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To study how adenomyosis changes during pregnancy and to possibly correlate these changes to maternal and fetal outcomes.Retrospective exploratory cohort study including 254 women with a pre-conceptional/first-trimester scan to document adenomyosis and known obstetric outcome. If visible, adenomyosis signs were documented in each trimester and postpartum. Mann-Whitney U tests or χA globular uterus was reported in 79% (n = 52) of women with adenomyosis in the first trimester, in 38% (n = 20) and 2% (n = 1) of women in the second and third trimesters, respectively, and postpartum in 77% (n = 34) of women. Asymmetrical thickening (n = 20, 30%) and cysts (n = 15, 23%) were only visible in 1st trimester. Adenomyosis was associated with miscarriage (odds ratio [OR] 5.9, 95% confidence interval [CI] 2.4-14.9, P 0.001) also in normal conception only (OR 5.1, 95% CI 1.8-14.2, P = 0.002) or adjusting for maternal age (adjusted OR 5.9, 95% CI 2.3-15.2, P 0.001). Gestational age at delivery was lower in adenomyosis (P = 0.004); the cesarean section rate was higher than in controls (OR 2.5, 95% CI 1.3-4.8, P = 0.007) also adjusting for age (adjusted OR 2.07, 95% CI 1.06-4.08, P = 0.035).Signs of adenomyosis were visible but progressively disappeared in pregnancy; adenomyosis was associated with an increased risk of early miscarriage. Prospective studies are needed to confirm our results.

To investigate the effect of a quality improvement project with an educational/motivational intervention in northern Italy on the implementation of the trial of labor after cesarean section (CS).A pre-post study design was used. Every birth center (n = 23) of the Emilia-Romagna region was included. Gynecologist opinion leaders were first trained about Italian CS recommendations. Barriers to implementation were discussed and shared. Educational/motivational interventions were implemented. Data of multipara with previous CS, with a single, cephalic pregnancy at term, were collected during two periods, before (2012-2014) and after (2017-2019) the intervention (2015-2016). The primary outcome was the rate of vaginal birth after CS (VBAC) and perinatal outcomes.A total of 20 496 women were included. The VBAC rate increased from 18.1% to 23.1% after intervention (P 0.001). The likelihood of VBAC-adjusted for age 40 years or older, Caucasian, body mass index (BMI, calculated as weight in kilograms divided by the square of height in meters) at least 30, previous vaginal delivery, and labor induction-was increased by the intervention by 42% (odds ratio 1.42, 95% confidence interval 1.31-1.54). Neonatal well-being was improved by intervention; neonates requiring resuscitation decreased from 2.1% to 1.6% (P = 0.001).Educating and motivating gynecologists toward the trial of labor after CS is worth pursuing. Health quality improvement is demonstrated by increased VBAC even improving neonatal well-being.

Facioscapulohumeral muscular dystrophy (FSHD) has been associated with the deletion of an integral number of 3.3 kb units of the polymorphic D4Z4 repeat array at 4q35. The prenatal identification of this defect can be carried out on chorionic villi or amniocytes, whereas preimplantation genetic testing for monogenic disorders (PGT-M) requires molecular markers linked to the D4Z4 allele of reduced size. In this context the reliability of this association is crucial. To test the informativeness of the nearby polymorphic markers we investigated recombination at 4q35 using the polymorphic markers D4S1523, D4S163 and D4S139 positioned at 0.55, 0.5 and 0.21 Mb proximal to the D4Z4 array respectively. We determined the probability of recombination events to occur in the D4Z4-D4S1523 interval considering 86 subjects belonging to 12 FSHD families and found a recombination frequency of 14% between D4Z4 and D4S1523. Our study also revealed the occurrence of de novo variants and germline mosaicism. These findings highlight the recombinogenic nature of the 4q subtelomere and indicate that caution should be taken when interpreting PGT-M results. It is advisable that a woman who underwent a PGT-M cycle undertakes a prenatal DNA analysis to confirm the size of the D4Z4 alleles carried by the fetus.

