Sentinel lymph node biopsy for breast cancer during pregnancy: A comprehensive update.

BACKGROUND: Pregnant patients diagnosed with breast cancer (PrBC) may receive substantially different treatments compared to general population, considering that certain treatment options cannot be applied during pregnancy due to their potential harmful effects to the foetus. Regarding the use of sentinel lymph node biopsy (SLNB) in pregnant patients, potential concerns include foetal harm from radiation exposure, possible teratogenic effects of blue dyes and maternal anaphylaxis to isosulfan. OBJECTIVE: The main objective of the present systematic review is to summarize and present current knowledge and up-to-date evidence about the safety and efficacy of SLNB in PABC. METHODS: MEDLINE, Google Scholar and UpToDate databases were searched up to 22 January 2023. Articles studying the safety and effectiveness of SLNB in patients for PrBC were eligible for inclusion in the present review. RESULTS: In total, 63 articles that met the inclusion criteria were included in this study. Forty-seven articles were strongly in favour of performing SLNB in PABC, 4 articles were partially in favour, 10 articles were strongly against and 2 articles were partially against performing SLNB in PABC. Sub-categorization based on type of study showed that the majority of studies in favour were of higher level of evidence than those against. Furthermore, there were overall 12 studies reporting on outcomes. There were overall 382 women with PrBC that underwent SLNB. Full data were reported for 237 cases. Overall live birth rate was 95.8%, while overall neonatal complication rate was 3.4%. No case of maternal side effects or anaphylactic reaction, maternal death, stillbirth and neonatal death was reported (0%). CONCLUSIONS: Sentinel lymph node biopsy seems to be safe and effective technique for breast cancer during pregnancy.

The effect of valacyclovir on secondary prevention of congenital cytomegalovirus infection, following primary maternal infection acquired periconceptionally or in the first trimester of pregnancy. An individual patient data meta-analysis.

OBJECTIVE: Recent studies have shown that a dosage of 8 g/d of oral valacyclovir reduces substantially the vertical transmission rate of cytomegalovirus in women with primary cytomegalovirus infection acquired periconceptionally or during the first trimester of pregnancy. This individual patient data meta-analysis aimed to assess the effectiveness and safety of valacyclovir treatment in the secondary prevention of congenital cytomegalovirus infection. DATA SOURCES: MEDLINE, Scopus, Cochrane Central Register of Controlled Trials, the US registry of clinical trials (www. CLINICALTRIALS: gov), and gray literature sources were searched from inception to March 2023. STUDY ELIGIBILITY CRITERIA: Randomized controlled trials and quasi-randomized studies administering 8 g/d of oral valacyclovir in pregnant women with primary cytomegalovirus infection acquired periconceptionally or during the first trimester of pregnancy were included. METHODS: All corresponding authors of the eligible studies were contacted. Cochrane's Risk of Bias 2 and Risk Of Bias In Non-randomised Studies - of Interventions tools were used for the risk of bias assessment. The result of amniocentesis was the primary outcome of interest. A 1-stage individual patient data meta-analysis was performed, using a generalized linear mixed model, clustered by the different trials. A subgroup analysis was performed, assessing separately the effect of valacyclovir in the periconceptional period and first trimester of pregnancy. RESULTS: Overall, 3 studies were included in the analysis (n=527 women). Valacyclovir reduced the vertical transmission rate of cytomegalovirus (adjusted odds ratio, 0.34; 95% confidence interval, 0.18-0.61). This reduction was apparent for both periconceptional period (adjusted odds ratio, 0.34; 95% confidence interval, 0.12-0.96) and first-trimester (adjusted odds ratio, 0.35; 95% confidence interval, 0.16-0.76) infections. Moreover, valacyclovir reduced the rate of neonatal infection (adjusted odds ratio, 0.30; 95% confidence interval, 0.19-0.47), in both periconceptional period (adjusted odds ratio, 0.30; 95% confidence interval, 0.14-0.61) and first-trimester (adjusted odds ratio, 0.30; 95% confidence interval, 0.17-0.54) infections. Furthermore, valacyclovir reduced the rate of termination of pregnancy because of cytomegalovirus-associated severe fetal findings (adjusted odds ratio, 0.23; 95% confidence interval, 0.22-0.24). The gestational age at the initiation of treatment has a positive correlation with all outcomes. The overall prevalence of severe side effects was 2.1%. CONCLUSION: A dosage of 8 g/d of oral valacyclovir reduced the vertical transmission rates of cytomegalovirus following primary maternal infection acquired periconceptionally or in the first trimester of pregnancy, with a low incidence of side effects.

Decreased flow-mediated dilation in gestational diabetes in pregnancy and post-partum. A systematic review and meta-analysis.

