Publications by authors named "Silvia Salvi"

28 Publications

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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

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

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

Autoimmune Congenital Heart Block: A Review of Biomarkers and Management of Pregnancy.

Front Pediatr 2020 22;8:607515. Epub 2020 Dec 22.

Fondazione Policlinico Universitario "A. Gemelli" IRCCS, Department of Obstetrics, Gynaecology and Pediatrics, Rome, Italy.

Autoimmune Congenital Heart Block (CHB) is an immune-mediated disease due to transplacental passage of circulating anti-Ro/SSA and anti-La/SSB autoantibodies. It occurs in 2% of anti-Ro/SSA-exposed pregnancies, and recurrence rate is nine times higher in subsequent pregnancies. Aim of this review is to identify biomarkers of CHB and treatment strategies. The Ro-system is constituted by two polypeptides targeted by the anti-Ro52 and anti-Ro60 autoantibodies. The central portion of Ro52 (p200), more than the full amino-acid sequence of Ro-52, is recognized to be the fine specificity of anti-Ro associated to the highest risk of cardiac damage. If anti-p200 antibody should be tested, as biomarker of CHB, over standard commercial ELISAs is still debated. Recent studies indicate that type I-Interferon (IFN) can activate fibroblasts in fetal heart. In the mother the anti-Ro/La antibodies activate the type I IFN-signature, and maternal IFN-regulated genes correlate with a similar neonatal IFN-gene expression. Evaluation of maternal IFN-signature could be used as novel biomarker of CHB. The measurement of "mechanical" PR interval with weekly fetal echocardiogram (ECHO) from 16 to at least 24 weeks of gestation is strongly recommended for CHB prenatal diagnosis. However, ECHO screening presents some limitations due to difficult identification of first-degree block and possible occurrence of a complete block from a normal rhythm in few days. Maternal administration of Hydroxychloroquine from the tenth week of gestation, modulating toll-like receptor and autoantibody-dependent type I IFN activation on the fetus, has an important role in preventing CHB in pregnant women with high risk for recurrent CHB.
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http://dx.doi.org/10.3389/fped.2020.607515DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7784711PMC
December 2020

Treatment of pregnancies complicated by intrauterine growth restriction with nitric oxide donors increases placental expression of Epidermal Growth Factor-Like Domain 7 and improves fetal growth: A pilot study.

Transl Res 2021 02 9;228:28-41. Epub 2020 Aug 9.

Department of Biomedicine and Prevention, University of Rome Tor Vergata, Rome, Italy. Electronic address:

Intrauterine growth restriction (IUGR) is a pathological condition of pregnancy with high perinatal mortality and morbidity, characterized by inadequate fetal growth associated to altered maternal hemodynamics with impaired uteroplacental blood flow and placental insufficiency. To date, iatrogenic premature delivery remains the elective therapeutic strategy. However, in recent years the possibility of a therapeutic approach with vasodilators and myorelaxants, such as nitric oxide (NO) donors, has gained interest. NO controls many endothelial cell functions, including angiogenesis and vascular permeability, by regulating the expression of angiogenic factors, such as Vascular Endothelial Growth Factor. In the present study, we investigated if treatment of pregnancies complicated by IUGR with NO donors affects the expression of Epidermal Growth Factor-Like Domain 7 (EGFL7), a secreted endothelial factor, previously demonstrated to be expressed by both endothelial and trophoblast cells and involved in proper placental development. NO donor treatment induced placental levels of EGFL7 and, in association with oral fluids, significantly improved fetal growth. Ex vivo experiments confirmed that NO donors increased expression and secretion of EGFL7 by villous explants. To specifically investigate the potential response of trophoblast cells to NO, we treated HTR8-sVneo cells with NO donors and observed induction of EGFL7 expression. Altogether, our findings indicate that NO induces endothelial and trophoblast expression of EGFL7 in the placenta and improves fetal growth, suggesting a correlation between placental levels of EGFL7 and pregnancy outcome.
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http://dx.doi.org/10.1016/j.trsl.2020.08.002DOI Listing
February 2021

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

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

The diagnosis of pneumonia in a pregnant woman with coronavirus disease 2019 using maternal lung ultrasound.