Preterm birth (PT) is defined as birth before 37 completed weeks of gestation, and it is one of the most frequent pregnancy complications and infections. Understanding susceptibility to infectious disease in preterm infants by identifying alterations in innate immune profile could pave the way to novel clinical intervention. Neonatal immunity is a developing structure that evolves gradually. Monocytes are the key players after birth and may change susceptibility to additional infectious or inflammatory. One of the main functions of monocytes is to activate the inflammasomes, whose levels are high in preterm newborns. Here, by using high-dimensional flow cytometry, gene expression and quantification of plasma cytokine levels in a total of 68 term and preterm newborns, we report that preterm newborns show higher plasmatic concentration of alarmin S100A8, higher proportion of CD56+/−CD16+NK cells, higher proportion of immature monocytes and a lower proportion of classical monocytes and lower inflammasome activation after in vitro monocyte stimulation. Our findings suggest that altered innate immunity and monocyte functional impairment characterize healthy preterm newborns, which display different proportions of innate immune cells and diverse pro-inflammatory plasmatic profile.

Molar degeneration of the trophoblast is a rare, yet possible, complication of pregnancies. Complete hydatidiform mole is the most common histological type among all trophoblastic tumors and it is the result of the fertilization of an empty oocyte from two sperms or by one sperm that then duplicates. Complete mole is characterized by hydropic degeneration of abnormal chorionic villi, diffused trophoblast hyperplasia and the absence of identifiable embryonic or fetal tissue; the hyperplastic trophoblast justifies the common finding of high serum beta HCG levels. Twin molar pregnancy is an uncommon obstetric event, and even less frequent are triplet/quadruplet molar pregnancies. We hereby report a case of a complete hydatidiform mole with two coexistent fetuses in a triplet pregnancy after in vitro fertilization procedure; the pregnancy ended with a therapeutic abortion. During the follow-up, the serum beta human chorionic gonadotropin concentration started to rise, and the diagnosis of post-molar gestational trophoblastic neoplasia was made and consequently methotrexate treatment was started. Due to the rarity of this condition, there are no specific guidelines for the management of multiple pregnancies complicated by complete hydatidiform mole. We therefore performed a review of the literature including all reported cases of triplets/quadruplets pregnancies complicated by complete mole of a fetus focusing on ultrasound diagnosis, treatment and outcomes of this rare and life-threatening condition.

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.

Neuromuscular junctions (NMJs) are specialized synapses, crucial for the communication between spinal motor neurons (MNs) and skeletal muscle. NMJs become vulnerable in degenerative diseases, such as muscle atrophy, where the crosstalk between the different cell populations fails, and the regenerative ability of the entire tissue is hampered. How skeletal muscle sends retrograde signals to MNs through NMJs represents an intriguing field of research, and the role of oxidative stress and its sources remain poorly understood. Recent works demonstrate the myofiber regeneration potential of stem cells, including amniotic fluid stem cells (AFSC), and secreted extracellular vesicles (EVs) as cell-free therapy. To study NMJ perturbations during muscle atrophy, we generated an MN/myotube co-culture system through XonaTM microfluidic devices, and muscle atrophy was induced in vitro by Dexamethasone (Dexa). After atrophy induction, we treated muscle and MN compartments with AFSC-derived EVs (AFSC-EVs) to investigate their regenerative and anti-oxidative potential in counteracting NMJ alterations. We found that the presence of EVs reduced morphological and functional in vitro defects induced by Dexa. Interestingly, oxidative stress, occurring in atrophic myotubes and thus involving neurites as well, was prevented by EV treatment. Here, we provided and validated a fluidically isolated system represented by microfluidic devices for studying human MN and myotube interactions in healthy and Dexa-induced atrophic conditions-allowing the isolation of subcellular compartments for region-specific analyses-and demonstrated the efficacy of AFSC-EVs in counteracting NMJ perturbations. ispartof: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES vol:24 issue:5 ispartof: location:Switzerland status: published

