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.

COVID-19 incidence in women of reproductive age: a population-based study in Reggio Emilia, northern Italy.

BACKGROUND: Despite being at higher risk of severe disease and pregnancy complications, evidence on susceptibility to SARS-CoV-2 infection in pregnancy is still limited. The aim of the study is to compare the likelihood of undergoing a SARS-CoV-2 test and testing positive for COVID-19 in pregnancy and puerperium with that of the general female population of reproductive age. METHODS: This is a retrospective population-based cohort study including 117,606 women of reproductive age (March 2020-September 2021) with 6608 (5.6%) women having ≥ 1 pregnancy. Women were linked to the pregnancy registry to be classified as "non-pregnant", "pregnant", and "puerperium"; then, according to the national case-based integrated COVID-19 surveillance system, all women undergoing a SARS-CoV-2 test during the study period were identified. The Incidence Rate Ratio was calculated to compare the likelihood of being tested for SARS-CoV-2 in pregnant, puerperium and non-pregnant women among all women included. The likelihood of having a COVID-19 diagnosis was calculated using two comparators (not-pregnant women and the person-time before/after pregnancy) by means of Cox proportional hazards models, adjusting for age and with the cluster option to control standard error calculation in repeated pregnancies. Only first infection and swabs before the first one positive were included. RESULTS: The probability of being tested for SARS-CoV-2 was 4.9 (95% CI: 4.8-5.1) and 3.6 times higher (95%CI: 3.4-3.9) in pregnancy (including spontaneous miscarriages) and in the puerperium, respectively. The Hazard Ratio (HR) of covid-19 diagnosis during pregnancy vs. non-pregnancy was 1.17 (95% CI 1.03-1.33) with similar results when comparing the risk during pregnancy with that of the same women outside pregnancy (puerperium excluded), with an HR of 1.13 (95% CI 0.96-1.33); the excess decreased when excluding the test performed at admission for delivery (HR 1.08 (95%CI 0.90-1.30). In the puerperium, the HR was 0.62 (95% CI 0.41-0.92) comparing women with ≥ 1childbirth with all other women and excluding the first two weeks of puerperium. CONCLUSIONS: Women during pregnancy showed a small increase in the risk of infection, compatible with a higher likelihood of being tested. A lower probability of infection during the puerperium was observed during the entire pandemic period, suggesting likely protective behaviors which were effective in reducing their probability of infection.

How adenomyosis changes throughout pregnancy: A retrospective cohort study.

OBJECTIVE: To study how adenomyosis changes during pregnancy and to possibly correlate these changes to maternal and fetal outcomes. METHODS: Retrospective exploratory cohort study including 254 women with a pre-conceptional/first-trimester scan to document adenomyosis and known obstetric outcome. If visible, adenomyosis signs were documented in each trimester and postpartum. Mann-Whitney U tests or χ2 tests were used for continuous and categorical variables, respectively. RESULTS: A globular uterus was reported in 79% (n = 52) of women with adenomyosis in the first trimester, in 38% (n = 20) and 2% (n = 1) of women in the second and third trimesters, respectively, and postpartum in 77% (n = 34) of women. Asymmetrical thickening (n = 20, 30%) and cysts (n = 15, 23%) were only visible in 1st trimester. Adenomyosis was associated with miscarriage (odds ratio [OR] 5.9, 95% confidence interval [CI] 2.4-14.9, P < 0.001) also in normal conception only (OR 5.1, 95% CI 1.8-14.2, P = 0.002) or adjusting for maternal age (adjusted OR 5.9, 95% CI 2.3-15.2, P < 0.001). Gestational age at delivery was lower in adenomyosis (P = 0.004); the cesarean section rate was higher than in controls (OR 2.5, 95% CI 1.3-4.8, P = 0.007) also adjusting for age (adjusted OR 2.07, 95% CI 1.06-4.08, P = 0.035). CONCLUSIONS: Signs of adenomyosis were visible but progressively disappeared in pregnancy; adenomyosis was associated with an increased risk of early miscarriage. Prospective studies are needed to confirm our results.

Semen cryopreservation in men undergoing cancer treatment: a ten-year study.