Am J Obstet Gynecol 2020 07 28;223(1):9-11. Epub 2020 Apr 28.

Dipartimento Scienze della Salute della Donna, del Bambino e di Sanità Pubblica, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy; Istituto di Ginecologia e Ostetricia, Università Cattolica del Sacro Cuore, Rome, Italy.

Lung ultrasound examination has been demonstrated to be an accurate imaging method to detect pulmonary and pleural conditions. During pregnancy, there is a need for rapid assessment of the maternal lung in patients with suspected coronavirus disease 2019. We report our experience on lung ultrasound examination in the diagnosis of coronavirus disease 2019 pneumonia in a pregnant woman. Typical ultrasound features of this pulmonary pathology, including diffuse hyperechoic vertical artifacts with thickened pleural line and "white lung" with patchy distribution, were observed. We suggest point-of-care lung ultrasound examination as a diagnostic imaging tool in pregnant women with suspected coronavirus disease 2019.
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http://dx.doi.org/10.1016/j.ajog.2020.04.020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7194742PMC
July 2020

Comparison of mediastinal shift angles obtained with ultrasound and magnetic resonance imaging in fetuses with isolated left sided congenital diaphragmatic hernia.

J Matern Fetal Neonatal Med 2020 Jan 23:1-6. Epub 2020 Jan 23.

Department of Medical and Surgical Neonatology, Fetal Medicine and Surgery Unit, Bambino Gesù Children's Hospital IRCCS, Rome, Italy.

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 ( = .419). Among the 29 cases, there were 21 alive infants, for an overall postnatal survival rate of 72.41%. After stratifying for postnatal survival, the best cutoffs with the highest discriminatory power in terms of sensibility and specificity were 42.1° for the US-MSA and 39.1° for the MRI-MSA. The performance of MRI-MSA in predicting postnatal survival was close to that of US-MSA in terms of sensitivity (62.5 versus 50.0%), specificity (80.9 versus 90.5%), positive predictive value (55.6 versus 66.7%), negative predictive value (85.0 versus 82.6%) and accuracy (75.9 versus 79.3%). There was no statistically significant difference between the two modalities ( > .05 for all). 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.
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http://dx.doi.org/10.1080/14767058.2020.1716714DOI Listing
January 2020

Autoimmunity in obstetrics and autoimmune diseases in pregnancy.

Best Pract Res Clin Obstet Gynaecol 2019 Oct 18;60:66-76. Epub 2019 Mar 18.

UOC di Patologia Ostetrica, Dipartimento Scienze della Salute della Donna, del Bambino e di Sanità Pubblica, Fondazione Policlinico Universitario A. Gemelli IRCCS, Roma, Italy; Istituto di Clinica Ostetrica e Ginecologica, Università Cattolica del Sacro Cuore, Roma, Italy.

Autoimmune diseases (AIDs) are associated with strong female preponderance and often present before or during the reproductive years; consequently, pregnancy and breastfeeding are topics of major interest for these patients. AIDs show different responses to pregnancy: some ameliorate, while others remain unchanged, and several AIDs aggravate. The response of the AIDs to the hormonal and immunological alterations of pregnancy reflects the different pathophysiology of each disease. Systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS) are associated with multiple autoantibodies, multiorgan involvement, more aggressive therapy, and increased impact on pregnancy outcome. For the management of pregnancy in patients with SLE and/or APS, it is important to individuate the correct risk profile for each woman and timing for treatment. The optimal timing for starting or modulating treatment is at preconception assessment to influence the placentation. In this chapter, we discuss the management of pregnancy in patients with AIDs.
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http://dx.doi.org/10.1016/j.bpobgyn.2019.03.003DOI Listing
October 2019

Increased circulating levels of Epidermal Growth Factor-like Domain 7 in pregnant women affected by preeclampsia.

Transl Res 2019 05 25;207:19-29. Epub 2018 Dec 25.

