Publications by authors named "Emma Bertucci"

28 Publications

  • Page 1 of 1

Comparison between Cerebroplacental Ratio and Umbilicocerebral Ratio in Predicting Adverse Perinatal Outcome in Pregnancies Complicated by Late Fetal Growth Restriction: A Multicenter, Retrospective Study.

Fetal Diagn Ther 2021 15;48(6):448-456. Epub 2021 Jun 15.

Center for High Risk Pregnancy and Fetal Care, Department of Obstetrics and Gynecology, University of Chieti, Chieti, Italy.

Introduction: The role of cerebroplacental ratio (CPR) or umbilicocerebral ratio (UCR) to predict adverse intrapartum and perinatal outcomes in pregnancies complicated by late fetal growth restriction (FGR) remains controversial.

Methods: This was a multicenter, retrospective cohort study involving 5 referral centers in Italy and Spain, including singleton pregnancies complicated by late FGR, as defined by Delphi consensus criteria, with a scan 1 week prior to delivery. The primary objective was to compare the diagnostic accuracy of the CPR and UCR for the prediction of a composite adverse outcome, defined as the presence of either an adverse intrapartum outcome (need for operative delivery/cesarean section for suspected fetal distress) or an adverse perinatal outcome (intrauterine death, Apgar score <7 at 5 min, arterial pH <7.1, base excess of >-11 mEq/mL, or neonatal intensive care unit admission).

Results: Median CPR absolute values (1.11 vs. 1.22, p = 0.018) and centiles (3 vs. 4, p = 0.028) were lower in pregnancies with a composite adverse outcome than in those without it. Median UCR absolute values (0.89 vs. 0.82, p = 0.018) and centiles (97 vs. 96, p = 0.028) were higher. However, the area under the curve, 95% confidence interval for predicting the composite adverse outcome showed a poor predictive value: 0.580 (0.512-0.646) for the raw absolute values of CPR and UCR, and 0.575 (0.507-0.642) for CPR and UCR centiles adjusted for gestational age. The use of dichotomized values (CPR <1, UCR >1 or CPR <5th centile, UCR >95th centile) did not improve the diagnostic accuracy.

Conclusion: The CPR and UCR measured in the week prior delivery are of low predictive value to assess adverse intrapartum and perinatal outcomes in pregnancies with late FGR.
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http://dx.doi.org/10.1159/000516443DOI Listing
June 2021

Diagnostic performance of cerebroplacental and umbilicocerebral ratio in appropriate for gestational age and late growth restricted fetuses attempting vaginal delivery: a multicenter, retrospective study.

J Matern Fetal Neonatal Med 2021 Jun 8:1-7. Epub 2021 Jun 8.

Fetal Medicine Unit, Maternal and Child Health and Development Network, Department of Obstetrics and Gynecology, University Hospital 12 de Octubre, Complutense University of Madrid, Madrid, Spain.

Background: Cerebroplacental Doppler studies have been advocated to predict the risk of adverse perinatal outcome (APO) irrespective of fetal weight.

Objective: To report the diagnostic performance of cerebroplacental (CPR) and umbilicocerebral (UCR) ratios in predicting APO in appropriate for gestational age (AGA) fetuses and in those affected by late fetal growth restriction (FGR) attempting vaginal delivery.

Study Design: Multicenter, retrospective, nested case-control study between 1 January 2017 and January 2020 involving five referral centers in Italy and Spain. Singleton gestations with a scan between 36 and 40 weeks and within two weeks of attempting vaginal delivery were included. Fetal arterial Doppler and biometry were collected. The AGA group was defined as fetuses with an estimated fetal weight and abdominal circumference >10th and <90th percentile, while the late FGR group was defined by Delphi consensus criteria. The primary outcome was the prediction of a composite of perinatal adverse outcomes including either intrauterine death, Apgar score at 5 min <7, abnormal acid-base status (umbilical artery pH < 7.1 or base excess of more than -11) and neonatal intensive care unit (NICU) admission. Area under the curve (AUC) analysis was performed.

Results: 646 pregnancies (317 in the AGA group and 329 in the late FGR group) were included. APO were present in 12.6% AGA and 24.3% late FGR pregnancies, with an odds ratio of 2.22 (95% CI 1.46-3.37). The performance of CPR and UCR for predicting APO was poor in both AGA [AUC: 0.44 (0.39-0.51)] and late FGR fetuses [AUC: 0.56 (0.49-0.61)].

Conclusions: CPR and UCR on their own are poor prognostic predictors of APO irrespective of fetal weight.
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http://dx.doi.org/10.1080/14767058.2021.1926977DOI Listing
June 2021

Ultrasound screening for fetal anomalies in a single center: diagnostic performances twenty years after the Eurofetus Study.

J Matern Fetal Neonatal Med 2021 Apr 28:1-8. Epub 2021 Apr 28.

Prenatal Medicine Unit, Obstetrics and Gynaecology Unit, Department of Medical and Surgical Sciences for Mother, Child and Adult, University of Modena and Reggio Emilia, Modena, Italy.

Purpose: To establish the accuracy of ultrasound in detecting fetal anomalies looking at the concordance between prenatal and postnatal diagnosis.

Materials And Methods: Retrospective analysis of concordance between prenatal and postnatal/autoptic diagnosis of fetuses with congenital abnormalities. Data are from a single center (Policlinico di Modena); all fetuses included were born between 2017 and 2018 and with a follow-up of at least 6 months. We included all deliveries (including perinatal deaths) and termination of pregnancy (TOP) for fetal indication. We calculated sensibility, sensitivity, Positive and Negative Likelihood Ratio, positive and negative predictive value of ultrasound.