BACKGROUND: The advancement of Assisted Reproductive Technologies and the improvement in sperm freezing made male fertility preservation widely available. This study aims to evaluate the impact of cancer diseases on semen parameters before cryopreservation and the reproductive outcomes of patients who have thawed their semen samples. METHODS: An observational, cohort study was conducted on cancer patients submitted to fertility preservation in AUSL-IRCCS of Reggio Emilia between 2007 and 2018. Semen samples were collected before cancer treatments, analyzed and frozen by rapid freezing. On request, these samples were thawed for Assisted Reproductive Technologies procedures. Semen parameters were compared between testicular versus other cancers. RESULTS: We included 329 patients with a successful cryopreservation in 94.5% of cases. Testicular cancer was associated with lower sperm volumes (P=0.041) and lower total sperm concentration (P=0.009) compared to other cancers. No difference was observed about sperm motility and morphology, while oligozoospermia was significantly more frequent in men with testicular cancer (P<0.001). In our cohort, the 8.4% of patients thawed their samples; the usage rate and the embryo transfer rate were significantly higher (P<0.05) among those with a testicular cancer, while pregnancy and livebirth rates did not differ. CONCLUSIONS: Male fertility preservation is feasible, easy to be performed, non-invasive and does not delay cancer treatments. Men affected by testicular cancer had worse semen parameters at cryopreservation but pregnancy and livebirth rates were similar to those achieved by men with other cancers and similar to those achieved with fresh sperm.

Prelabour rupture of the membranes at term: antibiotic overuse in Italy.

BACKGROUND: The proper management of women with premature rupture of membrane (PROM) and not spontaneously entering in labour remains controversial. The aim of this study was to identify the current management for women with PROM at term according to the Group B Streptococcus (GBS) status across different Italian hospitals. METHODS: Anonymous online survey evaluating: the current practice of women with PROM in terms of management (expectant management vs. induction of labour) and antibiotic prophylaxis according to GBS status. RESULTS: In case of negative GBS status, the 82.4% of respondents wait until 24 hours before labour induction. Antibiotics are administered for prophylaxis in 35.3%, 27.5% and 2% at 18, 12 and 24 hours respectively. The remaining 35.3% of respondents are divided between those using antibiotics only with signs of infections or according to different risk factors (i.e. meconium-stained amniotic fluid or suspected infection). Neonates born from a mother with negative GBS status almost never (90.2%) receive prophylactic antibiotics. In case of positive GBS status, induction is started as soon as possible by 49.1% of respondents; the remnants choose to wait 6 (15.7%), 12 (17.6%), 18 (3.9%) and 24 (13.7%) hours. Antibiotics are administered as soon as possible by 78.4% of clinicians. In the neonates, 51% of neonatologist administer antibiotics upon clinical indications (suspected sepsis); 15.7% use antibiotics routinely or with a short interval between maternal antibiotics and delivery (17.6%). CONCLUSIONS: The management after PROM is highly heterogeneous with an inappropriate extension of antibiotic prophylaxis in cases with negative GBS status.

Complete hydatidiform mole in higher-order multiple pregnancies.

Molar degeneration of the trophoblast is a rare, yet possible, complication of pregnancies. Complete hydatidiform mole is the most common histological type among all trophoblastic tumors and it is the result of the fertilization of an empty oocyte from two sperms or by one sperm that then duplicates. Complete mole is characterized by hydropic degeneration of abnormal chorionic villi, diffused trophoblast hyperplasia and the absence of identifiable embryonic or fetal tissue; the hyperplastic trophoblast justifies the common finding of high serum beta HCG levels. Twin molar pregnancy is an uncommon obstetric event, and even less frequent are triplet/quadruplet molar pregnancies. We hereby report a case of a complete hydatidiform mole with two coexistent fetuses in a triplet pregnancy after in vitro fertilization procedure; the pregnancy ended with a therapeutic abortion. During the follow-up, the serum beta human chorionic gonadotropin concentration started to rise, and the diagnosis of post-molar gestational trophoblastic neoplasia was made and consequently methotrexate treatment was started. Due to the rarity of this condition, there are no specific guidelines for the management of multiple pregnancies complicated by complete hydatidiform mole. We therefore performed a review of the literature including all reported cases of triplets/quadruplets pregnancies complicated by complete mole of a fetus focusing on ultrasound diagnosis, treatment and outcomes of this rare and life-threatening condition.

Screening for Low-Tract Genital Infections in Women with Threatened Preterm Labor: Which Role?