Department of Cell and Developmental Biology, Weill Cornell Medical College, New York, New York. Electronic address:

Proper placental development is crucial to establish a successful pregnancy. Defective placentation is the major cause of several pregnancy complications, including preeclampsia (PE). We have previously demonstrated that the secreted factor Epidermal Growth Factor-like Domain 7 (EGFL7) is expressed in trophoblast cells of the human placenta and that it regulates trophoblast migration and invasion, suggesting a role in placental development. In the present study, we demonstrate that circulating levels of EGFL7 are undetectable in nonpregnant women, increase during pregnancy and decline toward term. Close to term, circulating levels of EGFL7 are significantly higher in patients affected by PE when compared to normal pregnancies. Consistent with these results, villus explant cultures obtained from placentas affected by PE display increased release of EGFL7 in the culture medium when compared to those from normal placentas. Our results suggest that increased release of placenta-derived EGFL7 and increased circulating levels of EGFL7 are associated with the clinical manifestation of PE.
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http://dx.doi.org/10.1016/j.trsl.2018.12.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6486846PMC
May 2019

Antiphospholipid syndrome: An update on risk factors for pregnancy outcome.

Autoimmun Rev 2018 Oct 15;17(10):956-966. Epub 2018 Aug 15.

Department of Obstetrics, Gynaecology and Pediatrics, F.Policlinico Gemelli IRCCS, Università Cattolica del Sacro Cuore, Largo Francesco Vito 1, 00168 Rome, Italy.

Background: The optimal treatment of women with primary antiphospholipid syndrome (APS) is still debated. About 20-30% of women with APS remain unable to give birth to healthy neonates despite conventional treatment, consisting of prophylactic-dose heparin and low-dose aspirin. These cases are defined "refractory obstetric APS". The early identification of risk factors associated with poor pregnancy outcome could be the optimal strategy to establish criteria for additional therapies, such as hydroxychloroquine, steroids, intravenous immunoglobulin, and plasma exchange.

Purpose: The aim of the present study was to review current literature about risk factors for poor pregnancy outcome.

Search Methods: The PubMed database was used to search for peer-reviewed original and review articles concerning risk factors for pregnancy outcome in APS from 1st January 1990 to 15th January 2018.

Outcomes: History of pregnancy morbidity and/or thrombosis, the association with SLE and/or other autoimmune diseases are well known history-based predictive factors for obstetrical complications, such as miscarriage, maternal venous thromboembolism, intrauterine foetal demise, preeclampsia, and neonatal death. Moreover, laboratory findings associated with poor pregnancy outcome are:triple antiphospholipid antibodies aPL positivity, double aPL positivity, single aPL positivity, false-positive IgM for CMV, and hypocomplementemia. Triple positivity is confirmed as the most significant risk factor by a large body of evidence. Furthermore, the abnormal uterine arteries Doppler velocimetry results are confirmed to be strongly associated with poor pregnancy outcomes in APS. The good performance of the uterine arteries velocimetry, as a negative predictive factor, was reported by different studies. On the contrary, in case of abnormal uterine arteries results, the relevance of a careful surveillance is highlighted for the high risk of maternal-foetal complications. Nevertheless, this tool is a late indicator to suggest any additional treatments.

Conclusions: In order to prevent obstetrical complications and establish the optimal combination therapy, the knowledge at preconception or at the beginning of pregnancy of risk factors associated with poor pregnancy outcome could be a crucial step for management and treatment of APS. In addition, in the preconception assessment a regimen with low-dose aspirin, folic acid, and vitamin D supplementation should be offered, and a treatment strategy has to be established (conventional vs additional therapy). In fact, additional treatment has to be tailored for each patient.
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http://dx.doi.org/10.1016/j.autrev.2018.03.018DOI Listing
October 2018

Fetal cerebral and umbilical Doppler in pregnancies complicated by late-onset placental abruption.

J Matern Fetal Neonatal Med 2017 Jun 2;30(11):1320-1324. Epub 2016 Aug 2.

b Fetal Medicine Unit, St George's Hospital , London , UK.

Objective: To evaluate whether changes in the cerebroplacental Doppler and birth weight (BW) suggestive of chronic fetal hypoxemia, precede the development of late-onset placental abruption (PA) after 32 weeks.

Methods: In a multicenter retrospective study, the Doppler examinations of the fetal umbilical artery (UA) and middle cerebral artery (MCA) recorded after 32 weeks were collected in pregnancies subsequently developing PA. The BW centiles were calculated and the MCA pulsatility indices (PI), and UA PI were converted into multiples of the median (MoM). Afterwards, a comparison was made with a group of fetuses, which did not develop PA. Logistic regression was used to adjust for potential confounders and evaluate the feasibility of the prediction model.

