Publications by authors named "Antonio Lanzone"

137 Publications

Surgical Treatment of "Large Uterine Masses" in Pregnancy: A Single-Center Experience.

Int J Environ Res Public Health 2021 Nov 19;18(22). Epub 2021 Nov 19.

Università Cattolica del Sacro Cuore, 00168 Rome, Italy.

Uterine myomas or uterine fibroids are the most common benign uterine masses affecting women. The management of large myoma during pregnancy is challenging, and surgical treatment is a possible option. We report nine cases of pregnant women affected by uterine masses larger than 10 cm, who underwent surgical treatment during the second trimester of pregnancy. In all cases, the masses were preconceptionally unknown and diagnosed during the first trimester. In eight cases, no maternal and fetal complications arose during or after surgical treatment and delivery occurred at full term of pregnancy. In one case, spontaneous abortion was recorded. In all cases, histologic diagnosis demonstrated the benign nature. Women affected by large uterine masses diagnosed for the first time in pregnancy could be taken into consideration for surgical treatment in a referral center during the second trimester.
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http://dx.doi.org/10.3390/ijerph182212139DOI Listing
November 2021

Insulin-sensitizing effect and antioxidant action of alpha lipoic acid in oligomenorrheic women with polycystic ovary syndrome.

Minerva Obstet Gynecol 2021 Nov 26. Epub 2021 Nov 26.

Fondazione Policlinico Universitario A. Gemelli, IRCCS, Rome, Italy.

Background: Polycystic ovary syndrome (PCOS) is a low-grade inflammatory disease characterized by anovulation and hyperandrogenism, associated with insulin-resistance. The aim of our study was to investigate the effects of a treatment with alpha-lipoic acid on clinical, endocrine and metabolic features of women affected by PCOS.

Methods: In this pilot cohort study, 60 women (30 hyperinsulinemic and 30 normoinsulinemic patients; age 15-34 years) were enrolled and clinical, hormonal and metabolic parameters were evaluated before and after a six-months treatment with alpha-lipoic acid 800 mg/daily. Investigations were performed during the early follicular phase of the menstrual cycles (spontaneous or progestin-induced cycles): after fasting overnight for 10-12 h, blood samples were collected for hormonal and metabolic assays and oral glucose tolerance test and pelvic ultrasound were performed. Total Antioxidant Capacity was expressed as LAG time.

Results: The treatment was able to increase the number of menstrual cycles during the 6 months considered in all patients and to reduce BMI in the normoinsulinemic population. In hyperinsulinemic patients we observed a statistically significant reduction in AUC-I as well as an increase of total antioxidant capacity.

Conclusions: The relevant results in restoring menstrual cyclicity in both groups, in addition to the antioxidant effect, confirm that hyperinsulinemia influences only the metabolic response to the treatment, without predict the ovarian function. Even if alpha-lipoic acid mechanisms of action is not clear and further studies are needed to confirm these results, it could be considered a valid therapeutic alternative to traditional drugs, without side effects as reported.
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http://dx.doi.org/10.23736/S2724-606X.21.04983-6DOI Listing
November 2021

SARS-CoV-2 Infection in Pregnancy: Clinical Signs, Placental Pathology, and Neonatal Outcome-Implications for Clinical Care.

Front Med (Lausanne) 2021 8;8:676870. Epub 2021 Nov 8.

UOC di Ostetricia e Patologia Ostetrica, Dipartimento di Scienze della Salute della Donna e del Bambino e di Sanità Pubblica, Fondazione Policlinico Universitario A. Gemelli, IRCCS, Rome, Italy.

The current COVID-19 pandemic has been associated with high rates of mortality and significant morbidity. Both the risk of infection for pregnant women and the risk of vertical transmission have been evaluated, and the presence of the SARS-CoV-2 virus has been demonstrated both in the placenta and in the amniochorionic membranes. However, the actual effects of this pathogen on pregnancy and on placental morphology are still unclear. To describe histopathologic findings in the placentas of women with SARS-CoV-2 infection during pregnancy and their correlation with clinical signs and perinatal outcome. Placental tissues from pregnant women with SARS-CoV-2 infection delivering between March 2020 and February 2021 were analyzed. One hundred six placentas from women with SARS-CoV-2 infection during pregnancy who delivered in Fondazione Policlinico A. Gemelli were examined. Most of them were asymptomatic. All neonates had available test results for SARS-CoV-2 and only one resulted positive. Placental tissues mainly showed signs of maternal vascular malperfusion and of placenta injury in terms of syncytial node increase (96.2%), villar agglutination (77.3%), neointimal hyperplasia (76.4%), excessive fibrin deposition (43.3%), and chorangiosis (35.8%). No significant differences in the frequency of the histopathological lesions were observed according to maternal symptoms. Looking to placental tissues from SARS-CoV-2 positive women at the screening performed close to delivery, placental injuries could be detected without any correlation with fetal and neonatal outcomes. We hypothesize that short latency between SARS-CoV-2 infection and delivery is the main reason for these observations.
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http://dx.doi.org/10.3389/fmed.2021.676870DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8606406PMC
November 2021

Is Cardiomegaly an Indication of "Heart-Sparing Effect" in Small Fetuses?

Fetal Diagn Ther 2021 Oct 15:1-7. Epub 2021 Oct 15.

Fetal Medicine Unit, St. George's University Hospitals NHS Foundation Trust, London, United Kingdom.

Introduction: This study aimed to test the hypothesis that cardiac size is maintained in small fetuses presenting with cardiomegaly.

Materials And Methods: We identified singleton fetuses with estimated fetal weight <10th centile and with cardiomegaly without another more likely cardiac or extra-cardiac cause. We used Z-scores for cardiac and thoracic circumferences normalized for gestational age (GA), biparietal diameter (BPD), head circumference (HC), and femur length (FL), obtained from 188 normally grown fetuses.