Results: During the study period 5920 deliveries, including perinatal deaths, and 28 TOP for fetal indication were registered at our center. The prevalence of congenital malformations was 2.6% (153/5920). At least one ultrasound was performed in our center in 1250 women delivering in our unit. All 28 TOP had the anomaly scan performed in our center. Among the total 1278 women scanned in our unit, there were 128 (10%) suspicious scans. In 5/128 (3.9%) cases we diagnosed a false alarm; in 8/128 (6.2%) cases an evolutive malformation with in-utero regression. The prenatal diagnosis was confirmed in 77 (60.2%) cases at birth and in 28/128 (21.9%) at postmortem analysis while there were 10/128 false positive (7.8%). Among the 153 congenital malformations diagnosed at birth, the anomaly scan was performed in our Prenatal Medicine Unit in 92 (60.1%) fetuses. Among these, there were 15 false negatives (9.8%) while in 77/92 (83.7%) the malformation at birth agreed with the sonographic diagnosis. Sensitivity and specificity of ultrasound were 87.5% (IC95 80.2-92.8%) and 99.1% (IC95 98.4-99.6%) respectively with a Positive Likelihood Ratio and Negative Likelihood Ratio of 101.3 (IC95 54.5-188.5) and 0.13 (IC95 0.08-0.2); Positive Predictive Value and Negative Predictive Value were 91.3% (IC95 85-95.1%) and 98.7(IC95 98-99.2%).

Conclusion: Anomaly scan in pregnancy allows the diagnosis of congenital malformations with a sensibility of 87.5% and specificity of 99.1%. The main limitations of this study are its retrospective design and that it was conducted in a single referral center.
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http://dx.doi.org/10.1080/14767058.2021.1911994DOI Listing
April 2021

CD133 Expression in Placenta Chorioangioma Presenting as a Giant Asymptomatic Mass.

Medicina (Kaunas) 2021 Feb 11;57(2). Epub 2021 Feb 11.

Department of Diagnostic, Clinic and Public Health Medicine, University of Modena and Reggio Emilia, 41125 Modena, Italy.

: Placental chorioangioma is the most common benign non-trophoblastic neoplasm of the placenta. Its clinical relevance lies in the size of the tumor since larger masses cause pregnancy complications, including an unfavorable neonatal outcome. We report the case of a 34-year-old second gravida and nullipara at the 35th week of gestation, admitted to the gynecological department for antibiotic-resistant fever. The cardiotocography performed during hospitalization showed an abnormal fetal pattern. A 2250 g newborn was delivered by cesarean section. No complications were observed during childbirth and postpartum was insignificant. On gross inspection a white fleshy intraparenchymal mass blooming on the maternal surface was noted; routinely stained sections revealed features consistent with chorioangioma with vascular channels lined by inconspicuous endothelial cells immunoreactive for CD31 and CD133. Focal expression of CD133 was also observed in placental villi. CD133 expression indicated the presence of stem cells in chorioangioma, suggesting their possible role in the development of mesenchymal lesions including chorioangioma.
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http://dx.doi.org/10.3390/medicina57020162DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7917587PMC
February 2021

Unravelling Heterogeneity of Amplified Human Amniotic Fluid Stem Cells Sub-Populations.

Cells 2021 01 15;10(1). Epub 2021 Jan 15.

Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, 41124 Modena, Italy.

Human amniotic fluid stem cells (hAFSCs) are broadly multipotent immature progenitor cells with high self-renewal and no tumorigenic properties. These cells, even amplified, present very variable morphology, density, intracellular composition and stemness potential, and this heterogeneity can hinder their characterization and potential use in regenerative medicine. Celector (Stem Sel ltd.) is a new technology that exploits the Non-Equilibrium Earth Gravity Assisted Field Flow Fractionation principles to characterize and label-free sort stem cells based on their solely physical characteristics without any manipulation. Viable cells are collected and used for further studies or direct applications. In order to understand the intrapopulation heterogeneity, various fractions of hAFSCs were isolated using the Celector profile and live imaging feature. The gene expression profile of each fraction was analysed using whole-transcriptome sequencing (RNAseq). Gene Set Enrichment Analysis identified significant differential expression in pathways related to Stemness, DNA repair, E2F targets, G2M checkpoint, hypoxia, EM transition, mTORC1 signalling, Unfold Protein Response and p53 signalling. These differences were validated by RT-PCR, immunofluorescence and differentiation assays. Interestingly, the different fractions showed distinct and unique stemness properties. These results suggest the existence of deep intra-population differences that can influence the stemness profile of hAFSCs. This study represents a proof-of-concept of the importance of selecting certain cellular fractions with the highest potential to use in regenerative medicine.
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http://dx.doi.org/10.3390/cells10010158DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7830644PMC
January 2021

Homozygous n.64C>T mutation in mitochondrial RNA-processing endoribonuclease gene causes cartilage hair hypoplasia syndrome in two siblings.

Eur J Med Genet 2021 Feb 12;64(2):104136. Epub 2021 Jan 12.

Post-graduated School of Pediatrics, Department of Medical and Surgical Sciences for Mother, Children and Adults, University of Modena and Reggio Emilia, Italy.

Cartilage hair hypoplasia syndrome (OMIM # 250250) is a rare autosomal recessive metaphyseal dysplasia, characterized by disproportionate short stature, hair hypoplasia and variable extra-skeletal manifestations, including immunodeficiency, anemia, intestinal diseases and predisposition to cancers. Cartilage hair hypoplasia syndrome has a broad phenotype and it is caused by homozygous or compound heterozygous mutation in the mitochondrial RNA-processing endoribonuclease on chromosome 9p13. Although it is well known as a primordial dwarfism, descriptions of the prenatal growth are missing. To add further details to the knowledge of the phenotypic spectrum of the disease, we report on two siblings with cartilage hair hypoplasia syndrome, presenting n.64C > T homozygous mutation in the mitochondrial RNA-processing endoribonuclease gene. We describe the prenatal and postnatal growth pattern of the two affected patients, showing severe pre- and post-natal growth deficiency.
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http://dx.doi.org/10.1016/j.ejmg.2021.104136DOI Listing
February 2021

Disorder of sex development associated with a novel homozygous nonsense mutation in COG6 expands the phenotypic spectrum of COG6-CDG.