Results: Pregnancies complicated by late-onset PA (n = 31) presented lower MCA PI (p = 0.015) and were smaller (p < 0.001) than those who did not (n = 1294). Logistic regression analysis indicated that cerebral vasodilation was more important than umbilical flow in the explanation of PA (MCA PI OR = 0.106, p = 0.014 and UA PI OR 1.901, p = 0.32). In addition, the influence of BW exerted was residual (BW centile OR = 0.989, p = 0.15).

Conclusions: Fetuses developing late-onset PA demonstrate significant cerebral vasodilation with scarce placental dysfunction, suggesting the existence of some kind of chronic hypoxemia that follows the late-onset pattern.
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http://dx.doi.org/10.1080/14767058.2016.1212332DOI Listing
June 2017

Fetal hypoxia secondary to severe maternal anemia as a causative link between blueberry muffin baby and erythroblastosis: a case report.

J Med Case Rep 2016 Jun 13;10(1):155. Epub 2016 Jun 13.

High Risk Pregnancies Unit, Department of Obstetrics, Gynaecology and Paediatrics, Catholic University of the Sacred Heart, Largo F. Vito, 1, 00168, Rome, Italy.

Background: Neonatal blueberry muffin lesions are rare cutaneous eruptions, presenting as transient, non-blanching, red-violaceous papules, mostly localized in the trunk, head and neck, attributable to a marked dermal hematopoietic activity. Congenital infections of the TORCH complex (toxoplasmosis, other, rubella, cytomegalovirus and herpes) and hematological disorders have been classically associated with this neonatal dermatological manifestation. We report for the first time an unusual presentation of blueberry muffin lesions in a neonate born from a mother affected by severe anemia during pregnancy.

Case Presentation: A male, white Caucasian, neonate showed a cutaneous rash at birth, suggestive of "blueberry muffin"-like lesions. These cutaneous lesions were associated with marked elevation of the circulating nucleated red blood cells, and with ultrasound findings of peculiar brain ischemic porencephalic lesions. The clinical features of spontaneous disappearance and the association with marked erythroblastosis strongly suggest that these dermatological findings may be the consequence of an extramedullary hematopoiesis unexpectedly evoked by the intrauterine chronic exposure to hypoxia caused by severe maternal anemia.

Conclusions: In conclusion, fetal hypoxia secondary to severe maternal anemia may play a causative and unreported role in the development of neonatal blueberry muffin lesions.
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http://dx.doi.org/10.1186/s13256-016-0924-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4904358PMC
June 2016

Reliability of Doppler Assessment of the Middle Cerebral Artery in the Near and Far Fields in Healthy and Anemic Fetuses.

J Ultrasound Med 2015 Nov 2;34(11):2037-42. Epub 2015 Oct 2.

Fetal Medicine Unit, Academic Department of Obstetrics and Gynecology, St George's University of London, London, England (S.S., A.Bh.); Department of Obstetrics, Gynecology and Pediatrics, Catholic University of Sacred Heart, Rome, Italy (S.S.); and Chikitsa, Center for Excellence in Ultrasound, Mumbai, India (A.Ba., K.K.).

Objectives: The purpose of this study was to assess the reliability of the middle cerebral artery pulsatility index (PI) and peak systolic velocity (PSV) at the proximal portions of the near- and far-field vessel sites in healthy and anemic fetuses.

Methods: The middle cerebral artery PSV and PI were prospectively assessed in 50 normal singleton pregnancies. The Doppler waveforms for the middle cerebral artery PI and the PSV were recorded independently by 2 operators at the most proximal portions of the near- and far-field sites. Data for the PSV and PI at the proximal portions of both the near- and the far-field sites were also retrospectively collected in 7 anemic fetuses.

Results: No significant difference between the operators was detected for the middle cerebral artery PSV (P = .60) and PI (P = .88) measured in the conventionally used near-field proximal site in the 50 healthy fetuses. No significant difference between the proximal portions of the near- and far-field sites was detected for the PSV (P = .53) and PI (P = .23) in healthy or anemic fetuses.

