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Background. Neurotrophins, such as BDNF and NGF, are overexpressed in tumor cells in cervical cancer, and HIV infection is associated with the upregulation of neurotrophin expression. Therefore, we aimed to investigate whether BDNF and NGF are overexpressed in preneoplastic cervical disease from HIV-infected women. Methods. Women with preneoplastic cervical lesions (cervical intraepithelial neoplasia grade 2 or 3) were prospectively enrolled and grouped according to their HIV status. Samples from Loop Electrosurgical Excision Procedure (LEEP) for suspected cervical cancer were obtained, and immunohistochemistry was performed to evaluate BDNF and NGF expression. Results. We included in our analysis 12 HIV-infected patients who were matched with 23 HIV-negative patients as a control group. Immunohistochemistry analysis showed that BDNF expression was significantly higher in cervical preneoplastic lesions from HIV-positive women than in the lesions from the control group. In particular, BDNF was expressed in 8/12 HIV-positive patients and 7/23 HIV-negative patients (66.7% vs. 30.4%, χ2 = 4.227; p = 0.040). NGF expression was not significantly higher in cervical preneoplastic lesions from HIV-positive women compared with that in the lesions from the control group. In particular, NGF was expressed in 8/12 HIV-positive patients and in 12/23 HIV-negative patients (66.7% vs. 52.2% χ2 = 0.676; p = 0.411). Logistic regression analysis showed that the HIV status is an independent predictor of BDNF expression in pre-invasive preneoplastic cervical disease when considered alone (crude OR 4.6, 95% CI 0.027–20.347; p = 0.046) and when analyzed with other co-factors (adjusted OR 6.786, 95% CI 1.084–42.476; p = 0.041). Conclusions. In preneoplastic cervical disease, BDNF expression is higher in HIV-infected women than in non-infected controls, and this is independent of the clinical features of the patients and from the presence of the HPV-HR genotype. BDNF can play a key role as a link between the pathways by which HIV and HPV interact to accelerate cervical cancer progression and invasion. These data can be useful to better understand the role of neurotrophins in the cancerogenesis of cervical cancer and the possible therapeutic strategies to improve disease outcomes.

To assess the longitudinal variation of the ratio of umbilical and cerebral artery pulsatility index (UCR) in late preterm fetal growth restriction (FGR). A prospective European multicenter observational study included women with a singleton pregnancy, 32 856 women had 2770 measurements; 696 (81 %) had more than one measurement (median 3 (IQR 2-4). At inclusion, 63 (7 %) a UCR ≥ 0.9. These delivered earlier and had a lower birth weight and higher incidence of adverse outcome (30 % vs. 9 %, relative risk 3.2; 95 %CI 2.1-5.0) than women with a normal UCR at inclusion. Repeated measurements after an abnormal UCR at inclusion were abnormal again in 67 % (95 %CI 55-80), but after a normal UCR the chance of finding an abnormal UCR was 6 % (95 %CI 5-7 %). The risk of composite adverse outcome was similar using the first or subsequent UCR values. An abnormal UCR is likely to be abnormal again at a later measurement, while after a normal UCR the chance of an abnormal UCR is 5-7 % when repeated weekly. Repeated measurements do not predict outcome better than the first measurement, most likely due to the most compromised fetuses being delivered after an abnormal UCR.ZIEL: Beurteilung der longitudinalen Variation der umbilikozerebralen Ratio (UCR) der Pulsatilitätsindizes bei später fetaler Wachstumsrestriktion (FGR). Eine prospektive europäische multizentrische Beobachtungsstudie schloss Frauen mit Einlingsschwangerschaft (32 856 Frauen hatten 2770 Messungen; 696 (81 %) hatten mehr als eine Messung (Median 3, IQR 2–4). Bei Einschluss hatten 63 (7 %) eine UCR ≥ 0,9. Diese entbanden früher und hatten ein niedrigeres Geburtsgewicht und eine höhere Inzidenz für einen unerwünschten Outcome (30 % vs. 9 %, relatives Risiko 3,2; 95 %-KI 2,1–5,0) im Vergleich zu Frauen mit normaler UCR bei Einschluss. Wiederholte Messungen nach abnormaler UCR bei Einschluss waren in 67 % (95 %-KI 55–80) erneut abnormal, aber nach einer normalen UCR betrug die Wahrscheinlichkeit, eine abnormale UCR zu finden, 6 % (95 %-KI 5–7 %). Das Risiko für einen kombinierten unerwünschten Outcome war ähnlich, wenn man den ersten oder den nachfolgenden UCR-Wert verwendete. Eine abnormale UCR ist wahrscheinlich bei einer späteren Messung wieder abnormal, während nach einer normalen UCR die Wahrscheinlichkeit einer abnormalen UCR bei wöchentlicher Wiederholung 5–7 % beträgt. Wiederholte Messungen sagen das Ergebnis nicht besser voraus als die erste Messung, was höchstwahrscheinlich darauf zurückzuführen ist, dass die am stärksten gefährdeten Föten nach einer abnormalen UCR entbunden werden.

To investigate the use of computerized cardiotocography (cCTG) parameters in Intrauterine Growth Restriction (IUGR) pregnancies for the prediction of 1) complication with preeclampsia; 2) placental histological abnormalities, and 3) neonatal outcomes. A single-center observational retrospective case-control study was performed by reviewing medical records, cCTG databases and pathological reports of women with singleton pregnancy and IUGR uncomplicated (controls) and complicated by preeclampsia (cases). Primary endpoint was the association between cCTG parameters and preeclampsia in IUGR. Secondary endpoints were the association between cCTG parameters and 1) placental abnormalities, and 2) neonatal outcomes. The one-way ANOVA test was used to compare cCTG parameters in cases and controls. t-test was applied to compare neonatal outcomes and placental abnormalities in both groups. The Spearman Test value Correlation coefficients between the cCTG parameters and neonatal outcome in the two groups. A p value < .05 was considered significant for all analyses. Among all cCTG parameters, a significant association with preeclampsia in IUGR was found for Fetal Heart Rate (FHR, p = .008), Delta (p = .018), Short Term Variability (STV, p = .021), Long Term Variability (LTV, p = .028), Acceleration Phase Rectified Slope (APRS, p = .018) and Deceleration Phase Rectified Slope (DPRS, p = .038). Of all placental histologic abnormalities, only vascular alterations at least moderate were significantly associated with increased FHR (p = .02). About neonatal outcomes, all cCTG parameters were significantly associated with birth weight, Apgar index at 1 and 5 min, pH and pCO2. FHR, LTI, Delta, Approximate Entropy (ApEn) and LF were significantly associated with pO2; LTI, Interval Index (II) and ApEn with base excess. Among controls, Delta, ApEn, Low Frequency (LF) and High Frequency (HF) were significantly associated with pCO2, while among cases, STV and Delta were significantly associated with pH; STV, LTI, Delta, ApEn, LF and HF with pCO2; STV, LTI, Delta and ApEn with pO2; HF with base excess; FHR and LF with lactates. cCTG parameters may be useful to detect complication with preeclampsia in IUGR pregnancies. Regarding placental status, cCTG parameters may detect overall circulation alterations, but not specific histological abnormalities. Lastly, all cCTG parameters may predict neonatal outcomes, helping to tailor the patients’ management.