Am J Med Genet A 2021 04 4;185(4):1187-1194. Epub 2021 Jan 4.

Neonatology Unit, Mother-Child Department, University Hospital of Modena, Modena, Italy.

Congenital disorders of glycosylation (CDG) are an expanding group of metabolic disorders that result from abnormal protein glycosylation. A special subgroup of CDG type II comprises defects in the Conserved Oligomeric Golgi Complex (COG). In order to further delineate the genotypic and phenotypic spectrum of COG complex defect, we describe a novel variant of COG6 gene found in homozygosity in a Moroccan patient with severe presentation of COG6-CDG (OMIM #614576). We compared the phenotype of our patient with other previously reported COG6-CDG cases. Common features in COG6-CDG are facial dysmorphism, growth retardation, microcephaly, developmental disability, liver or gastrointestinal disease, recurrent infections, hypohidrosis/hyperthermia. In addition to these phenotypic features, our patient exhibited a disorder of sexual differentiation, which has rarely been reported in COG6-CDG. We hypothesize that the severe COG6 gene mutation interferes with glycosylation of a disintegrin and metalloprotease family members, inhibiting the correct gonadal distal tip cells migration, fundamental for the genitalia morphogenesis. This report broadens the genetic and phenotypic spectrum of COG6-CDG and provides further supportive evidence that COG6-CDG can present as a disorder of sexual differentiation.
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http://dx.doi.org/10.1002/ajmg.a.62061DOI Listing
April 2021

Amniotic Fluid Stem Cell-Derived Extracellular Vesicles Counteract Steroid-Induced Osteoporosis In Vitro.

Int J Mol Sci 2020 Dec 22;22(1). Epub 2020 Dec 22.

Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, 41125 Modena, Italy.

Background-Osteoporosis is characterized by defects in both quality and quantity of bone tissue, which imply high susceptibility to fractures with limitations of autonomy. Current therapies for osteoporosis are mostly concentrated on how to inhibit bone resorption but give serious adverse effects. Therefore, more effective and safer therapies are needed that even encourage bone formation. Here we examined the effect of extracellular vesicles secreted by human amniotic fluid stem cells (AFSC) (AFSC-EV) on a model of osteoporosis in vitro. Methods-human AFSC-EV were added to the culture medium of a human pre-osteoblast cell line (HOB) induced to differentiate, and then treated with dexamethasone as osteoporosis inducer. Aspects of differentiation and viability were assessed by immunofluorescence, Western blot, mass spectrometry, and histological assays. Since steroids induce oxidative stress, the levels of reactive oxygen species and of redox related proteins were evaluated. Results-AFSC-EV were able to ameliorate the differentiation ability of HOB both in the case of pre-osteoblasts and when the differentiation process was affected by dexamethasone. Moreover, the viability was increased and parallelly apoptotic markers were reduced. The presence of EV positively modulated the redox unbalance due to dexamethasone. Conclusion-these findings demonstrated that EV from hAFSC have the ability to recover precursor cell potential and delay local bone loss in steroid-related osteoporosis.
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http://dx.doi.org/10.3390/ijms22010038DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7792960PMC
December 2020

Pregnant woman infected by Coronavirus disease (COVID-19) and calcifications of the fetal bowel and gallbladder.

Minerva Obstet Gynecol 2021 Feb 30;73(1):121-124. Epub 2020 Nov 30.

Unit of Prenatal Medicine, Obstetrics and Gynecology, Department of Medical and Surgical Sciences for Mother, Child and Adult, University of Modena and Reggio Emilia, Modena, Italy -

COVID-19 was declared to be a pandemic due to the rapid increase of cases around the world, including the number of pregnant women. Data about vertical transmission of COVID-19 are still limited and controversial: in most cases, although a positive mother, the virus could not be isolated in amniotic fluid, cord blood, breast milk or neonatal throat swab in these patients. No data have been published about possible intrauterine sonographic signs of infection. A pregnant woman was diagnosed with SARS-CoV-2 at 35+5 weeks of gestation and managed conservatively at home. At transabdominal ultrasound at 38+3 weeks, fetal bowel and gallbladder calcifications were noted. CMV and other infectious agents were ruled out; an iterative caesarean section was performed at 38+5 weeks without complications. Placenta resulted negative for SARS-CoV-2; the umbilical cord blood sample was IgG positive and IgM negative as per maternal infection. The baby developed respiratory distress syndrome requiring endotracheal surfactant administration and nasal-CPAP for one day but nasopharyngeal swabs at birth and after 48 hours were SARS-CoV-2 negative. Neonatal abdominal ultrasound showed normal liver, acalculous gallbladder with mild parietal thickening. The baby was discharged in good conditions. Although gallbladder calcifications and echogenic bowel are highly suspicious of viral infection and were thought to be due to the vertical transmission of SARS-CoV-2, these findings were not corroborated by the results of our diagnostic tests; these sonographic findings might represent a false positive of fetal infection in mother affected by COVID-19 since vertical transmission appears to be rare.
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http://dx.doi.org/10.23736/S0026-4784.20.04717-6DOI Listing
February 2021

Oxidative Stress in Alzheimer's Disease: Therapeutic Effect of Amniotic Fluid Stem Cells Extracellular Vesicles.

Oxid Med Cell Longev 2020 24;2020:2785343. Epub 2020 Oct 24.

Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Modena 41125, Italy.