OBJECTIVES: The aim of this study was to evaluate the possible relationship between cultural specimens and preterm birth in women admitted for threatened preterm labor. Preterm birth is the leading cause of neonatal mortality and antenatal hospitalization; several risk factors including intrauterine infections have been identified, but its real causes remain poorly understood. DESIGN: This is a retrospective, multicenter, cohort study including 250 women admitted for threatened preterm labor. Methods, Participants/Materials, Setting: All women admitted for threatened preterm labor, i.e., presenting with cervical changes and uterine activity before 37 weeks at the obstetrics unit of the hospitals of Modena, Monza, Carate, and Vimercate were included in the study. We excluded twin pregnancies and cases with preterm premature rupture of membranes at admission. Data about maternal history, pregnancy complications, cervical length, vaginal swabs, and urine culture at admission and gestational age at delivery were collected from clinical records in order to compare the incidence of preterm birth according to some known risk factors, cervical length, and microbiological test at admission. RESULTS: 250 women were included in the study; preterm birth at less than 37 weeks occurred in 44.4% women admitted for threatened preterm labor. The incidence of preterm birth was not different between those with a positive or a negative vaginal swab (48.3 vs. 38.4%, p = 0.22) or positive versus negative urine culture (31.8 vs. 42.1%, p = 0.23) at admission. A shorter cervical length at admission was found in women with subsequent preterm birth (17 vs. 19.5 mm, p = 0.03). Cervical length <15 mm (OR 1.82, 95% CI: 1.03-3.23, p = 0.039) predicted the risk of preterm birth. Furthermore, only the history of a previous preterm birth (p = 0.02) and a previous uterine curettage (p = 0.045) was associated with preterm birth. LIMITATIONS: The observational and retrospective nature of the study and its small sample size are important limitations of the study. Moreover, women were not systematically or randomly assigned to the screening for vaginal or urinary infections. CONCLUSIONS: There is no evidence that the search for vaginal or urinary infections in women admitted for threatened preterm labor is helpful to identify those at increased risk of preterm birth. Although several studies have explored the role of screening for bacterial vaginosis in asymptomatic women and some studies evaluated vaginal or urinary infections in women with preterm birth, none of them focused on the possible role of microbiological specimens as a predictive tool in women admitted for threatened PTL. No association was found in our study, but prospective randomized controlled trials are required to confirm the results of this observation.

Role of balloon tamponade during cesarean section in women with placenta previa: a systematic review and meta-analysis.

INTRODUCTION: To explore the role of balloon tamponade insertion in pregnancies complicated by placenta previa. EVIDENCE ACQUISITION: Medline, Embase and ClinicalTrials.gov databases were searched electronically on October 17. Inclusion criteria were women with placenta previa undergoing, compared to those not undergoing, balloon tamponade insertion at the time of the cesarean section (CS). The outcomes observed were total, intra- and post-operative estimated blood loss (EBL), need for blood transfusion, admission to intensive care unit (ICU), hysterectomy and additional surgical or medical procedures to achieve hemostasis. Results were reported as pooled odd ratios (OR) or mean difference (MD) according to the outcome investigated. EVIDENCE SYNTHESIS: Four studies (593 women) were included. Total EBL was significantly lower in women undergoing balloon tamponade insertion during CS compared to controls (MD: -556.3, 95% CI -496 to -617.0, P=0.001). Likewise, women undergoing balloon tamponade insertion had significantly lower intra- (MD: -699.8, 95% CI -766.1 to -633.5, P=0.001) and post-operative (MD: -1162 mL (95% CI -1211.1 to -1134.4, P<0.001) compared to women who did undergo such procedure. Furthermore, women undergoing balloon tamponade insertion had a significantly lower risk of requiring additional surgical (OR: 0.16, 95% CI 0.1-0.5, I2=0%; P=0.001) or medical (OR: 0.02, 95% CI 0.003-0.1, I2=0; P=0.001) procedures to achieve hemostasis. Conversely, there was no significant difference in either the need for blood transfusion (P=0.071), admission to ICU (P=0.459) or need for hysterectomy (P=0.312) between women undergoing, compared to those not undergoing, balloon tamponade insertion during CS for placenta previa. CONCLUSIONS: Elective balloon tamponade insertion at the time of CS for placenta previa seems to be associated with a lower EBL and a reduced risk of additional medical and surgical procedures to control hemostasis. Large and adequately powered randomized controlled trials are needed to validate these results and introduce elective balloon tamponade insertion at the time of CS for placenta previa in clinical practice.

Ultrasound screening for fetal anomalies in a single center: diagnostic performances twenty years after the Eurofetus Study.