AIMS: Gestational diabetes mellitus (GDM) is a common medical complication during pregnancy. Endothelial dysfunction is considered an early step in the progression of atherosclerosis that may contribute to subclinical target organ damage. This meta-analysis aimed to systemically review the existing data regarding endothelial dysfunction between women with and without GDM during pregnancy and post-partum using flow-mediated dilation (FMD). MATERIALS AND METHODS: Eligible studies (cohort and observational) published until October 2021 were identified in the MEDLINE, Scopus, Cochrane Library database and grey literature sources were searched. RESULTS: The search yielded 2272 studies, of which 17 were fully reviewed and 12 studies (N = 740 pregnant women) were finally included. Pregnant women with GDM exhibited a significantly lower FMD compared to pregnant women without GDM (pooled mean difference -3.12; 95% CI -5.36 to -0.88). Moreover, in the immediate (1-6 months) post-partum period, women with previous GDM showed lower FMD compared to healthy women without GDM history (pooled mean difference -7.52; 95% CI -9.44 to -5.59), whereas FMD did not differ in the late post-partum period (more than 4 years). CONCLUSIONS: Flow-mediated dilation is decreased in women with GDM during pregnancy and in the immediate post-partum period, compared to women without GDM, indicating that the endothelial dysfunction noted during the pregnancy in those women persists in the immediate post-partum period too. CLINICAL TRIAL REGISTRATION: PROSPERO CRD42021283113 (www. CLINICALTRIALS: gov).

The Effect of Resolution Level and Targeted Design in the Diagnostic Performance of Prenatal Chromosomal Microarray Analysis.

INTRODUCTION: This study was performed to assess the optimal resolution for prenatal testing by array comparative genomic hybridization (aCGH), aiming to balance between maximum diagnostic yield and minimal detection of variants of uncertain significance (VOUS). METHODS: This was a prospective study using data of 2,336 fetuses that underwent invasive prenatal diagnosis, and the samples were analyzed by aCGH. In total, six different aCGH platforms were studied; four different resolutions (0.18 Mb, 0.5 Mb, 1 Mb, and 2 Mb) and two platform designs (whole-genome [WG] and targeted). The results of these designs were compared based on their diagnostic yield and VOUS rate. The performance of the different designs was further analyzed according to indication for invasive testing. RESULTS: The diagnostic yield of copy number variants increased with increasing level of analysis. The detection rates of clinically significant chromosomal abnormalities were almost the same across our targeted array designs; 7.2% with 0.18 Mb backbone/0.05 Mb versus 7.1% with 0.5 Mb backbone/0.05 Mb (p >0.05). However, a significant difference in the rate of VOUS was observed; 9.4% with 0.18 Mb backbone/0.05 Mb versus 6% with 0.5 Mb backbone/0.05 Mb (p <0.001). After analyzing the results across different indications for testing, we found that the application of non-targeted platform designs and lower levels of resolution analysis (such as 1 Mb WG or 0.5 MbL/1 MbG WG) would offer similar diagnostic yield in most cases with major congenital anomalies, with lower VOUS rates. However, the sample size for many indication groups was too small to extract robust associations. CONCLUSION: It appears that the targeted array platform with 0.5 Mb backbone resolution and 0.05 Mb on targeted gene-rich regions is optimal for routine chromosomal microarray analysis use in prenatal diagnosis. It may be beneficial to individualize the minimum resolution in specific referral indications as the indications for invasive prenatal testing may be quite heterogeneous.

The expression and possible role of corticotropin-releasing hormone family peptides and their corresponding receptors in gynaecological malignancies and premalignant conditions: a systematic review.

The aim of this systematic review is to investigate the impact of corticotropin-releasing hormone (CRH) family peptides and their corresponding receptors on human physiology and disease onset, with a specific focus on gynaecological malignancies such as breast, endometrial, ovarian, vulvar, and cervical cancer. A comprehensive systematic review of 3 medical databases was conducted by 2 independent reviewers. We reviewed studies that explored the expression and role of CRH peptides in various aspects of cancer biology, in the context of breast, endometrial, ovarian, vulvar, and cervical cancer. Our findings reveal that CRH family peptides and their receptors, CRHR1 and CRHR2, are expressed in diverse gynaecological tissues, including cancer cells. Notably, we observed differential expression patterns among different gynaecological cancer types and stages, indicating potential associations with tumour aggressiveness and patient prognosis. Furthermore, CRH peptides were found to exert significant influences on critical cellular processes, such as cell proliferation, migration, invasion, and immune response, in gynaecological cancers. These findings highlight the multifaceted roles of CRH family peptides in gynaecological malignancies and emphasize the need for further research in this field. Therefore, understanding the mechanisms underlying the involvement of CRH family peptides in tumourigenesis may open new avenues for targeted therapeutic strategies in gynaecological malignancies.

The role of endoglin and its soluble form in pathogenesis of preeclampsia.

