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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 overall high risk of bias, according to PROBAST. In the IPD meta-analysis, the models had summary C-statistics ranging from 0.53 to 0.65 and summary calibration slopes ranging from 0.40 to 0.88, with risk predictions that were generally too extreme compared with the observed risks. The models had little to no clinical utility, as assessed by net benefit. However, there remained uncertainty in the performance of some models due to small available sample sizes. Conclusions The three validated stillbirth prediction models showed generally poor and uncertain predictive performance in new data, with limited evidence to support their clinical application. The findings suggest methodological shortcomings in their development, including overfitting. Further research is needed to further validate these and other models, identify stronger prognostic factors and develop more robust prediction models. (c) 2021 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Objective To assess the performance of fetal magnetic resonance imaging (MRI) in detecting associated anomalies in fetuses diagnosed with isolated corpus callosal (CC) anomaly on multiplanar ultrasound evaluation of the fetal brain (neurosonography). Methods This was a multicenter, retrospective cohort study involving 14 fetal medicine centers in Italy, UK, Portugal, Canada, Austria and Spain. Inclusion criteria were fetuses with an apparently isolated CC anomaly, defined as an anomaly of the CC and no other additional central nervous system (CNS) or extra-CNS abnormality detected on expert ultrasound, including multiplanar neurosonography; normal karyotype; maternal age >= 18 years; and gestational age at diagnosis >= 18 weeks. The primary outcome was the rate of additional CNS abnormalities detected exclusively on fetal MRI within 2 weeks following neurosonography. The secondary outcomes were the rate of additional abnormalities according to the type of CC abnormality (complete (cACC) or partial (pACC) agenesis of the CC) and the rate of additional anomalies detected only on postnatal imaging or at postmortem examination. Results A total of 269 fetuses with a sonographic prenatal diagnosis of apparently isolated CC anomalies (207 with cACC and 62 with pACC) were included in the analysis. Additional structural anomalies of the CNS were detected exclusively on prenatal MRI in 11.2% (30/269) of cases, with malformations of cortical development representing the most common type of anomaly. When stratifying the analysis according to the type of CC anomaly, the rate of associated anomalies detected exclusively on MRI was 11.6% (24/207) in cACC cases and 9.7% (6/62) in pACC cases. On multivariate logistic regression analysis, only maternal body mass index was associated independently with the likelihood of detecting associated anomalies on MRI (odds ratio, 1.07 (95% CI, 1.01-1.14); P = 0.03). Associated anomalies were detected exclusively after delivery and were missed on both types of prenatal imaging in 3.9% (8/205) of fetuses with prenatal diagnosis of isolated anomaly of the CC. Conclusion In fetuses with isolated anomaly of the CC diagnosed on antenatal neurosonography, MRI can identify a small proportion of additional anomalies, mainly malformations of cortical development, which are not detected on ultrasound. (c) 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Obesity is a risk factor for the development of gestational hypertension, with important consequences for both the mother and fetus. This prospective observational study aims to propose an early prediction model of hypertensive disorders in pregnancy among obese women, through the bioelectrical impedance analysis (BIA) at the first trimester, thus allowing early recognition of obese women that are at risk to develop gestational hypertension, in order to target preventive interventions.Singleton obese women (BMI ≥ 30 kg/m2) between the 9th and 12th week of pregnancy were included in the study. The exclusion criteria were chronic diseases, like type 2 diabetes mellitus, hypertension, and other medical pre-existing conditions. Eligible women were followed up at 20, 28, and 36 weeks of gestation by measuring blood pressure, weight, and body composition with the use of the BIA. The diagnosis of gestational hypertension was made after the 20th week of gestation. Pregnancy and perinatal outcomes were then recorded.Of the 479 women included in the study, 85 (17.7%) developed gestational hypertension; the remaining 394 (82.3%) resulted to be normotensive. A higher rate of nulliparous women was found in the hypertensive group (50.6% vs. 37.6%, p = 0.02), together with a higher rate of induction of labor (55.3% vs. 40.9%, p = 0.02) and of small for gestational age (SGA) newborns (12.9% vs. 6.9%, p = 0.03). Significant differences emerged in the body composition between the two groups already from the first trimester, indeed women developing gestational hypertension showed elevated values of Total body Mass, FM, FFM, TBW (p0.02), and of leg's FM, FFM (p0.006). At the multivariate logistics regression, the risk of developing gestational hypertension resulted higher in women with elevated total body water levels in the first trimester (OR 1.10 95% CI 1.04 -1.92).The BIA is a rapid, easy, non-invasive, and inexpensive tool to evaluate the body composition of obese pregnant women. It represents a promising predictor of hypertensive disorders in pregnancy, which allows an early identification of the patients at risk of developing gestational hypertension, thus opening a window of opportunity for strictly monitoring and target preventive intervention.

Background Multiple gestations represent a considerable proportion of pregnancies delivering in the late preterm (LP) period. Only 30% of LP twins are due to spontaneous preterm labor and 70% are medically indicated; among this literature described that 16–50% of indicated LP twin deliveries are non-evidence based. As non-evidence-based delivery indications account for iatrogenic morbidity that could be prevented, the objective of our observational study is to investigate first neonatal outcomes of LP twin pregnancies according to gestational age at delivery, chorionicity and delivery indication, then non evidence-based delivery indications. Methods Prospective cohort study among twins infants born between 34 + 0 and 36 + 6 weeks, in Emilia Romagna, Italy, during 2013–2015. The primary outcome was a composite of adverse perinatal outcomes. Results Among 346 LP twins, 84 (23.4%) were monochorionic and 262 (75.7%) were dichorionic; spontaneous preterm labor accounted for 85 (24.6%) deliveries, preterm prelabor rupture of membranes for 66 (19.1%), evidence based indicated deliveries were 117 (33.8%), while non-evidence-based indications were 78 (22.5%). When compared to spontaneous preterm labor or preterm prelabor rupture of membranes, pregnancies delivered due to maternal and/or fetal indications were associated with higher maternal age (p p p p p p p p p p Conclusion Our study suggests that the decision to deliver or not twins in LP period should consider gestational age at delivery as the main determinant infants’ prognosis. Delivery indications should be accurately considered, to avoid iatrogenic early birth responsible of preventable complications.