Conclusions: The findings of this study suggest that the use of the far-field vessel is an acceptable alternative for measurement of the middle cerebral artery PI and PSV when investigation of the near-field vessel is technically difficult.
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http://dx.doi.org/10.7863/ultra.14.11078DOI Listing
November 2015

Development of a new fetal growth curve from a large sample of Italian population.

Minerva Pediatr 2017 Aug 10;69(4):245-250. Epub 2015 Sep 10.

Department of Obstetrics and Gynecology and Pediatrics, Catholic University of Sacro Cuore, Rome, Italy.

Background: Intrauterine growth curves are considered an essential instrument in prenatal medicine for an appropriate auxological classification of fetuses and they have a great importance in clinical practice. Nowadays, in Italy a national curve published in 1975, is the most used. It Is based on birth weights of 8458 newborns from physiological pregnancies. The aim of the present study was to develop a modern fetal growth curve based on accurately selection of 35 240 physiological singleton Italian pregnancies with sure gestational age confirmed by ultrasound.

Methods: This is a retrospective analysis of 35,240 pregnancies from "A. Gemelli" University Hospital in Rome and "S. Anna" University Hospital in Turin from January 2001 to December 2006. Non-resident pregnant women or coming from other countries, women with diabetes, hypertensive disorders of pregnancy, multiple pregnancies, fetuses with major malformations and/or chromosomal disorders and stillborn fetuses were excluded.

Results: An increasing trend of median neonatal weight, in comparison with the previous Italian National Curve drawn up in 1975, was found.

Conclusions: Combining data from two centers, a new fetal growth curve, in which the 10th and the 90th percentiles are clinically reliable, was performed, in order to have a better tool to evaluate the Italian fetal population. A trend towards an increase of birth weight was observed if compared to previous growth curve drawn up more than 30 years ago.
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http://dx.doi.org/10.23736/S0026-4946.16.04258-4DOI Listing
August 2017

Is gestational hypertension beneficial in twin pregnancies?

Pregnancy Hypertens 2015 Apr 9;5(2):171-6. Epub 2015 Feb 9.

Department of Obstetrics and Gynaecology, Catholic University of Sacred Heart, Rome, Italy.

Objectives: Hypertensive disorders of pregnancy are commonly associated with impaired foetal growth. However, some studies observed that gestational hypertension in twin pregnancy could be beneficial for foetal growth. The aim of this study is to investigate the influence of gestational hypertension on neonatal birth weight among twin pregnancies.

Study Design: This is a retrospective study about the comparison of 196 hypertensive twin pregnancies to 912 normotensive ones, who gave birth in the teaching hospital "A. Gemelli" in Rome from 1980 to 2006.

Main Outcome Measures: Birth weight, inter-twin weight discordance and rate of small for gestational age neonates in the first and second twin.

Results: Birth weight, inter-twin weight discordance and rate of small for gestational age neonates were similar between the two groups. In the normotensive group, the discordance >25% was associated with lower gestational age at the delivery (p<0.00001), data not observed in the hypertensive group. The rate of pregnancies with second twin small for gestational age rose while paralleling the degree of the discordance in both groups.

Conclusion: Gestational hypertension in twin pregnancies, if compared to normotensive ones, is not detrimental for foetal growth.
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http://dx.doi.org/10.1016/j.preghy.2015.01.003DOI Listing
April 2015

Use of an intrauterine inflated catheter balloon in massive post-partum hemorrhage: a series of 52 cases.

J Obstet Gynaecol Res 2014 Jun;40(6):1603-10

Department of Obstetrics and Gynaecology, Catholic University of Sacred Heart.

Aim: Massive post-partum hemorrhage (PPH) is an important cause of maternal death that occurs as a complication of delivery. We report a large case series to evaluate the efficacy of uterine balloon tamponade to treat PPH avoiding hysterectomy.

Material And Methods: This prospective study was conducted in two Italian hospitals (from December 2002 to July 2012). Fifty-two patients with PPH not responsive to uterotonics were treated by Rusch balloon. A follow-up was conducted among the study population to assess the subsequent fertility.