Preeclampsia remains till today a leading cause of maternal and fetal morbidity and mortality. Pathophysiology of the disease is not yet fully elucidated, though it is evident that it revolves around placenta. Cellular ischemia in the preeclamptic placenta creates an imbalance between angiogenic and anti-angiogenic factors in maternal circulation. Endoglin, a transmembrane co-receptor of transforming growth factor ß (TGF-ß) demonstrating angiogenic effects, is involved in a variety of angiogenesis-dependent diseases with endothelial dysfunction, including preeclampsia. Endoglin expression is up-regulated in preeclamptic placentas, through mechanisms mainly induced by hypoxia, oxidative stress and oxysterol-mediated activation of liver X receptors. Overexpression of endoglin results in an increase of its soluble form in maternal circulation. Soluble endoglin represents the extracellular domain of membrane endoglin, cleaved by the action of metalloproteinases, predominantly matrix metalloproteinase-14. Released in circulation, soluble endoglin interferes in TGF-ß1 and activin receptor-like kinase 1 signaling pathways and inhibits endothelial nitric oxide synthase activation, consequently deranging angiogenesis and promoting vasoconstriction. Due to these properties, soluble endoglin actively contributes to the impaired placentation observed in preeclampsia, as well as to the pathogenesis and manifestation of its clinical signs and symptoms, especially hypertension and proteinuria. The significant role of endoglin and soluble endoglin in pathophysiology of preeclampsia could have prognostic, diagnostic and therapeutic perspectives. Further research is essential to extensively explore the potential use of these molecules in the management of preeclampsia in clinical settings.

Pregnancy outcome of confined placental mosaicism: meta-analysis of cohort studies.

OBJECTIVE: This study aimed to assess the rate of adverse obstetrical and neonatal outcomes in pregnancies diagnosed with confined placental mosaicism relative to that of unaffected controls. DATA SOURCES: Web-based databases were searched using relevant key words, and articles published from 1980 to February 2022 were retrieved. STUDY ELIGIBILITY CRITERIA: Observational studies in English language including ≥10 cases of singleton pregnancies with diagnosis of confined placental mosaicism were included. The diagnosis was established after detection of any chromosomal abnormality at chorionic villus sampling for any indication, followed by normal karyotype from amniotic fluid or neonatal leukocyte culture. METHODS: Two authors independently screened the references for eligibility, data extraction, and assessment of methodological quality using the Newcastle-Ottawa scale. All available obstetrical and neonatal outcomes were recorded. Random-effect meta-analysis was performed to estimate pooled odds ratios and 95% confidence intervals of available outcomes in pregnancies with and without confined placental mosaicism. Statistical heterogeneity was evaluated with I2 statistics (International Prospective Register of Systematic Reviews registration number: CRD42021260319). RESULTS: Of the 80 articles reviewed, 8 retrospective matched-cohort studies (708 cases of confined placental mosaicism and 11,599 unaffected controls) compared cases with and without confined placental mosaicism and were included in the meta-analysis. The risk of delivering small-for-gestational-age neonates was significantly increased in confined placental mosaicism pregnancies according to crude analysis (odds ratio, 2.45; 95% confidence interval, 1.23-4.89; I2=72%) and to sensitivity analysis of high-quality studies (odds ratio, 3.65; 95% confidence interval, 2.43-5.57; I2=0%). Similarly, confined placental mosaicism resulted in an increased risk of birthweight below the third centile (odds ratio, 5.33; 95% confidence interval, 1.19-24.19; I2= 83%). Subgroup analysis revealed that the risk of delivering small-for-gestational-age neonates was 3-fold higher for confined placental mosaicism excluding trisomy 16, and 11-fold higher for cases including trisomy 16 only vs unaffected controls, respectively. No difference was found in the risk of low birthweight and preterm birth (at <37 weeks' gestation). Other outcomes were insufficiently reported, therefore they were not analyzed. CONCLUSION: Pregnant women prenatally diagnosed with confined placental mosaicism have an increased risk of impaired fetal growth, suggesting the need for intensified antenatal surveillance.

Impact of Marginal and Velamentous Cord Insertion on Uterine Artery Doppler Indices, Fetal Growth, and Preeclampsia.

OBJECTIVES: To assess the impact of marginal (MCI) or velamentous (VCI) cord insertion on uterine artery pulsatility index (UtA PI), preeclampsia (PE), and offspring's birthweight (BW). METHODS: A retrospective cohort study of singleton pregnancies, undergoing routine anomaly scan at 20+0 -23+6 gestational weeks, was conducted between 2016 and 2020. The effect of placental cord insertion on BW and UtA mean PI z-scores was assessed using the t test or analysis of variance and post-hoc tests; their association with PE was evaluated with the chi-square test. A multivariate logistic regression model was employed to assess the independent association of placental cord insertion and UtA PI z-score with PE, BW <10th, <5th centile, and intrauterine death (IUD), using specific confounders. RESULTS: The study population included 4453 pregnancies. Conception via assisted reproductive technology (ART) was associated with increased risk of abnormal cord insertion (odds ratio [OR]: 2.237; 95% confidence interval [CI]: 1.561-3.206; P < .001). Women with MCI/VCI had higher mean UtA PI z-score than those with central/eccentric (0.29 vs 0.01; mean difference: -0.28; 95% CI: -0.399 to -0.165; P < .001). MCI/VCI were associated with higher rates of BW <10th centile (central/eccentric: 16.2% vs MCI: 21.9% vs VCI: 35.7%; P < .001) and BW <5th centile (9.8 vs 15.1 vs 23.2%, respectively; P < .001). No association was identified between MCI/VCI and PE (P = .968). Finally, VCI (aOR: 13.717; 95% CI: 1.576-119.379; P = .018) and increased BMI (aOR: 1.167; 95% CI: 1.071-1.271; P < .001) significantly correlated with IUD. CONCLUSIONS: Abnormal cord insertion is more common in ART pregnancies. MCI/VCI are associated with higher mean UtA PI and lower BW centile, but not with increased risk of PE.