Background The COronaVIrus Disease 2019 (COVID-19) has spread in Italy since February 2020, inducing the government to call for lockdown of any activity, apart primary needs, during the months March–May 2020. During the lockdown, a reduction of admissions and hospitalizations for ischemic diseases was noticed. Purpose of this study was to observe if there has been the same reduction trend in Accident & Emergency (A&E) unit admissions also for obstetric-gynecological conditions. Methods Medical records and electronic clinical databases were searched for all patients who were admitted to the obstetric A&E department or hospitalized at the Gynecology and Obstetrics Unit of University hospital of Naples Federico II, during the quarter March–May in the years 2019 and 2020. The mean ± standard deviation (SD) of monthly admission to the obstetric A&E department and hospitalization of the year 2020 was compared with that of the year 2019, using the unpaired T test with α error set to 0.05 and 95% confidence intervals (95% CI). Results Admissions were 1483 in the year 2020 and 1786 in 2019. Of total, 1225 (37.5%) women were hospitalized: 583 in the year 2020, 642 in 2019. Mean ± SD of patients monthly admitted to our obstetric A&E department was 494 ± 33.7 in the year 2020, and 595.3 ± 30.9 in 2019, with a mean difference of − 101.3 (95% CI − 103.5 to − 99.1; p p Conclusion A significant decrease in the mean of monthly admissions and hospitalizations during the COVID-19 pandemic when compared to the previous year was found also for obstetric–gynecological conditions. Further studies are necessary to assess COVID-19 impact and to take the most appropriate countermeasures.

Singleton pregnancies obtained by assisted reproductive technology (ART) are at increased risk of adverse pregnancy outcome. Aim of this pilot study was to compare maternal hemodynamic profile in ART and spontaneous singleton pregnancies. Patients were enrollered during a third trimester routine obstetric examination. Maternal haemodynamic assessment was carried out by a single trained operator using an UltraSonic Cardiac Output Monitor in standardized conditions. Our pilot data suggests that women conceived after ART may have significantly lower Cardiac Output and significantly higher Systemic Vascular Resistance when compared to those conceiving spontaneously. These differences, if confirmed in larger studies, might explain the increased prevalence of adverse outcome, especially hypertensive disorders of pregnancy, in singleton ART pregnancies.

Objectives: To explore perinatal outcomes in SARS-CoV-2 vaccinated pregnant women comparing with unvaccinated counterparts. Methods: Search was conducted using Web of Science, Scopus, ClinicalTrial.gov, MEDLINE, Embase, OVID and Cochrane Library as electronic databases. We included observational studies evaluating pregnant women undergoing SARS-CoV-2 vaccination and compared pregnancy and perinatal outcomes with unvaccinated ones. Categorical variables were assessed using Odds Ratio (OR) with 95% Confidence Interval (CI), while for continuous variables results were expressed as Mean difference (MD) with their 95% Confidence Interval. All analyses were performed by adopting the random effect model of DerSimonian and Laird. Results: There is no difference in the probability of having a small for gestational age fetus (OR 0.97, 95% CI 0.85-1.09; p=0.570), while we observed a reduced probability of a non-reassuring fetal monitoring, a reduced gestational age at delivery and a reduced probability of premature delivery in vaccinated pregnant women versus unvaccinated ones. Conclusion: The probability of small for gestational age is similar between vaccinated and unvaccinated pregnant women, and the former had also a slightly reduced rate of premature delivery. Keywords: COVID-19; SARS-CoV-2; meta-analysis; pregnancy; preterm birth; small for gestational age; systematic review; vaccine.

Objective: To evaluate the use of computerized cardiotocography (C-CTG) in women with diabetes mellitus. Methods: This was a retrospective cohort study of women with diabetes mellitus referred to University of Naples Federico II from January 2018 to January 2020 for antenatal monitoring. Only women who underwent antenatal monitoring with C-CTG were included in the study. For the purpose of this study only the C-CTG recorded at the time of outpatient admission were analysed. Women were divided into four groups: 1. Women with diabetes mellitus type 1; 2. Women with diabetes mellitus type 2; 3. Women with gestational diabetes mellitus (GDM); 4. Control group without diabetes mellitus. The primary outcome of the study was the C-CTG short term variability (STV). Results: A total of 298 patients were included in the study, 89 with type 1 diabetes (group 1), 27 with type 2 diabetes (group 2), 77 with GDM (group 3) and 105 controls (group 4). Fetal heart rate was statistically higher in pregnant women with pre-pregnancy diabetes both Type 1 and 2 compared to gestational diabetes and physiological pregnancies. The parameters of STV, APRS and DPRS were statistically lower in the pregnant group with pre-pregnancy type 1 diabetes than in type 2 and compared to group 3 and 4. Conclusions: Fetal heart rate was statistically higher in pregnant women with pre-pregnancy diabetes, both Type 1 and 2, compared to gestational diabetes and controls. STV, APRS and DPRS were statistically lower in the pregnant group with pre-pregnancy type 1 diabetes than in type 2 and compared to group 3 and 4.

Artificial intelligence is finding several applications in healthcare settings. This study aimed to report evidence on the effectiveness of artificial intelligence application in obstetrics. Through a narrative review of literature, we described artificial intelligence use in different obstetrical areas as follows: prenatal diagnosis, fetal heart monitoring, prediction and management of pregnancy-related complications (preeclampsia, preterm birth, gestational diabetes mellitus, and placenta accreta spectrum), and labor. Artificial intelligence seems to be a promising tool to help clinicians in daily clinical activity. The main advantages that emerged from this review are related to the reduction of inter- and intraoperator variability, time reduction of procedures, and improvement of overall diagnostic performance. However, nowadays, the diffusion of these systems in routine clinical practice raises several issues. Reported evidence is still very limited, and further studies are needed to confirm the clinical applicability of artificial intelligence. Moreover, better training of clinicians designed to use these systems should be ensured, and evidence-based guidelines regarding this topic should be produced to enhance the strengths of artificial systems and minimize their limits.