PURPOSE: To establish the accuracy of ultrasound in detecting fetal anomalies looking at the concordance between prenatal and postnatal diagnosis. MATERIALS AND METHODS: Retrospective analysis of concordance between prenatal and postnatal/autoptic diagnosis of fetuses with congenital abnormalities. Data are from a single center (Policlinico di Modena); all fetuses included were born between 2017 and 2018 and with a follow-up of at least 6 months. We included all deliveries (including perinatal deaths) and termination of pregnancy (TOP) for fetal indication. We calculated sensibility, sensitivity, Positive and Negative Likelihood Ratio, positive and negative predictive value of ultrasound. RESULTS: During the study period 5920 deliveries, including perinatal deaths, and 28 TOP for fetal indication were registered at our center. The prevalence of congenital malformations was 2.6% (153/5920). At least one ultrasound was performed in our center in 1250 women delivering in our unit. All 28 TOP had the anomaly scan performed in our center. Among the total 1278 women scanned in our unit, there were 128 (10%) suspicious scans. In 5/128 (3.9%) cases we diagnosed a false alarm; in 8/128 (6.2%) cases an evolutive malformation with in-utero regression. The prenatal diagnosis was confirmed in 77 (60.2%) cases at birth and in 28/128 (21.9%) at postmortem analysis while there were 10/128 false positive (7.8%). Among the 153 congenital malformations diagnosed at birth, the anomaly scan was performed in our Prenatal Medicine Unit in 92 (60.1%) fetuses. Among these, there were 15 false negatives (9.8%) while in 77/92 (83.7%) the malformation at birth agreed with the sonographic diagnosis. Sensitivity and specificity of ultrasound were 87.5% (IC95 80.2-92.8%) and 99.1% (IC95 98.4-99.6%) respectively with a Positive Likelihood Ratio and Negative Likelihood Ratio of 101.3 (IC95 54.5-188.5) and 0.13 (IC95 0.08-0.2); Positive Predictive Value and Negative Predictive Value were 91.3% (IC95 85-95.1%) and 98.7(IC95 98-99.2%). CONCLUSION: Anomaly scan in pregnancy allows the diagnosis of congenital malformations with a sensibility of 87.5% and specificity of 99.1%. The main limitations of this study are its retrospective design and that it was conducted in a single referral center.

Diagnostic performance of cerebroplacental and umbilicocerebral ratio in appropriate for gestational age and late growth restricted fetuses attempting vaginal delivery: a multicenter, retrospective study.

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

Role of prenatal magnetic resonance imaging in fetuses with isolated severe ventriculomegaly at neurosonography: A multicenter study.

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

Comparison between Cerebroplacental Ratio and Umbilicocerebral Ratio in Predicting Adverse Perinatal Outcome in Pregnancies Complicated by Late Fetal Growth Restriction: A Multicenter, Retrospective Study.

INTRODUCTION: The role of cerebroplacental ratio (CPR) or umbilicocerebral ratio (UCR) to predict adverse intrapartum and perinatal outcomes in pregnancies complicated by late fetal growth restriction (FGR) remains controversial. METHODS: This was a multicenter, retrospective cohort study involving 5 referral centers in Italy and Spain, including singleton pregnancies complicated by late FGR, as defined by Delphi consensus criteria, with a scan 1 week prior to delivery. The primary objective was to compare the diagnostic accuracy of the CPR and UCR for the prediction of a composite adverse outcome, defined as the presence of either an adverse intrapartum outcome (need for operative delivery/cesarean section for suspected fetal distress) or an adverse perinatal outcome (intrauterine death, Apgar score <7 at 5 min, arterial pH <7.1, base excess of >-11 mEq/mL, or neonatal intensive care unit admission). RESULTS: Median CPR absolute values (1.11 vs. 1.22, p = 0.018) and centiles (3 vs. 4, p = 0.028) were lower in pregnancies with a composite adverse outcome than in those without it. Median UCR absolute values (0.89 vs. 0.82, p = 0.018) and centiles (97 vs. 96, p = 0.028) were higher. However, the area under the curve, 95% confidence interval for predicting the composite adverse outcome showed a poor predictive value: 0.580 (0.512-0.646) for the raw absolute values of CPR and UCR, and 0.575 (0.507-0.642) for CPR and UCR centiles adjusted for gestational age. The use of dichotomized values (CPR <1, UCR >1 or CPR <5th centile, UCR >95th centile) did not improve the diagnostic accuracy. CONCLUSION: The CPR and UCR measured in the week prior delivery are of low predictive value to assess adverse intrapartum and perinatal outcomes in pregnancies with late FGR.