Adverse perinatal outcomes following the prenatal diagnosis of isolated single umbilical artery in singleton pregnancies: a systematic review and meta-analysis.

OBJECTIVES: A systematic review and meta-analysis was conducted to quantitatively synthesize the current evidence on the association of prenatally diagnosed isolated single umbilical artery (iSUA) in singleton pregnancies with small for gestational age (SGA) neonates and other perinatal outcomes. METHODS: A search of PubMed/Medline, Scopus and The Cochrane Library was conducted, from inception to February 2021, in order to identify studies comparing the risk of SGA and other perinatal adverse outcomes in prenatally diagnosed iSUA singleton pregnancies vs. those with a 3-vessel cord (3VC). The quality of eligible studies was assessed according to the improved Newcastle-Ottawa Scale (NOS). The heterogeneity of results across the studies was tested using the I2 test. Funnel plots and Egger's test were used to assess the possibility of publication bias. Prospero RN: CRD42020182586. RESULTS: The electronic search identified 7,605 studies, of which 11 were selected, including three retrospective cohort and eight retrospective case control studies, overall reporting on 1,533 iSUA cases. The risk of delivering SGA neonates was increased in cases with iSUA (OR: 2.90; 95% CI: 2.02-4.18; p<0.00001; I2=71%). Similarly, iSUA was associated with an increased risk of pregnancy-induced hypertension (PIH) (OR: 2.23; 95% CI: 1.41-3.54; p<0.000; I2=1%), intrauterine death (IUD) (OR: 2.62; 95% CI: 1.43-4.79; p=0.002; I2=0%), preterm birth (PTB) (OR: 2.48; 95% CI: 1.73-3.56; p<0.00001; I2=56%), cesarean section (CS) (OR: 1.64; 95% CI: 1.11-2.41; p=0.01; I2=78%) and admission to neonatal intensive care unit (NICU) (OR: 2.28; 95% CI: 1.52-3.44; p<0.000001; I2=73%). CONCLUSIONS: In prenatally diagnosed iSUA there is a higher risk of SGA, PIH, IUD, PTB, CS and NICU admission. These findings support the value of prenatal diagnosis of iSUA, which may subsequently intensify surveillance for the detection of specific pregnancy complications.

Lymphadenectomy in endometrial cancer - achieving more with less?

The lymph node status of patients with endometrial cancer is known to be a crucial determinant for the prognosis of the disease. It also provides the indication for further adjuvant treatment. The staging of endometrial cancer by surgery has been a controversial issue for more than 30 years. The significant complication rate after lymphadenectomy and the development of minimally invasive surgery have led to the use of sentinel lymph node (SLN) mapping. In the present review, we present the development of surgical staging procedures in patients with endometrial cancer and summarize the recently expanding body of published literature on the subject. SLN mapping is a safe and accurate technique, especially when indocyanine green is used as a tracer. SLN mapping appears to reduce complication rates as well as costs without affecting the oncologic outcome. Large prospective studies are needed to establish the effects of SLN mapping on the outcome of disease, especially in high-risk patients with endometrial cancer. Furthermore, the need for additional systematic lymphadenectomy prior to adjuvant radio-chemotherapy in patients diagnosed with isolated lymph node metastasis during SLN biopsy must be investigated further. This might pave the way for a new surgical approach in patients with endometrial cancer.

Antenatal corticosteroids prior to planned caesarean at term for improving neonatal outcomes.