Background The clinical diagnosis of late Fetal Growth Restriction (FGR) involves the integration of Doppler ultrasound data and Fetal Heart Rate (FHR) monitoring through computer assisted computerized cardiotocography (cCTG). The aim of the study was to evaluate the diagnostic power of combined Doppler and cCTG parameters by contrasting late FGR –and healthy controls. Methods The study was conducted from January 2018 to May 2020. Only pregnant women who had the last Doppler measurement obtained within 1 week before delivery and cCTG performed within 24 h before delivery were included in the study. Two hundred forty-nine pregnant women fulfilling the inclusion criteria were enrolled in the study; 95 were confirmed as late FGR and 154 were included in the control group. Results Among the extracted cCTG parameters, Delta Index, Short Term Variability (STV), Long Term Variability (LTV), Acceleration and Deceleration Phase Rectified Slope (APRS, DPRS) values were lower in the late FGR participants compared to the control group. In the FGR cohort, Delta, STV, APRS, and DPRS were found different when stratifying by MCA_PI (MCA_PI 5th centile). STV and DPRS were the only parameters to be found different when stratifying by (UA_PI >95th centile or UA_PI The AUC of ROC curves were accurate for STV (0,70), Delta (0,68), APRS (0,65) and DPRS (0,71) when UA_PI values were > 95th centile while, the accuracy attributable to the prediction of MCA_PI was 0.76, 0.77, 0.73, and 0.76 for STV, Delta, APRS, and DPRS, respectively. An association of UA_PI>95th centile and MCA_PI Conclusions The results of this study show the contribution of advanced cCTG parameters and fetal Doppler to the identification of late FGR and the association of those parameters with the risk for NICU admission. Trial registration Retrospectively registered.

Background Congenital malformations of the central nervous system (CNS) consist of a wide range of birth defects of multifactorial origin. Methods Concentrations of 44 metals were determined by Inductively Coupled Plasma Mass Spectrometry in serum of 111 mothers in the second trimester of pregnancy who carried a malformed fetus and compared them with serum concentrations of the same metals in 90 mothers with a normally developed fetus at the same week of pregnancy. Data are reported as means ± standard deviations. Results We found a direct relationship between congenital defects of the CNS and maternal serum concentration of aluminum: it was statistically higher in women carrying a fetus with this class of malformation, compared both to mothers carrying a fetus with another class of malformation (6.45 ± 15.15 μg/L Vs 1.44 ± 4.21 μg/L, p Conclusion CAluminum may play a role in the onset of central nervous system malformations, although the exact Aluminum species and related specific type of malformation needs further elucidation.

Histological chorioamnionitis is associated with significant adverse maternal, perinatal and long-term outcome. We performed a meta-analysis of 30 observational studies in order to clarify the association between Histological chorioamnionitis and pulmonary complications, like respiratory distress syndrome and Bronchopulmonary Dysplasia. Unadjusted data extracted from all studies showed that Histological chorioamnionitis has no effect on development of RDS (RR 0.93, 95% CI 1.08-1.67), while it increased the risk of Bronchopulmonary Dysplasia (RR 1.75, 95% CI 1.37-2.23). However, when we restricted the analysis to the studies that adjust for Gestational Age, in order to exclude the influence of prematurity, we found that HCA reduced the risk of respiratory distress syndrome (RR 0.57, CI 95% 0.35-0.93) and it did not affect the development of Bronchopulmonary Dysplasia (RR 0.99, CI 0.76-1.3). Our results confirmed a possible role of prenatal inflammation on lung maturation. However, further prospective studies with a selected population are needed, in order to clarify the role of Histological chorioamnionitis in neonatal pulmonary complications.

X-linked Opitz G/BBB syndrome (XLOS) is a multiple congenital disorder inherited in an X-linked manner. XLOS may be suspected, in prenatal age, on the basis of sonographic findings in the second and/or third trimester of gestation. Pathogenetic variants in MID1 gene have been reported in individuals with XLOS. Prenatal genetic testing is offered for pregnancies at risk, in which the mutation in the family has been identified. To date no cases of prenatal diagnosis, based on first-trimester ultrasound data, have been reported. We present a case of a fetus at 12 gestational weeks with ultrasound multiple anomalies, including increased nuchal translucency, heart defects, cleft lip and palate, enlarged fourth ventricle absence of ductus venosus and family hystory of XLOS. The genetic prenatal test detected the c(0).1286-1G > T mutation of MID1 gene. Data about prenatal ultrasonographic findings consistent with XLOS are limited to second and third trimester. This is the first case reporting ultrasound detectable midline defects suggestive of XLOS as early as the first trimester of gestation. This case also suggests that when multiple anomalies are detected in a fetus with normal chromosomal structure, the possibility of a monogenic disorder must be considered.

Regenerative medicine represents a growing hot topic in biomedical sciences, aiming at setting out novel therapeutic strategies to repair or regenerate damaged tissues and organs. For this perspective, human mesenchymal stem cells (hMSCs) play a key role in tissue regeneration, having the potential to differentiate into many cell types, including chondrocytes. Accordingly, in the last few years, researchers have focused on several in vitro strategies to optimize hMSC differentiation protocols, including those relying on epigenetic manipulations that, in turn, lead to the modulation of gene expression patterns. Therefore, in the present study, we investigated the role of the class II histone deacetylase (HDAC) inhibitor, MC1568, in the hMSCs-derived chondrogenesis. The hMSCs we used for this work were the hMSCs obtained from the amniotic fluid, given their greater differentiation capacity. Our preliminary data documented that MC1568 drove both the improvement and acceleration of hMSCs chondrogenic differentiation in vitro, since the differentiation process in MC1568-treated cells took place in about seven days, much less than that normally observed, namely 21 days. Collectively, these preliminary data might shed light on the validity of such a new differentiative protocol, in order to better assess the potential role of the epigenetic modulation in the process of the hypertrophic cartilage formation, which represents the starting point for endochondral ossification.

The optimal gestational age at delivery for stable women with suspected placenta accreta is still subject of debate.To estimate the likelihood of vaginal bleeding necessitating expedited delivery in women with placenta accreta according to gestational age at planned cesarean hysterectomy.This was a multicenter cohort study. Singleton pregnancies at risk of placenta accreta because of placenta previa in the setting of prior cesarean delivery were included. Outcomes were compared in cohort of women who had planned cesarean hysterectomy at 34 0/7 - 34 6/7 weeks versus at 35 0/7 - 35 6/7 weeks. The primary outcome was incidence of vaginal bleeding severe enough to necessitate delivery.118 singleton pregnancies with placenta previa in the setting of prior cesarean delivery, and confirmed placenta accreta at the time of delivery were included in the study. Women who had planned cesarean hysterectomy at 34 weeks had lower episodes of vaginal bleeding severe enough to necessitate immediate or emergency delivery (20.6% vs 38.0%; odds ratio (OR) 0.42, 95% confidence interval (CI) 0.19 to 0.96). Eight women (11.8%) in the 34 weeks group and 6 women (12.0%) in the 35 weeks group delivered before the planned date due to onset of spontaneous labor (OR 0.98, 95% CI 0.32 to 3.02).In singleton gestations with suspected placenta accreta, planned cesarean hysterectomy at 34 0/7 - 34 6/7 weeks was associated with a decreased chance of unscheduled delivery due to severe vaginal bleeding.In case of placenta accreta, planned cesarean hysterectomy at 34 weeks was associated with decreased chance of unscheduled delivery due to severe vaginal bleeding.

