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Objective: Stillbirth is a potentially preventable complication of pregnancy. Identifying women at high risk of stillbirth can guide decisions on the need for closer surveillance and timing of delivery in order to prevent fetal death. Prognostic models have been developed to predict the risk of stillbirth, but none has yet been validated externally. In this study, we externally validated published prediction models for stillbirth using individual participant data (IPD) meta-analysis to assess their predictive performance. Methods: MEDLINE, EMBASE, DH-DATA and AMED databases were searched from inception to December 2020 to identify studies reporting stillbirth prediction models. Studies that developed or updated prediction models for stillbirth for use at any time during pregnancy were included. IPD from cohorts within the International Prediction of Pregnancy Complications (IPPIC) Network were used to validate externally the identified prediction models whose individual variables were available in the IPD. The risk of bias of the models and cohorts was assessed using the Prediction study Risk Of Bias ASsessment Tool (PROBAST). The discriminative performance of the models was evaluated using the C-statistic, and calibration was assessed using calibration plots, calibration slope and calibration-in-the-large. Performance measures were estimated separately in each cohort, as well as summarized across cohorts using random-effects meta-analysis. Clinical utility was assessed using net benefit. Results: Seventeen studies reporting the development of 40 prognostic models for stillbirth were identified. None of the models had been previously validated externally, and the full model equation was reported for only one-fifth (20%, 8/40) of the models. External validation was possible for three of these models, using IPD from 19 cohorts (491 201 pregnant women) within the IPPIC Network database. Based on evaluation of the model development studies, all three models had an overa

Objective: Preeclampsia (PE) is the major cause of maternal morbidity and mortality and the leading cause of premature delivery worldwide. As well as intrauterine growth restriction (IUGR), PE is associated with pathogenic evidence of placental malperfusion and ischemia. Recent literature has highlighted the potential of pravastatin in the prevention and treatment of these conditions. Aim of this study is to describe perinatal outcomes and placental histopathological findings in a small series of pregnant women with severe PE and IUGR treated with pravastatin on compassionate grounds. Two-year follow up of these babies is provided. Study design: Between October 2017 and October 2019 in Fondazione Policlinico Universitario Agostino Gemelli, IRCCS, Rome, Italy, women with singleton pregnancy between 19.6 and 27.6 gestational weeks, who presented with severe PE and IUGR were counselled for a compassionate treatment with Pravastatin 40 mg a day. Treated women were compared with controls identified with similar data in terms of gestational age at diagnosis, clinical maternal data, Doppler severity findings. Neonates were followed up for two years. Results: The median time from diagnosis to delivery was 39 days (IQR 20) for women in the pravastatin group and 20 days (IQR 20.5) for controls. Looking to maternal blood exams, in the group of women treated with pravastatin, maximum transaminase, creatinine levels were lower than in controls, where the minimum platelet count was higher. Placenta examination did not reveal any significant differences in placental histopathological findings. No significant differences were observed in the investigated perinatal data, as well as in infant follow-up, although an increased prenatal weight gain was found in treated pregnancies in comparison to controls. Conclusions: Our data did not allow us to find significant differences in pregnancy outcome and infant follow-up, as well as in placental histological picture in preeclamptic patient

CENNI DI ANATOMIA FUNZIONALE DEL PAVIMENTO PELVICO Lil pavimento pelvico è costituito da un insieme di strutture muscolari e fasciali che chiudono inferiormente lo scavo pelvico femminile, sostengono gli organi pelvici (vescica, vagina, utero, retto) e intervengono nei meccanismi della continenza urinaria e fecale, nell'attività sessuale e nel parto. La statica e la dinamica degli organi pelvici sono condizionate da due sistemi. - un sistema di sospensione costituito davanti dai legamenti pubo-vesci-co-uterini e dai legamenti rotondi, posteriormente dai legamenti ute-ro-sacrali, lateralmente dal legamento cardinale di Mackenrodt. Tale sistema collega i visceri pelvici alla parete della pelvi stessa e alla fascia endopelvica. - un sistema di sostegno, formato da un complesso di muscolatura striata e da tessuto connettivale (fascia endopelvica). Procedendo dall'interno verso l'esterno tale sistema è rappresentato: 1) dal diaframma pelvico, costituito dal muscolo elevatore dell'ano (con le sue componenti pubo-rettale, ileococcigea, pubococcigea e ischiococcigea) e dalla fascia endo-pelvica che lo riveste superiormente ed inferiormente; 2) dal diaframma urogenitale, situato inferiormente al diaframma pelvico, rappresentato da una lamina muscoloaponeurotica comprendente i legamenti pubo-uretra-li, uteropelvico e il muscolo traverso profondo del perineo; 3) dal piano dei muscoli superficiali del perineo (piano degli sfinteri) costituito dal muscolo bulbo-cavernoso, dall'ischio-cavernoso e dal trasverso superficiale dell'ano.