BACKGROUND: Infants born at term by elective caesarean section are more likely to develop respiratory morbidity than infants born vaginally. Prophylactic corticosteroids in singleton preterm pregnancies accelerate lung maturation and reduce the incidence of respiratory complications. It is unclear whether administration at term gestations, prior to caesarean section, improves the respiratory outcomes for these babies without causing any unnecessary morbidity to the mother or the infant. OBJECTIVES: The objective of this review was to assess the effect of prophylactic corticosteroid administration before elective caesarean section at term, as compared to usual care (which could be placebo or no treatment), on fetal, neonatal and maternal morbidity. We also assessed the impact of the treatment on the child in later life. SEARCH METHODS: For this update, we searched Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov (20 January 2021) and reference lists of retrieved studies. SELECTION CRITERIA: We included randomised controlled trials comparing prophylactic antenatal corticosteroid administration (betamethasone or dexamethasone) with placebo or with no treatment, given before elective caesarean section at term (at or after 37 weeks of gestation). Quasi-randomised and cluster-randomised controlled trials were also eligible for inclusion. DATA COLLECTION AND ANALYSIS: We used standard Cochrane Pregnancy and Childbirth methods for data collection and analysis. Two review authors independently assessed trials for inclusion, assessed risk of bias, evaluated trustworthiness (based on predefined criteria developed by Cochrane Pregnancy and Childbirth), extracted data and checked them for accuracy and assessed the certainty of the evidence using the GRADE approach. Our primary outcomes were respiratory distress syndrome (RDS), transient tachypnoea of the neonate (TTN), admission to neonatal special care for respiratory morbidity and need for mechanical ventilation. We planned to perform subgroup analyses for the primary outcomes according to gestational age at randomisation and type of corticosteroid (betamethasone or dexamethasone). We also planned to perform sensitivity analysis, including only studies at low risk of bias. MAIN RESULTS: We included one trial in which participants were randomised to receive either betamethasone or usual care. The trial included 942 women and 942 neonates recruited from 10 UK hospitals between 1995 and 2002. This review includes only trials that met predefined criteria for trustworthiness. We removed three trials from the analysis that were included in the previous version of this review. The risk of bias was low for random sequence generation, allocation concealment and incomplete outcome data. The risk of bias for selective outcome reporting was unclear because there was no published trial protocol, and therefore it is unclear whether all the planned outcomes were reported in full. Due to a lack of blinding we judged there to be high risk of performance bias and detection bias. We downgraded the certainty of the evidence because of concerns about risk of bias and because of imprecision due to low event rates and wide 95% confidence intervals (CIs), which are consistent with possible benefit and possible harm Compared with usual care, it is uncertain if antenatal corticosteroids reduce the risk of RDS (relative risk (RR) 0.34 95% CI 0.07 to 1.65; 1 study; 942 infants) or TTN (RR 0.52, 95% CI 0.25 to 1.11; 1 study; 938 infants) because the certainty of evidence is low and the 95% CIs are consistent with possible benefit and possible harm. Antenatal corticosteroids probably reduce the risk of admission to neonatal special care for respiratory complications, compared with usual care (RR 0.45, 95% CI 0.22 to 0.90; 1 study; 942 infants; moderate-certainty evidence). The proportion of infants admitted to neonatal special care for respiratory morbidity after treatment with antenatal corticosteroids was 2.3% compared with 5.1% in the usual care group. It is uncertain if antenatal steroids have any effect on the risk of needing mechanical ventilation, compared with usual care (RR 4.07, 95% CI 0.46 to 36.27; 1 study; 942 infants; very low-certainty evidence). The effect of antenatal corticosteroids on the maternal development of postpartum infection/pyrexia in the first 72 hours is unclear due to the very low certainty of the evidence; one study (942 women) reported zero cases. The included studies did not report any data for neonatal hypoglycaemia or maternal mortality/severe mortality. AUTHORS' CONCLUSIONS: Evidence from one randomised controlled trial suggests that prophylactic corticosteroids before elective caesarean section at term probably reduces admission to the neonatal intensive care unit for respiratory morbidity. It is uncertain if administration of antenatal corticosteroids reduces the rates of respiratory distress syndrome (RDS) or transient tachypnoea of the neonate (TTN). The overall certainty of the evidence for the primary outcomes was found to be low or very low, apart from the outcome of admission to neonatal special care (all levels) for respiratory morbidity, for which the evidence was of moderate certainty. Therefore, there is currently insufficient data to draw any firm conclusions.  More evidence is needed to investigate the effect of prophylactic antenatal corticosteroids on the incidence of recognised respiratory morbidity such as RDS. Any future trials should assess the balance between respiratory benefit and potential immediate adverse effects (e.g. hypoglycaemia) and long-term adverse effects (e.g. academic performance) for the infant. There is very limited information on maternal health outcomes to provide any assurances that corticosteroids do not pose any increased risk of harm to the mother.  Further research should consider investigating the effectiveness of antenatal steroids at different gestational ages prior to caesarean section. There are nine potentially eligible studies that are currently ongoing and could be included in future updates of this review.

Early delivery or expectant management for late preterm preeclampsia: A meta-analysis of randomized controlled trials.

INTRODUCTION: Currently, there is no consensus regarding the timing of delivery in women with non-severe preeclampsia at the late preterm period. The aim of the present meta-analysis is to compare expectant management with immediate delivery in pregnant women with preeclampsia between 34+0 and 36+6 gestational weeks, in terms of maternal and neonatal outcomes. MATERIAL AND METHODS: A search was conducted until October 1, 2020 and eligible studies were identified in MEDLINE, Scopus, Cochrane Central Register of Controlled Trials (Central), the US Registry of clinical trials (www.clinicaltrials.gov), and sources of gray literature without limitations concerning the publication dates and languages. Randomized controlled trials, comparing planned delivery vs expectant management in women with preeclampsia at 34-37 weeks were included. The primary outcomes were neonatal intensive care unit (NICU) admission and progression to eclampsia. Secondary outcomes were HELLP (hemolysis, elevated liver enzymes, and low platelet count) syndrome, severe preeclampsia, composite adverse maternal outcome (defined by the presence of any of the potential preeclampsia-related complications, ranging from severe hypertension to maternal death), neonatal respiratory disease, and respiratory distress syndrome. Relative risks (RRs) and mean differences with 95% CI were used for the estimation of the effect sizes; the quality of the evidence was assessed per GRADE guidelines. RESULTS: The electronic search yielded 10 721 potential studies, of which six were fully reviewed and three (1773 participants) were included in the meta-analysis. Immediate delivery increased the risk for NICU admission, (RR 1.23, 95% CI 1.05-1.45) and decreased the risk for the composite adverse maternal outcome (RR 0.86, 95% CI 0.78-0.93). There were no differences for eclampsia (RR 0.55, 95% CI 0.16-1.85), HELLP syndrome (RR 0.58, 95% CI 0.25-1.33), severe preeclampsia (RR 0.27, 95% CI 0.02-3.52), respiratory disease of neonate (RR 1.04, 95% CI 0.75-1.44), and respiratory distress syndrome (RR 2.3, 95% CI 0.73-7.25). CONCLUSIONS: Immediate delivery of women with non-severe preeclampsia at the period of late prematurity decreases the risk of a composite adverse maternal outcome by 14%, at the cost of an increase in NICU admissions by 23%. The overall quality of the evidence for these outcomes is high, indicating a high degree of certainty for the results.