Alzheimer's disease (AD) is characterized by abnormal protein aggregation, deposition of extracellular -amyloid proteins (A), besides an increase of oxidative stress. Amniotic fluid stem cells (AFSCs) should have a therapeutic potential for neurodegenerative disorders, mainly through a paracrine effect mediated by extracellular vesicles (EV). Here, we examined the effect of EV derived from human AFSCs (AFSC-EV) on the disease phenotypes in an AD neuron primary culture. We observed a positive effect of AFSC-EV on neuron morphology, viability, and A and phospho-Tau levels. This could be due to the apoptotic and autophagic pathway modulation derived from the decrease in oxidative stress. Indeed, reactive oxygen species (ROS) were reduced, while GSH levels were enhanced. This modulation could be ascribed to the presence of ROS regulating enzymes, such as SOD1 present into the AFSC-EV themselves. This study describes the ROS-modulating effects of extracellular vesicles alone, apart from their deriving stem cell, in an AD model, proposing AFSC-EV as a therapeutic tool to stop the progression of AD.
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http://dx.doi.org/10.1155/2020/2785343DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7641262PMC
May 2021

Prolonged hypoxia delays aging and preserves functionality of human amniotic fluid stem cells.

Mech Ageing Dev 2020 10 13;191:111328. Epub 2020 Aug 13.

University of Groningen, European Research Institute for the Biology of Ageing (ERIBA), University Medical Center, Groningen (UMCG), The Netherlands. Electronic address:

Human amniotic fluid stem cells (hAFSCs) are an emerging tool in regenerative medicine because they have the ability to differentiate into various lineages and efficiently improve tissue regeneration with no risk of tumorigenesis. Although hAFSCs are easily isolated from the amniotic fluid, their expansion ex vivo is limited by a quick exhaustion which impairs replicative potential and differentiation capacity. In this study, we evaluate various aging features of hAFSCs cultured at different oxygen concentrations. We show that low oxygen (1% O) extends stemness and proliferative features, and delays induction of senescence-associated markers. Hypoxic hAFSCs activate a metabolic shift and increase resistance to pro-apoptotic stimuli. Moreover, we observe that cells at low oxygen remain capable of osteogenesis for prolonged periods of time, suggesting a more youthful phenotype. Together, these data demonstrate that low oxygen concentrations might improve the generation of functional hAFSCs for therapeutic use by delaying the onset of cellular aging.
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http://dx.doi.org/10.1016/j.mad.2020.111328DOI Listing
October 2020

MRI of placenta accreta: diagnostic accuracy and impact of interventional radiology on foetal-maternal delivery outcomes in high-risk women.

Br J Radiol 2020 Oct 29;93(1114):20200267. Epub 2020 Jul 29.

Department of Radiology, Azienda ospedaliero- universitaria Policlinico di Modena, Modena, Italy.

Objective: To assess accuracy and reproducibility of MRI diagnosis of invasive placentation (IP) in high-risk patients and to evaluate reliability of MRI features. Secondary aim was to evaluate impact of interventional radiology (IR) on delivery outcomes in patients with IP at MRI.

Methods: 26 patients (mean age 36.24 y/o,SD 6.16) with clinical risk-factors and echographic suspicion of IP underwent 1.5 T-MRI. Two readers reviewed images. Gold-standard was histology in hysterectomised patients and obstetric evaluation at delivery for patients with preserved uterus. Accuracy and reproducibility of MRI findings were calculated.

Results: Incidence of IP was 50% (13/26) and of PP was 11.54% (3/26). MRI showed 100% sensitivity (95% CI = 75.3-100%) and 92.3% specificity (95% CI = 64.0-100%) in the diagnosis of IP. Gold-standard was histology in 10 cases and obstetric evaluation in 16. MRI findings with higher sensitivity were placental heterogeneity, uterine bulging and black intraplacental bands. Uterine scarring, placental heterogeneity, myometrial interruption and tenting of the bladder showed better specificity. MRI inter-rater agreement with Cohen's K was 1. 11 patients among 14 with MRI diagnosis of IP received IR assistance with positive impact on delivery outcomes in terms of blood loss, red cells count, intense care unit length of stay, days of hospitalisation and risk of being transfused.

Conclusion: MRI is an accurate and reproducible technique in prenatal diagnosis of IP. MRI helps planning a safe and appropriate delivery eventually assisted by IR, which positively affects foetal and maternal outcomes.

Advances In Knowledge: The adoption of MRI evaluation in patients with high risk of invasive placentation allows a more accurate diagnosis in terms of both presence of the disease and its extension to or through or even beyond the myometrium. This led to a better dedicated delivery management with eventual adoption of interventional radiology with a global positive effect on foetal and maternal outcomes.
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http://dx.doi.org/10.1259/bjr.20200267DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7548357PMC
October 2020

Role of prenatal magnetic resonance imaging in fetuses with isolated agenesis of corpus callosum in the era of fetal neurosonography: A systematic review and meta-analysis.

Acta Obstet Gynecol Scand 2021 01 24;100(1):7-16. Epub 2020 Aug 24.

Center for Fetal Care and High-risk Pregnancy, Department of Obstetrics and Gynecology, University Hospital of Chieti, Chieti, Italy.

Introduction: Corpus callosum agenesis (ACC) is frequently diagnosed during fetal life; its prognosis depends also on additional anomalies. The additional value of fetal magnetic resonance imaging (MRI) in fetuses with "isolated" complete (cACC) and partial (pACC) agenesis of the corpus callosum on ultrasound is still debated.

Material And Methods: We performed a systematic literature review and meta-analysis including fetuses with a prenatal diagnosis of cACC and pACC without associated structural anomalies on ultrasound, undergoing fetal MRI. The primary outcome was the rate of additional anomalies detected at fetal MRI. Further analyses assessed the effect of type of ultrasound assessment (neurosonography vs standard axial assessment), gestational age at fetal MRI and rate of postnatally detected brain anomalies. Random-effect meta-analyses of proportions were used to analyze the data.