L'incontinenza urinaria femminile rappresenta un problema socio assistenziale sottostimato e, per molti aspetti, irrisolto. Numerosi studi hanno messo in evidenza il notevole impatto negativo che essa ha su molti aspetti della vita della donna, tanto da condizionarne le attività quotidiane, le relazioni sociali e la vita privata, fino ad un intenso disagio psicologico ed a una profonda ripercussione sulla qualità di vita

Objective: To analyze perinatal outcome in singleton pregnancies complicated by gestational hypertension (GH), to investigate the rate of women developing preeclampsia (PE) and to describe maternal features associated with progression to PE. Study design: This is a population-based retrospective cohort-study involving 514 singleton pregnancies with a diagnosis of GH at admission. Results: In pregnancies with GH, a poorer pregnancy outcome in comparison to healthy controls was observed in terms of gestational age at delivery, birthweight and birthweight percentile. The observed overall rate of developing PE was 11.7 %. Of all pregnancies with GH at admission, two different groups were identified based on the diagnosis at delivery: GHPE, i.e. women who developed PE (60/514; 11.7 %), and GHnoPE, i.e. women who did not develop PE (454/514; 88.3 %). In the GHPE group it was observed that the 62 % of the women with diagnosis of GH earlier than 28 weeks developed PE while only 2% developed PE if the diagnosis of GH was performed later than 36 weeks. The observed rate of developing PE was 14.7 % in pharmacologically treated hypertensive women, whereas the diagnosis of PE has been made in only 3% of non-treated women. Conclusion: Pregnant women with raised blood pressure are at risk of having a less favourable perinatal outcome. The risk is mainly associated with the progression to PE. Major determinants of the risk of developing PE are the earlier gestational age at diagnosis of GH, the necessity of treatment and the number of anti-hypertensive drugs needed for controlling blood pressure.

Purpose: To assess changing trends, role of the triad patient–pregnancy–health professionals and health care cost in emergency peripartum hysterectomy (EPH). Methods: Demographics, indications, perinatal outcomes, perioperative complications in EPH cases performed in a 10-year period were extracted from the local birth registry. Experience of health professionals in the management of the post-partum haemorrhage was valued. Two subgroups (Period I, 2009–2013 vs. Period II, 2014–2018) were recognized. Overall and detailed EPH ratios/1000 deliveries were calculated. Cost analysis was achieved in agreement with the diagnosis-related group (DGR) system. Results: A total of 39 EPH were performed among 36,053 deliveries. EPH incidence increased from 0.8 to 1.32‰ across study periods (p < 0.001). The mean maternal age (36.9 ± 4.7 vs. 38.9 ± 5.9 years, p = 0.035) and the high socio-economic status (0 vs. 19.2%, p = 0.027) were statistically different. Multiparity (84.6 vs. 96.2%, p = 0.005), previous caesarean section (CS) (0.9 ± 0.9 vs. 1.2 ± 1.6, p = 0.049), and emergent CS (7.7 vs. 19.2%, p = 0.048) were found statistically different. In Period II, increased attempts in conservative approaches (7.7 vs. 36.8%, p = 0.007), reduction in blood loss (3184 ± 1753 vs. 2511 ± 1252 mL, p = 0.045), advanced age of gynecologists performing EPH (54.5 ± 9.2 vs. 60.3 ± 6.4 years, p = 0.024), and augmented health care costs (mean DRG of € 2.782 vs. 3.371,95, p < 0.001) were observed. Conclusions: As a “near-miss” event, advances on identification of EPH factors are mandatory. Time–trend analyses might add information and address novel strategies.

© 2017 Royal College of Obstetricians and Gynaecologists Objective: Develop a core outcome set of international consensus definitions for severe maternal morbidities. Design: Electronic Delphi study. Setting: International. Population: Eight expert panels. Methods: All 13 high-income countries represented in the International Network of Obstetric Surveillance Systems (INOSS) nominated five experts per condition of morbidity, who submitted possible definitions. From these suggestions, a steering committee distilled critical components: eclampsia: 23, amniotic fluid embolism: 15, pregnancy-related hysterectomy: 11, severe primary postpartum haemorrhage: 19, uterine rupture: 20, abnormally invasive placentation: 12, spontaneous haemoperitoneum in pregnancy: 16, and cardiac arrest in pregnancy: 10. These components were assessed by the expert panel using a 5-point Likert scale, following which a framework for an encompassing definition was constructed. Possible definitions were evaluated in rounds until a rate of agreement of more than 70% was reached. Expert commentaries were used in each round to improve definitions. Main outcome measures: Definitions with a rate of agreement of more than 70%. Results: The invitation to participate in one or more of eight Delphi processes was accepted by 103 experts from 13 high-income countries. Consensus definitions were developed for all of the conditions. Conclusion: Consensus definitions for eight morbidity conditions were successfully developed using the Delphi process. These should be used in national registrations and international studies, and should be taken up by the Core Outcomes in Women's and Newborn Health initiative. Tweetable abstract: Consensus definitions for eight morbidity conditions were successfully developed using the Delphi process.