Background Implementation of high-quality national audits for perinatal mortality are needed to improve the registration of all perinatal deaths and the identification of the causes of death. This study aims to evaluate the implementation of a Regional Audit System for Stillbirth in Emilia-Romagna Region, Italy. Methods For each stillbirth (≥ 22 weeks of gestation, ≥ 500 g) occurred between January 1, 2014 to December 1, 2016 (n = 332), the same diagnostic workup was performed and a clinical record with data about mother and stillborn was completed. Every case was discussed in a multidisciplinary local audit to assess both the cause of death (ReCoDe classification) and the quality of care. Data were reviewed by the Regional Audit Group. Stillbirth rates, causes of death and the quality of care were established for each case. Results Total stillbirth rate was 3.09 per 1000 births (332/107,528). Late stillbirth rate was 2.3 per 1000 (251/107,087). Sixteen stillbirths were not registered by the Regional Birth Register. The most prevalent cause of death was placental disorder (33.3%), followed by fetal (17.6%), cord (14.2%) and maternal disorders (7.6%). Unexplained cases were 14%. Compared to local audits, the regional group attributed different causes of death in 17% of cases. At multivariate analysis, infections were associated with early stillbirths (OR 3.38, CI95% 1.62–7.03) and intrapartum cases (OR 6.64, CI95% 2.61–17.02). Placental disorders were related to growth restriction (OR 1.89, CI95% 1.06–3.36) and were more frequent before term (OR 1.86, CI95% 1.11–3.15). Stillbirths judged possibly/probably preventable with a different management (10.9%) occurred more frequently in non-Italian women and were mainly related to maternal disorders (OR 6.64, CI95% 2.61–17.02). Conclusions Regional Audit System for Stillbirth improves the registration of stillbirth and allows to define the causes of death. Moreover, sub-optimal care was recognized, allowing to identify populations which could benefit from preventive measures.

Abstract. Vitamin D is a secosteroid hormone that plays a pivotal role in several metabolic and reproductive pathways in humans. Increasing evidence supports the role of vitamin D deficiency in metabolic disturbances and infertility in women with polycystic ovary syndrome (PCOS). Indeed, supplementation with vitamin D seems to have a beneficial role on insulin resistance (IR) and endometrial receptivity. On the other hand, exceedingly high levels of vitamin D appear to play a detrimental role on oocytes development and embryo quality. In the current review, we summarize the available evidence about the topic, aiming to suggest the best supplementation strategy in women with PCOS or, more generally, in those with metabolic disturbances and infertility. Based on the retrieved data, vitamin D seems to have a beneficial role on IR, insulin sensitivity and endometrial receptivity, but high levels and incorrect timing of administration seem to have a detrimental role on oocytes development and embryo quality. Therefore, we encourage a low dose supplementation (400–800 IU/day) particularly in vitamin D deficient women that present metabolic disturbances like PCOS. As far as the reproductive health, we advise vitamin D supplementation in selected populations, only during specific moments of the ovarian cycle, to support the luteal phase. However, ambiguities about dosage and timing of the supplementation still emerge from the clinical studies published to date and further studies are required.

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

BackgroundAs uterine rupture may affect as many as 11/1000 women with 1 prior cesarean birth and 5/10.000 women with unscarred uterus undergoing labor induction, we intended to estimate the prevalence of such rare outcome when PGE2 is used for cervical ripening and labor induction.MethodsWe searched MEDLINE, ClinicalTrials.gov and the Cochrane library up to September 1st 2020. Retrospective and prospective cohort studies, as well as randomized controlled trials (RCTs) on singleton viable pregnancies receiving PGE2 for cervical ripening and labor induction were reviewed. Prevalence of uterine rupture was meta-analyzed with Freeman-Tukey double arcsine transformation among women with 1 prior low transverse cesarean section and women with unscarred uterus.ResultsWe reviewed 956 full text articles to include 69 studies. The pooled prevalence rate of uterine rupture is estimated to range between 2 and 9 out of 1000 women with 1 prior low transverse cesarean (5/1000; 95%CI 2-9/1000, 122/9000). The prevalence of uterine rupture among women with unscarred uterus is extremely low, reaching at most 0.7/100.000 (ConclusionsUterine rupture is a rare event during cervical ripening and labor induction with PGE2.

INTRODUCTION: Obstetric history and maternal body composition and lifestyle may be associated with serious complications both for the mother, such as gestational diabetes mellitus (GDM), and for the fetus, including congenital malformations such as neural tube defects (NTDs). AREAS COVERED: In view of the recent knowledge, changes of nutritional and physical activity habits ameliorate glycemic control during pregnancy and in turn improve maternal and neonatal health outcomes. Recently, a series of small clinical and experimental studies indicated that supplementation with inositols, a family of insulin sensitizers, was associated with beneficial impact for both GDM and NTDs. EXPERT OPINION: Herein, we discuss the most significant scientific evidence supporting myo-inositol administration as a prophylaxis for the above-mentioned conditions.

BACKGROUND: The aim of this study was to assess the efficacy of PAMG-1 test (placental alpha microglobulin-1) in cervicovaginal secretions collected immediately following transvaginal ultrasound (TVUS) of women with signs and symptoms of preterm labor (PTL), clinically intact membranes and cervical length between 15 and 30 mm for the prediction of imminent spontaneous delivery (within 7 days of testing), as well as delivery

Introduction Antithrombin levels are often reduced in preeclampsia and infusion of antithrombin concentrates has been reported to prolong gestation in severe preeclampsia. We aimed to evaluate efficacy and safety of high-dose antithrombin (ATIII) supplementation in patients with single pregnancies and preeclampsia occurring before 30 weeks of gestation. Materials and methods In November 2004 a double-blind, placebo-controlled trial (code KB033) was started in 13 Italian centers. The planned sample size was of 240 patients (intention-to-treat, ITT population) to detect a 30% relative risk reduction of the primary endpoint, composite perinatal morbidity. Eligible patients were randomized to high dose AT (3000 IU/daily, ATIII Kedrion S.p.A., Italy), or placebo (1% glycine) for 7 days or less until delivery, whichever came first. The per-protocol (PP) population was restricted to patients receiving at least two days of treatment. Results The study was terminated by the sponsor in October 2007 after the enrolment of 38 evaluable patients – 20 randomized to high dose AT and 18 to placebo, 27 treated for 2 days or more – out of 164 screened patients. Enrolment failures were mainly represented by requirement for immediate delivery and consent refusal (91 patients). The primary endpoint occurred in 15 of 38 patients (39.5%), with a relative risk in the AT arm of 0.85 (95% CI 0.42–1.75) and 0.79 (95% CI 0.30-2.11) in the ITT and PP populations, respectively. Living neonates in the two arms had similar weight at birth, Apgar scores, and duration of hospitalization in neonatal ICU. In mothers, AT supplementation was associated with reduced blood loss at delivery and with surrogate laboratory markers (LDH, d -dimer). Conclusions The results of this markedly underpowered trial, albeit suggestive of a potential maternal benefit, cannot support high-dose AT supplementation to improve fetal/neonatal outcomes in early preeclampsia.