Results: When comparing chest size, small fetuses had significantly lower thoracic circumferences median Z-scores (IQR) for GA = -4.82 (-6.15 to -3.51), BPD = -2.42 (-4.04 to -1.48), HC = -2.72 (-4.53 to -1.90), and FL = -1.60 (-2.87 to -0.71); p < 0.001 for all. When comparing heart size, small fetuses showed lower cardiac circumferences median Z-scores (IQR) for GA = -1.59 (-2.79 to -0.16); p < 0.001, similar cardiac circumferences Z-scores for BPD = 0.29 (-0.65 to 1.28); p = 0.284 and HC = 0.11 (-1.13 to 0.96); p = 0.953, and higher cardiac circumferences Z-scores for FL = 0.94 (-0.05 to 2.13); p < 0.001.

Conclusions: Our results show that in small fetuses with cardiomegaly, the heart maintains normal dimensions when normalized to cranial diameters and higher dimensions when normalized to long bones. This provides insight into cardiac adaptation to adverse intrauterine environment.
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http://dx.doi.org/10.1159/000519059DOI Listing
October 2021

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

Eur J Obstet Gynecol Reprod Biol 2021 Oct 23;267:105-110. Epub 2021 Oct 23.

Department of Medicine and Surgery, Unit of Surgical Sciences, Obstetrics and Gynecology, University of Parma, Italy.

Objective: The aim of this study was to report the rate of additional anomalies detected exclusively at prenatal magnetic resonance imaging (MRI) in fetuses with isolated severe ventriculomegaly undergoing neurosonography.

Method: Multicenter, retrospective, cohort study involving 20 referral fetal medicine centers in Italy, United Kingdom, Spain and Denmark. Inclusion criteria were fetuses affected by isolated severe ventriculomegaly (≥15 mm), defined as ventriculomegaly with normal karyotype and no other additional central nervous system (CNS) and extra-CNS anomalies on ultrasound. In all cases, a multiplanar assessment of fetal brain as suggested by ISUOG guidelines on fetal neurosonography had been performed. The primary outcome was the rate of additional CNS anomalies detected exclusively at fetal MRI within two weeks from neurosonography. Subgroup analyses according to gestational age at MRI (
Results: 187 fetuses with a prenatal diagnosis of isolated severe ventriculomegaly on neurosonography were included in the analysis. Additional structural anomalies were detected exclusively at prenatal MRI in 18.1% of cases. When considering the type of anomaly, malformations of cortical development were detected on MRI in 32.4% cases, while midline or acquired (hypoxemic/hemorrhagic) lesions were detected in 26.5% and 14.7% of cases, respectively. There was no difference in the rate of additional anomalies when stratifying the analysis according to either gestational age at MRI or laterality of the lesion. At multivariate logistic regression analysis, the presence of additional anomalies only found at MRI was significantly higher in bilateral compared versus unilateral ventriculomegaly (OR: 4.37, 95% CI 1.21-15.76; p = 0.04), while neither maternal body mass index, age, severity of ventricular dilatation, interval between ultrasound and MRI, nor gestational age at MRI were associated with the likelihood of detecting associated anomalies at MRI.

Conclusion: The rate of associated anomalies detected exclusively at prenatal MRI in fetuses with isolated severe ventriculomegaly is lower than previously reported, but higher compared to isolated mild and moderate ventriculomegaly. Fetal MRI should be considered as a part of the prenatal assessment of fetuses presenting with isolated severe ventriculomegaly at neurosonography.
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http://dx.doi.org/10.1016/j.ejogrb.2021.10.014DOI Listing
October 2021

Circulating Placental Vesicles Carry HLA-DR in Pre-Eclampsia: A New Potential Marker of the Syndrome.

Front Immunol 2021 3;12:717879. Epub 2021 Sep 3.

Department of Biomedical Sciences, Humanitas University, Milan, Italy.

Background: Pre-eclampsia (PE) is a common disorder of pregnancy that usually presents with hypertension and proteinuria. The clinical presentation arises from soluble factors released into the maternal circulation from the placenta owing to the stress of syncytiotrophoblast, consequence of defective placentation occurring in the first half of pregnancy. Reduced tolerance of the semiallogeneic fetus by the maternal immune system has been proposed as first trigger leading to poor placentation. We previously observed aberrant expression of human leukocyte antigen (HLA)-DR molecules in the syncytiotrophoblast of a subset of women with PE. Aim of this study was to investigate abnormal expression of circulating HLA-DR in syncytiotrophoblast-derived extracellular vesicles (STBEVs) in women with PE compared to normal pregnant women.

Methods: peripheral venous blood was collected from 22 women with PE and 22 normal pregnant women. Circulating STBEVs were collected by ultra-centrifugation (120000 g) and analyzed for the expression of HLA-DR and placental alkaline phosphatase (PLAP), a specific marker of the placenta, by Western blot analysis and flow cytometry.

Results: circulating STBEVs positive for HLA-DR were observed in 64% of PE women while no HLA-DR positivity was detected in any of the controls (P<0.01).

Conclusions: Aberrant expression of HLA-DR in circulating STBEVs is specifically associated to PE. Further studies are required: a) to define the role of aberrant placental expression of HLA-DR molecules in the pathogenesis of PE; b) evaluate a possible application of detecting circulating HLA-DR positive STBEVs in the diagnosis and prediction of PE in the first and second trimester of pregnancy.
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http://dx.doi.org/10.3389/fimmu.2021.717879DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8446281PMC
September 2021

Circulating EGFL7 distinguishes between IUGR and PE: an observational case-control study.

Sci Rep 2021 09 9;11(1):17919. Epub 2021 Sep 9.

Department of Biomedicine and Prevention, University of Rome Tor Vergata, Via Montpellier 1, 00133, Rome, Italy.