Role of progesterone, cerclage and pessary in preventing preterm birth in twin pregnancies: A systematic review and network meta-analysis.

OBJECTIVE: To determine the role of progesterone, pessary and cervical cerclage in reducing the risk of (preterm birth) PTB in twin pregnancies and compare these interventions using pairwise and network meta-analysis. STUDY DESIGN: Medline, Embase, CINAHL and Cochrane databases were explored. The inclusion criteria were studies in which twin pregnancies were randomized to an intervention for the prevention of PTB (any type of progesterone, cervical cerclage, cervical pessary, or any combination of these) or to a control group (e.g. placebo or treatment as usual). Interventions of interest were either progesterone [vaginal or oral natural progesterone or intramuscular 17a-hydroxyprogesterone caproate (17-OHPC)], cerclage (McDonald or Shirodkar), or cervical pessary. The primary outcome was PTB < 34 weeks of gestation. Both primary and secondary outcomes were explored in an unselected population of twin pregnancies and in women at higher risk of PTB (defined as those with cervical length <25 mm). Random-effect head-to-head and a multiple-treatment meta-analyses were used to analyze the data and results expressed as risk ratios. RESULTS: 26 studies were included in the meta-analysis. When considering an unselected population of twin pregnancies, vaginal progesterone, intra-muscular17-OHPC or pessary did not reduce the risk of PTB < 34 weeks of gestation (all p > 0.05). When stratifying the analysis for spontaneous PTB, neither pessary, vaginal or intramuscular 17-OHPC were associated with a significant reduction in the risk of PTB compared to controls (all p > 0.05), while there was no study on cerclage which explored this outcome in an unselected population of twin pregnancies. When considering twin pregnancies with short cervical length (≤25 mm), there was no contribution of either pessary, vaginal progesterone, intra-muscular 17-OHPC or cerclage in reducing the risk of overall PTB < 34 weeks of gestation. CONCLUSIONS: Cervical pessary, progesterone and cerclage do not show a significant effect in reducing the rate of PTB or perinatal morbidity in twins, either when these interventions are applied to an unselected population of twins or in pregnancies with a short cervix.

Maternal and neonatal outcomes of pregnancies complicated by late fetal growth restriction undergoing induction of labor with dinoprostone compared with cervical balloon: A retrospective, international study.

INTRODUCTION: The aim of this study was to compare vaginal dinoprostone and mechanical methods for induction of labor (IOL) in pregnancies complicated by late fetal growth restriction. MATERIAL AND METHODS: Multicenter, retrospective, cohort study involving six referral centers in Italy and Spain. Inclusion criteria were pregnancies complicated by late fetal growth restriction as defined by Delphi consensus criteria. The primary outcome was the occurrence of uterine tachysystole; secondary outcomes were either cesarean delivery or operative vaginal delivery for non-reassuring fetal status, a composite score of adverse neonatal outcome and admission to neonatal intensive care unit (NICU). Univariate and multivariate logistic regression analysis was used to analyze the data. RESULTS: A total of 571 pregnancies complicated by late fetal growth restriction undergoing IOL (391 with dinoprostone and 180 with mechanical methods) were included in the analysis. The incidence of uterine tachysystole (19.2% vs. 5.6%; p = 0.001) was higher in women undergoing IOL with dinoprostone than in those undergoing IOL with mechanical methods. Similarly, the incidence of cesarean delivery or operative delivery for non-reassuring fetal status (25.6% vs. 17.2%; p = 0.027), composite adverse neonatal outcome (26.1% vs. 16.7%; p = 0.013) and NICU admission (16.9% vs. 5.6%; p < 0.001) was higher in women undergoing IOL with dinoprostone than in those undergoing IOL with mechanical methods. At logistic regression analysis, IOL with mechanical methods was associated with a significantly lower risk of uterine tachysystole (odds ratio 0.26, 95% confidence interval 0.13-0.54; p < 0.001). CONCLUSIONS: In pregnancies complicated by late fetal growth restriction, IOL with mechanical methods is associated with a lower risk of uterine tachysystole, cesarean delivery or operative delivery for non-reassuring fetal status, and adverse neonatal outcome compared with pharmacological methods.

