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Background:Assisted reproductive technologies (ART) are becoming widespread, accounting for approximately 2% of all births in the western countries. Concerns exist on the potential association of ART with congenital anomalies. Few studies have addressed if a relationship exists between ART and the development of anorectal malformation (ARM). Our aim was to analyze the relationship between ARM and ART.Methods:Single-center retrospective case control study of all patients treated for ARM between 2010 and 2017. Patients with bronchiolitis treated since 2014 were used as controls. Variables analyzed include the following: prevalence of ART, gestational age, birth weight, and maternal age. Patients with ARM born after ART were also compared with those naturally conceived for disease complexity. Fisher's exact and Mann-WhitneyU-tests were used as appropriate.Results:Three hundred sixty-nine patients were analyzed (143 cases and 226 controls). Prevalence of ART was significantly higher in ARM patients than in controls [7.6 vs. 3.0%; odds ratio: 2.59 (95% CI, 0.98–0.68);p= 0.05]. Among ARM patients, incidence of VACTERL association (17%) is more frequent in ART babies.Conclusion:Patients with ARM were more likely to be conceived following ART as compared with controls without congenital anomalies. Disease complexity of patients with ARM born after ART seems greater that those born after nonassisted conception.

Objective To quantify the mediastinal shift angle (MSA) in fetuses with isolated left congenital diaphragmatic hernia (CDH) by magnetic resonance imaging and evaluate survival. Method Fetuses from singleton pregnancies with isolated left CDH were matched for gestational age with controls without thoracic malformations. For all fetuses the MSA was determined by two operators and inter-operator variability and differences between cases and controls were investigated. For all cases total fetal lung volume (TFLV) was calculated and the correlation between MSA and TFLV was assessed, and its predictive value towards survival was determined. Results Thirty-four fetuses were included as cases and 42 as controls. The mean gestational age for assessment of CDH fetuses was 32 weeks (range 27-38). Twenty-four fetuses survived until discharge and 10 did not. There was an excellent inter-operator reliability for measuring the MSA and a significant difference between MSA in cases and controls. There was an inverse correlation between MSA values and survival, a correlation between TFLV and survival and an inverse correlation between MSA and TFLV. The area under the ROC curve for MSA in predicting survival was 0.931 (95% CI 0.851-1.000). Conclusion The MSA measured late in gestation correlates with postnatal survival in patients with isolated left CDH.

Some maternal infections, contracted before or during pregnancy, can be transmitted to the fetus, during gestation (congenital infection), during labor and childbirth (perinatal infection) and through breastfeeding (postnatal infection). The agents responsible for these infections can be viruses, bacteria, protozoa, fungi. Among the viruses most frequently responsible for congenital infections are Cytomegalovirus (CMV), Herpes simplex 1–2, Herpes virus 6, Varicella zoster. Moreover Hepatitis B and C virus, HIV, Parvovirus B19 and non-polio Enteroviruses when contracted during pregnancy may involve the fetus or newborn at birth. Recently, new viruses have emerged, SARS-Cov-2 and Zika virus, of which we do not yet fully know the characteristics and pathogenic power when contracted during pregnancy. Viral infections in pregnancy can damage the fetus (spontaneous abortion, fetal death, intrauterine growth retardation) or the newborn (congenital anomalies, organ diseases with sequelae of different severity). Some risk factors specifically influence the incidence of transmission to the fetus: the timing of the infection in pregnancy, the order of the infection, primary or reinfection or chronic, the duration of membrane rupture, type of delivery, socio-economic conditions and breastfeeding. Frequently infected neonates, symptomatic at birth, have worse outcomes than asymptomatic. Many asymptomatic babies develop long term neurosensory outcomes. The way in which the virus interacts with the maternal immune system, the maternal-fetal interface and the placenta explain these results and also the differences that are observed from time to time in the fetal‑neonatal outcomes of maternal infections. The maternal immune system undergoes functional adaptation during pregnancy, once thought as physiological immunosuppression. This adaptation, crucial for generating a balance between maternal immunity and fetus, is necessary to promote and support the pregnancy itself and the growth of the fetus. When this adaptation is upset by the viral infection, the balance is broken, and the infection can spread and lead to the adverse outcomes previously described. In this review we will describe the main viral harmful infections in pregnancy and the potential mechanisms of the damages on the fetus and newborn.