This study aims to develop a multivariable predictive model for the risk of placental vascular complications (PVC), by using biochemical, biophysical, anamnestic and clinical maternal features available at the first trimester. PVC include gestational hypertension, preeclampsia, placenta abruption, intrauterine growth restriction (IUGR), and stillbirth. Prospective study that included all singleton pregnancies attending the first-trimester aneuploidy screening (11 +0-12 +6 weeks) at Obstetrics Unit of the University Hospital of Modena, in Northern Italy, between June 2018 and December 2019. In a total of 503 women included in the analysis, 40 patients were in the PVC group. The final prediction model for PVC included the following independent variables: pre-pregnancy BMI ≥ 30 (OR = 2.65, 95% CI = 1.04; 6.75, p = 0.0415), increasing values of mean arterial pressure (OR = 1.06, 95% CI = 1.02; 1.10, p = 0.0008), PAPP-A 2.40465 U/L (OR = 0.43, 95% CI = 0.19; 0.96, p = 0.0388) and decreasing values of PlGf (MoM) (OR = 0.28, 95% CI = 0.10; 0.79, p = 0.0153). The area under the ROC curve was 79.4% indicating a satisfactory predictive accuracy. The best predictive cut-off for this score was equal to -2.562, which corresponds to a 7.2 % probability of having PVC. By using such a cut-off, the risk of PVC can be predicted in our sample with sensitivity equal to 82,4 % and specificity equal to 69,9 %. This model for early prediction of PVC is a promising tool to early identify women at greater risk for placenta vascular complications.

This is the first national population-based report about prenatal diagnosis for families with a history of facioscapulohumeral muscular dystrophy (FSHD), a complex hereditary disease. The incomplete disease penetrance and the phenotypic heterogeneity observed in carriers of D4Z4 alleles of reduced size, the FSHD molecular hallmark, make the estimate of genetic risk problematic.We considered all requests of preconception counseling and prenatal diagnosis received between January 2008 and December 2020 by the genetic counseling service associated with the Italian National Registry for FSHD (INRF). A multidisciplinary team managed the clinical and molecular data of each family.Between 2008 and 2020, 60 couples required preconception counseling (PC) for FSHD. In 52 couples was observed at least one partner carried a D4Z4 reduced allele (DRA). Out of these 52 couples, 47 had a follow-up visit routine yearly. Out of these 47, 26 (55.3%) couples had children: eight asked for prenatal diagnosis (PND), two had assisted reproduction by heterologous in vitro fertilization (IVF), and 16 did not require further assistance. Regarding PND, 50 prenatal analyses were performed for 36 couples. The test resulted positive in 27 pregnancies, 12 (44.4%) were terminated, and 15 (55.6%) were carried to term.The different choices made by the couples show the importance of an integrated approach to support genetic counseling for FSHD. These results remark the relevance of the clinical and molecular investigation of the extended family, preferably before conception.

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.

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&reg, (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&reg, 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.

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

Background: 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. Case presentation: 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. Discussion: CD133 expression indicated the presence of stem cells in chorioangioma, suggesting their possible role in the development of mesenchymal lesions including chorioangioma.

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.

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 −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 or CPR 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.

Introduction\ud 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.\ud \ud Material and methods\ud 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.\ud \ud Results\ud 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) fetal MRI could not be done for either cACC or pACC.\ud \ud Conclusions\ud 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.

Background&mdash, 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&mdash, 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&mdash, 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&mdash, these findings demonstrated that EV from hAFSC have the ability to recover precursor cell potential and delay local bone loss in steroid-related osteoporosis.

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.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.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.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.

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. 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. 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. 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.ZIEL: Beurteilung eines neuen sonografischen zervikalen Markers, dem sogenannten Jellyfish-Sign (JS), zur Prognose des Risikos der mütterlichen Morbidität bei ungewöhnlich invasiver Plazenta (AIP) previa totalis. Materialien und Methoden: Retrospektive Auswertung der transvaginalen (TV) und transabdominalen (TA) Scans in allen Einlingsschwangerschaften mit placenta previa totalis. JS, also die Abwesenheit der deutlichen Abgrenzung zwischen der Plazenta previa und dem Gebärmutterhals, wurde mittels TV-Scans ausgewertet. Das Vorkommen / die Schwere der AIP und die Häufigkeit der mütterlichen Morbidität standen mit dem JS in Relation. ERGEBNISSE: JS wurde bei 8/39 (20,5 %) der Patienten festgestellt. Die beiden analysierten Gruppen, das heißt mit und ohne JS, waren ähnlich. Die Spezifität von JS zur AIP-Diagnose, bei histologischen Befunden von accreta / increta / percreta, zur Notwendigkeit für Kaiserschnitt oder bei Blutverlust 2000ml lag zwischen 92 % und 96,2 %, mit dem PPV und NPV zwischen 71,4 % und 85,7 % und 61,3 % und 80,6 %. Die JS-Gruppe hatte einen deutlich höheren Blutverlust (ml) (p = 0,003), benötigte mehr Transfusionen (%) (p = 0,016) sowie rote Blutzellen (p = 0,002) und Plasma (p = 0,002), höhere Aufnahmerate in einer postoperativen Intensivstation (ICU) (%) (p = 0,002), Hospitalisierungslänge (p 0,001) und die Notwendigkeit eines Kaiserschnitts (%) (p 0,001). JS korrelierte unabhängig zu Kaiserschnitt- (OR 25,6; 95 % CI 2,0: 322,3, p = 0,012) und Blutverlust 2000 ml (OR 16,6, 95 % CI 1,5: 180,1, p = 0,021), auch in einem logistischen Regressionsmodell. SCHLUSSFOLGERUNG: Das JS ist hilfreich zur Prognose der Zunahme von mütterlicher Morbidität: höhere Transfusionraten, Aufnahme in ein ICU und Kaiserschnitt stehen im Zusammenhang mit intraoperativer Blutungen bei Patienten mit einer Previa AIP.