Results: Fourteen studies (798 fetuses) were included. In cases with isolated cACC, 10.9% (95% CI 4.1-20.6) and 4.3% (95% CI 1.4-8.8) additional anomalies were detected by fetal MRI and postnatally, respectively. Stratifying according to the type of ultrasound assessment, the rate of associated anomalies detected only on fetal MRI was 5.7% (95% CI 0.5-16.0) with dedicated neurosonography and 18.5% (95% CI 7.8-32.4) with a standard axial assessment. In fetuses with isolated pACC, 13.4% (95% CI 4.0-27.0) and 16.2% (95% CI 5.9-30.3) additional anomalies were detected by fetal MRI or postnatally, respectively. Stratifying according to the type of ultrasound assessment, the rate of associated anomalies detected only on fetal MRI was 11.4% (95% CI 2.7-25.0) when dedicated neurosonography was performed. Cortical and posterior fossa anomalies represented the most common anomalies missed at ultrasound with both cACC and pACC. Due to the very small number of included cases, stratification according to early (<24 weeks of gestation) and late (>24 weeks) fetal MRI could not be done for either cACC or pACC.

Conclusions: The rate of associated anomalies detected exclusively at fetal MRI in isolated ACC undergoing neurosonography is lower than previously reported. Cortical and posterior fossa anomalies are among the most common anomalies detected exclusively at MRI, thus confirming the crucial role of fetal MRI in determining the prognosis of these fetuses. However, some anomalies still go undetected prenatally and this should be stressed during parental counseling.
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http://dx.doi.org/10.1111/aogs.13958DOI Listing
January 2021

Comparison of the therapeutic effect of amniotic fluid stem cells and their exosomes on monoiodoacetate-induced animal model of osteoarthritis.

Biofactors 2020 Jan 18;46(1):106-117. Epub 2019 Oct 18.

Department of Surgical, Medical, Dental and Morphological Sciences with interest in Transplant, Oncology and Regenerative Medicine, University of Modena and Reggio Emilia, Modena, Italy.

The cartilage tissue engineering associated with stem cell-related therapies is becoming very interesting since adult articular cartilage has limited intrinsic capacity for regeneration upon injury. Amniotic fluid stem cells (AFSC) have been shown to produce exosomes with growth factors and immunomodulating molecules that could stop tissue degradation and induce cartilage repair. Based on this state of the art, the main aim of this study was to explore the efficacy of the secreted exosomes, compared to their AFSC source, in MIA-induced animal model of osteoarthritis mimicking a chronic and degenerative process, where inflammation is also involved and lead to irreversible joint damage. Exosomes, obtained by the use of a commercial kit, prior to the injection in animal knee joints, were characterized for the presence of typical markers and HGF, TGFβ, and IDO. Then, analyses were performed by histology, immunohistochemistry, and behavioral scoring up to 3 weeks after the treatment. Exosome-treated defects showed enhanced pain tolerance level and improved histological scores than the AFSC-treated defects. Indeed by 3 weeks, TGFβ-rich exosome samples induced an almost complete restoration of cartilage with good surface regularity and with the characteristic of hyaline cartilage. Moreover, cells positive for resolving macrophage marker were more easily detectable into exosome-treated joints. Therefore, a modulating role for exosomes on macrophage polarization is conceivable, as demonstrated also by experiments performed on THP1 macrophages. In conclusion, this study demonstrates for the first time the efficacy of human AFSC exosomes in counteract cartilage damage, showing a positive correlation with their TGFβ content.
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http://dx.doi.org/10.1002/biof.1576DOI Listing
January 2020

Hormonal contraception in women with endometriosis: a systematic review.

Eur J Contracept Reprod Health Care 2019 Feb 21;24(1):61-70. Epub 2019 Jan 21.

a Department of Medical and Surgical Sciences for Mothers, Children and Adults , University of Modena and Reggio Emilia, Azienda Ospedaliero Universitaria Policlinico , Modena , Italy.

Objective: A systematic review was carried out of studies of women with endometriosis, to examine the evidence for efficacy of the use of hormonal contraception to improve disease-related pain and decrease postoperative risk of disease recurrence.

Methods: A search of the Medline/PubMed and Embase databases was performed to identify all published English language studies on hormonal contraceptive therapies (combined hormonal contraceptives [CHCs], combined oral contraceptives [COCs], progestin-only pills [POPs] and progestin-only contraceptives [POCs]) in women with a validated endometriosis diagnosis, in comparison with placebo, comparator therapies or other hormonal therapies. Main outcome measures were endometriosis-related pain (dysmenorrhoea, pelvic pain and dyspareunia), quality of life (QoL) and postoperative rate of disease recurrence during treatment.

Results: CHC and POC treatments were associated with clinically significant reductions in dysmenorrhoea, often accompanied by reductions in non-cyclical pelvic pain and dyspareunia and an improvement in QoL. Only two COC preparations (ethinylestradiol [EE]/norethisterone acetate [NETA] and a flexible EE/drospirenone regimen) demonstrated significantly increased efficacy compared with placebo. Only three studies found that the postoperative use of COCs (EE/NETA, EE/desogestrel and EE/gestodene) reduced the risk of disease recurrence. There was no evidence that POCs reduced the risk of disease recurrence.

Conclusions: CHCs and POCs are effective for the relief of endometriosis-related dysmenorrhoea, pelvic pain and dyspareunia, and improve QoL. Some COCs decreased the risk of disease recurrence after conservative surgery, but POCs did not. There is insufficient evidence, however, to reach definitive conclusions about the overall superiority of any particular hormonal contraceptive.
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http://dx.doi.org/10.1080/13625187.2018.1550576DOI Listing
February 2019

The Jellyfish Sign: A New Sonographic Cervical Marker to Predict Maternal Morbidity in Abnormally Invasive Placenta Previa.

Ultraschall Med 2019 Feb 21;40(1):40-46. Epub 2017 Nov 21.

Obstetrics and Gynaecology Unit, Department of Medical and Surgical Sciences for Mother, Child and Adult, University of Modena and Reggio Emilia, Modena, Italy.

Purpose:  To investigate the value of a new cervical sonographic sign, called the jellyfish sign (JS), for predicting the risk of maternal morbidity in cases of abnormally invasive placenta (AIP) previa totalis.