How Can We Treat Vulvar Carcinoma in Pregnancy? A Systematic Review of the Literature.

According to our systematic literature review (PRISMA guidelines), only 37 vulvar squamous cell carcinomas (VSCCs) were diagnosed during pregnancy (age range: 17-41 years). The tumor size range was 0.3-15 cm. The treatment was performed after (14/37, 38%), before (10/37, 27%), or before-and-after delivery (11/37, 30%). We found that 21/37 (57%) cases were stage I, 2 II (5%), 11 III (30%), and 3 IVB (8%). HPV-related features (condylomas/warts; HPV infection; high-grade squamous intraepithelial lesion) were reported in 11/37 (30%) cases. We also found that 9/37 (24%) patients had inflammatory conditions (lichen sclerosus/planus, psoriasis, chronic dermatitis). The time-to-recurrence/progression (12/37, 32%) ranged from 0 to 36 (mean 9) months. Eight women died of disease (22%) 2.5-48 months after diagnosis, 2 (5%) were alive with disease, and 23 (62%) were disease-free at the end of follow-up. Pregnant patients must be followed-up. Even if they are small, newly arising vulvar lesions should be biopsied, especially in women with risk factors (HPV, dermatosis, etc.). The treatment of VSCCs diagnosed in late third trimester might be delayed until postpartum. Elective cesarean section may prevent vulvar wound dehiscence. In the few reported cases, pregnancy/fetal outcomes seemed to not be affected by invasive treatments during pregnancy. However, clinicians must be careful; larger cohorts should define the best treatment. Definite guidelines are lacking, so a multidisciplinary approach and discussion with patients are mandatory.

Role of prenatal magnetic resonance imaging in fetuses with isolated agenesis of corpus callosum in the era of fetal neurosonography: A systematic review and meta-analysis.

INTRODUCTION: Corpus callosum agenesis (ACC) is frequently diagnosed during fetal life; its prognosis depends also on additional anomalies. The additional value of fetal magnetic resonance imaging (MRI) in fetuses with "isolated" complete (cACC) and partial (pACC) agenesis of the corpus callosum on ultrasound is still debated. MATERIAL AND METHODS: We performed a systematic literature review and meta-analysis including fetuses with a prenatal diagnosis of cACC and pACC without associated structural anomalies on ultrasound, undergoing fetal MRI. The primary outcome was the rate of additional anomalies detected at fetal MRI. Further analyses assessed the effect of type of ultrasound assessment (neurosonography vs standard axial assessment), gestational age at fetal MRI and rate of postnatally detected brain anomalies. Random-effect meta-analyses of proportions were used to analyze the data. RESULTS: Fourteen studies (798 fetuses) were included. In cases with isolated cACC, 10.9% (95% CI 4.1-20.6) and 4.3% (95% CI 1.4-8.8) additional anomalies were detected by fetal MRI and postnatally, respectively. Stratifying according to the type of ultrasound assessment, the rate of associated anomalies detected only on fetal MRI was 5.7% (95% CI 0.5-16.0) with dedicated neurosonography and 18.5% (95% CI 7.8-32.4) with a standard axial assessment. In fetuses with isolated pACC, 13.4% (95% CI 4.0-27.0) and 16.2% (95% CI 5.9-30.3) additional anomalies were detected by fetal MRI or postnatally, respectively. Stratifying according to the type of ultrasound assessment, the rate of associated anomalies detected only on fetal MRI was 11.4% (95% CI 2.7-25.0) when dedicated neurosonography was performed. Cortical and posterior fossa anomalies represented the most common anomalies missed at ultrasound with both cACC and pACC. Due to the very small number of included cases, stratification according to early (<24 weeks of gestation) and late (>24 weeks) fetal MRI could not be done for either cACC or pACC. CONCLUSIONS: The rate of associated anomalies detected exclusively at fetal MRI in isolated ACC undergoing neurosonography is lower than previously reported. Cortical and posterior fossa anomalies are among the most common anomalies detected exclusively at MRI, thus confirming the crucial role of fetal MRI in determining the prognosis of these fetuses. However, some anomalies still go undetected prenatally and this should be stressed during parental counseling.

Pregnant woman infected by Coronavirus disease (COVID-19) and calcifications of the fetal bowel and gallbladder.

