likely to use an intrauterine device at 6 months than those advised to follow-up for placement during outpatient postpartum care. An implant is safe and effective for immediate postpartum contraception. There is insufficient evidence to support or refute the routine administration of micronutrient supplements in breastfeeding women. Placentophagia does not provide any benefits and exposes mothers and offspring to infectious risks. Therefore, it should be discouraged. Because of the low level of evidence, there is insufficient data to assess the efficacy of home visits in the postpartum period. There is insufficient evidence to recommend when to resume daily activities, and individuals should be counseled to return to prepregnancy level of activity or exercise when comfortable. Sexual activity, housework exercise, driving, climbing stairs, and lifting weights should be resumed as soon as postpartum individuals want. A behavioral educational intervention reduces depression symptoms and increases breastfeeding duration. Physical activity after delivery is protective against postpartum mood disorders. There is no strong evidence that supports early discharge after vaginal delivery compared with standard discharge (ie, ≥48 hours)., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Introduction: Limited data on the role of pharmacotherapy for patients with locally advanced, recurrent, or metastatic vulvar cancer are available., Areas Covered: This article aims to provide an overview of the current treatment options for patients with vulvar cancer. PubMed (MEDLINE), Embase, CENTRAL, Scopus, and Web of Science databases, as well as ClinicalTrials.gov were searched to review the current evidence as well as future perspectives on the role of pharmacotherapy in patients with vulvar carcinoma., Expert Opinion: There has been no consensus on the pharmacotherapy for patients with locally advanced, recurrent, or metastatic vulvar cancer. Concurrent platinum-based chemoradiation is the most widely used treatment modality for primary treatment or for neoadjuvant settings. Chemotherapy in metastatic disease is considered a palliative treatment. Anti-EGFR tyrosine kinase inhibitors seem to show promising anti-tumor activity in patients harboring EGFR alteration. Similarly, growing evidence supports the adoption of immune checkpoint inhibitors in both neoadjuvant and metastatic settings. Molecular and genomic profiling is advocated to identify target mutations. The PI3K/AKT/mTOR and HER/ErbB pathways might represent two intriguing treatment options. Treatments directed against HPV are discussed as well. Further evidence is warranted to identify the best treatment modalities for patients with locally advanced, recurrent, and metastatic disease.

Introduction: The aim of the study was to report the prognostic value of cytomegalovirus (CMV) viral load in the amniotic fluid (AF) in predicting the outcome of infected pregnancies., Methods: Multicenter retrospective study involving 11 Italian referral centers from 2012 to 2021 was conducted. Inclusion criteria were fetuses with confirmed congenital CMV infection. The primary outcome was the prognostic value accuracy of CMV quantitative polymerase chain reaction (qPCR) in AF in predicting the risk of additional anomalies detected either at follow-up ultrasound or fetal magnetic resonance imaging (MRI). The secondary outcome was prediction of postnatal clinical symptoms related to CMV infection. Multivariate logistic regression and area under the curve (AUC) analyses were used to analyze the data., Results: 104 fetuses were included. Associated anomalies detected at follow-up ultrasound or fetal MRI were detected in 14.4% of cases (15/104). Mean AF CMV viral load was significantly higher in fetuses with additional anomalies compared to those without additional anomalies at follow-up ultrasound or fetal MRI (3,346,634.27 ± 402,582.95 vs. 761,934 ± 222513,2 p < 0.001). At multivariate logistic regression analysis, CMV AF viral load was independently associated with the presence of additional anomalies at follow-up ultrasound or MRI, with an OR of 1.07 (p = 0.010), while maternal age (p = 0.24), trimester at maternal infection (p = 0.97), and type of infection (primary vs. non-primary) (p = 0.12) were not. CMV AF viral load had AUC of 0.755 for the occurrence of anomalies due to CMV infection, with an optimal cut-off point of >1,310,520 copies/mL, a sensitivity of 66.7%, a specificity of 84.3%, and a positive likelihood ratio of 4.24. Once excluding fetuses with anomalies at ultrasound or MRI, the diagnostic performance of qPCR in identifying fetuses with symptomatic infection after birth was low, with an AUC of 0.586., Conclusion: CMV viral load at second trimester amniocentesis has a moderate accuracy for the occurrence of CMV-related anomalies in fetuses with congenital infection and normal ultrasound at the initial diagnosis. Conversely, prediction of symptomatic infection is low., (© 2023 S. Karger AG, Basel.)