Objectives To evaluate the strength of association between maternal and pregnancy characteristics and the risk of adverse perinatal outcomes in pregnancies with laboratory confirmed COVID-19. Methods Secondary analysis of a multinational, cohort study on all consecutive pregnant women with laboratory-confirmed COVID-19 from February 1, 2020 to April 30, 2020 from 73 centers from 22 different countries. A confirmed case of COVID-19 was defined as a positive result on real-time reverse-transcriptase-polymerase-chain-reaction (RT-PCR) assay of nasal and pharyngeal swab specimens. The primary outcome was a composite adverse fetal outcome, defined as the presence of either abortion (pregnancy loss before 22 weeks of gestations), stillbirth (intrauterine fetal death after 22 weeks of gestation), neonatal death (death of a live-born infant within the first 28 days of life), and perinatal death (either stillbirth or neonatal death). Logistic regression analysis was performed to evaluate parameters independently associated with the primary outcome. Logistic regression was reported as odds ratio (OR) with 95% confidence interval (CI). Results Mean gestational age at diagnosis was 30.6±9.5 weeks, with 8.0% of women being diagnosed in the first, 22.2% in the second and 69.8% in the third trimester of pregnancy. There were six miscarriage (2.3%), six intrauterine device (IUD) (2.3) and 5 (2.0%) neonatal deaths, with an overall rate of perinatal death of 4.2% (11/265), thus resulting into 17 cases experiencing and 226 not experiencing composite adverse fetal outcome. Neither stillbirths nor neonatal deaths had congenital anomalies found at antenatal or postnatal evaluation. Furthermore, none of the cases experiencing IUD had signs of impending demise at arterial or venous Doppler. Neonatal deaths were all considered as prematurity-related adverse events. Of the 250 live-born neonates, one (0.4%) was found positive at RT-PCR pharyngeal swabs performed after delivery. The mother was tested positive during the third trimester of pregnancy. The newborn was asymptomatic and had negative RT-PCR test after 14 days of life. At logistic regression analysis, gestational age at diagnosis (OR: 0.85, 95% CI 0.8–0.9 per week increase; p Conclusions Early gestational age at infection, maternal ventilatory supports and low birthweight are the main determinants of adverse perinatal outcomes in fetuses with maternal COVID-19 infection. Conversely, the risk of vertical transmission seems negligible.

Cerebroplacental Doppler studies have been advocated to predict the risk of adverse perinatal outcome (APO) irrespective of fetal weight. 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. 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

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 (

Fetal aneuploidies are among the most common causes of miscarriages, perinatal mortality and neurodevelopmental impairment. During the last 70 years, many efforts have been made in order to improve prenatal diagnosis and prenatal screening of these conditions. Recently, the use of cell-free fetal DNA (cff-DNA) testing has been increasingly used in different countries, representing an opportunity for non-invasive prenatal screening of pregnant women. The aim of this narrative review is to describe the state of the art and the main strengths and limitations of this test for prenatal screening of fetal aneuploidies.

BACKGROUND: Since coronavirus disease 2019 vaccines have been distributed, a debate has raised on whether pregnant women should get the vaccine. No available data exist so far regarding the safety, efficacy, and toxicology of these vaccines when administered during pregnancy. Most of the Obstetrics and Gynecology societies suggested that pregnant could agree to be vaccinated, after a thorough counseling of risks and benefits with their gynecologists, thus leading to an autonomous decision. OBJECTIVE: This study aimed to evaluate the attitude to coronavirus disease 2019 vaccination in pregnant and breastfeeding women in Italy. STUDY DESIGN: A survey was made at the University of Naples Federico II and the Ospedale Cristo Re, Tor Vergata University of Rome, on pregnant and breastfeeding women asking their perspectives on the available vaccines after reading the recommendations issued by our national Obstetrics, Gynecology, and Neonatology societies. The questionnaire included 12 items finalized to evaluate general features of the women and 6 items specifically correlated to their attitudes toward the severe acute respiratory syndrome coronavirus 2 vaccination. Chi-square or Fisher's exact tests were used to compare group differences of categorical variables and Wilcoxon signed rank or Mann-Whitney U test for continuous variables. The study was approved by the institutional review boards of the University of Naples Federico II (ref. no. 409/2020) and the Ospedale Cristo Re, Tor Vergata University of Rome (ref. #Ost4-2020). RESULTS: Most of the included women did not agree to eventually receive severe acute respiratory syndrome coronavirus 2 vaccine during pregnancy (40 [28.2%] vs 102 [71.8%]). Being pregnant was considered a determinant factor to refuse the vaccine prophylaxis (99 [69.7%] vs 43 [30.3%]; chi-square test=24.187; P

Purpose: Meningioma is a benign tumor, more frequent in female population. During pregnancy, distinguishing a meningioma from other common conditions presenting with similar symptoms (headache, vomiting, visual impairment) is challenging. Moreover, the management must consider not only maternal but also fetal health. The rarity of the condition does not allow to define the features to which look in order to stratify the risk for the need of surgery during pregnancy. We reported three cases of meningioma in pregnant women treated at our department and reviewed those previously reported in the literature. The aim of this review is to evaluate which factors are more determinant in such management. Methods: Electronic databases were searched from year 2000 until June 2020, to identify clinical studies on management of meningioma diagnosed during pregnancy. The primary outcome was surgical timing. Secondary outcomes were delivery methods, maternal and neonatal outcomes. Results: Surgery after pregnancy is more frequently performed in PR + tumor (p-value 0.038) and with HA (p-value 0.0445), as well as in meningioma diagnosed during the third trimester, compared to those diagnosed before (p-value 0.0012). Surgery during pregnancy was more frequent in patients with visual loss (p-value 0.006). No significant differences were found in surgical management, according to age, WHO grade, tumor location, lesion diameter and ER positivity. Delivery method is independent from both hormonal receptor status and main symptoms, but women who had neurosurgery during pregnancy delivered more frequently with spontaneous vaginal delivery (p-value