Isolated intrauterine growth restriction (IUGR) and preeclampsia (PE) share common placental pathogenesis. Differently from IUGR, PE is a systemic disorder which may also affect liver and brain. Early diagnosis of these conditions may optimize maternal and fetal management. Aim of this study was to assess whether Epidermal Growth Factor-Like domain 7 (EGFL7) dosage in maternal blood discriminates between isolated IUGR and PE. A total of 116 women were enrolled in this case-control study: 12 non-pregnant women, 34 healthy pregnant women, 34 women presenting with isolated IUGR and 36 presenting with PE. Levels of circulating EGFL7 and other known pro- and anti-angiogenic factors were measured by ELISA at different gestational ages (GA). Between 22-25 weeks of gestation, EGFL7 levels in early-onset PE (e-PE) plasma samples were significantly higher than those measured in controls or isolated IUGR samples (69.86 ± 6.17 vs. 19.8 ± 2.5 or 18.8 ± 2.8 µg/ml, respectively). Between 26-34 weeks, EGFL7 levels remained significantly higher in e-PE compared to IUGR. At term, circulating and placental EGFL7 levels were comparable between IUGR and late-onset PE (l-PE). In contrast, circulating levels of PlGF were decreased in both IUGR- and PE- complicated pregnancies, while levels of both sFLT-1 and sENDOGLIN were increased in both conditions. In conclusion, EGFL7 significantly discriminates between isolated IUGR and PE.
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http://dx.doi.org/10.1038/s41598-021-97482-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8429426PMC
September 2021

Continuous Glucose Monitoring in Women with Normal OGTT in Pregnancy.

J Diabetes Res 2021 23;2021:9987646. Epub 2021 Aug 23.

Department of Obstetrics and Gynecology, Catholic University of Sacred Heart, Fondazione Polclinico Universitario Agostino Gemelli IRCCS, Rome, Italy.

Continuous glucose monitoring (CGM) might be an effective tool to improve glycemic control in gestational diabetes mellitus (GDM). Few data are available about its utilization as a diagnostic tool to find potential alterations of glycemia in subjects with normal oral glucose tolerance test (OGTT). In this preliminary prospective real-life observational study, we aimed to analyze the glycemic pattern in normal and gestational diabetes mellitus (GDM) women by continuous glucose monitoring (CGM) in order to detect potential differences between the two groups and glycemic alterations despite a normal OGTT. After the screening for GDM, subjects were connected to a CGM system for seven consecutive days. The areas under the curve of the first 60 minutes after each meal and 60 minutes before breakfast were analyzed. Women with normal OGTT that during CGM showed impaired glycemic values (more than 95 fasting or more than 140 one hour after meals or more than 120 two hours after meals) performed one week of self-monitoring of blood glucose (SMBG). After OGTT, 53 women considered normal and 46 affected by GDM were included. CGM parameters did not show any differences between the two groups with impaired glycemic excursions found in both groups. After CGM period, 33 women with normal OGTT showed abnormal glycemic patterns. These 33 women then performed one week of SMBG. After evaluation of one week of SMBG, 21 required diet therapy and 12 required insulin treatment and were followed until the delivery. An increase in gestational weight gain was observed in normal women with normal OGTT but this was not significant. No significant data were found regarding neonatal outcomes in the two groups of women. In conclusion, CGM use in pregnancy might help to detect glycemic fluctuations in women with normal OGTT, improving their treatment and outcomes.
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http://dx.doi.org/10.1155/2021/9987646DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8408006PMC
August 2021

PTH-rP and PTH-R1 Expression in Placentas from Pregnancies Complicated by Gestational Diabetes: New Insights into the Pathophysiology of Hyperglycemia in Pregnancy.

Diagnostics (Basel) 2021 Jul 28;11(8). Epub 2021 Jul 28.

Obstetrics and High-Risk Pregnancy Unit, Department of Woman, Child Health and Public Health, Fondazione Policlinico Universitario A. Gemelli IRCCS, Largo Agostino Gemelli 8, 00168 Rome, Italy.

Background: this study investigated the expression of parathyroid hormone-related protein (PTH-rP) and PTH/PTH-rP receptor PTH-R1 in placentas from women with gestational DM (GDM), and the relationship between PTH-R1 and PTH-rP expression and pregnancy characteristics.

Methods: we prospectively enrolled 78 pregnant women with GDM, and immunochemistry for PTH-rP and PTH-R1 was performed on placentas. Patients were grouped according to the positivity of PTH-R1 or PTH-rP expression, and pregnancy characteristics were compared between the two groups.

Results: PTH-rP and PTH-R1 expression were highest in the extravillous cytotrophoblast and in the decidua. In extravillous cytotrophoblast, PTH-rP expression was higher in women with abnormal at fasting glycemia compared to women with abnormal 60' or 120' glycemia (25/25, 50% vs. 6/28, 21.4%, χ2 = 6.12, = 0.01), and PTH-R1 expression was higher in women with abnormal oral glucose tolerance test (OGTT) at fasting glycemia compared to women with abnormal 60' or 120' glycemia (37/50, 74% vs. 15/28, 53.6%, χ2 = 3.37, = 0.06). In syncytiotrophoblast, PTH-rP-positive placentas were characterized by higher incidence of 1 min Apgar score < 7 (2/9, 22.2% vs. 2/69, 2.9%, χ2 = 6.11, = 0.01) and maternal obesity (4/9, 44.4% vs. 11/69, 16.7%, χ2 = 3.81, = 0.05).

Conclusion: placental PTH-rP and PTH-R1 expression is dependent on the type of maternal hyperglycemia, and it is associated with adverse pregnancy outcomes.
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http://dx.doi.org/10.3390/diagnostics11081356DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8394866PMC
July 2021

Third Trimester Myocardial Performance Index in Fetuses from Women with Hyperglycemia in Pregnancy: A Systematic Review and Meta-Analysis.

Ultraschall Med 2021 Aug 23. Epub 2021 Aug 23.

Obstetrics and High-Risk Pregnancy Unit, Fondazione Policlinico A. Gemelli IRCCS, Rome, Italy.