A 35-year-old woman with recurrent severe placenta-mediated pregnancy complications in her 2 pregnancies asks: Will low-molecular-weight heparin help prevent recurrent placenta-mediated pregnancy complications in my next pregnancy? We performed a meta-analysis of randomized controlled trials (RCTs) comparing low-molecular-weight heparin (LMWH) vs no LMWH for the prevention of recurrent placenta-mediated pregnancy complications. We identified six RCTs that included a total of 848 pregnant women with prior placenta-mediated pregnancy complications. The primary outcome was a composite of pre-eclampsia (PE), birth of a small-for-gestational-age (SGA) newborn (20 weeks. Overall, 67 (18.7%) of 358 of women being given prophylactic LMWH had recurrent severe placenta-mediated pregnancy complications compared with 127 (42.9%) of 296 women with no LMWH (relative risk reduction, 0.52; 95% CI, 0.32 to 0.86; P = .01; I2, 69%, indicating moderate heterogeneity). We identified similar relative risk reductions with LMWH for individual outcomes, including any PE, severe PE, SGA

OBJECTIVE: To assess the efficacy of progestogens for maintenance tocolysis in women undelivered after their first preterm labor episode. METHODS: Women with singleton pregnancies between 22 0/7 and 31 6/7 weeks of gestation with arrested preterm labor and a cervical length 25 mm or less at hospital discharge were eligible. Patients with a previous preterm birth were excluded. In a randomized controlled trial conducted in five university hospitals, women were randomized to receive vaginal progesterone (200 mg per day) or intramuscular 17α-hydroxyprogesterone caproate (341 mg per week) or to an observation groups (control group). The primary outcome was the proportion of women with preterm birth at less than 37 weeks of gestation. A sample size of 160 per group (n=480) was planned to compare vaginal progesterone and 17ahydroxyprogesterone caproate groups with those in the control group. The sample size estimation was based on the hypothesis that the risk of experiencing preterm birth in the control group would be 30% and that 17α-hydroxyprogesterone caproate or progesterone would decrease this risk to 15%. A P value of ≤.025 was defined as statistically significant. At planned interim analysis (n=254), the trial was stopped for futility. RESULTS: Between July 2010 and June 2015, 257 women were eligible and 254 were subsequently randomly assigned to vaginal progesterone (n=86), 17α-hydroxyprogesterone caproate (n=87), or observation (n=81). Nineteen (8%) were excluded from the analysis because they either dropped out or information was missing, leaving 235 women available for analysis. Demographic characteristics were similar across groups. The preterm birth rate did not differ significantly between groups: 23% in the 17a-hydroxyprogesterone caproate group, 39% in the vaginal progesterone group, and 22% in the women in the control group (P=.949 for 17a-hydroxyprogesterone caproate compared with the women in the control group and P=.027 for vaginal progesterone compared with women in the control group). CONCLUSION: The use of progestogens for maintenance tocolysis in women with a short cervix did not reduce the rate of preterm birth.

AIM: To evaluate pregnancy outcome in women with fetal membranes at or beyond external os who underwent exam-indicated cerclage or conservative management. MATERIAL AND METHODS: Retrospective cohort study including 52 patients with fetal membranes at or beyond external os between 17 and 27 weeks of gestation, treated in two third-level hospitals, between January 2001 and April 2009. The outcomes of interest of the study, prolongation of pregnancy and neonatal survival rate, were stratified according to type of management, parity, clinical conditions and blood tests at admission and calculated using the Kaplan-Meier algorithm. RESULTS: Of 52 women, 37 received exam-indicated cerclage and 15 were managed conservatively. The rate of patients still pregnant beyond 180 days within the cerclage group differed significantly from those of the conservative management group (80% vs 0%, respectively) (P-value

To assess whether antithrombotic prophylaxis with low-molecular-weight heparin effectively prevents recurrence of late pregnancy complications, 135 women with previous history of preeclampsia, hemolytic anemia, elevated liver enzymes and low platelet count syndrome, intrauterine fetal death, fetal growth restriction, or placental abruption who had been referred within the 12th gestational week were randomized to medical surveillance alone (n = 68) or combined to open-label nadroparin (3800 IU daily subcutaneous injections) treatment (n = 67) in the setting of a randomized, parallel-group, superiority trial, run in Italy from April 2007 to April 2010. Primary outcome was a composite end point of late-pregnancy complications. Analysis was by intention to treat. The study was stopped for futility at the time of the first planned interim analysis. Among the 128 women eventually available for final analyses, 13 of the 63 (21%) randomized to nadroparin compared with 12 of the 65 (18%) on medical surveillance alone progressed to the primary end point. The absolute event risk difference between treatment arms (2.2; −1.6 to 16.0) was not statistically significant (P = .76). Thus, nadroparin did not prevent late-pregnancy complications in women at risk of recurrence. This finding challenges the role of antithrombotic prophylaxis with low-molecular-weight heparin in the prevention of recurrent late pregnancy complications The trial was registered at http://ricerca-clinica.agenziafarmaco.it as EudraCT 2006-004205-26.

In this study, we want to evaluate which are the risk factors involved in early pre-term delivery (PTD). Spontaneous PTD results from two clinical conditions: (1) spontaneous pre-term labour (PTL) leading to PTD (idiopathic) and (2) pre-term premature rupture of membranes (pPROM). This is a multicentric, observational, retrospective, cross-sectional study, which includes 7,631 women admitted in the Obstetric units of Siena, Perugia, Torino, Trieste, Milano, Modena, Ancona, Foggia and Catania. Data were obtained from all patients having delivered spontaneously, pre-term or at term. The present study reveals the involvement of inflammation/infection in pathogenetic mechanisms leading to early PTD in the Italian population. A higher incidence of both clinical and pathological parameters of inflammation/infection - pPROM, genitourinary tract infections, placenta histopathological inflammation, WBC and C-reactive protein (CRP) - in early pre-term delivery in respect to late pre-term delivery and delivery at term, were shown.

Objective The aim of this study was to identify maternal risk factors for spontaneous preterm birth (PTB) compared to delivery at term, in order to recognize high risk women and to provide a global overview of the Italian situation. Study design A multicenter, observational and retrospective, cross-sectional study was designed. The study population comprised 7634 women recruited in 9 different University Maternity Hospitals in Italy. The main criteria for inclusion were: women having had vaginal preterm or term spontaneous delivery in each participating centre during the study period. The records related to deliveries occurring between April and December 2008. A multivariable logistic regression was employed to identify independent predictors of spontaneous preterm birth. Odds ratios (ORs) and 95% confidence intervals (95% CI) were reported with two-tailed probability ( p ) values. Statistical calculations were carried out using SAS version 9.1. A two-tailed p -value of 0.05 was used to define statistical significant results. Results A significant increased risk of PTB was found in women with BMI>25 (OR=1.662; 95% CI=1.033–2.676; p -value=0.0365) and in women employed in heavy work (OR=1.947; 95% CI=1.182–3.207; p -value=0.0089). Moreover there was a significant association between PTB and previous reproductive history. In fact a history of previous abortion (OR=1.954; 95% CI=1.162–3.285; p -value=0.0116) or previous cesarean section (OR=2.904; 95% CI=1.066–7.910; p -value=0.0371) was positively correlated to the increased risk of PTB and an important statistically significant association was calculated between PTB and previous pre-term delivery (OR=3.412; 95% CI=1.342–8.676; p -value=0.0099). All the other covariates examined as potential risk factors for PTB were not found to be statistically significantly related ( p -value>0.05). Conclusions The present study, applied to a substantial sample of Italian population, demonstrates that there are peculiar risk factors for spontaneous PTB in the Italian population examined. It shows an association between preterm delivery and certain maternal factors as: BMI, employment, previous abortions, previous PTBs and previous cesarean section.