Results: The most frequent cause of PPH was atony (59.6%), followed by placenta previa (21.2%), placenta accreta (9.6%), and placenta previa and accreta (9.6%). The balloon success rate to control hemorrhage was 75%. From the sample of 52 patients, 13 patients needed additional procedures. In three failure cases, other conservative techniques were used and the overall effectiveness of them was 80.7%. The follow-up group consisted of 31 women. Of these women, 24 women (77.4%) had no further pregnancies, but only one due to sterility. Four of seven patients with subsequent pregnancies made it to term without complications.

Conclusions: The Rusch balloon is effective in controlling non-traumatic PPH in 75% of cases. It is simple to use, readily available and cheap. If necessary, this technique does not exclude other procedures. We suggest that this balloon should be included routinely in the PPH protocol.
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http://dx.doi.org/10.1111/jog.12404DOI Listing
June 2014

Novel expression of EGFL7 in placental trophoblast and endothelial cells and its implication in preeclampsia.

Mech Dev 2014 Aug 19;133:163-76. Epub 2014 Apr 19.

Department of Cell and Developmental Biology, Weill Cornell Medical College, 1300 York Avenue, Box 60, New York, NY 10065, United States. Electronic address:

The mammalian placenta is the site of nutrient and gas exchange between the mother and fetus, and is comprised of two principal cell types, trophoblasts and endothelial cells. Proper placental development requires invasion and differentiation of trophoblast cells, together with coordinated fetal vasculogenesis and maternal vascular remodeling. Disruption in these processes can result in placental pathologies such as preeclampsia (PE), a disease characterized by late gestational hypertension and proteinuria. Epidermal Growth Factor Like Domain 7 (EGFL7) is a largely endothelial-restricted secreted factor that is critical for embryonic vascular development, and functions by modulating the Notch signaling pathway. However, the role of EGFL7 in placental development remains unknown. In this study, we use mouse models and human placentas to begin to understand the role of EGFL7 during normal and pathological placentation. We show that Egfl7 is expressed by the endothelium of both the maternal and fetal vasculature throughout placental development. Importantly, we uncovered a previously unknown site of EGFL7 expression in the trophoblast cell lineage, including the trophectoderm, trophoblast stem cells, and placental trophoblasts. Our results demonstrate significantly reduced Egfl7 expression in human PE placentas, concurrent with a downregulation of Notch target genes. Moreover, using the BPH/5 mouse model of PE, we show that the downregulation of Egfl7 in compromised placentas occurs prior to the onset of characteristic maternal signs of PE. Together, our results implicate Egfl7 as a possible factor in normal placental development and in the etiology of PE.
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http://dx.doi.org/10.1016/j.mod.2014.04.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4177412PMC
August 2014

Cord entanglement.

Arch Dis Child Fetal Neonatal Ed 2014 Nov 19;99(6):F457. Epub 2014 Apr 19.

Department of Paediatrics, Division of Neonatology, Catholic University of Sacred Heart, Rome, Italy.

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http://dx.doi.org/10.1136/archdischild-2013-305861DOI Listing
November 2014

The impact of primary Sjogren's syndrome on pregnancy outcome: our series and review of the literature.

Autoimmun Rev 2014 Feb 14;13(2):103-7. Epub 2013 Sep 14.

Department of Obstetrics, Gynaecology, and Pediatrics, Catholic University of Sacred Heart, Rome, Italy. Electronic address:

Objective: Firstly, to investigate the pregnancy outcome of women with primary Sjogren's Syndrome (pSS) in a case-control study; secondly, to perform a review of the literature in order to clarify if the pregnancy outcome is affected by pSS and influenced by the disease clinical onset.

Method Of Study: Thirty-four pregnancies with pSS and 136 controls were retrospectively collected.

Results: Six pregnancies occurred before the pSS diagnosis and 28 after the pSS diagnosis. Two cases were complicated by intrauterine atrio-ventricular block. A statistically significant increase of the rate of spontaneous abortions, preterm deliveries and cesarean section was found in pSS pregnancies. The mean neonatal birth weight and the mean neonatal birth weight percentile were significantly lower in the offspring of women with pSS in comparison to controls. Similar pregnancy outcome was observed in women with pSS diagnosis before and after the index pregnancy.