To serially assess fetal cardiac dimensions in congenital diaphragmatic hernia (CDH) and their relation to disease severity. Retrospective analysis of CDH cases and matched controls. Mitral (MVd) and tricuspid (TVd) valve diameters, left (LV) and right (RV) ventricular length and area, Z-scores, were serially assessed at 24–26, 30–32, and 35–37 weeks gestational age (GA). In CDH cases MVd, MVd Z-score, and LV area were significantly reduced at 24–26 and 35–37 weeks GA. TVd, TVd Z-score, and RV area were significantly reduced at 24–26 weeks. RV area Z-score increased with advancing GA. MVd and MVd Z-score were significantly lower at 24–26 weeks GA in CDH who had a combined outcome of death and/or ECMO. LV hypoplasia in CDH is characterized by reduced MVd from 24 weeks GA. MVd, and the ratio of mitral and tricuspid valve diameters at later gestations, may be potential predictors of disease severity.

In spite of the increasing, accumulating knowledge on the novel pandemic coronavirus severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), questions on the coronavirus disease-2019 (COVID-19) infection transmission from mothers to fetuses or neonates during pregnancy and peripartum period remain pending and have not been addressed so far. SARS-CoV-2, a RNA single-stranded virus, has been detected in the amniotic fluid, in the cord blood and in the placentas of the infected women. In the light of these findings, the theoretical risk of intrauterine infection for fetuses, or of peripartum infection occurring during delivery for neonates, has a biological plausibility. The extent of this putative risk might, however, vary during the different stages of pregnancy, owing to several variables (physiological modifications of the placenta, virus receptors' expression, or delivery route). This brief review provides an overview of the current evidence in this area. Further data, based on national and international multicenter registries, are needed not only to clearly assess the extent of the risk for vertical transmission, but also to ultimately establish solid guidelines and consistent recommendations. KEY POINTS: · Questions on the COVID-19 infection transmission from mothers to fetuses or neonates during pregnancy and peripartum period remain pending so far.. · The theoretical risk of intrauterine infection for fetuses, or of neonatal infection during delivery for neonates, has a biological plausibility.. · A caution is recommended in the interpretation of clinical and laboratory data in neonates..

To compare ultrasound (US) and magnetic resonance imaging (MRI) in the assessment of mediastinal shift angles (MSAs) in fetuses affected by isolated left congenital diaphragmatic hernia (CDH). The use of MRI-MSA and US-MSA as prognostic factor for postnatal survival in fetal left CDH was also explored.This was an observational study of 29 fetuses with prenatally diagnosed isolated left CDH, assessed with both US and MRI examinations between January 2015 and December 2018. The US-MSA measurements performed within 2 weeks from the MRI assessment were considered for the analysis. The primary outcome was the postnatal survival rate.No significant difference between US and MRI MSAs was detected (MRI and US can be interchangeably used for the assessment of MSA in prenatally diagnosed isolated left CDH. Moreover, MSA measured by both US and MRI was confirmed to be correlated with perinatal outcome in terms of survival.

Objectives: To quantify mediastinal shift in isolated congenital diaphragmatic hernia (CDH), by the introduction of a new ultrasonographic (US) marker, defined as mediastinal shift angle (M...

The authors report a positive experience in controlling severe postpartum hemorrhage after cesarean section performed for placenta praevia by using an inflated intrauterine balloon and avoiding any further invasive surgery.

Colorectal carcinoma presenting during pregnancy is an extremely rare condition associated with a poor prognosis. In this report we studied a patient referred to our hospital at 26 weeks of gestation with the diagnosis of rectal adenocarcinoma. Tumor resection with a colostomy was planned in the attempt to preserve pregnancy until fetal viability could be reached. Blended anesthesia (general and epidural) was chosen to avoid surgical and anesthesiological risks; in fact this technique allows either an optimal block of neurohormonal response or a good control of surgical stress to be obtained. In order to monitor fetal well being during surgery, Doppler evaluations of fetal heart rate and umbilical artery flow velocity waveforms were performed. The patient was dismissed in good health and then rehospitalized at 32 weeks of gestation in order to perform an elective cesarean section. In conclusion we suggest that, with the choice of a good anesthesiological technique and monitoring of fetal well being, surgical treatment in case of rectal cancer could be performed without affecting the course of pregnancy.

The aim of our study was to evaluate flow-velocity waveforms from ovarian tumors with color Doppler, in order to test the predictivity of malignancy and to compare the Doppler technique with some morphological scoring systems. Color Doppler examination of ovarian neoplasms was performed in 122 patients within 2-3 days from surgery and, based on vascular characteristics and on Doppler resistance index, a "vascular" score was calculated. One hundred one women had benign and 21 had malignant tumors on histopathology. In all of the malignant lesions color Doppler was able to detect vascular patterns, whereas only 43% of the benign tumors showed recognizable vessels (P < 0.001). Malignant masses showed significantly greater vascular scores than those of benign tumors (P < 0.001). Doppler ultrasonography achieved better specificity and PPV when compared to morphological scores (96% vs 61-75% and 82% vs 35-48%). Color Doppler ultrasonography of ovarian tumors seems to be a reliable method in the presurgical characterization of ovarian neoplasms.