The aim of the study was to describe the pregnancy outcome of a large cohort of women with toxoplasmosis seroconversion in pregnancy and to investigate the relation between maternal lymphadenopathy and risk of congenital toxoplasmosis (CT). This was a retrospective study involving women with confirmed toxoplasmosis seroconversion in pregnancy between 2001 and 2017. Women were clinically evaluated for lymphadenopathy and classified as follows: lymphadenopathy absent (L-) or lymphadenopathy present (L+). The mothers were treated and followed-up according to local protocol, and neonates were monitored at least for 1 year in order to diagnose CT. A total of 218 women (one twin pregnancy) were included in the analysis. Pregnancy outcome was as follows: 149 (68%) of children not infected, 62 (28.3%) infected, 4 (1.8%) first trimester termination of pregnancy, 2 (0.9%) first trimester miscarriages, and 3 (1.4%) stillbirths (of which one already counted in the infected cohort). 13.8% of women were L+ , and they were nearly three times more likely to have a child with CT compared to L- women (aOR, 2.90; 95%CI, 1.28-6.58). Moreover, the result was still statistically significant when the analysis was restricted to 81 children whose mothers were clinically examined and received treatment within 5 weeks from estimated time of infection. In conclusion, there is a positive association between L+ status in pregnant women, and risk of CT also confirmed when restricting the analysis to women with early diagnosis of seroconversion and treatment. This data could be very useful in counselling pregnant women with toxoplasmosis seroconversion and lead to direct a more specific therapeutic and diagnostic protocol.

WOS:000613461600006 PubMed ID: 32926494 Objectives To evaluate the maternal and perinatal outcomes of pregnancies affected by SARS-CoV-2 infection. Methods This was a multinational retrospective cohort study including women with a singleton pregnancy and laboratory-confirmed SARS-CoV-2 infection, conducted in 72 centers in 22 different countries in Europe, the USA, South America, Asia and Australia, between 1 February 2020 and 30 April 2020. Confirmed SARS-CoV-2 infection was defined as a positive result on real-time reverse-transcription polymerase chain reaction (RT-PCR) assay of nasopharyngeal swab specimens. The primary outcome was a composite measure of maternal mortality and morbidity, including admission to the intensive care unit (ICU), use of mechanical ventilation and death. Results In total, 388 women with a singleton pregnancy tested positive for SARS-CoV-2 on RT-PCR of a nasopharyngeal swab and were included in the study. Composite adverse maternal outcome was observed in 47/388 (12.1%) women; 43 (11.1%) women were admitted to the ICU, 36 (9.3%) required mechanical ventilation and three (0.8%) died. Of the 388 women included in the study, 122 (31.4%) were still pregnant at the time of data analysis. Among the other 266 women, six (19.4% of the 31 women with first-trimester infection) had miscarriage, three (1.1%) had termination of pregnancy, six (2.3%) had stillbirth and 251 (94.4%) delivered a liveborn infant. The rate of preterm birth before 37 weeks' gestation was 26.3% (70/266). Of the 251 liveborn infants, 69/251(27.5%) were admitted to the neonatal ICU, and there were five (2.0%) neonatal deaths. The overall rate of perinatal death was 4.1% (11/266). Only one (1/251, 0.4%) infant, born to a mother who tested positive during the third trimester, was found to be positive for SARS-CoV-2 on RT-PCR. Conclusions SARS-CoV-2 infection in pregnant women is associated with a 0.8% rate of maternal mortality, but an 11.1% rate of admission to the ICU. The risk of vertical transmission seems to be negligible. (C) 2020 International Society of Ultrasound in Obstetrics and Gynecology.

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 −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 or CPR 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.

The use of Coronavirus 2 (SARS-CoV-2) vaccine in pregnant women is controversial and still not performed in Italy. Our objective was to evaluate the propensity of a population of Italian women to receive the vaccine and its psychological impact.A prospective, observational study was performed on pregnant women attending Ospedale Cristo Re Università Roma TorVergata. A multi-section questionnaire was sent to each included woman on the first day of available SARS-CoV-2 vaccination. Part-A was finalized to acquire maternal characteristics and to test the women's perception of vaccinations in pregnancy and their fear-induced by vaccines. Part-B included the State-Trait-Anxiety-Inventory (STAI) a validated test for scoring trait anxiety (basal anxiety, STAI-T) and state anxiety (STAI-S). An abnormal value of STAI was considered when ≥40. Comparisons of maternal variables were performed according to their vaccine attitude.The questionnaire was completed by 161 women (80.5% of the population considered). A positive attitude toward the vaccine was present in 136 (84.5%) women (positive) while the remaining 25.5% considered the vaccine not useful (negative). Among the former group 52.9% were favorable to obtain the vaccine during pregnancy despite the current national limitations, a percentage significantly higher (The majority of pregnant women considered have a positive attitude to SARS-CoV-2 vaccine. Vaccine campaign seems to increase the maternal level of anxiety and this increase is more marked with a negative attitude toward the vaccine.

Objective Heart anomalies represent nearly one-third of all congenital anomalies. They are currently diagnosed using ultrasound. However, there is a strong need for a more accurate and less operator-dependent screening method. Here we report a metabolomics characterization of maternal serum in order to describe a metabolomic fingerprint representative of heart congenital anomalies. Methods Metabolomic profiles were obtained from serum of 350 mothers (280 controls and 70 cases). Nine classification models were built and optimized. An ensemble model was built based on the results from the individual models. Results The ensemble machine learning model correctly classified all cases and controls. Malonic, 3-hydroxybutyric and methyl glutaric acid, urea, androstenedione, fructose, tocopherol, leucine and putrescine were determined as the most relevant metabolites in class separation. Conclusion The metabolomic signature of second trimester maternal serum from pregnancies affected by a fetal heart anomaly is quantifiably different from that of a normal pregnancy. Maternal serum metabolomics is a promising tool for the accurate and sensitive screening of such congenital defects. Moreover, the revelation of the associated metabolites and their respective biochemical pathways allows a better understanding of the overall pathophysiology of affected pregnancies. This article is protected by copyright. All rights reserved.