Conclusions: Women with pSS experienced complicated pregnancies more frequently than controls, regardless of the onset of the symptoms, showing that the immunological disturbance is present throughout the reproductive life.
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http://dx.doi.org/10.1016/j.autrev.2013.09.003DOI Listing
February 2014

Isolated cerebral sinovenous thrombosis: a rare case of neonatal antiphospholipid syndrome.

Indian Pediatr 2012 May;49(5):411-2

Division of Neonatology, Department of Paediatrics, Catholic University of Sacred Heart, Rome, Italy.

We describe a case of neonatal cerebral sinovenous thrombosis associated with the presence of anti-phospholipid antibodies (aPL). We recommend that in all cases of neonatal thrombosis, the couple mother-infant should be extensively tested for the presence of both acquired (aPL) and congenital thrombophilia.
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May 2012

P7. Role of EGF-like domain 7 (Egfl7) in placental development and implantation.

Pregnancy Hypertens 2011 Jul-Oct;1(3-4):275-6. Epub 2011 Sep 29.

University of Rome "Tor Vergata" , Rome, Italy.

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http://dx.doi.org/10.1016/j.preghy.2011.08.068DOI Listing
May 2015

Risk factors for pregnancy failure in patients with anti-phospholipid syndrome treated with conventional therapies: a multicentre, case-control study.

Rheumatology (Oxford) 2011 Sep 7;50(9):1684-9. Epub 2011 Jun 7.

Department of Clinical and Experimental Medicine, Rheumatology Unit, University of Padua, Padua, Italy.

Objective: To identify the risk factors associated with pregnancy failure in patients with APS treated with conventional therapy.

Methods: A multicentre, case-control study was conducted to compare APS patients with successful and unsuccessful pregnancy outcomes. We retrospectively considered 410 pregnancies of women diagnosed with primary APS. The study focused on 57 unsuccessful pregnancies (considered the study population) and 57 successful pregnancies (considered the control population) matched for age and therapy. All the patients had been treated with conventional protocol treatments including low-dose aspirin and/or heparin. The clinical and laboratory features of the two groups of women diagnosed with APS were compared.

Results: The independent risk factors for pregnancy failure were: (i) the presence of SLE or other autoimmune diseases [odds ratio (OR) 6.0; 95% CI 1.7, 20.8; P = 0.01]; (ii) history of both thrombosis and pregnancy morbidity (OR 12.1; 95% CI 1.3, 115.3; P = 0.03); and (iii) triple [Immunoglobulin (Ig) G/IgM aCLs plus IgG/IgM anti-β(2) glycoprotein I antibodies plus LA] aPL positivity (OR 4.1; 95% CI 1.0, 16.7; P = 0.05). APS patients diagnosed on the basis of a single positive test and/or history of pregnancy morbidity alone were generally found to have successful pregnancies.

Conclusion: It would seem from these findings that the risk of pregnancy failure in APS women planning to conceive can be stratified on the basis of some specific clinical and laboratory features.
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http://dx.doi.org/10.1093/rheumatology/ker139DOI Listing
September 2011

Maternal-neonatal vitamin K deficiency secondary to maternal biliopancreatic diversion.

Blood Coagul Fibrinolysis 2011 Jun;22(4):334-6

Division of Neonatology, Department of Pediatrics, Catholic University of Sacred Heart, Largo A. Gemelli 8, Rome, Italy.

Bariatric surgery has become a common therapeutic approach for severe obesity, in case of unsuccessful behavioural and/or medical interventions. During the past years, the number of obese women who underwent bariatric surgery in childbearing age has progressively increased. We report a case of vitamin K deficiency, due to maternal biliopancreatic diversion, resulting in a symptomatic clinical presentation in the mother and in a hypocoagulable state in her neonate.
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http://dx.doi.org/10.1097/MBC.0b013e328345c04cDOI Listing
June 2011

Predictors of pregnancy outcome in antiphospholipid syndrome: a review.

Clin Rev Allergy Immunol 2010 Apr;38(2-3):116-24

Department of Obstetrics and Gynecology, Catholic University of Sacred Hearth, Rome, Italy.

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.
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http://dx.doi.org/10.1007/s12016-009-8144-zDOI Listing
April 2010
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