To determine whether the major congenital heart diseases (CHDs) can modify the cerebrovascular flow dynamics and the biometrical parameters in fetuses at third trimester of pregnancy.We studied 60 fetuses with CHD. Data included prenatal versus postnatal cardiac diagnosis, cerebral and umbilical artery doppler, fetal biometrical parameters, fetal weight, and gestational age. The pulsatility index (PI) was used to determine blood flow velocities in the umbilical artery (UA) and middle cerebral artery (MCA), while the cerebro/placental ratio (CPR) was assessed as a measure of cerebral autoregulation. Fetuses with CHD were compared to normal controls and then analyzed after being divided into groups based on specific defects.Compared with control fetuses, those with CHD showed a decrease of resistance blood flow in the middle cerebral artery (1.76 vs 1.92 PI) especially considering the CPR (1.66 vs 2.03 PI) (p0.01). Furthermore, fetuses with CHD also had smaller head circumferences (30.6 cm vs 31.5 cm p0.01) and head/abdominal (HC/AC) ratio (1 vs 1.05 p0.01). When stratified for single cardiac diseases, fetuses with hypoplasic left heart syndrome showed a lower CPR and HC/AC ratio.Cerebrovascular resistance is significantly lower in fetuses with CHD, especially in cases of left side obstruction. The cerebro/placental hemodynamic changes are similar to that described in fetuses with placental insufficiency and may contribute to their abnormal neurologic development.

In pregnant women, antiphospholipid syndrome (APS) is associated with an increased risk of preeclampsia, fetal intrauterine growth restriction, and other complications related to uteroplacental insufficiency. In the last two decades, several studies were performed to identify the predictive role of some parameters in relation to obstetric outcome in APS patients. Among these, the uterine velocimetry Doppler is the most studied. It provides a non-invasive method for the study of uteroplacental blood flow, being able to detect a condition of impaired placental perfusion, due to the presence of circulating antiphospholipid antibodies (aPL). To date, the uterine artery Doppler velocimetry resulted to be a useful tool to identify APS pregnancies at higher risk of adverse pregnancy outcome. False-positive IgM for toxoplasmosis, others, rubella, cytomegalovirus, herpes viruses (TORCH) complex is associated to a worse pregnancy outcome because it reflects a dysregulation of the immune system which may amplify placental autoimmune damage. Moreover low levels of complement components are related to an increased incidence of obstetrical complications, suggesting that placental deposition of immune complexes and activation of complement cascade may contribute to placental failure APS related. The abnormal uterine Doppler velocimetry, false-positive TORCH IgM and low levels of complement components can be considered prognostic indexes of poor pregnancy outcome in APS.

During the foetal-neonatal period, rhabdomyomas represent the majority of cardiac tumours and are closely associated with tuberous sclerosis. Cardiac rhabdomyomas may be completely asymptomatic and are incidentally discovered during an echocardiogram, or may cause cardiac dysfunctions requiring medical and/or surgical intervention. During foetal life and the early neonatal period, life-threatening conditions, mostly due to arrhythmias, cardiac failure or obstruction, do occur on rare occasions. We reviewed the medical records of all cases of cardiac rhabdomyomas diagnosed prenatally or postnatally over an 8-year period. The present study reviews 7 cases of life-threatening conditions. Arrhythmic episodes were described in 5 patients, and blood flow obstruction was reported in 2 cases. Antiarrhythmic agents successfully controlled the clinical and electrophysiological conditions. Obstructive conditions were associated with poor outcomes. In conclusion, when prenatal diagnosis of rhabdomyoma is made, appropriate planning at delivery for the management of potential haemodynamic complications may prevent adverse neonatal outcomes. The clinical outcome is more influenced by obstructive rather than by dysrhythmic complications. Appropriate antiarrhythmic treatment is of primary importance. In all cases discovered through prenatal and/or neonatal life-threatening conditions, an accurate follow-up should always be performed to anticipate the development of tuberous sclerosis.