Materials And Methods:  Retrospective evaluation of transvaginal (TV) and transabdominal (TA) scans performed in all singleton pregnancies with placenta previa totalis. JS, i. e. the absence of the normal linear demarcation between the placenta previa and the cervix, was evaluated by TV scans. The presence/severity of AIP and outcomes of maternal morbidity were related to this sign.

Results:  JS was noted in 8/39 (20.5 %) patients. The two analyzed groups, i. e. with and without JS, were similar. The specificity of JS in AIP diagnosis, histological findings of accreta/increta/percreta, need for caesarean hysterectomy or blood loss > 2000 ml ranges between 92 % and 96.2 %, with the PPV and NPV ranging between 71.4 % and 85.7 % and 61.3 % and 80.6 %, respectively. The JS group had a significant increase in blood loss (ml) (p = 0.003), transfusions (%) (p = 0.016), red blood cells (p = 0.002) and plasma (p = 0.002), admission to an postoperative intensive care unit (ICU) (%) (p = 0.002), hospitalization length (p < 0.001) and the need of cesarean hysterectomy (%) (p < 0.001). JS was independently correlated to cesarean hysterectomy (OR 25.6; 95 % CI 2.0:322.3, p = 0.012) and blood loss > 2000 ml (OR 16.6; 95 % CI 1.5:180.1, p = 0.021) also in a logistic regression model.

Conclusion:  JS is useful in predicting the increase in maternal morbidity: massive transfusion, admission to the ICU and cesarean hysterectomy related to intraoperative bleeding in patients with a previa AIP.
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http://dx.doi.org/10.1055/s-0043-119872DOI Listing
February 2019

Pre- and post-natal growth in two sisters with 3-M syndrome.

Eur J Med Genet 2016 Apr 2;59(4):232-6. Epub 2016 Feb 2.

Medical Genetics, Department of Medical and Surgical Sciences, University Hospital of Modena, Italy. Electronic address:

3-M syndrome (OMIM #273750) is a rare autosomal recessive growth disorder characterized by severe pre- and post-natal growth restriction, associated with minor skeletal abnormalities and dysmorphisms. Although the 3-M syndrome is well known as a primordial dwarfism, descriptions of the prenatal growth are missing. We report a family with variable phenotypic features of 3-M syndrome and we describe the prenatal and postnatal growth pattern of two affected sisters with a novel homozygous CUL7 mutation (c.3173-1G>C), showing a pre- and post-natal growth deficiency and a normal cranial circumference.
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http://dx.doi.org/10.1016/j.ejmg.2016.01.009DOI Listing
April 2016

Prenatal diagnosis and follow-up of a case of branchio-oto-renal syndrome displays renal growth impairment after the second trimester.

J Obstet Gynaecol Res 2015 Nov 30;41(11):1831-4. Epub 2015 Jul 30.

Medical Genetics, Department of Medical and Surgical Sciences, University Hospital of Modena, Modena, Italy.

Branchio-oto-renal syndrome combines branchial arch defects, hearing impairment and renal malformations or hypoplasia. Due to the high phenotypic variability, prenatal diagnosis has a limited prognostic value in mutation-positive cases. We report the first branchio-oto-renal syndrome molecular prenatal diagnosis and ultrasonographic follow-up, showing a normal renal growth until the 24th week of pregnancy, a growth deceleration during the third trimester and a renal volume recovery during the first months of life.
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http://dx.doi.org/10.1111/jog.12791DOI Listing
November 2015

Fetal thymus volume estimation by virtual organ computer-aided analysis in normal pregnancies.

J Ultrasound Med 2015 May;34(5):847-52

Prenatal Medicine Unit, Department of Obstetrics and Gynecology, Policlinico Modena, Modena, Italy (C.R., E.B., V.M.); and Department of Obstetrics and Gynecology, Chaim Sheba Medical Center, Tel-Hashomer, Affiliated with the Sackler School of Medicine, Tel-Aviv University, Ramat Gan, Israel (A.W.-B., R.A., L.G.).

Objectives: The thymus has a pyramidal shape, which is best shown in coronal planes. The aim of this study was to evaluate the potential of virtual organ computer-aided analysis to estimate fetal thymus volume in normal pregnancies.

Methods: Three-dimensional volume data sets from the axial upper mediastinal section were acquired from 37 normal pregnancies between 12 and 35 weeks' gestation. Thymus volume was calculated by virtual organ computer-aided analysis by 2 separate examiners. In 12 cases, volumes were also acquired with 4-dimensional sonography and spatiotemporal image correlation software to assess the variability in thymus size between the systolic and diastolic periods of fetal heart motion. Linear regression analysis was used to assess the relationship between the fetal thymus volume and gestational age. Paired Student t tests were used to evaluate both the level of agreement for interobserver and intraobserver variability and the difference between diastolic and systolic thymus volumes.

Results: Identification of the borders of the thymus and calculation of its volume were successful in 28 patients (77.7%). Statistically significant linear growth of the thymus during pregnancy, from 12 to 35 weeks, was found. The growth coefficient for each gestational age was 0.43 (95% confidence interval, 0.355 to 0.504; P < .001). The difference in thymus size between systole and diastole was minor (0.0798 cm(3); 95% confidence interval, -0.044 to 0.203 cm(3)). Interobserver and intraobserver variability was not statistically significant.

Conclusions: Although the thymus has a complex shape, it was possible to determine its borders and to calculate its volume by virtual organ computer-aided analysis in 77.7% of cases. Linear growth during pregnancy was found, and the minor changes during systole and diastole could be explained by condensation of the soft tissue of the thymus secondary to cardiac activity.
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http://dx.doi.org/10.7863/ultra.34.5.847DOI Listing
May 2015

Surface rendering of external genitalia of a fetus at the 32nd week of gestation affected by partial androgen insensitivity syndrome.

Case Rep Obstet Gynecol 2013 19;2013:325714. Epub 2013 Aug 19.

Prenatal Medicine Unit, Policlinico Modena, Via Largo Del Pozzo 71, 41124 Modena, Italy.