Introduction:  The myocardial performance index (MPI) has been proposed to evaluate cardiac dysfunction in newborns from diabetic mothers. Although MPI is routinely assessed in newborns, its role in the evaluation of fetuses from women with hyperglycemia in pregnancy (HIP) is still under evaluation. We aimed to evaluate the differences in third trimester fetal MPI in pregnant women with hyperglycemia compared to healthy controls.

Materials And Methods:  Seven electronic databases were searched for all studies assessing women with HIP who underwent evaluation of fetal left MPI during pregnancy compared to a control group. The summary measures were reported as mean differences (MD) in the mean fetal left MPI between women with HIP and healthy controls, with a 95 % confidence interval (CI). A post hoc subgroup analysis based on the type of HIP - pregestational diabetes, GDM, or gestational impaired glucose tolerance (GIGT) - was performed as an additional analysis.

Results:  14 studies assessing 1326 fetuses (580 from women with HIP and 746 from controls) were included. Women with HIP had a significantly higher mean left fetal MPI compared to controls (MD 0.08; 95 %CI: 0.05 to 0.11; p < 0.00 001). Subgroup analysis according to the type of HIP concurred with the overall analysis for women with DM (MD 0.07; 95 %CI: 0.01 to 0.13; p = 0.02) and for women with GDM (MD 0.012; 95 %CI: 0.07 to 0.17; p < 0.00 001) but not for women with GIGT (MD -0.01, 95 % CI -0.28 to 0.27; p = 0.96).

Conclusion:  Fetal left MPI is increased in pregnancies with HIP appearing as a potential marker of cardiac dysfunction.
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http://dx.doi.org/10.1055/a-1499-7265DOI Listing
August 2021

Severe Acute Respiratory Syndrome Coronavirus 2 and Pregnancy Outcomes According to Gestational Age at Time of Infection.

Emerg Infect Dis 2021 Oct 5;27(10):2535-2543. Epub 2021 Aug 5.

We conducted an international multicenter retrospective cohort study, PregOuTCOV, to examine the effect of gestational age at time of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on obstetric and neonatal outcomes. We included all singleton pregnancies with a live fetus at 10 weeks' gestation in which pregnancy outcomes were known. The exposed group consisted of patients infected with SARS-CoV-2, whereas the unexposed group consisted of all remaining patients during the same period. Primary outcomes were defined as composite adverse obstetric outcomes and composite adverse neonatal outcomes. Of 10,925 pregnant women, 393 (3.60%) were infected with SARS-CoV-2 (exposed group). After matching for possible confounders, we identified statistically significant increases in the exposed group of composite adverse obstetric outcomes at >20 weeks' gestation and of composite adverse neonatal outcomes at >26 weeks' gestation (p<0.001). Vaccination programs should target women early in pregnancy or before conception, if possible.
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http://dx.doi.org/10.3201/eid2710.211394DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8462348PMC
October 2021

Ectopic deciduosis in a paratubal cyst: A report of the first case.

Int J Gynaecol Obstet 2021 Aug 12;154(2):376-378. Epub 2021 Jun 12.

Department of Woman and Child Health and Public Health, Section of Pathology, Fondazione Policlinico Universitario A. Gemelli IRCCS - Università Cattolica del Sacro Cuore, Rome, Italy.

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http://dx.doi.org/10.1002/ijgo.13765DOI Listing
August 2021

Comparison of ropivacaine plasma concentration after posterior Quadratus Lumborum Block in Cesarean Section with ropivacaine with epinephrine vs. plane.

Minerva Anestesiol 2021 09 3;87(9):979-986. Epub 2021 May 3.

Department of Emergency, Anesthesiological and Reanimation Sciences, IRCCS A. Gemelli University Polyclinic Foundation, Rome, Italy.

Background: The posterior quadratus lumborum block (pQLB) has been used in postoperative pain management after cesarean section (CS). However, clinicians have no data about pQLB safety in pregnants, at increased risk of local anesthetic systemic toxicity (LAST). The purpose of the present study was to explore the efficacy and the safety of adding epinephrine to ropivacaine for bilateral pQLB vs. bilateral pQLB performed with ropivacaine alone in CS.

Methods: In this prospective trial 52 pregnants, ASA 2 physiological status, were consecutively allocated to one of two groups, e-pQLB and pQLB; e-pQLB group received 0.375% ropivacaine+100 mcg epinephrine, 20 mL each side; pQLB received 0.375% ropivacaine alone, 20 mL each side. The primary and secondary outcomes were to evaluate if the adjunct of epinephrine to ropivacaine increases efficacy and safety of pQLB, respectively.

Results: Authors found in e-pQLB group vs. p-QLB group: a total mean morphine consumption statistically lower during the first 24 postoperative hours (5.08±3.12, vs. 9.11±4.67 SD mg, P=0.0002); NRS values statistically lower at six hours from block, both at rest (1.73±1.88 SD vs. 2.88±2.53, P=0.03) and with movement (3.03±1.98 SD vs. 4.23±2.87, P=0.04); a longer time between block and the first opioid request (5.92±2.48 vs. 3.78±2.68 SD hrs, P<0.003); venous ropivacaine concentrations significantly lower at any time of samples but at 120 minutes.

Conclusions: Adding epinephrine to ropivacaine increases efficacy and duration of pQLB. Moreover it increases block safety, reducing peak and mean venous ropivacaine concentration.
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http://dx.doi.org/10.23736/S0375-9393.21.15354-4DOI Listing
September 2021

Enhancement of Vaccination Attitude and Flu Vaccination Coverage among Pregnant Women Attending Birthing Preparation Course.

Vaccines (Basel) 2021 Feb 21;9(2). Epub 2021 Feb 21.

Women, Children and Public Health Sciences Department, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy.