Objective: To investigate the role of fetal brain magnetic resonance imaging (MRI) in detecting associated anomalies in fetuses with congenital cytomegalovirus (CMV) infection and normal neurosonography., Methods: This was a multicenter, retrospective cohort study of patients examined between 2012 and 2021 in 11 referral fetal medicine centers in Italy. Inclusion criteria were fetuses with congenital CMV infection diagnosed by polymerase chain reaction analysis of amniotic fluid, pregnancies that underwent detailed multiplanar ultrasound assessment of the fetal brain as recommended by the International Society of Ultrasound in Obstetrics and Gynecology, maternal age ≥ 18 years, normal fetal karyotype and MRI performed within 3 weeks after the last ultrasound examination. The primary outcome was the rate of central nervous system (CNS) anomalies detected exclusively on MRI and confirmed after birth or autopsy in fetuses with a prenatal diagnosis of congenital CMV infection and normal neurosonography at diagnosis. Additional CNS anomalies were classified into anomalies of the ventricular and the periventricular zone, intracranial calcifications in the basal ganglia or germinal matrix, destructive encephalopathy in the white matter, malformations of cortical development, midline anomalies, posterior fossa anomalies and complex brain anomalies. We evaluated the relationship between the incidence of structural CNS malformations diagnosed exclusively on fetal MRI and a number of maternal and gestational characteristics. Univariate and multivariate logistic regression analyses were used to identify and adjust for potential independent predictors of the MRI diagnosis of fetal anomalies., Results: The analysis included 95 fetuses with a prenatal diagnosis of congenital CMV infection and normal neurosonography referred for prenatal MRI. The rate of structural anomalies detected exclusively at fetal MRI was 10.5% (10/95). When considering the type of anomaly, malformations of cortical development were detected on MRI in 40.0% (4/10) of fetuses, destructive encephalopathy in 20.0% (2/10), intracranial calcifications in the germinal matrix in 10.0% (1/10) and complex CNS anomalies in 30.0% (3/10). On multivariate logistic regression analysis, only CMV viral load in the amniotic fluid, expressed as a continuous variable (odds ratio (OR), 1.16 (95% CI, 1.02-1.21); P = 0.02) or categorical variable (> 100 000 copies/mL) (OR, 12.0 (95% CI, 1.2-124.7); P = 0.04), was independently associated with the likelihood of detecting fetal anomalies on MRI. Associated anomalies were detected exclusively at birth and missed by both prenatal neurosonography and fetal MRI in 3.8% (3/80) of fetuses with congenital CMV infection., Conclusions: Fetal brain MRI can detect additional anomalies in a significant proportion of fetuses with congenital CMV infection and negative neurosonography. Viral load in the amniotic fluid was an independent predictor of the risk of associated anomalies in these fetuses. The findings of this study support a longitudinal evaluation using fetal MRI in congenital CMV infection, even in cases with negative neurosonography at diagnosis. © 2022 International Society of Ultrasound in Obstetrics and Gynecology., (© 2022 International Society of Ultrasound in Obstetrics and Gynecology.)

Introduction: Ovarian cancer is one of the most lethal gynecological tumors with a lack of effective treatment modalities especially in advanced/recurrent disease. Nevertheless, recently, new small molecules have emerged as an effective approach for the management of ovarian cancer patients, especially in the maintenance setting., Areas Covered: This review summarizes the role of small molecules used in the management of high-grade serous ovarian cancer. The authors performed a critical review of current evidence and ongoing studies. Of note, tyrosine kinase inhibitors (TKIs) and poly(ADP-ribose) polymerase (PARP) inhibitors are the most intriguing medications in this setting., Expert Opinion: Protein-targeted therapies against tumor tissues have progressed significantly in the last years due to an enhanced knowledge of the biological and molecular processes of carcinogenesis. Treatment with small molecules allows the targeting of specific proteins involved in cancer biology. TKIs seem promising but further data are necessary to assess the pros and cons of adopting this treatment modality. PARP inhibitors represent the new standard of care for ovarian cancer patients harboring either a BRCA mutation or with homologous recombination deficiency (HRD). Interestingly, the accumulation of data has highlighted that PARP inhibitors provide benefits even in patients with HR proficient tumors.