Background: Placenta previa-accreta is associated with severe hemorrhage occurring while separating the placenta during cesarean delivery and hysterectomy is considered the treatment of choice. Conservative management has recently been proposed. Case: A 26-year-old woman had pregnancy complicated by placenta previa with suspected accreta. During elective cesarean section a prophylactic double bilateral ligation of uterine arteries was performed before removal of the placenta; subsequently, the continuous small bleeding from the placental bed was stopped by tamponade with a balloon catheter filled with saline solution. The patient was discharged 5 days later. An ultrasonographic color Doppler follow-up demonstrated a renewed uterine vascularization. Conclusion: Double bilateral ligation of uterine arteries can be used as a prophylactic surgical treatment when a severe bleeding because of placenta previa-accreta is expected, in order to avoid hysterectomy.

In pregnant women, antiphospholipid syndrome (APS) is associated with an increased risk for preeclampsia, fetal intrauterine growth restriction, and other complications related to uteroplacental insufficiency. In normal pregnancy, impedance to flow in the uterine arteries decreases with gestation, as the likely consequence of the physiologic change of spiral arteries into low-resistance vessels. The presence of antiphospholipid antibodies can impair this vascular adaptation, resulting in a reduced placental perfusion. Doppler investigation provides a noninvasive method for the study of uteroplacental blood flow. Several studies were performed to detect the predictive role of uterine artery Doppler velocimetry in relation to pregnancy outcome in APS patients. In some studies, a high resistance index in the uterine arteries strongly predicted the subsequent development of obstetric complications. In other studies, persistent bilateral uterine artery notches identified the risk of preeclampsia and fetal intrauterine growth restriction. To date, the uterine artery Doppler velocimetry resulted to be a useful tool for identifying APS pregnancies at risk for adverse pregnancy outcome. These findings might have important implications for the management of these patients.

There is evidence from epidemiologic studies that gestational hypertension (GH) carries an increased risk of cardiovascular disease later in life. This study was an attempt to determine whether GH in a previous pregnancy, defined as newly developed hypertension after 20 weeks gestation, is associated with endothelial dysfunction or carbohydrate and lipid metabolic changes typical of insulin resistance in currently healthy women. Endothelium-dependent brachial artery flow-mediated dilatation (FMD) and endothelium-independent nitroglycerin-induced dilatation were estimated ultrasonically in 15 women with a history of GH and 15 others who had had normal pregnancies. The interval between delivery and evaluation was at least 12 months and averaged 20 months. Women with gestational diabetes were not included. Apart from blood pressure, there were no significant demographic or pregnancy differences between the 2 groups of women. Fasting insulin levels were 60% higher in women with previous GH, and insulin resistance, expressed as homeostasis model assessment (HOMA), was 80% greater. Fasting glucose levels were comparable in the 2 groups and all women had normal lipid profiles. Nevertheless, previous GH was associated with 20% lower levels of high-density lipoprotein (HDL) cholesterol and 60% higher levels of free fatty acids. Women with past GH had higher total and free testosterone levels, which, however, remained within the normal range. Although all women were normotensive, both systolic and diastolic pressures were significantly higher in those with previous GH. FMD in the previous GH group was nearly 55% that of control women, but there was no difference in nitroglycerin-induced dilatation. Linear regression analysis showed that total testosterone correlated strongly and negatively with FMD; correlation with free testosterone was somewhat less. FMD also correlated negatively and closely with HOMA and fasting insulin, and it correlated positively with HDL cholesterol and body mass index. Total testosterone accounted for 34% of the variance in FMD, and HOMA contributed 22% more. Endothelial dysfunction is characteristic in healthy women having GH diagnosed in a previous pregnancy. There also are early signs of disordered carbohydrate, lipid, and hormone metabolism. These findings might help to explain reports of increased cardiovascular disease in these women.

Objective: The aim of this study was to assess the value of uterine artery Doppler velocimetry performed at 18–20 and 22–24 weeks of gestation in predicting preeclampsia and adverse pregnancy outcome in low- and high-risk patients. Methods: 865 pregnant women were evaluated: 335 and 530 pregnant women represented the high- and low-risk groups, respectively. Doppler ultrasound examination of the uterine arteries was performed at 18–20 weeks of gestation in 385 patients and at 22–24 weeks of gestation in 659 patients. Pregnancy outcome was evaluated in terms of: onset of preeclampsia; birth weight Results: At 18–20 weeks of gestation the sensitivity for the prediction of preeclampsia was 100 and 94% in low- and high-risk groups, respectively. Excellent negative predictive values towards birth weight Conclusion: Doppler evaluation of the uterine artery at 18–20 and 22–24 weeks of gestation represents a useful predictive test in high-risk pregnancy and can also be used in prenatal surveillance of a low-risk population.