Most vaccinations are recommended within the 15th month of life, in order to reduce risks and to protect children from the initial stages of their lives. A vaccination training session was carried out during the birthing preparation course, aimed at increasing the attitude toward vaccination in maternal-child age. A questionnaire on vaccination awareness was administered before and after the training session and on-site flu vaccination was offered to women and their companions. The percentage of participants who consider the preparatory course a useful tool to obtain information about vaccines increases significantly from 30.34% at pre-intervention to 64.56% at post-intervention ( < 0.001). There is a significant increase in the mean number of vaccinations that the participants want their children to get. The number of participants believing that there is no relationship between vaccination and autism rose from 41.05 to 72.97% ( < 0.001). In total, 48 out of 119 (40.34%) pregnant women participating in the course and 39 companions were vaccinated for influenza. Vaccination knowledge and attitude significantly increased after a training session dedicated to vaccination as a part of the pregnant pre-birth course, whose aim can be therefore extended to the management of the health of the child, well beyond the period of pregnancy, according to the life-course approach to health.
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http://dx.doi.org/10.3390/vaccines9020183DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7926478PMC
February 2021

Fetal cardiac dimensions in congenital diaphragmatic hernia: relationship with gestational age and postnatal outcomes.

J Perinatol 2021 07 1;41(7):1651-1659. Epub 2021 Mar 1.

Department of Neonatology, Royal Hospital for Children, Glasgow, UK.

Objective: To serially assess fetal cardiac dimensions in congenital diaphragmatic hernia (CDH) and their relation to disease severity.

Study Design: 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).

Results: 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.

Conclusions: 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.
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http://dx.doi.org/10.1038/s41372-021-00986-yDOI Listing
July 2021

Practical Clinical and Diagnostic Pathway for the Investigation of the Infertile Couple.

Front Endocrinol (Lausanne) 2020 19;11:591837. Epub 2021 Jan 19.

Section of Andrology and Reproductive Medicine & Centre for Male Gamete Cryopreservation, Department of Medicine, University of Padova, Padova, Italy.

Capsule: This expert opinion summarizes current knowledge on risk factors for infertility and identifies a practical clinical and diagnostic approach for the male and female partners of an infertile couple aimed to improve the investigation and management of fertility problems.

Background: Infertility represents an important and growing health problem affecting up to 16% of couples worldwide. In most cases, male, female, or combined factor can be identified, and different causes or risk factors have been related to this condition. However, there are no standardized guidelines on the clinical-diagnostic approach of infertile couples and the recommendations concerning infertility are sometimes lacking, incomplete, or problematic to apply.

Objective: The aim of this work is to provide an appropriate clinical and diagnostic pathway for infertile couples designed by a multidisciplinary-team of experts. The rationale is based on the history and physical examination and then oriented on the basis of initial investigations. This approach could be applied in order to reduce variation in practice and to improve the investigation and management of fertility problems.

Methods: Prominent Italian experts of the main specialties committed in the ART procedures, including gynecologists, andrologists, embryologists, biologists, geneticists, oncologists, and microbiologists, called "InfertilItaly group", used available evidence to develop this expert position.

Outcomes: Starting from the individuation of the principal risk factors that may influence the fertility of females and males and both genders, the work group identified most appropriate procedures using a gradual approach to both partners aimed to obtain a precise diagnosis and the most effective therapeutic option, reducing invasive and occasionally redundant procedures.

Conclusions: This expert position provides current knowledge on risk factors and suggests a diagnostic workflow of infertile couples. By using this step-by-step approach, health care workers involved in ART, may individuate a practical clinical management of infertile couples shared by experts.
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http://dx.doi.org/10.3389/fendo.2020.591837DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7851076PMC
June 2021

Reference values for pulsatility index of fetal anterior and posterior cerebral arteries in prolonged pregnancy.

J Clin Ultrasound 2021 Mar 26;49(3):199-204. Epub 2021 Jan 26.

Department of "Scienze della Salute della Donna, del Bambino e di Sanità Pubblica" della, Fondazione Policlinico Universitario A Gemelli IRCCS, Rome, Italy.

Objective: To establish consistent normal reference values for fetal anterior cerebral artery (ACA) and posterior cerebral artery (PCA) pulsatility index (PI) in prolonged pregnancy.

Methods: This prospective cross-sectional observational study included singleton normal prolonged pregnancies into two study groups according to the gestational age: from 40 + 0 to 40 + 6 and from 41 + 0 to 41 + 6 weeks. The PI was assessed in both anatomical segments of ACA (ACA-S1 and ACA-S2) and of PCA (PCA-S1 and PCA-S2) with color Doppler imaging and pulsed Doppler examination, and reference centiles charts were generated. PI values from the two investigated segments of each vessel were also compared.

Results: Data were obtained in 771 patients: n = 448 in the 40 + 0 and 40 + 6 weeks group, and n = 323 in the 41 + 0 and 41 + 6 weeks group. A moderate decrease in PI was observed as pregnancy progressed. No differences in PI values were found between the two anatomical segments of ACA and PCA.

Conclusion: This study provides Doppler reference values for the fetal ACA and PCA PI. It also shows that Doppler examination could be performed indifferently in one of the two anatomical segments of these arteries.
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http://dx.doi.org/10.1002/jcu.22979DOI Listing
March 2021

"An unnecessary cut?" multilevel health systems analysis of drivers of caesarean sections rates in Italy: a systematic review.

BMC Pregnancy Childbirth 2020 Dec 10;20(1):770. Epub 2020 Dec 10.

Catholic University of Sacred Heart, 00168, Rome, Italy.

Background: Improvements in medical technologies have seen over-medicalization of childbirth. Caesarean section (CS) is a lifesaving procedure proven effective in reducing maternal and perinatal mortality across the globe. However, as with any medical procedure, the CS intrinsically carries some risk to its beneficiaries. In recent years, CS rates have risen alarmingly in high-income countries. Many exceeding the World Health Organisation (WHO) recommendation of a 10 to 15% annual CS rate. While this situation poses an increased risk to women and their children, it also represents an excess human and financial burden on health systems. Therefore, from a health system perspective this study systematically summarizes existing evidence relevant to the factors driving the phenomenon of increasing CS rates using Italy as a case study.