Timing of primary maternal cytomegalovirus infection and rates of vertical transmission and fetal consequences.

OBJECTIVE: Cytomegalovirus infection is the most frequent congenital infection and a major cause of long-term neurologic morbidity. The aim of this meta-analysis was to calculate the pooled rates of vertical transmission and fetal impairments according to the timing of primary maternal infection. DATA SOURCES: From inception to January 2020, MEDLINE, Scopus, Cochrane Library, and gray literature sources were used to search for related studies. STUDY ELIGIBILITY CRITERIA: Cohort and observational studies reporting the timing of maternal cytomegalovirus infections and rate of vertical transmission or fetal impairments were included. The primary outcomes were vertical transmission and fetal insult, defined as either prenatal findings from the central nervous system leading to termination of pregnancy or the presence of neurologic symptoms at birth. The secondary outcomes included sensorineural hearing loss or neurodevelopmental delay at follow-up and prenatal central nervous system ultrasonography findings. STUDY APPRAISAL AND SYNTHESIS METHODS: The pooled rates of the outcomes of interest with their 95% confidence intervals (CI) were calculated for primary maternal infection at the preconception period, periconception period, first trimester, second trimester, and third trimester. RESULTS: A total of 17 studies were included. The pooled rates of vertical transmission (10 studies, 2942 fetuses) at the preconception period, periconception period, first trimester, second trimester, and third trimester were 5.5% (95% CI, 0.1-10.8), 21.0% (95% CI, 8.4-33.6), 36.8% (95% CI, 31.9-41.6), 40.3% (95% CI, 35.5-45.1), and 66.2% (95% CI, 58.2-74.1), respectively. The pooled rates of fetal insult in case of transmission (10 studies, 796 fetuses) were 28.8% (95% CI, 2.4-55.1), 19.3% (95% CI, 12.2-26.4), 0.9% (95% CI, 0-2.4%), and 0.4% (95% CI, 0-1.5), for maternal infection at the periconception period, first trimester, second trimester, and third trimester, respectively. The pooled rates of sensorineural hearing loss for maternal infection at the first, second, and third trimester were 22.8% (95% CI, 15.4-30.2), 0.1% (95% CI, 0-0.8), and 0% (95% CI, 0-0.1), respectively. CONCLUSION: Vertical transmission after maternal primary cytomegalovirus infection increases with advancing pregnancy, starting from the preconception period. However, severe fetal impairments are rare after infection in the first trimester of pregnancy.

Emergency cerclage in singleton pregnancies with painless cervical dilatation: A meta-analysis.

INTRODUCTION: Emergency cerclage is the most common active intervention in pregnant women with cervical insufficiency. This meta-analysis aimed to compare the effectiveness of emergency cerclage vs expectant management on maternal and perinatal outcomes, and to assess the current status of evidence. MATERIAL AND METHODS: A search was conducted from 1 June 2019 until 1 September 2019 and eligible studies were identified in the MEDLINE, Scopus, Cochrane and US clinical trials registry without limitations concerning the publication dates and languages. Randomized controlled trials (RCTs), non-RCTs and observational studies comparing emergency cerclage with no cerclage/expectant management, in women presenting with painless cervical dilatation were included. RESULTS: The electronic search yielded 3607 potential studies, of which 38 were fully reviewed and 12 observational studies (1021 participants) were included. Cerclage was superior to expectant management for the primary outcomes of preterm birth before 28 and 32 gestational weeks, OR 0.25 (95% CI 0.16-0.39, five studies, N = 392, I2 = 41%, low quality) and 0.08 (95% CI 0.02-0.29, four studies, N = 176, I2 = 51%, low quality), respectively. Cerclage was also superior to expectant management for the secondary outcomes of fetal loss OR 0.26 (95% CI 0.12-0.56, 8 studies, N = 455, I2 = 46%, very low-quality), pregnancy prolongation in days mean difference 47.45 (95% CI 39.89-55.0, 12 studies, N = 1027 I2 = 86%, very low quality), gestational age at birth in weeks mean difference 5.68 (95% CI 4.69-6.67, 9 studies, N = 892, I2 = 73%, very low quality), admission to neonatal intensive care OR 0.21 (95% CI 0.07-0.70, two studies, N = 79, I2 = 36%, very low quality) and neonatal death OR 0.12 (95% CI 0.04-0.34, five studies, N = 130, I2 = 0%, very low quality). There were no differences between cerclage and expectant management concerning premature rupture of membranes during or after the procedure OR 0.68 (95% CI 0.31-1.48, two studies, N = 155, I2 = 85%, very low quality) and chorioamnionitis OR 1.14 (95% CI 0.31-4.25, three studies, N = 88, I2 = 33%, very low quality). CONCLUSIONS: Emergency cerclage in pregnant women with painless cervical dilatation seems to decrease preterm births, prolong the pregnancy, and decrease the neonatal deaths and fetal losses, but does not increase the risk of chorioamnionitis and premature rupture of membranes. Despite the extremely favorable estimates for cerclage, the results should be viewed with caution because, as a result of the lack of randomized control trials, the quality of evidence is low to very low.