Objective: To evaluate the relationship between insulin levels and uter-oplacental vascular resistance in third-trimester pregnancies complicated by impaired carbohydrate tolerance.Methods: Fifty-two patients were admitted to the study. After a 3–h oral glucose tolerance test (OGTT), a color Doppler evaluation of uterine and umbilical arteries was performed.Results: According to O'Sullivan criteria, 14 patients had impaired gestational glucose tolerance (IGGT), 18 patients had gestational diabetes (GDM), and 20 subjects had normal glucose tolerance and served as controls. On the basis of the insulinemic response to OGTT, the patients were then classified as normoinsulinemic or hyperinsulinemic, with a cutoff value for the area under the curve of 240,360 pmol/L × 180 min.Hyperinsulinemic patients showed greater values of the “highest” uterine artery resistance index (RI) when compared to controls (P < 0.01); the “lowest” uterine artery RI was slightly, but not significantly, increased. Moreover, a signific...

Results: 101 and 67 patients were enrolled in group A and group B, respectively. For each patient a median of 2.9 evaluations (group A = 2.1, group B = 3.7; P = n.s.) was performed. The indications of hospital admission were: decreased volumes of amniotic fluid (AFI

OBJECTIVE To determine whether uterine artery velocimetry is a useful tool for identifying pregnancies with antiphospholipid syndrome at risk for adverse outcome. METHODS Twenty-four women with antiphospholipid syndrome, who had experienced 56 fetal losses in 63 previous pregnancies (88.9%), were treated with prednisone (40 mg/day) and aspirin (100 mg/day) during 28 pregnancies. Color Doppler ultrasound was performed at 18-24 weeks' gestation to investigate the resistance index of the uterine arteries. RESULTS Treated women delivered 23 live infants in the 28 pregnancies (82.1%). Three infants weighed less than the tenth percentile (13%). Five pregnancies were complicated by preeclampsia and ten by nonproteinuric gestational hypertension. Positive results for all three assays for antiphospholipid antibodies (anticardiolipin antibodies, lupus anti-coagulant, VDRL) at conception identified pregnancies destined to have poor fetal outcome and a significantly lower birth weight compared to pregnancies not having all three assays positive. An abnormal resistance index of the uterine arteries predicted pregnancies with poor fetal outcome in terms of week of delivery, birth weight, and birth percentile, as well as four of five cases of preeclampsia. CONCLUSIONS Three assays positive for antiphospholipid antibodies at conception and an abnormal resistance index of the uterine arteries at 18-24 weeks' gestation predicted pregnancies at major risk for obstetric complications. Future studies should determine whether treatment can be modulated based on the Doppler findings.

Altres ajuts: The study is partially made possible by support of the 'Programme Hospitalier de Recherche Clinique and 'La Foundation de la Recherche Médicale (grant number DEQ20170336759, France). M.T. was supported by the Polish Mothers Memorial Hospital Research Institute (internal grant number 2016/IV/54-GW. LvdZ is supported by a Kolff grant from the Dutch Kidney Foundation (13OKJ36) and a ZonMW-VENI grant from the Netherlands Organisation for Scientific Research (91618036). This project has been supported by ERN ERKNet and ERN eUROGEN, which are partly co-funded by the European Union within the framework of the Third Health Programme 'ERN-2016-Framework Partnership Agreement 2017-2021'. Posterior urethral valves (PUV) account for 17% of paediatric end-stage renal disease. A major issue in the management of PUV is prenatal prediction of postnatal renal function. Fetal ultrasound and fetal urine biochemistry are currently employed for this prediction, but clearly lack precision. We previously developed a fetal urine peptide signature that predicted in utero with high precision postnatal renal function in fetuses with PUV. We describe here the objectives and design of the prospective international multicentre ANTENATAL (multicentre validation of a fetal urine peptidome-based classifier to predict postnatal renal function in posterior urethral valves) study, set up to validate this fetal urine peptide signature. Participants will be PUV pregnancies enrolled from 2017 to 2021 and followed up until 2023 in >30 European centres endorsed and supported by European reference networks for rare urological disorders (ERN eUROGEN) and rare kidney diseases (ERN ERKNet). The endpoint will be renal/patient survival at 2 years postnatally. Assuming α = 0.05, 1-β = 0.8 and a mean prevalence of severe renal outcome in PUV individuals of 0.35, 400 patients need to be enrolled to validate the previously reported sensitivity and specificity of the peptide signature. In this largest multicentre study of antenatally detected PUV, we anticipate bringing a novel tool to the clinic. Based on urinary peptides and potentially amended in the future with additional omics traits, this tool will be able to precisely quantify postnatal renal survival in PUV pregnancies. The main limitation of the employed approach is the need for specialized equipment. Accurate risk assessment in the prenatal period should strongly improve the management of fetuses with PUV.