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.

Safety and efficacy of a class II medical device based on highly purified and standardized plant extracts in the management of post-menopausal patients with vulvar and vaginal atrophy: a single-center prospective observational study.

BACKGROUND: Despite the gold standard treatment for genitourinary syndrome of menopause (GSM) is based on the use of local or systemic estrogen-containing products, the typical long-term side effects of hormonal treatments and, most importantly, the contraindications in patients with history of breast and endometrial neoplasms do limit in some extent its use. As hyaluronic acid and some highly purified botanicals have clearly demonstrated their anti-inflammatory and mucosa-protecting properties, we have tested, in women with GSM, a class II vaginal medical device containing hyaluronate gel and a mucoadhesive active enriched with purified alkylamides from Zanthoxylum bungeanum, triterpenes from Centella asiatica and high molecular weight polysaccharides from Tamarindus indica. METHODS: Our single-center, open-label, prospective and observational study was conducted on 50 menopausal women enrolled at the Department of Maternal-Fetal Medicine at Umberto I Polyclinic Hospital in Rome, Italy. Gel administration lasted 150 days and was performed daily for the first 12 days and every 48 hours for the remaining 138 days. Clinical evaluations were performed at baseline and after 12, 57 and 150 days. Besides product safety, main outcomes of our study were: 1) vaginal health (by Vaginal Health Index score [VHI]); 2) sexual quality of life (by Female Sexual Distress Scale [FSDS]); and 3) percentage of women declaring regular sexual activity. RESULTS: The product was safe with no specific adverse events reported. It significantly improved VHI (about 5% after 57 days and 8% after 150 days), FSDS (about 7% after 57 days and 10% after 150 days), and sexual activity (about 20% after 150 days). It also reduced dryness, dyspareunia, burning, itching, and dysuria incidence, respectively by about 18%, 14%, 14%, 27% and 11% after 150 days. CONCLUSIONS: In women with GSM, the intravaginal administration of a hyaluronate-based gel enriched with purified botanical actives endowed with anti-inflammatory and mucosal-protecting properties, reduced painful sensation during sexual acts and increased regular sexual activity.

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.

Use of non-steroidal anti-inflammatory drugs in pregnancy and oligohydramnios: a review.

OBJECTIVE: The aim of this review is to evaluate the relationship between the use of non-steroidal anti-inflammatory drugs (NSAIDs) during last trimesters of the pregnancy and the reduction of amniotic fluid. METHODS: Electronic databases were searched (PubMed, Medline, and Scopus). Selection criteria included studies reporting the relationship between oligohydramnios and use of NSAID during pregnancy. We analyzed the median age of women, weeks of pregnancy at the beginning of the drug administration, kind of medication, period of exposure and dosage, deepest vertical pocket (DVP), and amniotic fluid index (AFI). RESULTS: Of the 68 records identified, we analyzed 29 studies investigating the administration of NSAIDs, including 11 studies examined the administration of the Indomethacin, four articles have focused on the use of Nimesulide, and only two manuscripts considered the use of Diclofenac. We found a strict correlation between the development of oligohydramnios and the use of NSAIDs. The oligohydramnios is reversible, and the normal amount of amniotic fluid is restored after the interruption of the treatment. CONCLUSIONS: The use of NSAIDs should be considered when maternal benefits outweigh the potential fetal risk, at the lowest effective dose for shortest duration. Beyond 48 h of NSAIDs treatment, we consider ultrasound monitoring of amniotic fluid, and we suggest stopping therapy if a decline AFI is present.

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.

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.

Safety of gender affirming treatment in assigned female at birth transgender people and association of androgen and estrogen ß receptor polymorphisms with clinical outcomes.

PURPOSE: Gender affirming hormone treatment (GAHT) with androgens in assigned female at birth (AFAB) people with Gender Incongruence (GI) can induce and maintain variable phenotypical changes, but individual response may be genetically determined. To clarify the role of AR and ERß polymorphisms we prospectively evaluated AFAB subjects undergoing virilizing GAHT. METHODS: Fifty-two AFAB people with confirmed GI were evaluated before (T0) and after 6 (T6) and 12 months (T12) of testosterone enanthate 250 mg i.m. every 28 days. Hormone profile (testosterone, estradiol), biochemical (blood count, glyco-metabolic profile) and clinical parameters (Ferriman-Gallwey score, pelvic organs) were evaluated at each time-point, as well as number of CAG and CA repeats for AR and ERß, respectively. RESULTS: All subjects have successfully achieved testosterone levels within normal male ranges and improved their degree of virilization, in absence of significant side effects. Hemoglobin, hematocrit and red blood cells were significantly increased after treatment, but within normal ranges. Ultrasound monitoring of pelvic organs showed their significant reduction already after 6 months of GATH, in absence of remarkable abnormalities. Furthermore, a lower number of CAG repeats was associated with a higher Ferriman-Gallwey score post treatment and a higher number of CA repeats was associated with uterine volume reduction. CONCLUSION: We confirmed safety and efficacy of testosterone treatment on all measured parameters. This preliminary data hints a future role of genetic polymorphisms to tailor GAHT in GI people, but evaluation on a larger cohort is necessary as the reduced sample size could limit data generalization at this stage.