Background: Cerebroplacental Doppler studies have been advocated to predict the risk of adverse perinatal outcome (APO) irrespective of fetal weight., Objective: To report the diagnostic performance of cerebroplacental (CPR) and umbilicocerebral (UCR) ratios in predicting APO in appropriate for gestational age (AGA) fetuses and in those affected by late fetal growth restriction (FGR) attempting vaginal delivery., Study Design: Multicenter, retrospective, nested case-control study between 1 January 2017 and January 2020 involving five referral centers in Italy and Spain. Singleton gestations with a scan between 36 and 40 weeks and within two weeks of attempting vaginal delivery were included. Fetal arterial Doppler and biometry were collected. The AGA group was defined as fetuses with an estimated fetal weight and abdominal circumference >10th and <90th percentile, while the late FGR group was defined by Delphi consensus criteria. The primary outcome was the prediction of a composite of perinatal adverse outcomes including either intrauterine death, Apgar score at 5 min <7, abnormal acid-base status (umbilical artery pH < 7.1 or base excess of more than -11) and neonatal intensive care unit (NICU) admission. Area under the curve (AUC) analysis was performed., Results: 646 pregnancies (317 in the AGA group and 329 in the late FGR group) were included. APO were present in 12.6% AGA and 24.3% late FGR pregnancies, with an odds ratio of 2.22 (95% CI 1.46-3.37). The performance of CPR and UCR for predicting APO was poor in both AGA [AUC: 0.44 (0.39-0.51)] and late FGR fetuses [AUC: 0.56 (0.49-0.61)]., Conclusions: CPR and UCR on their own are poor prognostic predictors of APO irrespective of fetal weight.

Introduction: The aim of our systematic review and meta-analysis was to evaluate the risk of neural tube defects (NTDs) according to the pre-pregnancy body mass index., Materials and Methods: Electronic databases were searched (MEDLINE, EMBASE, Web of Sciences, Scopus, ClinicalTrial.gov, OVID, and Cochrane Library). Selection criteria included prospective and retrospective cohort studies reporting the prevalence of fetal NTDs in obese, overweight, and underweight pregnant women. Odds ratios (ORs) comparing risk among these subsets of pregnancies with normal weight mothers were determined with 95% confidence intervals (CI). The evaluated outcome was the association between maternal underweight, overweight, and obesity and the risk of NTDs., Results: We included ten studies published between 2000 and 2017, including underweight, overweight, and obese pregnant women with fetal NTD (cases) and pregnant women with recommended BMI with fetal NTD (controls). Compared with normal BMI women, obese mothers were at significantly higher risk of fetal NTDs (0.53 vs. 0.33%; OR 1.62 95% CI 1.32-1.99, p  < .0001), while no difference for the risk of NTDs was found when comparing overweight (0.34 vs. 0.32%; OR 1.09 95% CI 0.92-1.3, p  = .3) and underweight (0.65 vs. 0.24%; OR 1.34 95% CI 0.73-2.47, p  = .34) with normal weight pregnant women., Discussion: Obese pregnant women are at significantly higher risk NTDs, while no significant difference has been found in overweight and underweight pregnant women. Key message Obese pregnant women are at significantly higher risk of NTDs, such as spina bifida compared with normal weight women. No difference was found when comparing overweight and underweight with normal weight women.

Objective: We aimed to decrease our surgical site infection (SSI) rate by 30% by sequential implementation of vaginal cleansing and azithromycin for women who underwent a cesarean delivery (CD) after having labored or experienced rupture of membranes., Methods: This is a quality improvement project that assessed the stepwise implementation of two interventions within three time periods: (1) 12 months prior to implementation of either intervention; (2) 14 months of vaginal cleansing as infection prophylaxis; (3) 16 months of vaginal cleansing and azithromycin as infection prophylaxis. The primary outcome measure was the SSI as defined by the Center for Disease Control and Prevention and analyzed by control charts. The process measures were compliance rates of vaginal cleansing and azithromycin. Significance was detected by rules for determining a special cause variation. This study followed the SQUIRE 2.0 guidelines for reporting on quality improvement., Results: There were 1033 patients included from the three study periods. The total rate of SSI decreased from 22.8% to 15.2% after implementing vaginal cleansing. Special cause variation was detected with an 8-point shift starting 4 months after implementation of vaginal cleansing. This decrease was sustained during the following 26 months. Adding azithromycin did not significantly lower the SSI rate further. When examined separately, deep SSI ( p = .009) and endometritis ( p = .001) significantly decreased in the post-intervention periods. Pre-operative vaginal cleansing compliance rose to 74%, and then further increased to 85% 1 year after implementation. Azithromycin compliance rose to 75%. Total length of postpartum stay decreased over the study periods from 3.5 ± 1.4 days to 3.2 ± 0.8 days ( p  = .001)., Conclusion: In this quality improvement study, implementation of vaginal cleansing decreased the SSI rate by 33%, from 22.8% to 15.2%. The addition of azithromycin did not result in any additional change in SSI rate.