COVID-19 was declared to be a pandemic due to the rapid increase of cases around the world, including the number of pregnant women. Data about vertical transmission of COVID-19 are still limited and controversial: in most cases, although a positive mother, the virus could not be isolated in amniotic fluid, cord blood, breast milk or neonatal throat swab in these patients. No data have been published about possible intrauterine sonographic signs of infection. A pregnant woman was diagnosed with SARS-CoV-2 at 35+5 weeks of gestation and managed conservatively at home. At transabdominal ultrasound at 38+3 weeks, fetal bowel and gallbladder calcifications were noted. CMV and other infectious agents were ruled out; an iterative caesarean section was performed at 38+5 weeks without complications. Placenta resulted negative for SARS-CoV-2; the umbilical cord blood sample was IgG positive and IgM negative as per maternal infection. The baby developed respiratory distress syndrome requiring endotracheal surfactant administration and nasal-CPAP for one day but nasopharyngeal swabs at birth and after 48 hours were SARS-CoV-2 negative. Neonatal abdominal ultrasound showed normal liver, acalculous gallbladder with mild parietal thickening. The baby was discharged in good conditions. Although gallbladder calcifications and echogenic bowel are highly suspicious of viral infection and were thought to be due to the vertical transmission of SARS-CoV-2, these findings were not corroborated by the results of our diagnostic tests; these sonographic findings might represent a false positive of fetal infection in mother affected by COVID-19 since vertical transmission appears to be rare.

Perinatal outcomes of twin pregnancies complicated by late twin-twin transfusion syndrome: A systematic review and meta-analysis.

INTRODUCTION: Untreated twin-to-twin transfusion syndrome (TTTS) is associated with a high risk of perinatal mortality and morbidity. Laser surgery is recommended before 26 weeks of gestation. However, the optimal management in case of late TTTS (occurring after 26 weeks of gestation) is yet to be established. MATERIAL AND METHODS: We conducted a systematic review and meta-analysis to evaluate the outcomes of monochorionic-diamniotic twin pregnancies complicated by late TTTS according to different management options (expectant, laser therapy, amnioreduction, or delivery). The primary outcome was mortality, including single and double intrauterine, neonatal, and perinatal death. Secondary outcomes were composite morbidity, neuromorbidity, respiratory distress syndrome, admission to neonatal intensive care unit, intact survival (ie, free from neurological complications), and preterm birth before <32 weeks of gestation. Outcomes were reviewed according to the management and reported for the overall population of twins and disease status (ie, donor and recipient separately). Random-effect meta-analyses of proportions were used to analyze the data. RESULTS: Nine studies including 796 twin pregnancies affected by TTTS were included. No randomized controlled trials were available for inclusion. TTTS occurred at ≥26 weeks of gestation in 8.7% (95% CI 6.9%-10.9%; 67/769) of cases reporting TTTS at all gestations. Intrauterine death occurred in 17.7% (95% CI 4.9%-36.2%) of pregnancies managed expectantly, 5.3% (95% CI 0.9%-12.9%) of pregnancies treated with laser, and 0% (95% CI 0%-9%) after amnioreduction. Neonatal death occurred in 42.5% (95% CI 17.5%-69.7%) of pregnancies managed expectantly, in 2.8% (95% CI 0.3%-7.7%) of cases treated with laser, and in 20.2% (95% CI 6%-40%) after amnioreduction. Only one study (10 cases) reported data on immediate delivery after diagnosis with no perinatal deaths. Perinatal death incidence was 55.7% (95% CI 31.4%-78.6%) in twin pregnancies managed expectantly, 5.6% (95% CI 0.5%-15.3%) in those treated with laser, and 20.2% (95% CI 6%-40%) in those after amnioreduction. Intact survival was reported in 44.4%, 96.4%, and 78% of fetuses managed expectantly, with laser or amnioreduction, respectively. CONCLUSIONS: Evidence regarding perinatal mortality and morbidity in twin pregnancies complicated by late TTTS according to the different managements was of very low quality. Therefore further high-quality research in this field is needed to elucidate the optimal management of these pregnancies.

Perinatal outcomes of twin pregnancies affected by early twin-twin transfusion syndrome: A systematic review and meta-analysis.