Methods: Employing the WHO Health System Framework (WHOHSF), this systematic review used the PRISMA guidelines to report findings. PubMed, SCOPUS, MEDLINE, Cochrane Library and Google Scholar databases were searched up until April 1, 2020. Findings were organised through the six dimensions of the WHOHSF framework: service delivery, health workforce, health system information; medical products vaccine and technologies, financing; and leadership and governance.

Results: CS rates in Italy are affected by complex interactions among several stakeholder groups and contextual factors such as the hyper-medicalisation of delivery, differences in policy and practice across units and the national context, issues pertaining to the legal and social environment, and women's attitudes towards pregnancy and childbirth.

Conclusion: Mitigating the high rates of CS will require a synergistic multi-stakeholder intervention. Specifically, with processes able to attract the official endorsement of policy makers, encourage concensus between regional authorities and local governments and guide the systematic compliance of delivery units with its clinical guidelines.
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http://dx.doi.org/10.1186/s12884-020-03462-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7731545PMC
December 2020

Ultrasonographic evidence of persistent hyperextension of the fetal neck: is it a true sign? A diagnostic and prognostic challenge.

J Matern Fetal Neonatal Med 2020 Sep 30:1-7. Epub 2020 Sep 30.

Dipartimento Scienze Salute della Donna, del Bambino e di Sanità Pubblica - UOC Ostetricia e Patologia Ostetrica, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy.

Objective: The purpose of this study was to evaluate the clinical evolution, structural anomalies associated and neonatal outcomes of fetal neck hyperextension in two cases with prenatal ultrasound diagnosis in two different gestational ages.

Methods: In 2019, two cases of fetal hyperextension came to our attention. Follow-up information was obtained from hospital medical records and obstetrical care providers.

Results: Two woman were investigated in our institution for the presence of fetal abnormalities in the II and III trimester, respectively. In both cases, fetal attitude presented persistent fetal neck hyperextension. One of the two fetuses had a mild ventriculomegaly and suspected for micrognathia. Both had an amniotic fluid increase. One of two had no movement in the lower and upper limbs in ultrasound scans associated with club foot and suspected scoliosis. Both were born by cesarean section with pretty different prognosis: one healthy baby had a retarded psychomotor development and the other one died after 6 months. A precise diagnosis was possible only in one case.

Conclusion: The early identification of a fetus with persistent hyperextension of the fetal head should require a detailed ultrasound exam for structural abnormalities and a careful prenatal counseling due to possible postnatal outcome.
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http://dx.doi.org/10.1080/14767058.2020.1818223DOI Listing
September 2020

Risk factors associated with adverse fetal outcomes in pregnancies affected by Coronavirus disease 2019 (COVID-19): a secondary analysis of the WAPM study on COVID-19.

J Perinat Med 2020 11;48(9):950-958

Department of Obstetrics and Gynaecology, Ospedale di San Leonardo, Castellammare di Stabia, Italy.

Objectives To evaluate the strength of association between maternal and pregnancy characteristics and the risk of adverse perinatal outcomes in pregnancies with laboratory confirmed COVID-19. Methods Secondary analysis of a multinational, cohort study on all consecutive pregnant women with laboratory-confirmed COVID-19 from February 1, 2020 to April 30, 2020 from 73 centers from 22 different countries. A confirmed case of COVID-19 was defined as a positive result on real-time reverse-transcriptase-polymerase-chain-reaction (RT-PCR) assay of nasal and pharyngeal swab specimens. The primary outcome was a composite adverse fetal outcome, defined as the presence of either abortion (pregnancy loss before 22 weeks of gestations), stillbirth (intrauterine fetal death after 22 weeks of gestation), neonatal death (death of a live-born infant within the first 28 days of life), and perinatal death (either stillbirth or neonatal death). Logistic regression analysis was performed to evaluate parameters independently associated with the primary outcome. Logistic regression was reported as odds ratio (OR) with 95% confidence interval (CI). Results Mean gestational age at diagnosis was 30.6±9.5 weeks, with 8.0% of women being diagnosed in the first, 22.2% in the second and 69.8% in the third trimester of pregnancy. There were six miscarriage (2.3%), six intrauterine device (IUD) (2.3) and 5 (2.0%) neonatal deaths, with an overall rate of perinatal death of 4.2% (11/265), thus resulting into 17 cases experiencing and 226 not experiencing composite adverse fetal outcome. Neither stillbirths nor neonatal deaths had congenital anomalies found at antenatal or postnatal evaluation. Furthermore, none of the cases experiencing IUD had signs of impending demise at arterial or venous Doppler. Neonatal deaths were all considered as prematurity-related adverse events. Of the 250 live-born neonates, one (0.4%) was found positive at RT-PCR pharyngeal swabs performed after delivery. The mother was tested positive during the third trimester of pregnancy. The newborn was asymptomatic and had negative RT-PCR test after 14 days of life. At logistic regression analysis, gestational age at diagnosis (OR: 0.85, 95% CI 0.8-0.9 per week increase; p<0.001), birthweight (OR: 1.17, 95% CI 1.09-1.12.7 per 100 g decrease; p=0.012) and maternal ventilatory support, including either need for oxygen or CPAP (OR: 4.12, 95% CI 2.3-7.9; p=0.001) were independently associated with composite adverse fetal outcome. Conclusions Early gestational age at infection, maternal ventilatory supports and low birthweight are the main determinants of adverse perinatal outcomes in fetuses with maternal COVID-19 infection. Conversely, the risk of vertical transmission seems negligible.
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http://dx.doi.org/10.1515/jpm-2020-0355DOI Listing
November 2020

Impact of maternal obesity on the risk of preterm delivery: insights into pathogenic mechanisms.

J Matern Fetal Neonatal Med 2020 Sep 17:1-6. Epub 2020 Sep 17.

Dipartimento di Scienze della Salute della Donna, del Bambino e di Sanità Pubblica, Fondazione Policlinico Universitario A. Gemelli IRCCS, U.O.C. di Ostetricia e Patologia Ostetrica, Rome, Italy.