Severe maternal thrombocytopenia and prenatal invasive procedures: still a grey zone.

Management of severe thrombocytopenia, particularly of ITP, in pregnancy is mainly based on expert consensus and clinical experience while there are no clear indications about the minimum platelet count requested for prenatal diagnosis invasive procedures. Since the lack of specific recommendations we reported our clinical management of a patient suffering from severe thrombocytopenia, undergoing amniocentesis. Due to the anecdotic possibility of maternal and fetal bleeding in case of severe thrombocytopenia, prophylaxis with IVIG or even corticosteroids could be considered as a safer strategy to prevent post-procedural adverse outcomes.

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.

Echocardiographic features and outcome of restrictive foramen ovale in fetuses with and without cardiac malformations: Literature review.

Foramen ovale is a small communication between the left and the right atrium and its restriction is a rare congenital heart anomaly. There is no consensus on diagnosis and management of fetal restrictive foramen ovale (RFO). In our paper we included 11 studies about fetuses affected by isolated RFO, RFO with D-Transposition of the Great Arteries (dTGA) and RFO with hypoplastic left heart syndrome (HLHS). While fetuses affected from HLHS and dTGA with RFO have a poor prognosis, premature RFO in an otherwise structurally normal heart, if found in later gestation, have an overall good outcome.

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.

The role of ultrasonographic adipose tissue thickness measurement in the first trimester in predicting gestational diabetes: a prospective study.

BACKGROUND: This prospective observational study aimed to assess the association between maternal abdominal subcutaneous and visceral fat thickness measured with ultrasound scan during the first trimester and the risk of developing gestational diabetes mellitus (GDM). METHODS: We recruited 43 non-diabetic women with singleton pregnancy between 11 and 14 week of gestation and evaluated ultrasonographic measurements of subcutaneous fat thickness (SFT) and preperitoneal fat (PF) above the umbilicus. During the 2nd trimester, GDM screening was performed by 75 g two-hour oral glucose tolerance test (OGTT) and diagnosis was made when one or more plasma glucose values meets or exceeds the values indicated by International Association of the Diabetes and Pregnancy Study Groups (IADPSG). RESULTS: Among the 43 woman, 8 developed GDM (18.6%). Of these 37,5% (N.=3) had been diagnosed with GDM during a previous pregnancy, with a statistically significant correlation (P=0.035). Mean SFT for all patients was significantly higher in the GDM group compared to non-GDM group (27.30±8.78 mm vs. 18.56±9.99 mm; P=0.049). Mean PF for all women showed a statistically significant correlation with GDM (13.27±9.07 mm for non GDM group vs. 23.52±10.24 mm for GDM group; P=0.038). CONCLUSIONS: Abdominal adiposity, both subcutaneous and visceral, seem to be a suitable predictor of GDM in early pregnancy and it can be easily assessed during a first trimester routine ultrasound, although further studies are needed to evaluate their role in the screening protocols.

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.

Case Series of Acute Meconium Peritonitis Secondary to Perforation of the Ileum in the Antepartum Period.

Perforation of the ileum in the antepartum period resulting in meconial peritonitis is a condition that, although rare, is burdened by several complications. In 80-90% of cases, meconial ileus is the first manifestation of a disease, cystic fibrosis. In the remaining 10-20% of cases, it is caused by other situations, such as prematurity. In most cases, the diagnosis of meconial ileus occurs after birth, although in some cases it can be suspected prenatally, with the finding of a hyperechoic intestine on second trimester ultrasound. The prognosis depends on the gestational age, the location of the obstruction and the presence of fetal abnormalities. Mortality is very high and the recovery of intestinal function in the postoperative course is very high risk. In this case series, we describe two meconial peritonitis and our experience at the center.

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.