The phenomenon of stillbirth has been poorly addressed in terms of reported statistics and as a clinical issue. A Study Group of the European Association of Perinatal Medicine reviewed the topic and highlighted specific issues. Such proposal was discussed in an open workshop held in Modena, Italy last year and this paper reports the final recommendations. Briefly, at least 22 completed weeks of gestation was endorsed as definition for including SB in statistics and for clinical studies. A minimum diagnostic work-up was suggested together with the emphasis toward a local, multidisciplinary audit process, in order to comprehend causality. Attention for parents emotional support and appropriate counselling was believed as essential part of the clinical process. Finally, the need for funding comprehensive research programs in SB through international, multidisciplinary involvement was believed mandatory for developing effective preventative strategies to avert the devastating occurrence of stillbirth.

Several reports have suggested the use of acupuncture as a useful treatment for hyperemesis gravidarum (HG), in particular the effects on nausea intensity was underlined. The aim of this study was to compare the efficacy of acupuncture sessions plus acupressure with a metoclopramide/vitamin B12 treatment.In this study we randomized 88 pregnant patients suffering from HG to receive either acupuncture sessions plus acupressure (acupuncture group) or metoclopramide infusion (metoclopramide group) supplemented by vitamin B12 complex. Somatic symptoms and the ability to achieve the daily routine activity (functioning) were evaluated. Acupuncture sessions were performed at the hospital twice a week for 2 weeks according to the traditional Chinese medicine criteria. Acupression was applied for 6-8 h/day. In the metoclopramide group, patients received at hospital metoclopramide infusion (20 mg/500 mL saline for 60 min) twice a week for 2 weeks. An oral supplementation with vitamin B12 complex (30 mg/day) was also prescribed.Both treatments reduced vomiting episodes and then nausea intensity with a consequent improvement in the rate of food intake. The effect of acupuncture seems to be progressive, increasing at the end of treatment whereas pharmacological approach has a prompt effect in responders remaining stable thereafter. Moreover, acupuncture was significantly more effective than drugs in improving functioning.In our study for the first time acupuncture, applied accordingly to Chinese formula, was compared to drugs demonstrating the same effect of both treatments on HG symptoms. Interestingly, functioning was significantly improved just by acupuncture. Even if the effect of acupuncture on HG discomfort remains to be confirmed, the reports on the effect of acupuncture on psychosocial variables could represent a further advantage of acupuncture application and provide an incentive to widen the base of the research.

In mammals, proopiomelanocortin (POMC)-related peptides are involved in reproductive processes at both the hypothalamopituitary and ovarian levels. Through immunocytochemical and physiological in vitro studies, evidence for a diffuse POMC-related opioid system in the lizard Podarcis s. sicula is provided. In the lizard ovary, beta-endorphin (beta-EP)-like immunoreactive cells were observed within the granulosa layer; the immunoresponse showed seasonal variation, being most pronounced in the winter ovary. HPLC followed by immunoassay showed that acetyl beta-EP is the main form of POMC-related peptide in both pituitary and ovary. In vitro studies showed that picomolar amounts of beta-EP stimulate follicular estrogen production during both the reproductive and winter phases; induction was found to be higher in the reproductive phase. The data reported here provide evidence for the physiological role played by beta-EP in the reproductive function of Podarcis s. sicula via induction of ovarian production of estradiol-17 beta, which is the main factor responsible for the vitellogenic process.

Several effects of melatonin are modulated by gonadal steroids and are reduced in ageing women. Administration of melatonin reduces internal carotid artery pulsatility index (PI), and blood pressure in young individuals. Whether these effects are conserved in postmenopausal women and are influenced by hormone replacement therapy (HRT), was herein investigated.Randomised, double-blind placebo controlled study.Twenty-three postmenopausal women of which 11 were unreplaced with HRT and 12 on the oestrogenic phase of continuous transdermal estradiol (50 microg/day) plus cyclic medroxyprogesterone acetate (5 mg/day x 12 days every 28 days).Internal carotid PI, by colour Doppler, and supine blood pressure were evaluated 90, 180 and 240 minutes following the oral administration of melatonin (1 mg) or placebo. Levels of nitrites/nitrates (NOx), the stable derivatives of nitric oxide, were also evaluated in samples collected 90 minutes following the administration of placebo or melatonin.In women not on replacement therapy melatonin was ineffective. In HRT-treated women, melatonin reduced internal carotid artery PI (P = 0.005). The effect was maximal within 90 minutes, and maintained for at least 240 minutes, with melatonin levels in the nocturnal physiological range. Systolic and diastolic blood pressures were reduced of 8 mmHg (P = 0.038) and 4 mmHg (P = 0.045), respectively, while NOx levels were significantly increased (P = 0.024).The circulatory response to melatonin is conserved in postmenopausal women with but not without hormone replacement therapy. Maintenance of the cardiovascular response to melatonin, may be implicated in the reduced cardiovascular risk of postmenopausal women with hormone replacement therapy.

A dietary approach has proven to be effective in alleviating symptoms of premenstrual syndrome. In our previous studies, magnesium improved premenstrual irritability and mood scoings. In this double-blind, placebo-controlled study, we evaluated the effects of a new dietetic preparation (Sillix Donna, Giuliani) in 40 patients affected by mild to moderate premenstrual syndrome. Premenstrual symptoms were scored in both follicular and luteal phases, at baseline, at 2nd, 4th and 6th month of treatment by using the Menstrual Distress Questionnaire (MDQ). Twenty patients were randomised to receive the active preparation and 20 placebo. MDQ scores at baseline were similar in the two groups. Five patients of the placebo group dropped out because of treatment failure. No side effects were observed. Both treatments reduced symptoms already in the 2nd month, but the active preparation was more effective at all time controls (p0.05); at the 6th month it significantly reduced premenstrual MDQ scores to 18% of baseline values, placebo only to 73%. These data demonstrate that Sillix Donna is effective in reducing premenstrual distress.

Several reports indicate a number of changes in the control of the release of PRL, LH, FSH, GH and beta-endorphin (B-EP) as a result of insulin-dependent diabetes mellitus (IDDM). In this study we evaluate the presence of non-specific pituitary responses to releasing hormones in IDDM children and adolescents.The non-specific effects of TRH on plasma GH, LH and B-EP levels and of GnRH on plasma GH, PRL, TSH and B-EP levels were measured in 16 IDDM children and in 16 healthy children matched by age and sex. All subjects were tested with injection of TRH (200 micrograms i.v. bolus) and GnRH (50 micrograms i.v. bolus). GH, TSH, PRL, LH and B-EP levels were evaluated with radioimmunological methods on blood samples collected before and after stimulation by releasing hormones.GH and B-EP non-specific responses to TRH and GnRH were significantly more pronounced in IDDM patients than in controls. All patients showed at least one non-specific response to one of the two releasing hormones. No significant correlations were found between non-specific pituitary responses and the patient's age, the duration and onset of disease or the degree of metabolic control.These observations may indicate that: in IDDM hypothalamus-pituitary regulating mechanism is altered; the hormones whose levels are most often found to be abnormal in IDDM (other than insulin) are also hormones which respond non specifically to the neuropeptides TRH and GnRH.