Proper placental development is crucial to establish a successful pregnancy. Defective placentation is the major cause of several pregnancy complications, including preeclampsia (PE). We have previously demonstrated that the secreted factor Epidermal Growth Factor-like Domain 7 (EGFL7) is expressed in trophoblast cells of the human placenta and that it regulates trophoblast migration and invasion, suggesting a role in placental development. In the present study, we demonstrate that circulating levels of EGFL7 are undetectable in nonpregnant women, increase during pregnancy and decline toward term. Close to term, circulating levels of EGFL7 are significantly higher in patients affected by PE when compared to normal pregnancies. Consistent with these results, villus explant cultures obtained from placentas affected by PE display increased release of EGFL7 in the culture medium when compared to those from normal placentas. Our results suggest that increased release of placenta-derived EGFL7 and increased circulating levels of EGFL7 are associated with the clinical manifestation of PE.

Objective: To report the experience developed in a Third Level Referral Center in performing a multifaceted intervention strategy to reduce Caesarian Sections (CS) rate. A comparison of our results with the performance of the best Italian hospitals for number of deliveries and CS has been performed. Methods: A monitoring system was set up, based on a prospective collection of all deliveries from 2013 to 2017, according to Robson’s classification. Data have also been collected retrospectively at a regional and national level to compare our results to other institutions. The multi-approach intervention consisted of evidence based tools: process management, training, multiprofessionalism, development of planning and control systems, continuous monitoring, audit and feedback. Results: The percentage of primary CS decreased from 26.71% in 2013 to 15.03% in 2017 (RR adjusted considering the regional average: 0.87 in 2013; 0.57 in 2017, p < .001). A raise of 19.76% in the annual volume of deliveries was registered. Such results have also been confirmed after comparing to the best performing Italian centers. From 2013 to 2016 the percentage of primary CS decreased from 27.02% to 18.04% (RR adjusted considering the regional average: 1.04 in 2013, p > .05; 0.74 in 2016, p < .001), while there was an increase in the annual volume of deliveries from 3,311 to 4,219. Conclusions: Our study confirms that multifaceted interventions can strengthen a continuous quality and safety improvement approach. This is of crucial relevance in the obstetric field and in the Italian country, where overall performance in CS needs to be improved.

Objective To investigate the role of maternal characteristics and epidural analgesia (EA) on caesarean section (CS) rates in selected groups by using the Robson 10-Group Classification System (RTGCS).Design Cohort study.Setting Department of Obstetrics and Gynaecology, Fondazione Policlinico Universitario 'A. Gemelli', Rome, Italy.Patients A total of 12 098 deliveries in periods I (19981999) and II (2010-2011).Main outcome measures CS rates in groups 1 and 3 of RTGCS.Results In group 1, 1144 (20%) patients were assigned to period I and 1302 (20.4%) to period II, while in group 3, 1587 (27.8%) were assigned to period I and 1502 (23.5%) to period II. CS rates were 16.4% and 23.1% in group 1 and 12.7% and 10.9% in group 3 in periods I and II, respectively. In group 1, significant and independent contributions to CS rate were provided by maternal age (p=0.018; OR 0.95 (95% CI 0.85 to 0.97)), body mass index (BMI) (p=0.022; OR 0.89 (95% CI 0.85 to 0.91)) and EA administration (p=0.037; OR 0.59 (95% CI 0.43 to 0.77)). In group 3, maternal age (p<0.001; OR 0.93 (95% CI 0.89 to 0.96)) and BMI (p=0.023; OR 0.98 (95% CI 0.96 to 0.99)) were found to be significantly associated with CS.Conclusions RTGCS is an effective tool for analysing changes in obstetric care, allowing for the recognition of maternal age, BMI and EA administration in the strategic planning for mitigation of CS rates in selected groups.