Purpose: Preterm delivery (PTD) represents the leading cause of neonatal death and disability. Among risk factors for PTD, maternal obesity (MO) is becoming an ever more relevant condition in developed countries, although the mechanisms relating this condition to higher risk of PTD is not clear. Aim of this narrative review is to summarize evidences from clinical and translational research showing how MO might negatively impact on pregnancy and neonatal outcomes, particularly, by increasing the risk of PTD.

Methods: We performed comprehensive review of the literature in PubMed and Google Scholar databases for studies from 1998 to 2018 linking MO to PTD and inflammation.

Results: Chronic inflammatory status associated to increased synthesis of adipokines and cytokines from fat tissue has been shown in obesity. Obese women have a higher risk of both spontaneous and medically induced PTD. In about 50% of cases of spontaneous PTD, an infection-induced chorion amnionitis can be detected while in the remaining 50% a sterile inflammatory response has been described. Activation of uterine innate immunity system in intra-amniotic cavity and in chorioamniotic membranes might represent the missing link between MO and the pathogenesis of PTD.

Conclusion: Tissue inflammation might represent the pathogenic link between MO and increased occurrence of PTD. The achievement of pre-pregnancy normal maternal weight and body mass index is a fundamental aim of public health to reduce the incidence of PTD and get optimal reproductive outcomes.
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http://dx.doi.org/10.1080/14767058.2020.1817370DOI Listing
September 2020

Lung ultrasonography for early management of patients with respiratory symptoms during COVID-19 pandemic.

J Ultrasound 2020 Dec 7;23(4):449-456. Epub 2020 Jul 7.

Pulmonary Medicine Unit, Department of Medical and Surgical Sciences, Fondazione Policlinico Universitario A. Gemelli IRCCS, Largo Gemelli, 8, 00168, Rome, Italy.

COVID-19 pandemic is representing a serious challenge to worldwide public health. Lung Ultrasonography (LUS) has been signaled as a potential useful tool in this pandemic contest either to intercept viral pneumonia or to foster alternative paths. LUS could be useful in determining early lung involvement suggestive or not of COVID-19 pneumonia and potentially plays a role in managing decisions for hospitalization in isolation or admission in general ward. In order to face pandemic, in a period in which a large number of emergency room accesses with suspicious symptoms are expected, physicians need a standardized ultrasonographic approach, fast educational processes in order to be able to recognize both suggestive and not suggestive echographic signs and shared algorithms for LUS role in early management of patients.
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http://dx.doi.org/10.1007/s40477-020-00501-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7338342PMC
December 2020

Role of Human Leukocyte Antigens at the Feto-Maternal Interface in Normal and Pathological Pregnancy: An Update.

Int J Mol Sci 2020 Jul 4;21(13). Epub 2020 Jul 4.

Dipartimento di Scienze della Salute della Donna, del Bambino e di Sanità Pubblica, U.O.C. di Ostetricia e Patologia Ostetrica, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy.

The successful maternal tolerance of the semi-allogeneic fetus provides an apparent immunologic paradox. Indeed, deep invasion of placental trophoblast cells into maternal uterine tissue and the following growth of the fetus have to be tolerated by a pregnant woman's immune system. Among the various possible protective mechanisms that may be involved in human pregnancy, the expression of a non-classical pattern of human leukocyte antigen (HLA) class I molecules and the complete lack of expression of HLA class II molecules in placental tissues seem to be the most relevant mechanisms of fetal escape from maternal immune recognition. The importance of HLA molecules in fetal toleration by the maternal immune system is highlighted by pregnancy complications occurring in cases of abnormal HLA molecule expression at the maternal-fetal interface. In this review, we summarize evidences about the role of placental HLA molecules in normal and pathological pregnancies.
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http://dx.doi.org/10.3390/ijms21134756DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7370064PMC
July 2020

Perinatal outcome in gestational hypertension: Which role for developing preeclampsia. A population-based cohort study.

Eur J Obstet Gynecol Reprod Biol 2020 Aug 1;251:218-222. Epub 2020 Jun 1.

UOC di Patologia Ostetrica, Dipartimento Scienze della Salute della Donna, del Bambino e di Sanità Pubblica, Fondazione Policlinico Universitario A. Gemelli IRCCS, Largo A. Gemelli 8, 00168, Roma, Italy; Istituto di Clinica Ostetrica e Ginecologica, Università Cattolica del Sacro Cuore, L.go Francesco Vito 1, Roma, Italy. Electronic address:

Objective: To analyze perinatal outcome in singleton pregnancies complicated by gestational hypertension (GH), to investigate the rate of women developing preeclampsia (PE) and to describe maternal features associated with progression to PE.

Study Design: This is a population-based retrospective cohort-study involving 514 singleton pregnancies with a diagnosis of GH at admission.

Results: In pregnancies with GH, a poorer pregnancy outcome in comparison to healthy controls was observed in terms of gestational age at delivery, birthweight and birthweight percentile. The observed overall rate of developing PE was 11.7 %. Of all pregnancies with GH at admission, two different groups were identified based on the diagnosis at delivery: GHPE, i.e. women who developed PE (60/514; 11.7 %), and GHnoPE, i.e. women who did not develop PE (454/514; 88.3 %). In the GHPE group it was observed that the 62 % of the women with diagnosis of GH earlier than 28 weeks developed PE while only 2% developed PE if the diagnosis of GH was performed later than 36 weeks. The observed rate of developing PE was 14.7 % in pharmacologically treated hypertensive women, whereas the diagnosis of PE has been made in only 3% of non-treated women.

Conclusion: Pregnant women with raised blood pressure are at risk of having a less favourable perinatal outcome. The risk is mainly associated with the progression to PE. Major determinants of the risk of developing PE are the earlier gestational age at diagnosis of GH, the necessity of treatment and the number of anti-hypertensive drugs needed for controlling blood pressure.
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http://dx.doi.org/10.1016/j.ejogrb.2020.05.064DOI Listing
August 2020

Postnatal Health in Children Born to Women After Bariatric Surgery.