It is well known that pregnancy is a condition in which plasma magnesium falls because of accumulation of the ion in the placenta and fetus. Magnesium (Mg) is therefore widely given as a supplement during pregnancy, particularly in cases of preterm labour. In our experience, the combination of oral Mg (magnesium pyrrolidone carboxylic acid) at a dose of 360 mg/day with conventional ritodrine treatment allows a reduction in ritodrine dosage, accompanied by a significant reduction in side effects. We therefore evaluated changes in fetal blood flow, using pulsed Doppler, in women submitted to combined magnesium and ritodrine treatment compared to those treated with ritodrine plus placebo. The Mg-treated group showed a decrease in vessel resistance both in the umbilical artery and in the fetal middle cerebral artery, indicating that fetal vasculature is sensitive to exogenous Mg. Measurement of plasma and mononuclear cell Mg showed an intracellular increase in the cation of about 10 per cent. We conclude that oral magnesium supplementation in pregnancy is safe and that it has a positive effect on the fetal circulation.

Plasma levels of beta-endorphin and beta-lipotropin in 18 heroin addicts were found to be similar to those in pregnant control subjects at all stages of gestation. In contrast, amniotic fluid levels of beta-endorphin were significantly lower in heroin abusers than in controls in both the first and second trimesters. Amniotic fluid levels of beta-lipotropin were reduced only in the second trimester. At term, when the patients were almost drug free, the amniotic fluid levels of both peptides were in the control range. These data support the existence of a specific control mechanism for amniotic fluid levels of beta-endorphin and beta-lipotropin, independent of the maternal pituitary, and show that exogenous opiates interfere with it negatively.

The present study evaluates the plasma level changes in beta-lipotropin and beta-endorphin in nine women at term throughout spontaneous labor, in ten pregnant women undergoing elective cesarean section in the absence of uterine contractions, and in ten women submitted to emergency cesarean section because of fetal distress occurring during labor. A basal plasma sample was taken before labor in the 39th week of pregnancy. Two subsequent samples were then obtained before and after parturition, together with umbilical cord samples at birth. beta-lipotropin and beta-endorphin were measured by radioimmunoassay after silicic acid plasma extraction and gel filtration. In cases of spontaneous labor, there was a progressive increase in opioid concentrations as labor progressed, the maximal values being observed after delivery. Cord values were similar to those observed in the mother, without showing any relationship to them. Pregnant women undergoing cesarean section in the absence of labor show constant beta-lipotropin and beta-endorphin concentrations both before and after fetal extraction, both values being significantly lower than those found at delivery after spontaneous labor. beta-Endorphin neonatal levels were significantly higher than in the respective mothers and were in the same range as those of infants born through vaginal delivery. In the third group (cesarean section performed at the first stage of labor), presurgical opioid levels were higher than in women at the same stage of spontaneous labor, whereas postextraction values showed a wide range, with mean values similar to those observed after spontaneous delivery.(ABSTRACT TRUNCATED AT 250 WORDS)

Mean plasma levels of beta-endorphin (beta EP), beta-lipotropin (beta LPH) and ACTH were significantly higher in 22 patients with primary affective disorders (PAD) and in 2 schizoaffective subjects off therapy since 10 days than in 22 age- and sex-matched healthy controls. Desimipramine therapy (50-100 mg/day per os for 3-5 weeks) induced in parallel psychological improvement and fall in beta LPH-beta EP in 6 of 8 PAD patients treated, and a normalization of beta EP-beta LPH levels with minimal mood improvement in the 2 schizoaffective subjects. These results indicate that the opioid levels are increased in PAD and schizoaffective patients and normalized by the desimipramine therapy in those patients in whom the affective disorders improved.

In order to investigate the role of the adrenal gland in the pathogenesis of polycystic ovarian disease (PCOD), we evaluated the adrenal steroid response to an opiate receptor blockade. Six healthy menstruating volunteers and 6 patients with PCOD were given a saline or naloxone (4 mg i.v.) injection in the early follicular phase. Blood samples were taken prior to the injections and every 15-30 minutes in the following 2 hours. Cortisol, androstenedione (A) and dehydroepiandrosterone (DHA) plasma levels were determined by RIA after extraction (cortisol) and celite chromatography (A and DHA). While in controls naloxone increased only cortisol concentrations, in PCOD patients DHA plasma levels also were stimulated by the opiate receptor antagonist. In PCOD patients the increase of cortisol (p less than 0.05) and of DHA (p less than 0.001) levels resulted significantly higher than in controls. In both groups A plasma levels remained unchanged after naloxone administration. These data confirm that endogenous opioids exert an inhibitory control on the pituitary-adrenal axis. In PCOD patients the response to naloxone led to a hypersecretion of adrenal delta 5-androgens, which could account for the development of the syndrome.

On the basis of the behaviour during menstrual cycle of the pituitary hormones plasma levels, the Authors have studied during the different periods of the cycle (follicular, ovulatory and luteal) the effects of OGTT and ITT's on the plasma levels of Glucose, insulin, HGH and Cortisol. Significantly lower levels of IRI, HGH and Cortisol were found in follicular phase compared to ovulatory period and luteal phase except for Cortisol in luteal phase. A slightly higher glucose tolerance was found in follicular phase as well as a reduced hypoglicemia under insulin load. Reduced HGH response to ITT was found in follicular phase as well as a reduced Cortisol response compared to the results observed in ovulatory and luteal phase. These data sustain the concept that hormonal variations occurring in an ovulatory cycle are also capable of modifying the woman's body response to various stimuli such as OGTT and ITT.

In order to evaluate the relationships between endogenous opioid activity and premenstrual complaints, we subjected three groups of patients in the mid (days 8-12 prior to menses) and late (days 1-5 prior to menses) luteal phases of the cycle to a naloxone test and some of the patients to a luteinizing-hormone-releasing hormone (LHRH) test. The premenstrual syndrome (PMS) group was composed of nine patients complaining of dizziness, irritability and depression close to menses for at least three years. The menstrually related migraine (MM) group was composed of 15 patients complaining of premenstrually related migraine. The common migraine (CM) group was made up of 16 women suffering from common migraine for years whose attacks occurred independently of menstrual cycle events. A group of seven fertile women served as controls. Every two days the patients filled out the Menstrual Distress Questionnaire for evaluation of their complaints. After the evaluation of spontaneous LH pulsatility for one hour, 4 mg of naloxone was injected as a bolus, and samples were collected every 15 minutes for 2 hours. Both estradiol (E2) and progesterone (P) were measured in basal samples from each naloxone test. LH responsiveness to LHRH was similar in the mid and late luteal phases and did not change between groups. In the mid luteal phase the LH response to naloxone in PMS and MM patients was similar to that in normal subjects, while CM patients had impaired LH secretion. In the premenstrual phase only the controls maintained an LH responsiveness similar to that observed in the mid luteal phase, while both PMS and MM lost the naloxone-induced LH release.(ABSTRACT TRUNCATED AT 250 WORDS)

Plasma estradiol (E2), progesterone (P), beta-endorphin (beta-EP) and beta-lipotropin (beta-LPH) were measured in the luteal phase of 8 patients affected by menstrually-related migraine (M) and in 3 cases of catamenial epilepsy (CE). Plasma P and E2 of the M patients were lower than in the CE group. Both beta-LPH and beta-EP showed a reduction in M patients near menses, while the opposite pattern was found in CE. These data demonstrate that premenstrual syndrome is sustained by different, neurobiological dysfunction even if endogenous opioids could be involved in both migraine and epilepsy.