Objectives. To demonstrate the feasibility of the prenatal diagnosis of partial androgen insensitivity syndrome by 3D-4D ultrasound. Methods. To report prenatal diagnosis of partial androgen insensitivity syndrome at 32nd week of gestation by 3D-4D ultrasound in a fetus with a 46XY karyotype, testing negative to the mutation analysis of SRY gene and the 5 α -reductase 2 gene (SRD5A2). Results. 3D-4D surface rendering allows the detection of external and internal genital malformations and can address the prenatal diagnosis of PAIS and can exclude associated complications. Conclusions. Prenatal diagnosis of PAIS allows an adequate parental counseling and an early optimal management of the condition, not only for the psychological and social reflections but also for the avoidance of complications and postnatal morbidity due to misdiagnosis or delays in the treatment of the genital ambiguity.
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http://dx.doi.org/10.1155/2013/325714DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3760284PMC
September 2013

Early visualization and measurement of the pericallosal artery: an indirect sign of corpus callosum development.

J Ultrasound Med 2012 Feb;31(2):231-7

Prenatal Medicine Unit, Department of Obstetrics and Gynecology, University of Modena, via del Pozzo 71, 41100 Modena, Italy.

Objectives: The purpose of this study was to evaluate the feasibility of visualization and measurement of the pericallosal artery during early stages of gestation.

Methods: The study group comprised 80 pregnant women between 12 and 21 weeks' gestation who attended our ultrasound unit. Transabdominal or transvaginal sonography was performed to obtain the optimal angle of a midsagittal section. High-definition flow power Doppler imaging was used to visualize the pericallosal artery. In a sagittal plane, the lengths of the pericallosal artery were measured using a straight line to connect the most anterior and posterior points. All patients were reexamined at a later stage of pregnancy to verify the existence of the corpus callosum and pericallosal artery.

Results: Visualization of the pericallosal artery was evident in 71 fetuses, in all of whom the biparietal diameter was greater than 20 mm. We were able to verify normal anatomy and the existence of the pericallosal artery in these fetuses between 30 and 32 weeks' gestation. A positive linear association was found between the length of the pericallosal artery and the gestational age (R(2) = 0.95) and the biparietal diameter at each gestational age (R(2) = 0.99).

Conclusions: Our data show that it is feasible to visualize and measure the pericallosal artery from an early stage of gestation, and this measurement could be an indirect indication of normal corpus callosum development.
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http://dx.doi.org/10.7863/jum.2012.31.2.231DOI Listing
February 2012

Vermian biometric parameters in the normal and abnormal fetal posterior fossa: three-dimensional sonographic study.

J Ultrasound Med 2011 Oct;30(10):1403-10

Prenatal Medicine Unit, Department of Obstetrics and Gynecology, Modena Hospital, Modena and Reggio Emilia University, Largo del Pozzo 71, 41123 Modena, Italy.

Objectives: The purposes of this study were to describe a 3-dimensional sonographic technique for evaluation of the fetal vermis and to compare vermian biometric parameters in fetuses with a normal and an abnormal posterior fossa.

Methods: A prospective study was conducted from 2006 through 2008 on 12 fetuses with an abnormal posterior fossa and 73 healthy control fetuses from 18 to 35 weeks' gestation. Three-dimensional scans of the fetal head were performed in the axial plane, using static volume contrast imaging in the C-plane. The vermian perimeter, cross-sectional area, and superoinferior diameter were measured and compared between abnormal and normal fetuses using the Wilcoxon nonparametric test. Linear regression analysis was used to describe trends of the vermis during gestation. The z scores for perimeter, cross-sectional area, and superoinferior diameter measurements in the abnormal posterior fossa group in each 2-week interval were calculated.

Results: Twelve fetuses with an abnormal posterior fossa were recruited: 3 with a Blake pouch cyst, 1 vermian cyst, 1 enlarged cisterna magna, 2 Dandy-Walker malformation, 4 partial vermian agenesis, and 1 hemicerebellar hypoplasia. The vermian cross-sectional area was reduced significantly in the fetuses with an abnormal posterior fossa compared with the control fetuses starting at 18 to 19 weeks' gestation (P = .01); the mean vermian superoinferior diameter was lower only from 22 to 23 weeks (P = .01); and the mean vermian perimeter was decreased from 28-29 weeks' gestation (P = .03). Linear regression analysis of the parameters showed that fetuses with an abnormal posterior fossa had a statistically significantly lower growth rate than control fetuses during gestation (P < .001).

Conclusions: Measurements of the cross-sectional area were more useful than those of the perimeter and superoinferior diameter in distinguishing between fetuses with a normal and an abnormal posterior fossa during the early stages of gestation.
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http://dx.doi.org/10.7863/jum.2011.30.10.1403DOI Listing
October 2011

Second trimester amniocentesis is not a risk factor for very low birth weight and extremely low birth weight.

ISRN Obstet Gynecol 2011 3;2011:313206. Epub 2011 Aug 3.

Prenatal Medicine Unit, Department of Obstetrics and Gynecology, University of Modena and Reggio Emilia, 41121 Modena, Italy.

Objectives. To assess the risk of very low birth weight (VLBW) and extremely low birth weight (ELBW) attributable to second trimester amniocentesis. Methods. Records of 4,877 consecutive amniocentesis, performed between 1997 and 2003, were analyzed. Only VLBW and ELBW in the study population (exposed) and in the control group (unexposed) were evaluated. Comparisons were made between the amniocentesis group versus nonexposed. Odds ratios (OR) and 95% confidence intervals (95% CI) were calculated for VLBW and ELBW classes. Results. In the study population, the VLBW were 35 (0.71%) and the ELBW were 20 (0.41%). In the control group, the VLBW were 220 (0.67%) and the ELBW were 112 (0.34%). The Odds ratios of the VLBW between the study and the control group did not show any statistical significant risk (OR = 1.07, 95% CI = 0.72-1.54). Also in ELBW odds ratios between study and control group were not statistically significant (OR = 1.20, 95% CI = 0.7-1.95). Conclusions. No effect of the second trimester amniocentesis was noted on VLBW and ELBW.
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http://dx.doi.org/10.5402/2011/313206DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3151515PMC
November 2011

Preterm delivery and exposure to active and passive smoking during pregnancy: a case-control study from Italy.