The myocardial performance index (MPI) has been proposed to evaluate cardiac dysfunction in newborns from diabetic mothers. Although MPI is routinely assessed in newborns, its role in the evaluation of fetuses from women with hyperglycemia in pregnancy (HIP) is still under evaluation. We aimed to evaluate the differences in third trimester fetal MPI in pregnant women with hyperglycemia compared to healthy controls. Seven electronic databases were searched for all studies assessing women with HIP who underwent evaluation of fetal left MPI during pregnancy compared to a control group. The summary measures were reported as mean differences (MD) in the mean fetal left MPI between women with HIP and healthy controls, with a 95 % confidence interval (CI). A post hoc subgroup analysis based on the type of HIP - pregestational diabetes, GDM, or gestational impaired glucose tolerance (GIGT) - was performed as an additional analysis. 14 studies assessing 1326 fetuses (580 from women with HIP and 746 from controls) were included. Women with HIP had a significantly higher mean left fetal MPI compared to controls (MD 0.08; 95 %CI: 0.05 to 0.11; p 0.00 001). Subgroup analysis according to the type of HIP concurred with the overall analysis for women with DM (MD 0.07; 95 %CI: 0.01 to 0.13; p = 0.02) and for women with GDM (MD 0.012; 95 %CI: 0.07 to 0.17; p 0.00 001) but not for women with GIGT (MD -0.01, 95 % CI -0.28 to 0.27; p = 0.96). Fetal left MPI is increased in pregnancies with HIP appearing as a potential marker of cardiac dysfunction.ZIEL: Der myokardiale Performance-Index (MPI) wurde vorgeschlagen, um die kardiale Dysfunktion bei Neugeborenen von Müttern mit Diabetes zu beurteilen. Obwohl der MPI routinemäßig bei Neugeborenen bestimmt wird, ist seine Rolle bei der Beurteilung von Föten von Schwangeren mit Hyperglykämie (HIP) noch in der Evaluierung. Unser Ziel war es, die Unterschiede im fetalen MPI im dritten Trimester bei schwangeren Frauen mit Hyperglykämie im Vergleich zu gesunden Kontrollen zu bewerten. Sieben elektronische Datenbanken wurden nach allen Studien durchsucht, in denen Frauen mit HIP untersucht wurden, bei denen während der Schwangerschaft eine Bewertung des fetalen linken MPI im Vergleich zu einer Kontrollgruppe durchgeführt wurde. Die zusammenfassenden Messungen wurden als mittlere Differenzen (MD) des mittleren fetalen linken MPI zwischen Frauen mit HIP und gesunden Kontrollen mit einem 95 %-Konfidenzintervall (KI) angegeben. Eine Post-hoc-Subgruppenanalyse basierend auf dem HIP-Typ – präkonzeptioneller Diabetes, Gestationsdiabetes mellitus (GDM) oder Gestations-bedingte Glukosetoleranzstörung (GIGT) – wurde als zusätzliche Analyse durchgeführt. 14 Studien mit 1326 Föten (580 von Frauen mit HIP und 746 von Kontrollpersonen) wurden eingeschlossen. Frauen mit HIP hatten einen signifikant höheren mittleren linken fetalen MPI im Vergleich zu den Kontrollen (MD 0,08; 95 %-KI 0,05–0,11; p 0,00 001). Die Subgruppenanalyse nach dem HIP-Typ stimmte mit der Gesamtanalyse für Frauen mit DM (MD 0,07; 95 %-KI 0,01–0,13; p = 0,02) und für Frauen mit GDM (MD 0,012; 95 %-KI 0,07–0,17; p 0,00 001) überein, nicht aber für Frauen mit GIGT (MD –0,01; 95 %-KI –0,28–0,27; p = 0,96). Der fetale linke MPI ist bei Schwangerschaften mit HIP erhöht und könnte sich somit als potenzieller Marker für die kardiale Dysfunktion erweisen.

The cesarean section is utilized to deliver babies since the late 19th century. Nowadays, the frequency of cesarean section is enormously increased, mainly because of the low rate of complications and for the increasing demand from future mothers, scared by the idea of painful labor. Although the technique to perform cesarean section has been refined over time, infections, hemorrhage, pain and other consequences still represent matter of debate. To try to reduce the incidence of these complications many trials, randomized or not, have been performed, with the aim to analyse different technical aspects of this surgery. The aim of our review is to resume all the evidence-based instructions on how to best approach to cesarean section practice, in a step-to-step fashion, considering pre-operative actions, opening and closing steps, and post-operative prophylaxis.

Induction of labor at 39 weeks of gestation is associated with better maternal and perinatal outcomes than expectant management. However, a policy of induction of labor implies the identification of women who will deliver after 40 weeks, who are at higher risk of adverse outcome.This study primarily aimed to elucidate the role of antepartum ultrasound in predicting the onset of spontaneous labor in a cohort of low-risk singleton pregnancies, and secondarily to compare its diagnostic performance with that of other ultrasonographic and clinical parameters.This was a prospective study including singleton nulliparous women undergoing a dedicated ultrasound assessment at 36 to 38 weeks of gestation. The primary outcome was delivery ≥40 weeks of gestation. The ultrasound parameters explored were cervical length, posterior cervical angle, angle of progression, and head-perineum distance. Multivariate logistic regression, Kaplan-Meier, and area under the curve analyses were used to test the strength of association and diagnostic performance of variables considered in predicting delivery ≥40 weeks.A total of 457 women were included, and 49.2% delivered ≥40 weeks. Cervical length was longer (30 vs 19 mm; P≤.0001) and posterior cervical angle wider (105° vs 98°, P≤.0001) in women delivering ≥40 weeks than those delivering40 weeks. Similarly, head-perineum distance was longer (48 vs 40 mm; P=.001) and angle of progression narrower (93° vs 95°; P=.04) in pregnancies delivering after 40 weeks. Conversely, there was no difference in the modified Bishop score between the 2 study groups (P=.689). In multivariable logistic regression analysis, cervical length (adjusted odds ratio, 1.307) and head-perineum distance (adjusted odds ratio, 1.227) were independently associated with delivery ≥40 weeks. Cervical length showed an area under the curve of 0.896 in predicting a delivery after 40 weeks. Integration of head-perineum distance in the diagnostic algorithm did not increase the performance of the model. A cervical length of 24 mm at 36 to 37 weeks of gestation showed the best combination of sensitivity and specificity in predicting delivery ≥40 weeks, with a shorter latency between ultrasound assessment and birth.Antepartum ultrasound can reliably identify a subset of nulliparous women at higher risk of delivering beyond 40 weeks. A cervical length24 mm at 36 to 37 weeks of gestation shows the optimal combination of sensitivity and specificity in predicting delivery ≥40 weeks. The findings from this study can help in identifying those women for whom elective induction of labor at 39 weeks of gestation would be beneficial in reducing the risk of adverse pregnancy outcome.