INTRODUCTION: Twin-to-twin transfusion syndrome (TTTS) is associated with a high risk of perinatal mortality and morbidity if not treated. However, the optimal timing and management in case of early (occurring < 18 weeks) TTTS has not been established yet. MATERIAL AND METHODS: This is a systematic review and meta-analysis aiming at evaluating the outcomes of monochorionic diamniotic twin pregnancies complicated by early (ie before 18 weeks) TTTS according to different management options (expectant, laser therapy, amnioreduction or cord occlusion). The primary outcome was mortality, including single and double intrauterine, neonatal and perinatal death. Secondary outcomes were: composite morbidity, neuromorbidity, respiratory distress syndrome, admission to neonatal intensive care unit, intact survival (defined as survival free from neurological complications) and preterm birth < 32 weeks of gestation. All outcomes were reviewed according to the different management options (expectant, laser therapy, amnioreduction or cord occlusion) and reported FOR the overall population of twins, and for the donor and recipient separately. Subgroup analysis for TTTS occurring before 16 weeks of gestation was performed. Random-effect meta-analyses of proportions were used to analyse the data. RESULTS: Thirteen studies were included. Early TTTS occurred in 14.3% (95% confidence interval [CI] 11.9-17.0) of cases. The incidence of intrauterine death was 19.0% (95% CI 2.6-45.5) in twins managed expectantly, 32.4% (95% CI 16.5-50.7) in those who received laser treatment and 12.5% (95% CI 4.8-23.0) in those treated with amnioreduction. The incidence of neonatal death was 22.6% (95% CI 4.2-49.8) in twins managed expectantly, 24.7% (95% CI 0.5-80.3) in those who received laser and 20.2 (95% CI 5.8-43.4) in those who had amnioreduction; it was not possible to compute the incidence of these outcomes in twins undergoing cord occlusion because of insufficient sample and lack of reporting of most of the observed outcomes. Overall, the incidence of perinatal death was 43.9% (95% CI 5.9-87.7) in twins managed expectantly, 47.3% (95% CI 21.4-70.0) in those treated with laser and 28.5% in those who had amnioreduction. CONCLUSIONS: Twin pregnancies affected by early TTTS are at substantial risk of perinatal mortality and morbidity; however, the data come from very small studies with a high risk of selection bias.

Outcome of isolated fetal talipes: A systematic review and meta-analysis.

INTRODUCTION: The aim of this systematic review was to explore the outcome of fetuses with a prenatal diagnosis of isolated talipes. MATERIAL AND METHODS: Medline, Embase, Cinahl, and Clinicaltrials.gov databases were searched. The outcomes explored were: associated anomalies detected at follow-up ultrasound examination; fetal magnetic resonance imaging (MRI) and birth; chromosomal abnormalities detected with standard and chromosomal microarray analysis, intrauterine, neonatal, and perinatal death, and termination of pregnancy; rate of surgical and nonsurgical treatment; neurodevelopmental outcome; and false-positive rate of prenatal diagnosis. Meta-analyses of proportions were used to combine data. RESULTS: Twenty-five studies (1567 fetuses) were included. Associated anomalies were detected in 7.8% (95% CI 0.1%-29.3%) of cases at follow-up ultrasound, and in 4.0% (95% CI 0.1%-13.2%) of cases, fetal MRI identified anomalies not detected at ultrasound assessment. Similarly, 7.0% (95% CI 3.4%-11.7%) of cases labeled as isolated talipes on prenatal imaging were found to have associated anomalies at birth. Abnormal karyotype was present in 3.6% (95% CI 1.7%-6.2%) of fetuses, whereas no anomaly was found at chromosomal microarray analysis, although this outcome was reported by only 1 study. Intrauterine death occurred in 0.99% (95% CI 0.4%-1.9%) of fetuses, whereas the corresponding figures for neonatal death and termination of pregnancy were 1.5% (95% CI 0.6%-2.6%) and 2.2% (95% CI 1.2%-3.4%), respectively. Surgical management of anomalies after birth was found in 41.7% (95% CI 27.0%-57.2%) of fetuses with isolated talipes, and 54.8% (95% CI 31.5%-77.0%) had nonsurgical management of the anomalies after birth. Abnormal neurodevelopmental outcome was reported in 7.6% (95% CI 1.0%-19.4%) of children, although this analysis was affected by the small number of included cases and short time of follow up. CONCLUSIONS: Isolated talipes detected on prenatal ultrasound carries a generally good prognosis. The incidence of additional abnormalities detected on fetal MRI, aneuploidy, or neurodevelopmental disability is relatively low. However, longitudinal ultrasound assessment during pregnancy and a thorough postnatal evaluation are recommended to rule out associated anomalies that may significantly impact short- and long-term prognosis.