Diagnostic performance of third-trimester ultrasound for the prediction of late-onset fetal growth restriction: a systematic review and meta-analysis.

OBJECTIVE: The objective of the study was to establish the diagnostic performance of ultrasound screening for predicting late smallness for gestational age and/or fetal growth restriction. DATA SOURCES: A systematic search was performed to identify relevant studies published since 2007 in English, Spanish, French, Italian, or German, using the databases PubMed, ISI Web of Science, and SCOPUS. STUDY ELIGIBILITY CRITERIA: We used rrospective and retrospective cohort studies in low-risk or nonselected singleton pregnancies with screening ultrasound performed at ≥32 weeks of gestation. STUDY APPRAISAL AND SYNTHESIS METHODS: The estimated fetal weight and fetal abdominal circumference were assessed as index tests for the prediction of birthweight <10th (i.e. smallness for gestational age), less than the fifth, and less than the third centile and fetal growth restriction (estimated fetal weight less than the third or estimated fetal weight <10th plus Doppler signs). Quality of the included studies was independently assessed by 2 reviewers, using the Quality Assessment of Diagnostic Accuracy Studies-2 tool. For the meta-analysis, hierarchical summary receiver-operating characteristic curves were constructed, and quantitative data synthesis was performed using random-effects models. The sensitivity of the abdominal circumference <10th centile and estimated fetal weight <10th centile for a fixed 10% false-positive rate was derived from the corresponding hierarchical summary receiver-operating characteristic curves. Heterogeneity between studies was visually assessed using Galbraith plots, and publication bias was assessed by funnel plots and quantified by Deeks' method. RESULTS: A total of 21 studies were included. Observed pooled sensitivities of abdominal circumference and estimated fetal weight <10th centile for birthweight <10th centile were 35% (95% confidence interval, 20-52%) and 38% (95% confidence interval, 31-46%), respectively. Observed pooled specificities were 97% (95% confidence interval, 95-98%) and 95% (95% confidence interval, 93-97%), respectively. Modeled sensitivities of abdominal circumference and estimated fetal weight <10th centile for 10% false-positive rate were 78% (95% confidence interval, 61-95%) and 54% (95% confidence interval, 46-52%), respectively. The sensitivity of estimated fetal weight <10th centile was better when aimed to fetal growth restriction than to smallness for gestational age. Meta-regression analysis showed a significant increase in sensitivity when ultrasound evaluation was performed later in pregnancy (P = .001). CONCLUSION: Third-trimester abdominal circumference and estimated fetal weight perform similar in predicting smallness for gestational age. However, for a fixed 10% false-positive rate extrapolated sensitivity is higher for abdominal circumference. There is evidence of better performance when the scan is performed near term and when fetal growth restriction is the targeted condition.

Three-dimensional ultrasound in the diagnosis and the classification of congenital uterine anomalies using the ESHRE/ESGE classification: a diagnostic accuracy study.

STUDY OBJECTIVE: To estimate the diagnostic accuracy of three-dimensional ultrasonography (3D US) compared to hysteroscopy/laparoscopy, in the investigation of uterine congenital anomalies using the ESHRE/ESGE classification of female genital tract congenital anomalies. DESIGN: Prospective blind, comparative, cohort study. SETTING: University Tertiary Hospital and affiliated private Hospital. PATIENTS AND METHODS: Sixty-two women consecutively referred with a suspected diagnosis of uterine congenital anomalies. The ESHRE/ESGE classification of congenital anomalies of the female genital tract was used for the description of abnormal findings. INTERVENTIONS: All patients underwent (1) 3D US and (2) hysteroscopy with laparoscopy to establish the final diagnosis. RESULTS: Concordance between 3D US and hysteroscopy with laparoscopy about the type and the classification of uterine anomaly was verified in 61 cases, including all those with septate uterus, dysmorphic uterus, bicorporeal, hemi-uterus or unicorporeal, and aplastic uterus and one out of two with normal uterus. For the diagnosis of septate uteri, which was the most common anomaly, the sensitivity of 3D US was 100%, the specificity was 92.3%, the PPV was 98% and the NPV was 100%, with kappa index 0.950. For bicorporeal, dysmorphic uterus, hemi-uteri or unicorporeal and aplastic uterus the sensitivity, specificity, PPV and NPV were all 100% with K = 1.00. Overall, 3D US showed perfect diagnostic accuracy (Kappa index = 0.945) in the detection of congenital uterine anomalies. CONCLUSION: 3D US appears to be a very accurate method for the diagnosis of congenital uterine anomalies.

Implementation of Fetal Cardiac Guidelines for the Routine Second-Trimester Heart Examination: A Feasibility Study.