Cancer is the leading cause of death in women of reproductive age. During the last decades and especially in developed countries, the incidence of cancer is increasing dramatically, with an incidence of 1 in 1,000 pregnancies. This is mostly related to delay of pregnancy into the late reproductive years. The aim of this study was to investigate the outcome of pregnancy in women with diagnosis of cancer; in particular, neonatal morbidity and mortality, after in utero exposure to chemotherapy, were evaluated. A total of 59 singletons and one twin pregnancy complicated by cancer were followed at our tertiary centre over the last 15 years. A different treatment, based on surgery and/or chemotherapy in pregnancy or delayed to the postpartum period, was employed. There were 59 live births (97%), one foetal loss and one stillbirth at 28 weeks. The congenital malformation rate was 5% (n = 3). The rate of preterm birth was 83%. The mean birthweight and mean birthweight percentile were 2,098 g (740–3930) and 46 (7–93), respectively; 32% of neonates were small for gestational age (SGA). Dividing the population into treated or untreated with chemotherapy, the rate of SGA was not statistically significant different between the two groups. Our results showed that chemotherapy administered during the second trimester or later did not influence intrauterine foetal growth, but the high prevalence of SGA neonates in the two groups, exposed or not exposed to chemotherapy, suggests an influence of maternal cancer per se on foetal growth.

Cancer is the leading cause of death in women of reproductive age. During the last decades and especially in developed countries, the incidence of cancer is increasing dramatically, with an incidence of 1 in 1,000 pregnancies. This is mostly related to delay of pregnancy into the late reproductive years. The aim of this study was to investigate the outcome of pregnancy in women with diagnosis of cancer; in particular, neonatal morbidity and mortality, after in utero exposure to chemotherapy, were evaluated. A total of 59 singletons and one twin pregnancy complicated by cancer were followed at our tertiary centre over the last 15 years. A different treatment, based on surgery and/or chemotherapy in pregnancy or delayed to the postpartum period, was employed. There were 59 live births (97%), one foetal loss and one stillbirth at 28 weeks. The congenital malformation rate was 5% (n = 3). The rate of preterm birth was 83%. The mean birthweight and mean birthweight percentile were 2,098 g (740-3930) and 46 (7-93), respectively; 32% of neonates were small for gestational age (SGA). Dividing the population into treated or untreated with chemotherapy, the rate of SGA was not statistically significant different between the two groups. Our results showed that chemotherapy administered during the second trimester or later did not influence intrauterine foetal growth, but the high prevalence of SGA neonates in the two groups, exposed or not exposed to chemotherapy, suggests an influence of maternal cancer per se on foetal growth.

Objective We performed an individual participant data (IPD) metaanalysis to calculate the recurrence risk of hypertensive disorders of pregnancy (HDP) and recurrence of individual hypertensive syndromes. Study Design We performed an electronic literature search for cohort studies that reported on women experiencing HDP and who had a subsequent pregnancy. The principal investigators were contacted and informed of our study; we requested their original study data. The data were merged to form one combined database. The results will be presented as percentages with 95% confidence interval (CI) and odds ratios with 95% CI. Results Of 94 eligible cohort studies, we obtained IPD of 22 studies, including a total of 99,415 women. Pooled data of 64 studies that used published data (IPD where available) showed a recurrence rate of 18.1% (n = 152,213; 95% CI, 17.9-18.3%). In the 22 studies that are included in our IPD, the recurrence rate of a HDP was 20.7% (95% CI, 20.4-20.9%). Recurrence manifested as preeclampsia in 13.8% of the studies (95% CI,13.6-14.1%), gestational hypertension in 8.6% of the studies (95% CI, 8.4-8.8%) and hemolysis, elevated liver enzymes and low platelets (HELLP) syndrome in 0.2% of the studies (95% CI, 0.16-0.25%). The delivery of a small-for-gestational-age child accompanied the recurrent HDP in 3.4% of the studies (95% CI, 3.2-3.6%). Concomitant HELLP syndrome or delivery of a small-for-gestational-age child increased the risk of recurrence of HDP. Recurrence increased with decreasing gestational age at delivery in the index pregnancy. If the HDP recurred, in general it was milder, regarding maximum diastolic blood pressure, proteinuria, the use of oral antihypertensive and anticonvulsive medication, the delivery of a small-for-gestational-age child, premature delivery, and perinatal death. Normotensive women experienced chronic hypertension after pregnancy more often after experiencing recurrence (odds ratio, 3.7; 95% CI, 2.3-6.1). Conclusion Amon