Paediatr Perinat Epidemiol 2007 May;21(3):194-200

Department of Public Health Sciences, University of Modena and Reggio Emilia, Modena, Italy.

The aim of this study was to assess the relationship between preterm/early preterm delivery and active smoking as well as environmental tobacco smoke (ETS) exposure in a sample of pregnant Italian women. A case-control study was conducted in nine cities in Italy between October 1999 and September 2000. Cases of preterm birth were singleton babies born before the 37th gestational week; babies born before the 35th gestational week were considered early preterm births. Controls were babies with gestational ages >or= 37th week. A total of 299 preterm cases (including 105 early preterm) and 855 controls were analysed. A self-administered questionnaire was used to assess active smoking and ETS exposure, as well as potential confounders. Multivariable logistic regression analysis showed a relationship between active smoking during pregnancy and preterm/early preterm delivery [adjusted ORs: 1.53; 95% CI 1.05, 2.21 and 2.00; 95% CI 1.16, 3.45, respectively]. A dose-response relationship was found for the number of cigarettes smoked daily. The adjusted ORs were 1.54 and 1.69 for preterm babies and 1.90 and 2.46 for early preterm babies for 1-10 and >10 cigarettes/day respectively. ETS exposure was associated with early preterm delivery [adjusted OR 1.56; 95% CI 0.99, 2.46] with a dose-response relationship with the number of smokers in the home. Smoking during pregnancy was strongly associated with preterm delivery with a dose-response effect. ETS exposure in non-smoking women was associated only with early preterm delivery.
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http://dx.doi.org/10.1111/j.1365-3016.2007.00815.xDOI Listing
May 2007

Age-specific risk of fetal loss post second trimester amniocentesis: analysis of 5043 cases.

Prenat Diagn 2007 Feb;27(2):180-3

Prenatal Medicine Unit, Department of Obstetrics and Gynecology, Modena and Reggio Emilia University, Italy.

Objectives: To assess the risk of fetal loss attributable to second trimester amniocentesis in singleton pregnancies through a cross-sectional study.

Methods: Records of 5043 consecutive second trimester amniocentesis, performed by a single operator between 1997 and 2003, were analyzed. Fetal loss post amniocentesis was calculated by grouping pregnant women in age classes and assessing observed/expected (O/E) rate.

Results: Total fetal losses were 40 (0.81%): 33 cases (0.67%) occurred before the 24th week, 37 cases (0.76%) before the 28th gestational week, and 3 cases (0.06%) after the 28th week of pregnancy. An age-dependent increase of the rate of fetal loss, not statistically significant (Chi-Square = 0.349, p = 0.505) was observed. The total O/E ratio values did not show any statistically significant risk (O/E ratio = 1.25, CI = 0.86-1.64). The analysis of the single age classes did not detect any statistical significance. The excess fetal loss rate associated with amniocentesis was 0.16%.

Conclusions: No effect of the 2nd trimester amniocentesis was noted on fetal loss.
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http://dx.doi.org/10.1002/pd.1647DOI Listing
February 2007

Corticotropin-releasing hormone, its binding protein and receptors in human cervical tissue at preterm and term labor in comparison to non-pregnant state.

Reprod Biol Endocrinol 2006 May 31;4:29. Epub 2006 May 31.

Dept. of Woman and Child Health, Karolinska Institute, Stockholm, Sweden.

Background: Preterm birth is still the leading cause of neonatal morbidity and mortality. The level of corticotropin-releasing hormone (CRH) is known to be significantly elevated in the maternal plasma at preterm birth. Although, CRH, CRH-binding protein (CRH-BP), CRH-receptor 1 (CRH-R1) and CRH-R2 have been identified both at mRNA and protein level in human placenta, deciduas, fetal membranes, endometrium and myometrium, no corresponding information is yet available on cervix. Thus, the aim of this study was to compare the levels of the mRNA species coding for CRH, CRH-BP, CRH-R1 and CRH-R2 in human cervical tissue and myometrium at preterm and term labor and not in labor as well as in the non-pregnant state, and to localize the corresponding proteins employing immunohistochemical analysis.

Methods: Cervical, isthmic and fundal (from non-pregnant subjects only) biopsies were taken from 67 women. Subjects were divided in 5 groups: preterm labor (14), preterm not in labor (7), term labor (18), term not in labor (21) and non-pregnant (7). Real-time RT-PCR was employed for quantification of mRNA levels and the corresponding proteins were localized by immunohistochemical analysis.

Results: The levels of CRH-BP, CRH-R1 and CRH-R2 mRNA in the pregnant tissues were lower than those in non-pregnant subjects. No significant differences were observed between preterm and term groups. CRH-BP and CRH-R2 mRNA and the corresponding proteins were present at lower levels in the laboring cervix than in the non-laboring cervix, irrespective of gestational age. In most of the samples, with the exception of four myometrial biopsies the level of CRH mRNA was below the limit of detection. All of these proteins could be detected and localized in the cervix and the myometrium by immunohistochemical analysis.

Conclusion: Expression of CRH-BP, CRH-R1 and CRH-R2 in uterine tissues is down-regulated during pregnancy. The most pronounced down-regulation of CRH-BP and CRH-R2 occurred in laboring cervix, irrespective the length of gestation. The detection of substantial expression of the CRH and its receptor proteins, as well as receptor mRNA in the cervix suggests that the cervix may be a target for CRH action. Further studies are required to elucidate the role of CRH in cervical ripening.
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http://dx.doi.org/10.1186/1477-7827-4-29DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1513580PMC
May 2006
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