To test the hypothesis that labor onset could be the result of a reduced release of nitric oxide (NO).Out of 91 consecutive healthy nulliparous women at term serum citrulline (Cit) and arginine (Arg) levels were measured at least twice in 37 subjects, by the means of HPLC with fluorometric detection. Twenty cases underwent a spontaneous onset of labor (group A) while in 17 cases labor was induced (group B) because of pregnancy prolongation or amniotic fluid reduction.Cit and Arg levels were unaffected by the gestational age. In group A, Cit levels undergo a progressive decrease toward the day of labor (from 32.9+/-4.7 microM/L the day - 18,-5 to 27.7+/-7.8 the day -4,0; p=0.012) whilst they remained stable in group B (from 33.3+/-7.7 to 34.2+/-9.2). No significant changes were observed in Arg levels. Cit/Arg ratio remained stable in group A whereas it showed a trend to increase in group B.These data indirectly suggest a reduced release of NO toward term. This phenomenon could play a permissive role in the spontaneous onset of labor of healthy nulliparous women.

The most striking effect of increased survival and improved quality of life in HIV-infected women undergoing antiretroviral therapy is the feasibility of motherhood-desire satisfaction. However, such advantages are often associated with drug-related metabolic toxicities, particularly relevant in the pregnancy context. Recent guidelines provide recommendations and trends for the use of antiretroviral therapy in pregnant women, but current literature falls short of providing specific insights on the need for metabolic monitoring and treatment in HIV-infected pregnant women. In this review we provide specific insight into the state-of-the-art of: detection, evaluation, and management of metabolic alterations in this special population. Pregnancy is in fact a metabolic transition process, potentially associated with specific diseases in the mother, in the newborn, and in the adulthood of the child. We will not simply discuss antiretroviral therapy metabolic toxicities, but rather their interaction with the physiological metabolic changes occurring during pregnancy. Close monitoring is needed to diagnose metabolic alterations that can lead to adverse outcomes in the mother, in the newborn, and potentially in adulthood. Lifestyle interventions and an appropriate metabolic tailoring of antiretroviral therapy drugs need to be considered in the prevention and treatment of metabolic alteration during pregnancy.

Reduced magnesium (Mg) levels have been reported in women affected by premenstrual syndrome (PMS). To evaluate the effects of an oral Mg preparation on premenstrual symptoms, we studied, by a double-blind, randomized design, 32 women (24-39 years old) with PMS confirmed by the Moos Menstrual Distress Questionnaire. After 2 months of baseline recording, the subjects were randomly assigned to placebo or Mg for two cycles. In the next two cycles, both groups received Mg. Magnesium pyrrolidone carboxylic acid (360 mg Mg) or placebo was administered three times a day, from the 15th day of the menstrual cycle to the onset of menstrual flow. Blood samples for Mg measurement were drawn premenstrually, during the baseline period, and in the second and fourth months of treatment. The Menstrual Distress Questionnaire score of the cluster "pain" was significantly reduced during the second month in both groups, whereas Mg treatment significantly affected both the total Menstrual Distress Questionnaire score and the cluster "negative affect." In the second month, the women assigned to treatment showed a significant increase in Mg in lymphocytes and polymorphonuclear cells, whereas no changes were observed in plasma and erythrocytes. These data indicate that Mg supplementation could represent an effective treatment of premenstrual symptoms related to mood changes.

In the present study we hypothesized that a derangement of the L-arginine-nitric oxide system could be involved in the development of the hypercoagulative status found during preeclampsia. In order to verify such hypothesis we have compared the effects of nitric oxide substrate, L-arginine on platelet aggregation. Moreover, we have also measured the L-citrulline plasma levels as a stochiometric metabolite resulting from the conversion L-arginine to nitric oxide.Nine preeclamptic women and 11 normotensive pregnant women were enrolled for the study. Subjects were infused with saline and with 30gr of L-arginine. Blood samples were drawn during the saline infusion (30 min), during L-arginine administration (30 min) and 30 min thereafter. ADP and collagen-induced platelet aggregation was studied as per Born with a dual-channel aggregometer (Chrono-Log, Mascia Brunelli, Italy) and L-citrulline was measured by HPLC.In normotensive women the infusion significantly decreased ADP and collagen-induced aggregation after 15 minutes of L-arginine load; whereas no effects were observed in preeclamptic women. Similarly in normotensive but not in preeclamptic women L-arginine load was able to increase L-citrulline plasma levels.In normotensive women the in vivo L-arginine administration decreases platelet aggregation with an increase of L-citrulline plasma levels. On the contrary, no effects were observed in preeclamptic women. These findings confirm that a hypercoagulative status characterizes preeclampsia and that such phenomenon could be explained by a derangement of the platelet L-arginine-nitric oxide pathway.

BACKGROUND: Antiphospholipid syndrome is an autoimmune, hypercoagulable state that is caused by antiphospholipid antibodies. Anticardiolipin antibodies, anti-β2 glycoprotein-I, and lupus anticoagulant are the main autoantibodies found in antiphospholipid syndrome. Despite the amassed body of clinical knowledge, the risk of obstetric complications that are associated with specific antibody profile has not been well-established. OBJECTIVE: The purpose of this study was to assess the risk of obstetric complications in women with primary antiphospholipid syndrome that is associated with specific antibody profile. STUDY DESIGN: The Pregnancy In Women With Antiphospholipid Syndrome study is a multicenter, retrospective, cohort study. Diagnosis and classification of antiphospholipid syndrome were based on the 2006 International revised criteria. All women included in the study had at least 1 clinical criteria for antiphospholipid syndrome, were positive for at least 1 antiphospholipid antibody (anticardiolipin antibodies, anti-β2 glycoprotein-I, and/or lupus anticoagulant), and were treated with low-dose aspirin and prophylactic low molecular weight heparin from the first trimester. Only singleton pregnancies with primary antiphospholipid syndrome were included. The primary outcome was live birth, defined as any delivery of a live infant after 22 weeks gestation. The secondary outcomes were preeclampsia with and without severe features, intrauterine growth restriction, and stillbirth. We planned to assess the outcomes that are associated with the various antibody profile (test result for lupus anticoagulant, anticardiolipin antibodies, and anti-β2 glycoprotein-I). RESULTS: There were 750 singleton pregnancies with primary antiphospholipid syndrome in the study cohort: 54 (7.2%) were positive for lupus anticoagulant only; 458 (61.0%) were positive for anticardiolipin antibodies only; 128 (17.1%) were positive for anti-β2 glycoprotein-I only; 90 (12.0%) were double positive and lupus anticoagulant negative, and 20 (2.7%) were triple positive. The incidence of live birth in each of these categories was 79.6%, 56.3%, 47.7%, 43.3%, and 30.0%, respectively. Compared with women with only 1 antibody positive test results, women with multiple antibody positive results had a significantly lower live birth rate (40.9% vs 56.6%; adjusted odds ratio, 0.71; 95% confidence interval, 0.51-0.90). Also, they were at increased risk of preeclampsia without (54.5% vs 34.8%; adjusted odds ratio, 1.56; 95% confidence interval, 1.22-1.95) and with severe features (22.7% vs 13.8%, adjusted odds ratio, 1.66; 95% confidence interval, 1.19-2.49), of intrauterine growth restriction (53.6% vs 40.8%; adjusted odds ratio, 2.31; 95% confidence interval, 1.17-2.61) and of stillbirth (36.4% vs 21.7%; adjusted odds ratio, 2.67; 95% confidence interval, 1.22-2.94). In women with only 1 positive test result, women with anti-β2 glycoprotein-I positivity present alone had a significantly lower live birth rate (47.7% vs 56.3% vs 79.6%; P1 antibody positivity, triple-positive women had a lower live birth rate (30% vs 43.3%; adjusted odds ratio,0.69; 95% confidence interval, 0.22-0.91) and a higher incidence of intrauterine growth restriction (70.0% vs 50.0%; adjusted odds ratio,2.40; 95% confidence interval, 1.15-2.99) compared with double positive and lupus anticoagulant negative women. CONCLUSION: In singleton pregnancies with primary antiphospholipid syndrome, anticardiolipin antibody is the most common sole antiphospholipid antibody present, but anti-β2 glycoprotein-I is the one associated with the lowest live birth rate and highest incidence of preeclampsia, intrauterine growth restriction, and stillbirth, compared with the presence of anticardiolipin antibodies or lupus anticoagulant alone. Women with primary antiphospholipid syndrome have an increased risk of obstetric complications and lower live birth rate when