Antiphospholipid (aPL) antibodies are recognised risk factors for adverse obstetric outcomes. Recently, carriers of the M2 haplotype in theAntiphospholipid (aPL) -Antikörper sind anerkannte Risikofaktoren für ungünstige geburtshilfliche Ergebnisse. Kürzlich wurde gezeigt dass Träger des M2-Haplotyps im Annexin-A5-Gen eine höhere Anfälligkeit für die Entwicklung von aPL-Antikörpern aufweisen. In einer allgemeinen geburtshilflichen Population untersuchten wir prospektiv die mögliche Beziehung zwischen: (1) aPL-Antikörpern und M2-Haplotyp; und (2) aPL-Antikörper und / oder M2-Haplotyp und geburtshilfliche Ergebnisse. Aus einer Kohorte von 3.097 konsekutiven Schwangeren wurden 1.286 Proben auf das Vorhandensein von sowohl Anti-Cardiolipin- als auch Anti-Human-β2-Glykoprotein-I-Antikörpern analysiert; Proben mit verfügbarer DNA (n = 606) wurden ebenfalls auf den M2-Haplotyp untersucht. Insgesamt zeigten 41 / 1.286 (32%) Frauen das Vorhandensein von aPL-Antikörpern. Unter ihnen hatten 2 (48%) einen Schwangerschaftsverlust und 38 (927%) gaben lebendgeborene Babys zur Welt (p-Wert = nicht-signifikant gegenüber denen ohne aPL-Antikörper). Der M2-Haplotyp wurde bei 140 (231%) von 606 Frauen mit verfügbarer DNA identifiziert: 3/140 (21%) M2-Träger und 17/466 (36%) Nichtträger die positiv auf aPL-Antikörper getestet wurden (p-Wert = nicht signifikant). Insgesamt litten 15/150 (10%) M2- und / oder aPL-Antikörperträger und 38/445 (85%) Nicht-aPL-Antikörper und / oder M2-Träger an geburtshilflichen Komplikationen (p-Wert = nicht signifikant). Es wurde keine Beziehung zwischen aPL-Antikörpern und M2-Haplotypen gefunden. Darüber hinaus sind weder aPL-Antikörper noch der M2-Haplotyp mit geburtshilflichen Komplikationen assoziiert.

OBJECTIVE: To assess the risk of preeclampsia in women who underwent chorionic villus sampling (CVS). STUDY DESIGN: This is a retrospective, single-center, cohort study. All consecutive singleton gestations who underwent chorionic villus sampling from January 2014 to January 2016 were included in the study. The primary outcome was the incidence of preeclampsia. Subgroup analysis in women with beta thalassemic trait was performed. Logistic regression, presented as adjusted odds ratio (aOR) with the 95% of confidence interval (CI), was performed. RESULTS: Five hundred forty-seven women who underwent CVS, and 1532 women who did not were analyzed. Women who underwent CVS had a significantly lower risk of preeclampsia (4.4 versus 8.0%; aOR 0.53, 95%CI 0.34-0.83), and late-onset preeclampsia (3.3 versus 6.1%; aOR 0.52, 95%CI 0.31-0.87). No statistically significant differences were found in preeclampsia with severe features, early-onset preeclampsia, and preterm birth (PTB). Women who underwent CVS due to thalassemic trait had a lower incidence of preeclampsia compare to those women who did not undergo CVS (3.3 versus 8.0%; aOR 0.39, 95%CI 0.14-0.87), while no differences were found comparing women who underwent CVS due to thalassemic trait with women who underwent CVS due to other reasons. CONCLUSIONS: Women who underwent first trimester CVS had a lower risk of preeclampsia compared to those who did not.

Key Clinical Message A prenatal case presenting with congenital diaphragmatic hernia (CDH) and distal 16p11.2 microdeletion suggests two possible causative hypotheses: (1) a functional effect of chromatin loopings between the distal and the proximal 16p11.2 microdeletion traits, associated with CHD; (2) a possible role of ATP2A1, a deleted gene involved in diaphragm development.

Nutritional imbalance and metabolic alterations associated with maternal obesity during pregnancy predispose offspring to obesity and/or to type 2 diabetes, but the mechanisms underlying these effects are still obscure. In this context, we evaluated whether the two main energy-producing pathways (glycolysis and mitochondrial oxidative phosphorylation) are impaired in obesity during pregnancy thus contributing to metabolic intrauterine alterations. Specifically, we studied metabolic abnormalities in the intrauterine life of newborns using stem cells isolated from amnion and umbilical cord (hA- and hUC-MSCs). We isolated, at delivery, neonatal hUC-MSCs from 13 obese (Ob) and 10 normal weight control (Co) women (prepregnancy body mass index >30 and

OBJECTIVE: To evaluate the benefits and harms of discontinuation of oxytocin after the active phase of labor is reached. DATA SOURCES: Electronic databases (ie, MEDLINE, Scopus, ClinicalTrials.gov, EMBASE, ScienceDirect, the Cochrane Library at the CENTRAL Register of Controlled Trials, Scielo) were searched from their inception until April 2017. METHODS OF STUDY SELECTION: We included all randomized controlled trials comparing discontinuation (ie, intervention group) and continuation (ie, control group) of oxytocin infusion after the active phase of labor is reached, either after induction or augmentation of labor. Discontinuation of oxytocin infusion was defined as discontinuing oxytocin infusion when the active phase of labor was achieved. Continuation of oxytocin infusion was defined as continuing oxytocin infusion until delivery. Only trials in singleton gestations with vertex presentation at term were included. The primary outcome was the incidence of cesarean delivery. TABULATION, INTEGRATION, AND RESULTS: Nine randomized controlled trials, including 1,538 singleton gestations, were identified as relevant and included in the meta-analysis. All nine trials included only women undergoing induction of labor. In the discontinuation group, if arrest of labor occurred, usually defined as no cervical dilation in 2 hours or inadequate uterine contractions for 2 hours or more, oxytocin infusion was restarted. Women in the control group had oxytocin continued until delivery usually at the same dose used at the time the active phase was reached. Women who were randomized to have discontinuation of oxytocin infusion after the active phase of labor was reached had a significantly lower risk of cesarean delivery (9.3% compared with 14.7%; relative risk 0.64, 95% CI 0.48-0.87) and of uterine tachysystole (6.2% compared with 13.1%; relative risk 0.53, 95% CI 0.33-0.84) compared with those who were randomized to have continuation of oxytocin infusion until delivery. Discontinuation of oxytocin infusion was associated with an increase in the duration of the active phase of labor (mean difference 27.65 minutes, 95% CI 3.94-51.36). CONCLUSION: In singleton gestations with cephalic presentation at term undergoing induction, discontinuation of oxytocin infusion after the active phase of labor at approximately 5 cm is reached reduces the risk of cesarean delivery and of uterine tachysystole compared with continuous oxytocin infusion. Given this evidence, discontinuation of oxytocin infusion once the active stage of labor is established in women being induced should be considered as an alternative management plan.