PURPOSE: This study aimed to explore the feasibility of implementation of the ISUOG 2013 guidelines on routine second-trimester examination of the fetal heart. MATERIALS AND METHODS: This was a prospective study in 357 women with singleton pregnancy undergoing their routine second-trimester scan. The fetal heart was examined using B-mode in different planes according to the guidelines. Potential maternal and fetal factors that can affect the rates of diagnostic-quality imaging for each of the recommended views were tested, using regression analysis. The intra- and interobserver agreement was analyzed in stored video loops. RESULTS: Most cardiac structures could be successfully examined with rates at or close to 100 %. Structures with a successful examination rate of ≤ 85 % included the ventricular wall fine details (55.2 %), tricuspid valve insertion (82.6 %), aortic root with clear walls (77.9 %), pulmonary artery walls (65.8 %) and clear view of the great artery walls (66.7 %). Common factors affecting the likelihood of successful examination of these structures included maternal BMI, skin-to-crux distance and the orientation of the cardiac axis. A post-hoc analysis indicated that a lack of pre-defined criteria for diagnostic quality was a constant reason for the interobserver variation. CONCLUSION: Most of the cardiac views can be consistently and reliably obtained, with maternal habitus being the primary factor limiting the quality of visualization. As offline interpretation may be subjective, using pre-defined quality criteria for the assessment of the images might improve interrater agreement.

The Use of Handheld Ultrasound Devices - An EFSUMB Position Paper.

The miniaturization of ultrasound equipment in the form of tablet- or smartphone-sized ultrasound equipment is a result of the rapid evolution of technology and handheld ultrasound devices (HHUSD). This position paper of the European Federation of Societies in Ultrasound and Medicine (EFSUMB) assesses the current status of HHUSD in abdominal ultrasound, pediatric ultrasound, targeted echocardiography and heart ultrasound, and we will report position comments on the most common clinical applications. Also included is a SWOT (Strength - Weaknesses - Opportunities - Threats) analysis, the use for handheld devices for medical students, educational & training aspects, documentation, storage and safety considerations.

Greek gynecology healthcare professionals towards quality management systems.

PURPOSE: Today, quality management systems (QMS) are a promising candidate for the improvement of healthcare services. The purpose of this paper is to investigate the opinions/attitudes of gynecology healthcare professionals toward quality and quality management in healthcare facilities (HFs) in Greece. DESIGN/METHODOLOGY/APPROACH: An anonymous self-administered questionnaire was distributed to healthcare professionals, asking for opinions on quality objectives associated with the everyday workflow in HFs (e.g. management of patients, resources, etc.) and on QMS. The study was conducted in Hippokration Hospital of Thessaloniki, including 187 participants. Statistical assessment and analysis of the questionnaires were carried out. FINDINGS: Although 87.5 percent recognized the importance of potential QMS implementation and accreditation, over 50 percent believed that it would lead rather to increased workload and bureaucracy than to any considerable quality improvement. More than 60 percent were completely unaware of the implementation of quality objectives such as quality handbook, quality policy, audit meetings and accreditation status in their HFs. This unawareness was also reported in terms of patient, data, human and general resources management. Finally, awareness over medical malpractice and positive attitude toward official reporting were detected. ORIGINALITY/VALUE: Most respondents acknowledged the significance of quality, QMS implementation and accreditation in Greek hospitals. However, there was a critical gap in knowledge about quality management objectives/processes that could be possibly resolved by expert teams and well-organized educational programs aiming to educate personnel regarding the various quality objectives in Greek HFs.

Gynecology healthcare professionals towards safety procedures in operation rooms aiming to enhanced quality of medical services in Greece.

PURPOSE: The purpose of this paper is to investigate the attitudes of healthcare professionals in Greece toward safety practices in gynecological Operation Rooms (ORs). DESIGN/METHODOLOGY/APPROACH: An anonymous self-administered questionnaire was distributed to surgical personnel asking for opinions on safety practices during vaginal deliveries (VDs) and gynecological operations (e.g. sponge/suture counting, counting documentation, etc.). The study took place in Hippokration Hospital of Thessaloniki including 227 participants. The team assessed and statistically analyzed the questionnaires. FINDINGS: Attitude toward surgical counts and counting documentation, awareness of existence and/or implementation in their workplace of other surgical safety objectives (e.g. WHO safety control list) was assessed. In total, 85.2 percent considered that surgical counting after VDs is essential and 84.9 percent admitted doing so, while far less reported counting documentation as a common practice in their workplace and admitted doing so themselves (50.5/63.3 percent). Furthermore, while 86.5 percent considered a documented protocol as necessary, only 53.9 percent admitted its implementation in their workplace. Remarkably, 53.1 percent were unaware of the WHO safety control list for gynecological surgeries. ORIGINALITY/VALUE: Most Greek healthcare professionals are well aware of the significance of surgical counting and counting documentation in gynecology ORs. However, specific tasks and assignments are unclear to them. Greek healthcare professionals consider surgical safety measures as important but there is a critical gap in knowledge when it comes to responsibilities and standardized processes during implementation. More effective implementation and increased personnel awareness of the surgical safety protocols and international guidelines are necessary for enhanced quality of surgical safety in Greece.