PURPOSE This meta-analysis aims to combine and analyze randomized clinical trials comparing computed tomography lung screening (CTLS) versus either no screening (NS) or chest x-ray (CXR) in subjects with cigarette smoking history, to provide a precise and reliable estimation of the benefits and harms associated with CTLS. MATERIALS AND METHODS Data from all published randomized trials comparing CTLS versus either NS or CXR in a highly tobacco-exposed population were collected, according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Subgroup analyses by comparator (NS or CXR) were performed. Pooled risk ratio (RR) and relative 95% CIs were calculated for dichotomous outcomes. The certainty of the evidence was assessed using the GRADE approach. RESULTS Nine eligible trials (88,497 patients) were included. Pooled analysis showed that CTLS is associated with: a significant reduction of lung cancer–related mortality (overall RR, 0.87; 95% CI, 0.78 to 0.98; NS RR, 0.80; 95% CI, 0.69 to 0.92); a significant increase of early-stage tumors diagnosis (overall RR, 2.84; 95% CI 1.76 to 4.58; NS RR, 3.33; 95% CI, 2.27 to 4.89; CXR RR, 1.52; 95% CI, 1.04 to 2.23); a significant decrease of late-stage tumors diagnosis (overall RR, 0.75; 95% CI, 0.68 to 0.83; NS RR, 0.67; 95% CI, 0.56 to 0.80); a significant increase of resectability rate (NS RR, 2.57; 95% CI, 1.76 to 3.74); a nonsignificant reduction of all-cause mortality (overall RR, 0.99; 95% CI, 0.94 to 1.05); and a significant increase of overdiagnosis rate (NS, 38%; 95% CI, 14 to 63). The analysis of lung cancer–related mortality by sex revealed nonsignificant differences between men and women ( P = .21; I-squared = 33.6%). CONCLUSION Despite there still being uncertainty about overdiagnosis estimate, this meta-analysis suggested that the CTLS benefits outweigh harms, in subjects with cigarette smoking history, ultimately supporting the systematic implementation of lung cancer screening worldwide.

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 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.

Introduction: The aim of this study was to investigate the relationships between maternal vascular malperfusions (MVM) and second trimester uterine arteries pulsatility index (UtA-PI) in cases of stillbirth (SB), compared to live-birth (LB) matched controls. Methods: This was a multicentre, observational, matched case-control study performed at five referral maternity centres over a 4-year period including SB and LB control pregnancies at high-risk for preeclampsia (PE) and/or fetal growth restriction (FGR), matched and stratified for UtA-PI MoM quartiles values of the SB cases. Logistic regression was used to assess the rates of each MVM finding, within each increasing MoM quartile subcategory in SB and matched LB controls. Results: 82 SB and 82 LB matched high-risk pregnancies were included. Placental hypoplasia, placental infarction, retroplacental hematoma, distal villous hypoplasia and accelerated villous maturation showed a significant correlation with UtA-PI. At univariable analysis, placental infarction and distal villous hypoplasia were more highly associated with the increasing quartile uterine Doppler measurements (odds ratio 2.24 and 2.23, respectively). Logistic regressions showed a significant positive and independent association between rates of retroplacental hematoma or distal villous hypoplasia and stillbirth within corresponding UtA-PI MoM quartiles (odds ratio 5.21 and 2.28, respectively). Discussion: We are providing evidence for characterization of two major etiological stillbirth categories, characterized by a positive or absent association with UtA-PI impairment and specific histopathological placental MVM lesions. Our results support a strict third trimester follow-up of cases with increased second trimester UtA-PI, in order to improve the reproductive chances of these pregnant patients.

Aim.Although obesity has been associated with endometrioid (type I) and, to a lesser extent, with serous(type II) endometrial cancer (EC), the association with the same histotypes of ovarian cancer (OC) remains un-clear. Therefore, we intended to compare the role of BMI in carcinogenesis of endometrioid and the serous ma-lignancies, at both ovarian and endometrial level.Methods.A retrospective case-to-case study was performed in the University Hospital of Bologna (Italy),through the review of primary EC matched with the corresponding OC cases in the same period (1988–2017).Results.We included 1052 women diagnosed with EC (n= 897 endometrioid,n= 52 serous) and 955women affected by OC (n= 132 endometrioid,n= 627 serous). EC patients had higher median BMI thanwomen diagnosed with OC (27.3 [23.4–31.9] vs 24.9 [21.7–27.5],pb0.01). After controlling for confounding, 1unit increase in BMI was associated with a 5% higher odds of endometrial as opposed to ovarian cancer (OR forovarian as opposed to endometrial cancer 0.95; 95% CI 0.91–0.98,p=0.004).Conclusions.Increasing BMI is associated with endometrial rather than ovarian cancer, among both serousand endometrioid histotypes.

Objective: To investigate the role of CTLA-4, PD-1 (programmed death-1), and PD-L1 (programmed death-ligand 1) single nucleotide polymorphisms (SNPs) in predicting clinical outcome of patients with advanced non-small cell lung cancer (NSCLC) treated with immune checkpoint inhibitors (ICIs). Methods: A total of 166 consecutive patients were included. We correlated SNPs with clinical benefit, progression-free survival, time to treatment failure, and overall survival and evaluated the incidence of SNPs in nonresponder and long clinical benefit groups. Results: Considering the entire cohort, no correlation was found between SNPs and clinical outcome; however, PD-L1 rs4143815 SNP and the long clinical benefit group showed a statistically significant association ( p = 0.02). The nonresponder cohort displayed distinctive PD-L1 haplotype ( p = 0.05). Conclusion: PD-L1 SNPs seem to be marginally involved in predicting clinical outcome of NSCLC treated with ICI, but further investigations are required.

