Outcome of fetal congenital pulmonary malformations: a systematic review and meta-analysis.

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.

Outcome of prelabor rupture of membranes before or at the limit of viability: systematic review and meta-analysis.

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.

Counseling in fetal medicine: Congenital cytomegalovirus infection.

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.

Diffusion-sensitized magnetic resonance imaging highlights placental microstructural damage in patients with previous SARS-CoV-2 pregnancy infection.

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.

Effects of gender on fetal cortical development: a secondary analysis of a prospective cross-sectional study.

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.

Planned cesarean delivery vs planned vaginal delivery: a systematic review and meta-analysis of randomized controlled trials.

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.

Obstetrical outcomes following amniocentesis performed after 24 weeks of gestation: A systematic review and meta-analysis.

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.

Hyperechogenic fetal bowel: Current evidence-based prenatal diagnosis and management.

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.

Modeling fetal cortical development by quantile regression for gestational age and head circumference: a prospective cross sectional study.

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.

Removal versus retention of cervical cerclage with preterm prelabor rupture of membranes: Systematic review and meta-analysis.

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.

Evidence-based labor management: postpartum care after vaginal delivery (part 6).

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).

Three-tiered fetal heart rate interpretation system and adverse neonatal and maternal outcomes: a systematic review and meta-analysis.

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.

Prognostic Value of Amniotic Fluid Viral Load to Predict Adverse Outcome in Pregnancies Complicated by Congenital Cytomegalovirus Infection: A Multicenter Study.

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.

Advances in small molecule maintenance therapies for high-grade serous ovarian cancer.

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.

Prenatal predictors of adverse perinatal outcome in congenital cytomegalovirus infection: a retrospective multicenter study.

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.

An update on current pharmacotherapy for vulvar cancer.

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.

Neuroimaging and Cerebrovascular Changes in Fetuses with Complex Congenital Heart Disease.

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.

Methodological Quality of Fetal Brain Structure Charts for Screening Examination and Targeted Neurosonography: A Systematic Review.

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.