Background: Congenital heart diseases (CHDs) are often associated with significant neurocognitive impairment and neurological delay. This study aims to elucidate the correlation between type of CHD and Doppler velocimetry and to investigate the possible presence of fetal brain abnormalities identified by magnetic resonance imaging (MRI). Methods: From July 2010 to July 2020, we carried out a cross-sectional study of 63 singleton pregnancies with a diagnosis of different types of complex CHD: LSOL (left-sided obstructive lesions; RSOL (right-sided obstructive lesions) and MTC (mixed type of CHD). All patients underwent fetal echocardiography, ultrasound evaluation, a magnetic resonance of the fetal brain, and genetic counseling. Results: The analysis of 63 fetuses shows statistically significant results in Doppler velocimetry among the different CHD groups. The RSOL group leads to higher umbilical artery (UA-PI) pressure indexes values, whereas the LSOL group correlates with significantly lower values of the middle cerebral artery (MCA-PI) compared to the other subgroups ( p = 0.036), whereas the RSOL group shows a tendency to higher pulsatility indexes in the umbilical artery (UA-PI). A significant correlation has been found between a reduced head circumference (HC) and the presence of brain injury at MRI ( p = 0.003). Conclusions: Congenital left- and right-sided cardiac obstructive lesions are responsible for fetal hemodynamic changes and brain growth impairment. The correct evaluation of the central nervous system (CNS) in fetuses affected by CHD could be essential as prenatal screening and the prediction of postnatal abnormalities.

Objectives: To identify predictors of adverse perinatal outcome in congenital cytomegalovirus (CMV) infection., Methods: In a multicenter study fetuses with congenital CMV infection diagnosed by PCR on amniotic fluid and normal prenatal imaging at the time of diagnosis were included. Primary outcome was the occurrence of structural anomalies at follow-up ultrasound or prenatal magnetic resonance imaging (MRI). Secondary outcomes were the occurrence of anomalies detected exclusively postnatally and the rate of symptomatic infection., Results: One hundred and four fetuses with congenital CMV were included in the study. Anomalies were detected at follow-up ultrasound or MRI in 18.3% (19/104) cases. Additional anomalies were found after birth in 11.9% (10/84) of cases and 15.5% (13/85) of newborns showed clinical symptoms related to CMV infection. There was no difference in either maternal age (p=0.3), trimester (p=0.4) of infection and prenatal therapy (p=0.4) between fetuses with or whiteout anomalies at follow-up. Conversely, median viral load in the amniotic fluid was higher in fetuses with additional anomalies at follow-up (p=0.02) compared to those without. At multivariate logistic regression analysis, high viral load in the amniotic fluid, defined as ≥100,000 copies/mL was the only independent predictor for the occurrence of anomalies detected exclusively at follow-up ultrasound assessment or MRI, with an OR of 3.12., Conclusions: Viral load in the amniotic fluid is a strong predictor of adverse perinatal outcome in congenital CMV infection. The results of this study emphasize the importance of adequate follow up even in case of negative neurosonography to better predict postnatal adverse outcomes of infected newborns, especially in amniotic fluid high viral load., (© 2022 Walter de Gruyter GmbH, Berlin/Boston.)

Antibody-Drug Conjugates (ADCs) are growing in importance for the treatment of both solid and haematological malignancies. There is a demand for new payloads with novel mechanisms of action that may offer enhanced therapeutic efficacy, especially in patients who develop resistance. We report here a class of Cyclopropabenzindole-Pyridinobenzodiazepine (CBI-PDD) DNA cross-linking payloads that simultaneously alkylate guanine (G) and adenine (A) bases in the DNA minor groove with a defined sequence selectivity. The lead payload, FGX8-46 (6), produces sequence-selective G-A cross-links and affords cytotoxicity in the low picomolar region across a panel of 11 human tumour cell lines. When conjugated to the antibody cetuximab at an average Drug-Antibody Ratio (DAR) of 2, an ADC is produced with significant antitumour activity at 1 mg/kg in a target-relevant human tumour xenograft mouse model with an unexpectedly high tolerability (i.e., no weight loss observed at doses as high as 45 mg/kg i.v., single dose)., (© 2022. The Author(s).)