Epidermal growth factor-like domain 7 (Egfl7) is a gene that encodes a partially secreted protein and whose expression is largely restricted to the endothelia. We recently reported that EGFL7 is also expressed by trophoblast cells in mouse and human placentas. Here, we investigated the molecular pathways that are regulated by EGFL7 in trophoblast cells. Stable EGFL7 overexpression in a Jeg3 human choriocarcinoma cell line resulted in significantly increased cell migration and invasiveness, while cell proliferation was unaffected. Analysis of mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3-kinase (PI3K) pathways showed that EGFL7 promotes Jeg3 cell motility by activating both pathways. We show that EGFL7 activates the epidermal growth factor receptor (EGFR) in Jeg3 cells, resulting in downstream activation of extracellular regulated kinases (ERKs). In addition, we provide evidence that EGFL7-triggered migration of Jeg3 cells involves activation of NOTCH signaling. EGFL7 and NOTCH1 are co-expressed in Jeg3 cells, and blocking of NOTCH activation abrogates enhanced migration of Jeg3 cells overexpressing EGFL7. We also demonstrate that signaling through EGFR and NOTCH converged to mediate EGFL7 effects. Reduction of endogenous EGFL7 expression in Jeg3 cells significantly decreased cell migration. We further confirmed that EGFL7 stimulates cell migration by using primary human first trimester trophoblast (PTB) cells overexpressing EGFL7. In conclusion, our data suggest that in trophoblast cells, EGFL7 regulates cell migration and invasion by activating multiple signaling pathways. Our results provide a possible explanation for the correlation between reduced expression of EGFL7 and inadequate trophoblast invasion observed in placentopathies.

OBJECTIVE: We performed an individual participant data (IPD) metaanalysis to calculate the recurrence risk of hypertensive disorders of pregnancy (HDP) and recurrence of individual hypertensive syndromes. STUDY DESIGN: We performed an electronic literature search for cohort studies that reported on women experiencing HDP and who had a subsequent pregnancy. The principal investigators were contacted and informed of our study; we requested their original study data. The data were merged to form one combined database. The results will be presented as percentages with 95% confidence interval (CI) and odds ratios with 95% CI. RESULTS: Of 94 eligible cohort studies, we obtained IPD of 22 studies, including a total of 99,415 women. Pooled data of 64 studies that used published data (IPD where available) showed a recurrence rate of 18.1% (n=152,213; 95% CI, 17.9-18.3%). In the 22 studies that are included in our IPD, the recurrence rate of a HDP was 20.7% (95% CI, 20.4-20.9%). Recurrence manifested as preeclampsia in 13.8% of the studies (95% CI,13.6-14.1%), gestational hypertension in 8.6% of the studies (95% CI, 8.4-8.8%) and hemolysis, elevated liver enzymes and low platelets (HELLP) syndrome in 0.2% of the studies (95% CI, 0.16-0.25%). The delivery of a small-for-gestational-age child accompanied the recurrent HDP in 3.4% of the studies (95% CI, 3.2-3.6%). Concomitant HELLP syndrome or delivery of a small-for-gestational-age child increased the risk of recurrence of HDP. Recurrence increased with decreasing gestational age at delivery in the index pregnancy. If the HDP recurred, in general it was milder, regarding maximum diastolic blood pressure, proteinuria, the use of oral antihypertensive and anticonvulsive medication, the delivery of a small-for-gestational-age child, premature delivery, and perinatal death. Normotensive women experienced chronic hypertension after pregnancy more often after experiencing recurrence (odds ratio, 3.7; 95% CI, 2.3-6.1). CONCLUSION: Am

OBJECTIVE: Due to continuous rise of cesarean section (CS) rate in recent decades to analyze this trend using Robson Ten Group Classification System (RTGCS) and identify the main contributor of the CS rate in an Italian tertiary level hospital. STUDY DESIGN: A total of 17,886 deliveries in six (1998, 1999, 2004, 2005, 2010, 2011) of a 13-year period was analyzed using RTGCS. RESULTS: From 1998 to 2011 a rising CS birth rate from 38.7 to 43.7 per 100 births was calculated (p<0.001) in association with a significant reduction of vaginal delivery (VD) (59.7 vs. 53.7%; p<0.001). In multiparous women with a previous CS (Group 5) a repeat CS was performed routinely, resultant the most contributor of CS rate (15.4 vs. 16.2%; p<0.001). Nulliparous women with singleton cephalic full-term pregnancy in spontaneous or induced labor onset resulted the second contributor (Group 1, 3.3 vs. 4.7%; p<0.001; Group 2, 3.6 vs. 4.5%; p<0.001). CONCLUSIONS: The RTGCS allows easy identification of the leading contributing patients groups. To propose and evaluate interventions for improving the labor management in nulliparous women and promote vaginal delivery after cesarean (VBAC) could help to mitigate further increases in the future.