INTRODUCTION: The lowest incidence of perinatal morbidity and mortality occurs around 39-40 weeks. Therefore, some have advocated induction of uncomplicated singleton gestations once they reach full-term. The aim of the study was to evaluate the risk of cesarean delivery, and any maternal and perinatal effects of a policy of induction of labor in women with full-term uncomplicated singleton gestations. MATERIAL AND METHODS: We performed an electronic search from inception of each database to August 2018. All results were then limited to randomized trial. No restrictions for language or geographic location were applied. Inclusion criteria were randomized clinical trials of asymptomatic women with uncomplicated, singleton gestations at full-term (ie, between 39+0 and 40+6 weeks) who were randomized to either planned induction of labor or control (ie, expectant management). Only trials on asymptomatic singleton gestations without premature rupture of membranes or any other indications for induction evaluating the effectiveness of planned induction of labor in full-term singleton gestations were included. The primary outcome was the incidence of cesarean delivery. RESULTS: Seven randomized clinical trials, including 7598 participants were analyzed. Three studies enrolled only women with favorable cervix, defined as a Bishop score of ≥5 in nulliparous women or ≥4 in multiparous women. One trial included only women aged 35 years or older. Women randomized to the planned induction of labor, received scheduled induction usually at 39+0 to 39+6 weeks of gestation, whereas women in the control group received expectant management usually until 41-42 weeks of gestation, or earlier if medically indicated. Methods of induction usually included cervical ripening, with either misoprostol or Foley catheter, in conjunction with or followed by oxytocin for women with unfavorable cervix, and oxytocin and artificial rupture of membranes for those with favorable cervix. Five trials also used artificial rupture of membranes as a method for induction. Uncomplicated full-term singleton gestations that were randomized to receive induction of labor had similar incidence of cesarean delivery compared with controls (18.6% vs 21.4%; relative risk 0.96, 95% CI 0.78-1.19). Regarding neonatal outcomes, induction of labor at full-term was associated with a significantly lower rate of meconium-stained amniotic fluid (4.0% vs 13.5%; relative risk 0.32, 95% CI 0.18-0.57), and lower mean birthweight (mean difference -98.96 g, 95% CI -126.29 to -71.63) compared with the control group. There were no between-group differences in other adverse neonatal outcomes. CONCLUSIONS: Induction of labor at about 39 weeks is not associated with increased risk of cesarean delivery.

Objective The aim of our study is to evaluate if pregestational diabetes affects fetal heart rate (FHR) readings at 11–14 weeks of pregnancy. Study design For each patient, we recorded age, body mass index (BMI), presence of pregestational diabetes, nuchal translucency (NT), FHR, crown-rump length (CRL), biparietal diameter (BPD) and gestational age. Pregnancies were grouped according to the presence or absence of pregestational diabetes and maternal and fetal variables were compared. Ordinal regression analysis was performed to assess the influence of maternal and fetal variables on the FHR. Results We included 994 pregnancies from 2009 to 2016. Kruskal-Wallis test showed that median FHR was higher in women with pregestational diabetes than in controls (161; IQR 11 vs. 158; IQR 10, χ2 = 5.13, p = 0.02). Ordinal regression analysis showed that differences in FHR were significantly correlated with the presence of pregestational diabetes (p = 0.007) and the CRL (p = 0.042) but not with the maternal BMI, maternal age, gestational age, BPD and NT. Conclusions First trimester FHR is higher in diabetic pregnancies than in non-diabetic pregnancies. Therefore, further research is needed to assess whether these pregnancies may benefit from a correction of FHR for a better estimation of the chromosomal abnormalities risk.

Objectives:The primary objective was to quantify the risk of perinatal mortality in non‐anomalous monochorionic monoamniotic (MCMA) twin pregnancies complicated by birth‐weight (BW) discordance. The secondary objectives were to investigate the effect of inpatientvsoutpatient fetal monitoring on the risk of mortality in weight‐discordant MCMA twin pregnancies, and to explore the predictive accuracy of BW discordance for perinatal mortality. Methods:This analysis included data on 242 MCMA twin pregnancies (484 fetuses) from three major research collaboratives on twin pregnancy (MONOMONO, STORK and NorSTAMP). The primary outcomes were the risks of intrauterine (IUD), neonatal (NND) and perinatal (PND) death, according to weight discordance at birth from ≥ 10% to ≥ 30%. The secondary outcomes were the association of inpatientvsoutpatient fetal monitoring with the risk of mortality in weight‐discordant pregnancies, and the accuracy of BW discordance in predicting mortality. Logistic regression and receiver‐operating‐characteristics‐curve analyses were used to analyze the data. Results:The risk of IUD was significantly increased in MCMA twin pregnancies with BW discordance ≥ 10% (odds ratio (OR), 2.2; 95% CI, 1.1–4.4;P= 0.022) and increased up to an OR of 4.4 (95% CI, 1.3–14.4;P= 0.001) in those with BW discordance ≥ 30%. This association remained significant on multivariate logistic regression analysis for BW‐discordance cut‐offs ≥ 20%. However, weight discordance had low predictive accuracy for mortality, with areas under the receiver‐operating‐characteristics curve of 0.60 (95% CI, 0.46–0.73), 0.52 (95% CI, 0.33–0.72) and 0.57 (95% CI, 0.45–0.68) for IUD, NND and PND, respectively. There was no difference in the risk of overall IUD, single IUD, double IUD, NND or PND between pregnancies managed as an inpatient compared with those managed as an outpatient, for any BW‐discordance cut‐off. Conclusions:MCMA twin pregnancies with BW discordance are at increased risk of fetal death, signaling a need for increased levels of monitoring. Despite this, the predictive accuracy for mortality is low; thus, detection of BW discordance alone should not trigger intervention, such as iatrogenic delivery. The current data do not demonstrate an advantage of inpatient over outpatient management in these cases. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Purpose: The aim of our study was to identify maternal characteristics of women who are responsive to the second application of vaginal dinoprostone in a cohort of patients with a low Bishop Score. Secondarily, we compared the outcome of the patients' response to a single application to that of the women's response to a double application. Materials and methods: This was a retrospective observational cohort study. Patients undergoing preinduction of labor with dinoprostone 10mg controlled-release vaginal device were included. Results: Among 216 included patients, 192 women (88.9%) achieved a cervical ripening after a single application of dinoprostone, while 24 (11.1%) required a second application. Patients notresponding to the first application of dinoprostone had a significantly higher body mass index (27.4 ± 6.7 kg/m2 vs 24.9 ± 5.2 kg/m2; p < 0.05) and a significant increase in gestational weight gain (14 ± 5.2 kg vs 11.6 ± 6.1; p < 0.005). Double application of dinoprostone resulted in spontaneousdelivery in 58.4% of cases, but it was related to poorer neonatal outcome, compared to a single application. Conclusions: Obese women, not responding to the first application of dinoprostone could respond to the second application of this vaginal prostaglandin. However, data related to the use of a double application are still very limited to recommend its use as a standardized procedurefor not responsive patients.