Objective: This systematic review and meta-analysis of randomized controlled trials aimed to assess whether negative pressure wound therapy affects the rate of wound complications when applied to women with obesity after cesarean delivery compared with standard postoperative dressings., Data Sources: This research used PubMed, Scopus, ClinicalTrials.gov, and the Cochrane Central Register of Controlled Trials as electronic databases, from the inception of each database to January 2021, with randomized controlled trial as the publication type. There was no restriction applied for language or geographic location., Study Eligibility Criteria: The selection criteria included only randomized controlled trials comparing the effect of negative pressure wound therapy with that of standard dressings on wound complications in women with obesity undergoing cesarean delivery., Methods: The primary outcome was a wound complication composite outcome (wound infection, separation or dehiscence, hematoma, seroma, or readmission secondary to a wound concern). The wound complication composite was analyzed by counting events once per patient. The summary measures were reported as relative risk or as mean difference with 95% confidence intervals using the random-effects model of DerSimonian and Laird. An I-squared (Higgins I 2 ) value of >0% was used to identify heterogeneity., Results: Overall, 11 randomized controlled trials, which included 5746 participants with obesity undergoing cesarean delivery, were included. Of those participants, 2869 (49.9%) were randomized to the intervention group (negative pressure wound therapy), and 2877 (50.1%) were randomized to the control group (standard dressing). Prophylactic negative pressure wound therapy was not associated with a significant change in the rate of wound complications (relative risk, 1.00; 95% confidence interval, 0.81-1.23) compared with standard postoperative dressings. However, the use of negative pressure wound therapy decreased the rate of wound infections (relative risk, 0.79; 95% confidence interval, 0.66- 0.96) and increased the frequency of skin reactions (relative risk, 4.59; 95% confidence interval, 1.29-16.38). Negative pressure wound therapy did not result in a significant difference in the rate of dehiscence, hematoma, seroma, readmission, reoperation, and antibiotic use for wound infection., Conclusion: Compared with standard postoperative incision dressings, negative pressure wound therapy did not affect the rate of wound complications but decreased the frequency of wound infections when applied to women with obesity after cesarean delivery. However, results should be interpreted with caution, as wound infection outcome includes different definitions per the individual trials., Condensation: Prophylactic negative pressure wound therapy has no effect on overall wound complications in women with obesity after cesarean delivery compared with standard dressings., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objective: This study aimed to assess the efficacy of sonographic assessment of fetal occiput position before operative vaginal delivery to decrease the number of failed operative vaginal deliveries., Data Sources: The search was conducted in MEDLINE, Embase, Web of Science, Scopus, ClinicalTrial.gov, Ovid, and Cochrane Library as electronic databases from the inception of each database to April 2021. No restrictions for language or geographic location were applied., Study Eligibility Criteria: Selection criteria included randomized controlled trails of pregnant women randomized to either sonographic or clinical digital diagnosis of fetal occiput position during the second stage of labor before operative vaginal delivery., Methods: The primary outcome was failed operative vaginal delivery, defined as a failed fetal operative vaginal delivery (vacuum or forceps) extraction requiring a cesarean delivery or forceps after failed vacuum. The summary measures were reported as relative risks or as mean differences with 95% confidence intervals using the random effects model of DerSimonian and Laird. An I 2 (Higgins I 2 ) >0% was used to identify heterogeneity., Results: A total of 4 randomized controlled trials including 1007 women with singleton, term, cephalic fetuses randomized to either the sonographic (n=484) or clinical digital (n=523) diagnosis of occiput position during the second stage of labor before operative vaginal delivery were included. Before operative vaginal delivery, fetal occiput position was diagnosed as anterior in 63.5% of the sonographic diagnosis group vs 69.5% in the clinical digital diagnosis group (P=.04). There was no significant difference in the rate of failed operative vaginal deliveries between the sonographic and clinical diagnosis of occiput position groups (9.9% vs 8.2%; relative risk, 1.14; 95% confidence interval, 0.77-1.68). Women randomized to sonographic diagnosis of occiput position had a significantly lower rate of occiput position discordance between the evaluation before operative vaginal delivery and the at birth evaluation when compared with those randomized to the clinical diagnosis group (2.3% vs 17.7%; relative risk, 0.16; 95% confidence interval, 0.04-0.74; P=.02). There were no significant differences in any of the other secondary obstetrical and perinatal outcomes assessed., Conclusion: Sonographic knowledge of occiput position before operative vaginal delivery does not seem to have an effect on the incidence of failed operative vaginal deliveries despite better sonographic accuracy in the occiput position diagnosis when compared with clinical assessment. Future studies should evaluate how a more accurate sonographic diagnosis of occiput position or other parameters can lead to a safer and more effective operative vaginal delivery technique., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Blunt thoracic aortic injury (BTAI) is an uncommon yet serious diagnosis in trauma patients, with high on-scene mortality. BTAI typically occurs from rapid deceleration such as in motor vehicle collisions or high-altitude falls shearing the aorta just proximal to the ligamentum arteriosum. We report a case of a man in his 50s falling from a height of 15 m who presented hypotensive with retrosternal chest pain. Mobile chest X-ray showed a widened mediastinum with left-sided haemothorax. CT revealed a contained free aortic rupture just inferior to the origin of the left subclavian artery with bleeding into the mediastinum and left pleural space. The patient underwent urgent thoracic endovascular aortic repair (TEVAR) but arrested on-table due to a left-sided tension haemothorax requiring chest-drain decompression and haemostatic resuscitation. After return of spontaneous circulation, TEVAR was successfully performed. BTAI is a dynamic process; hence, timely imaging and minimally invasive surgical treatment are key to patients surviving grade III and IV aortic injuries., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To evaluate the methodology of studies reporting reference ranges for fetal brain structures on magnetic resonance imaging (MRI)., Methods: MEDLINE, EMBASE, CINAHL and the Web of Science databases were searched electronically up to 31 December 2020 to identify studies investigating biometry and growth of the fetal brain and reporting reference ranges for brain structures using MRI. The primary aim was to evaluate the methodology of these studies. A list of 26 quality criteria divided into three domains, including 'study design', 'statistical and reporting methods' and 'specific aspects relevant to MRI', was developed and applied to evaluate the methodological appropriateness of each of the included studies. The overall quality score of a study, ranging between 0 and 26, was defined as the sum of scores awarded for each quality criterion and expressed as a percentage (the lower the percentage, the higher the risk of bias)., Results: Fifteen studies were included in this systematic review. The overall mean quality score of the studies evaluated was 48.7%. When focusing on each domain, the mean quality score was 42.0% for 'study design', 59.4% for 'statistical and reporting methods' and 33.3% for 'specific aspects relevant to MRI'. For the 'study design' domain, sample size calculation and consecutive enrolment of women were the items found to be at the highest risk of bias. For the 'statistical and reporting methods' domain, the presence of regression equations for mean and SD for each measurement, the number of measurements taken for each variable and the presence of postnatal assessment information were the items found to be at the highest risk of bias. For the 'specific aspects relevant to MRI' domain, whole fetal brain assessment was not performed in any of the included studies and was therefore considered to be the item at the highest risk of bias., Conclusions: Most of the previously published studies reporting fetal brain reference ranges on MRI are highly heterogeneous and have low-to-moderate quality in terms of methodology, which is similar to the findings reported for ultrasound studies. © 2021 International Society of Ultrasound in Obstetrics and Gynecology., (© 2021 International Society of Ultrasound in Obstetrics and Gynecology.)