Obes Surg 2020 Oct;30(10):3898-3904

Istituto di Clinica Ostetrica e Ginecologica, Università Cattolica del Sacro Cuore, Rome, Italy.

Introduction: The aim of this study is to evaluate short- and long-term consequences in children born to women after different bariatric surgery (BS) procedures.

Methods: A questionnaire survey was given to the mothers referred from 1994 to 2019 to our center for pregnancy and delivery management after BS procedures: (a) malabsorptive surgery, (b) restrictive procedures, and (c) combined restrictive-malabsorptive procedures.

Results: Data from 74 children born after BS, aged 0 month to 12 years, were analyzed. The prevalence of children with underweight was 5.4%, normal weight 59.5%, overweight 16.2%, and obesity 18.9%. The prevalence of obesity was higher in children pre-school aged than that in school-aged ones. Neurodevelopmental disorders were more frequent if maternal BMI before bariatric surgery was ≥ 41 kg/m (p = 0.008), as well as if the pregnancy occurred less than 18 months after BS (p = 0.028). In school-aged children conceived within 18 months after BS, the highest risk of neurodevelopmental disorders (p = 0.028) and overweight (p = 0.018) was observed. The prevalence of neurodevelopmental disorders was much higher for small for gestational age babies (p = 0.048). Children born after biliopancreatic diversion (BPD) showed less maternal breastfeeding, shorter breastfeeding duration, more overweight, and more occurrence of atopic dermatitis in comparison with children born after other bariatric procedures.

Conclusions: Postnatal health in children born to women after BS was impaired by long-term consequences and by other diseases later in life. Children born after BPD were particularly at higher risk for short and long term consequences when compared to children born after other BS procedures.
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http://dx.doi.org/10.1007/s11695-020-04738-3DOI Listing
October 2020

What is new in the landscape of insulin-sensitizing agents for polycystic ovary syndrome treatment.

Ther Adv Reprod Health 2020 Jan-Dec;14:2633494120908709. Epub 2020 Feb 27.

Department of Woman, Child Health and Public Health, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Università Cattolica del Sacro Cuore, Rome, Italy.

Polycystic ovary syndrome, the most common gynecological endocrinopathy, is burdened with a state of hyperinsulinemia and insulin resistance in 50-80% of affected women. Wherever the origin of these metabolic abnormalities lies, their pathogenetic role in determining, perpetuating, and worsening the clinical traits of the syndrome is ascertained. Many studies have already highlighted possible mechanisms: hyperinsulinemia and insulin resistance may contribute to hyperandrogenemia, chronic anovulation, and other comorbidities of the syndrome by differentially affecting the endocrine glands (ovaries, adrenals, and pituitary) and peripheral tissues (fat mass and skeletal muscle). Based on these evidences, in the past years, thorough research has been focused on the possible role of insulin-sensitizing agents in the treatment of polycystic ovary syndrome. Many compounds were tested to verify their efficacy against polycystic ovary syndrome-related metabolic dysfunction, both relying on previous acquired experiences in the field of diabetes mellitus and experimenting new agents, in particular, those belonging to the class of nutraceuticals. We sought to summarize the most relevant aspects of insulin-sensitizing treatments in polycystic ovary syndrome, by reporting the relevant literature on this topic and by keeping an attentive eye on the newly published international guidelines on polycystic ovary syndrome 2018. This overview encompasses metformin, thiazolidinediones, inositols, alpha-lipoic acid, and GLP1-R analogues. Starting from the analysis of the mechanisms of action, we anchored to the state of the art of the use of these drugs in polycystic ovary syndrome, to the most recent evidences for clinical practice and to the remaining open questions around indications, dose, treatment schedules, and side effects.
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http://dx.doi.org/10.1177/2633494120908709DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7236839PMC
February 2020

Persistence of right umbilical vein: a singular case.

Turk J Pediatr 2020 ;62(2):338-342

Departments of Obstetrics, Gynaecology, Fondazione Policlinico Gemelli IRCCS, Università Cattolica del Sacro Cuore, Largo Francesco Vito 1, 00168 Rome, Italy.

Background: Persistent right umbilical vein (PRUV) is one of the most common prenatally detected venous anomaly. In the intrahepatic variant (I-PRUV) the right umbilical vein fuses with right portal vein and through the ductus venous drains into inferior vena cava, while in the uncommon extrahepatic variant (E-PRUV), the vein bypasses the liver completely. E-PRUV has a worse prognosis compared to I-PRUV, due either to severe hemodynamic effects or to the frequent association with other severe fetal malformations.

Case: Here we report a case of E-PRUV with good outcome. Prenatal fetal ultrasonography (US) performed at 33 weeks of gestation in 28-year old woman, highlights the presence of E-PRUV with right UV draining in inferior vena cava. In the male neonate born at 35 weeks of gestation by C-section, the Apgar Score was 95`- 1010 and no other associated malformations and hemodynamic decompensation were found. Postnatal abdominal US showed the presence of enlarged paraumbilical veins.

Conclusions: The association of E-PRUV draining into the inferior vena cava with shunt through paraumbilical veins, could have preserved offspring by severe cardiac overload, positively affecting prognosis.
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http://dx.doi.org/10.24953/turkjped.2020.02.024DOI Listing
August 2021

Pregnancy outcome and left ventricular ejection fraction in women with history of myocardial infarction.

Eur J Obstet Gynecol Reprod Biol 2020 Jul 29;250:74-75. Epub 2020 Apr 29.

Dipartimento Scienze della Salute della Donna, del Bambino, e di Sanità Pubblica, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Università Cattolica del Sacro Cuore, Largo Agostino Gemelli 8, Roma, Italy. Electronic address:

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http://dx.doi.org/10.1016/j.ejogrb.2020.04.052DOI Listing
July 2020
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