Background BRCA1 mutation carriers are recommended to undergo prophylactic risk-reducing salpingo-oophorectomy (RRSO) between the ages of 35 and 40 or when child bearing is complete, with a possible delay until age 40–45 for BRCA2 mutation carriers. Study Question Primary outcome was the rate of unsuspected cancer findings during RRSO in a region of northern Italy (Emilia Romagna) and secondary outcomes were details of RRSO: age at surgical intervention, the venue of the procedures in relation to the surgical/pathological quality and the rate/role of concomitant opportunistic hysterectomies. Study Design Multicentre data collection by invitation to report current RRSO practices. Results A total of 222 RRSOs (54.5 % BRCA1, 34.7 % BRCA2, 1.8 % BRCA1 and BRCA2 combined, 5.8 % BRCA-VUS and 3.2 % BRCA not better specified) were reported from 9 different centres, half in non-university hospitals and the remainder in university hospitals. Breast cancer survivors (56.3 %) underwent the RRSO at a younger age (47.8 vs 50.6 years, p = 0.02). The mean and median ages at surgical intervention (49.0 and 48.0, respectively) were similar for BRCA1 and BRCA2 mutation carriers, as was the temporal trend in age distribution, and proportions treated in university and non-university hospitals. A diagnosis of ovarian invasive cancer was reported in 3.5 % of subjects, all BRCA1 or BRCA-combined subjects, at a median and mean age of 57 years (range 42–68). Abnormal tubal findings, such as serous tubal intraepithelial lesions (STIL) (100 %), secretory cell outgrowth (SCOUT) (100 %) and STIC (71.4 %), were mainly reported by pathologists in university hospitals. Of the 222 procedures, 15 (6.7 %) included hysterectomies: in none of these cases was a primitive uterine endometrioid or serous cancer found. Conclusions The results from this multicentre regional study should guide future preventive health policies for RRSO in BRCA mutation carriers.

Novel treatment strategies incorporating PD-1/PD-L1 inhibitors in the first-line setting of advanced non-small-cell lung cancer (NSCLC) provided relevant improvements in survival outcomes. Among NSCLC patients with PD-L1 tumor proportion score ≥50%, identifying the ones to be addressed to pembrolizumab monotherapy or chemo-immunotherapy combinations is a matter of debate, taking into account the risks of overtreatment and toxicity. Here we report the clinical stories of four NSCLC patients with PD-L1 tumor proportion score ≥50% and good performance status, sharing high tumor burden including serosal involvement. After having rapidly progressed on first-line PD-1/PD-L1 inhibitors, they achieved major clinical and radiological response to pembrolizumab-chemotherapy combination. These cases prove the feasibility and effectiveness of salvage chemo-immunotherapy in pembrolizumab-refractory NSCLC patients.

Objective: Expectant management in patients with prelabor preterm rupture of membranes between between 340/7 and 36 6/7 weeks (late preterm pPROM or LpPROM) has been shown to decrease the burden of prematurity, when compared to immediate delivery. As the severity of prematurity depends on gestational age (GA) at PROM, and PROM to delivery interval, we first investigated how such variables affect neonatal outcomes (NO). Second, we assessed the risk of neonatal sepsis. Study design: retrospective cohort study on neonatal morbidity among singleton infants born to expectantly managed mothers with LpPROM in five hospitals affiliated with three Italian academic institutions. The primary NO was a composite of neonatal death, non-invasive (cPAP) or invasive (mechanical ventilation) respiratory support, hypoglycemia (< 44 mg/dl needing therapy), newborn sepsis, confirmed seizures, stroke, intraventricular hemorrhage (IVH), basal nuclei anomalies, cardiopulmonary resuscitation, umbilical-cord-blood arterial pH < 7.0 or base excess < -12.5, and prolonged hospitalization (≥ 5 days). Univariate analysis described differences in the population according to GA at delivery. Multivariate logistic regression was then used to investigate the effects of GA at PROM, and PROM to delivery interval on the NO. Results: 258/606 (42.6 %) women with LpPROM were expectantly managed, as they did not deliver within the first 24 h. The median latency duration was 2 (95 %CI 1−3) days, having no effect on neonatal morbidity on multivariate analysis. Multivariate analysis also showed increased risks of adverse NO among PROM at 34 (OR 2.3 95 %CI 1.03−5.1) but not at 35 weeks when compared to 36 weeks, and among women receiving antenatal corticosteroids (OR 3.6 95 %CI 1.3−9.7), while antibiotic treatment showed a non-significant protective effect (OR 0.2 95 %CI 0.04−1.02). Prevalence of neonatal sepsis was 0.8 % (2/258) Conclusion: Expectant management of LpPROM should be encouraged especially between 34+0 and 34+6 weeks’, when the burden of prematurity is the greatest. Antibiotics may have beneficial effects, while careful consideration should be given to antenatal corticosteroids until future studies specifically address LpPROM.

Objective To report mode of delivery and immediate neonatal outcome in women infected with COVID‐19. Design Retrospective study. Setting Twelve hospitals in northern Italy. Participants Pregnant women with COVID‐19‐confirmed infection who delivered. Exposure COVID 19 infection in pregnancy. Methods SARS‐CoV‐2‐infected women who were admitted and delivered from 1 to 20 March 2020 were eligible. Data were collected from the clinical records using a standardised questionnaire on maternal general characteristics, any medical or obstetric co‐morbidity, course of pregnancy, clinical signs and symptoms, treatment of COVID 19 infection, mode of delivery, neonatal data and breastfeeding. Main outcome and measures Data on mode of delivery and neonatal outcome. Results In all, 42 women with COVID‐19 delivered at the participating centres; 24 (57.1%, 95% CI 41.0–72.3) delivered vaginally. An elective caesarean section was performed in 18/42 (42.9%, 95% CI 27.7–59.0) cases: in eight cases the indication was unrelated to COVID‐19 infection. Pneumonia was diagnosed in 19/42 (45.2%, 95% CI 29.8–61.3) cases: of these, 7/19 (36.8%, 95% CI 16.3–61.6) required oxygen support and 4/19 (21.1%, 95% CI 6.1–45.6) were admitted to a critical care unit. Two women with COVID‐19 breastfed without a mask because infection was diagnosed in the postpartum period: their newborns tested positive for SARS‐Cov‐2 infection. In one case, a newborn had a positive test after a vaginal operative delivery. Conclusions Although postpartum infection cannot be excluded with 100% certainty, these findings suggest that vaginal delivery is associated with a low risk of intrapartum SARS‐Cov‐2 transmission to the newborn. Tweetable abstract This study suggests that vaginal delivery may be associated with a low risk of intrapartum SARS‐Cov‐2 transmission to the newborn., Tweetable abstract This study suggests that vaginal delivery may be associated with a low risk of intrapartum SARS‐Cov‐2 transmission to the newborn. This article includes Author Insights, a video abstract available at https://vimeo.com/rcog/authorinsights16278