Objective: This study was aimed to report the incidence of neonatal morbidity in monochorionic monoamniotic (MCMA) twin pregnancies according to gestational age at birth and type of management adopted (inpatient or outpatient)., Study Design: Medline and Embase databases were searched. Inclusion criteria were nonanomalous MCMA twins. The primary outcome was a composite score of neonatal morbidity, defined as the occurrence of at least one of the following outcomes: respiratory morbidity, overall neurological morbidity, severe neurological morbidity, and infectious morbidity, necrotizing enterocolitis at different gestational age windows (24-30, 31-32, 33-34, and 35-36 weeks). Secondary outcomes were the individual components of the primary outcome and admission to neonatal intensive care unit (NICU). Subanalysis according to the type of surveillance strategy (inpatient compared with outpatient) was also performed. Random effect meta-analyses were used to analyze the data., Results: A total of 14 studies including 685 MCMA twin pregnancies without fetal anomalies were included. At 24 to 30, 31 to 32, 33 to 34, and 35 to 36 weeks of gestation, the rate of composite morbidity was 75.4, 65.5, 37.6, and 18.5%, respectively, the rate of respiratory morbidity was 74.2, 59.1, 35.5, and 12.2%, respectively, while overall neurological morbidity occurred in 15.3, 10.2, 4.3, and 0% of the cases, respectively. Infectious morbidity complicated 13, 4.2, 3.1, and 0% of newborns while 92.1, 81.6, 58.7, and 0% of cases required admission to NICU. Morbidity in pregnancies delivered between 35 and 36 weeks of gestation was affected by the very small sample size of cases included. When comparing the occurrence of overall morbidity according to the type of management (inpatient or outpatient), there was no difference between the two surveillance strategies ( p  = 0.114)., Conclusion: MCMA pregnancies are at high risk of composite neonatal morbidity, mainly respiratory morbidity that gradually decreases with increasing gestational age at delivery with a significant reduction for pregnancies delivered between 33 and 34 weeks. We found no difference in the occurrence of neonatal morbidity between pregnancies managed as inpatient or outpatient., Key Points: · MCMA pregnancies are at high risk of composite neonatal morbidity, mainly respiratory morbidity.. · Neonatal morbidity gradually decreases with increasing GA at delivery, mostly between 33 and 34 weeks.. · There is no difference in the occurrence of neonatal morbidity between in- or outpatient management.., Competing Interests: None declared., (Thieme. All rights reserved.)

Introduction: Several fetal brain charts have been published in the literature and are commonly used in the daily clinical practice. However, the methodological quality of these charts has not been critically appraised., Material and Methods: MEDLINE, EMBASE, CINAHL, and the Web of Science databases were searched electronically up to December 31, 2020. The primary outcome was to evaluate the methodology of the studies assessing the growth of fetal brain structures throughout gestation. A list of 28 methodological quality criteria divided into three domains according to "study design," "statistical and reporting methods," and "specific relevant neurosonography aspects" was developed in order to assess the methodological appropriateness of the included studies. The overall quality score was defined as the sum of low risk of bias marks, with the range of possible scores being 0-28. This quality assessment was applied to each individual study reporting reference ranges for fetal brain structures. Furthermore, we performed a subgroup analysis according to the different brain structures (ventricular and periventricular, fore-brain and midbrain cerebral and posterior fossa)., Results: Sixty studies were included in the systematic review. The overall mean quality score of the studies included in this review was 51.3%. When focusing on each of the assessed domains, the mean quality score was 53.7% for "study design," 54.2% for "statistical and reporting methods," and 38.6% for "specific relevant neurosonography aspects." The sample size calculation, the correlation with a postnatal imaging evaluation, and the whole fetal brain assessment were the items at the highest risk of bias for each domain assessed, respectively. The subgroup analysis according to different anatomical location showed the lowest quality score for ventricular and periventricular structures and the highest for cortical structures., Conclusions: Most previously published studies reporting fetal brain charts suffer from poor methodology and are at high risk of biases, mostly when focusing on neurosonography issues. Further prospective longitudinal studies aiming at constructing specific growth charts for fetal brain structures should follow rigorous methodology to minimize the risk of biases, guarantee higher levels of reproducibility, and improve the standard of care., (© 2022 S. Karger AG, Basel.)

We presented the case of stillbirth in a paucisymptomatic mother affected by SARS-CoV-2. At gross examination, the placenta showed a diffuse marble appearance and a focal hemorrhagic area. Multiple areas of hemorrhagic or ischemic necrosis with central and peripheral villous infarctions and thrombosis of several maternal and fetal vessels with luminal fibrin and platelet deposition were observed. All lesions seemed to be synchronous. Virus particles were identified within the cytoplasm of endothelial cells using electron microscopy, whereas SARS-CoV-2 RNA was detected in the placental tissue using real-time reverse transcription-polymerase chain reaction. Here, fetal vascular malperfusion was associated with infection; in fact, electron microscopy images showed that marked SARS-CoV-2 endotheliotropism involved the intravillous fetal capillaries. Furthermore, we confirmed that syncytiotrophoblast is the major target cell type for SARS-CoV-2 infection of the placenta. In conclusion, the possible consequences of the action of the placentotropic SARS-CoV-2 included the occurrence of vertical transmission, as reported in the literature, and/or stillbirth: the latter possibility may be triggered by a hampered maternal and/or fetal perfusion of the placenta. The diffuse thrombosis and subsequent ischemia of fetal capillaries induced by COVID-19 cannot be predicted by standard clinical surveillance., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: SARS-CoV-2 vaccine has been recommended to pregnant women, but survey studies showed contrasting findings worldwide in relation to the willingness to accept vaccination during pregnancy., Objective: To evaluate the evidence from the literature regarding the acceptance rate of the SARS-CoV-2 vaccine in pregnant and breastfeeding women., Study Design: We performed a systematic review on the main databases (MEDLINE (PubMed), Scopus, ISI Web of Science) searching for all the peer-reviewed survey studies analyzing the eventual acceptance rate of the SARS-CoV-2 vaccine among pregnant and breastfeeding women. To combine data meta-analyses of proportions and pooled proportions with their 95% confidence intervals (CI) were calculated., Results: 15 studies including 25,839 women were included in the analysis. The proportion of women actually willing to be vaccinated during pregnancy is 49.1% (95% CI, 42.3-56.0), and the proportion of breastfeeding women is 61.6% (95% CI, 50.0-75.0)., Conclusion: The cumulative SARS-CoV-2 vaccine acceptance rate among pregnant women appears still low. Vaccinal campaign are urgently needed to drive more confidence into the vaccine to help reducing the spread of the infection and the possible consequences during pregnancy., 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 © 2021 Elsevier B.V. All rights reserved.)

Objective: The aim of this study was to report the rate of additional anomalies detected exclusively at prenatal magnetic resonance imaging (MRI) in fetuses with isolated severe ventriculomegaly undergoing neurosonography., Method: Multicenter, retrospective, cohort study involving 20 referral fetal medicine centers in Italy, United Kingdom, Spain and Denmark. Inclusion criteria were fetuses affected by isolated severe ventriculomegaly (≥15 mm), defined as ventriculomegaly with normal karyotype and no other additional central nervous system (CNS) and extra-CNS anomalies on ultrasound. In all cases, a multiplanar assessment of fetal brain as suggested by ISUOG guidelines on fetal neurosonography had been performed. The primary outcome was the rate of additional CNS anomalies detected exclusively at fetal MRI within two weeks from neurosonography. Subgroup analyses according to gestational age at MRI (

Background: Intrahepatic cholestasis of pregnancy (ICP) is characterized by the elevation of total bile acids (TBAs). The primary concern in women with ICP is the increased risk of stillbirth. ICP is generally considered as "mild" when TBA levels range from 10 to 39 µmol/L and "severe" with levels greater than 40 µmol/L, although levels of TBA ≥100 µmol/L have been also considered as a further threshold of severity., Objective: To quantify the association between different severities of ICP (TBA 10-39, 40-99, and ≥100 µmol/L) and perinatal death., Data Sources: Medline, Embase, Scopus, Web of Sciences, and ClinicalTrial.gov were searched from the inception of each database to February 2019., Methods of Study Selection: Randomized, cohort, case-control, or case series studies reporting maternal and perinatal outcomes on women with ICP by the three prespecified TBA levels (10-39, 40-99, and ≥100 µmol/L) were included. We excluded multiple gestations and trials which included an intervention. The analysis was performed with Pearson chi-square and Fisher's exact test as appropriate. Continuous outcomes were compared using metaregression with inverse variance weighting using reported sample sizes and standard deviations. Pairwise comparisons used a Bonferroni correction to control for multiple testing., Tabulation, Integration, and Results: Six articles including 1280 singleton pregnancies affected by ICP were included in the systematic review. Out of the 1280 singleton pregnancies affected by ICP included, 118 had ICP with TBA ≥100 µmol/L. Perinatal death was more common in women with TBA ≥100 µmol/L (0.4% for TBA 10-39 μmol/L versus 0.3% for TBA 40-99 μmol/L versus 6.8% for TBA ≥ 100 μmol/L, p  < .0001). Of the 8 perinatal deaths in the TBA ≥100 µmol/L group, 3 occurred ≥34 weeks. TBA ≥100 µmol/L increased the risk of spontaneous preterm birth (PTB) (5.4% versus 8.6% versus 18.2% respectively, p  < .0001) and iatrogenic PTB (10.8% versus 21.6% versus 35.8% respectively, p <.0001) as well as meconium-stained amniotic fluid (9.0% versus 18.4% versus 31.6% respectively, p  < .0001)., Conclusions: Maternal TBA ≥100 µmol/L is associated with a 6.8% incidence of perinatal death, most of which (5.9% overall) are stillbirths, while TBA <100 µmol/L are associated with an incidence of perinatal death of 0.3%. It may be reasonable to consider late preterm delivery (at about 35-36 weeks) in women with TBA ≥100 µmol/L.

Background and Aim: The treatment of burn alopecia is still considered a challenging task for plastic surgeons. Tissue expansion has been extensively described as a useful technique used in order allow the reconstruction of large scalp defects with reliable hair-bearing tissue, enhancing the final aesthetic outcome., Case Report: We present the case of a 43-tear-old woman affected by scarring burn alopecia of left parietal area, treated with staged tissue expansion and local flap reconstruction. Despite the complete flap survival, a reversible acute hair loss 12 days after surgery, ascribable as Telogen Effluvium (TE), was reported., Conclusions: TE is a rare and self-limiting condition potentially related with any kind surgery or stressful events. Plastic surgeons should be aware of this condition, particularly when performing scalp reconstruction, as it can be misled with other local complications. Clinical diagnosis is of paramount importance to avoid useless or even harmful treatments: reassuring the patient remains the most effective therapeutic pathway.