Alzheimer’s disease (AD) is characterized by abnormal protein aggregation, deposition of extracellular β-amyloid proteins (Aβ), 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 Aβ 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 in vitro model, proposing AFSC-EV as a therapeutic tool to stop the progression of AD.

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.

Objectives: To assess the role of fetal magnetic resonance imaging (MRI) in detecting associated anomalies in fetuses presenting with mild or moderate isolated ventriculomegaly (VM) undergoing multiplanar ultrasound evaluation of the fetal brain. Methods: This was a multicenter, retrospective, cohort study involving 15 referral fetal medicine centers in Italy, the UK and Spain. Inclusion criteria were fetuses affected by isolated mild (ventricular atrial diameter, 10.0–11.9 mm) or moderate (ventricular atrial diameter, 12.0–14.9 mm) VM on ultrasound, defined as VM with normal karyotype and no other additional central nervous system (CNS) or extra-CNS anomalies on ultrasound, undergoing detailed assessment of the fetal brain using a multiplanar approach as suggested by the International Society of Ultrasound in Obstetrics and Gynecology guidelines for the fetal neurosonogram, followed by fetal MRI. The primary outcome of the study was to report the incidence of additional CNS anomalies detected exclusively on prenatal MRI and missed on ultrasound, while the secondary aim was to estimate the incidence of additional anomalies detected exclusively after birth and missed on prenatal imaging (ultrasound and MRI). Subgroup analysis according to gestational age at MRI (< 24 vs ≥ 24 weeks), laterality of VM (unilateral vs bilateral) and severity of dilatation (mild vs moderate VM) were also performed. Results: Five hundred and fifty-six fetuses with a prenatal diagnosis of isolated mild or moderate VM on ultrasound were included in the analysis. Additional structural anomalies were detected on prenatal MRI and missed on ultrasound in 5.4% (95% CI, 3.8–7.6%) of cases. When considering the type of anomaly, supratentorial intracranial hemorrhage was detected on MRI in 26.7% of fetuses, while polymicrogyria and lissencephaly were detected in 20.0% and 13.3% of cases, respectively. Hypoplasia of the corpus callosum was detected on MRI in 6.7% of cases, while dysgenesis was detected in 3.3%. Fetuses with an associated anomaly detected only on MRI were more likely to have moderate than mild VM (60.0% vs 17.7%; P < 0.001), while there was no significant difference in the proportion of cases with bilateral VM between the two groups (P = 0.2). Logistic regression analysis showed that lower maternal body mass index (adjusted odds ratio (aOR), 0.85 (95% CI, 0.7–0.99); P = 0.030), the presence of moderate VM (aOR, 5.8 (95% CI, 2.6–13.4); P < 0.001) and gestational age at MRI ≥ 24 weeks (aOR, 4.1 (95% CI, 1.1–15.3); P = 0.038) were associated independently with the probability of detecting an associated anomaly on MRI. Associated anomalies were detected exclusively at birth and missed on prenatal imaging in 3.8% of cases. Conclusions: The incidence of an associated fetal anomaly missed on ultrasound and detected only on fetal MRI in fetuses with isolated mild or moderate VM undergoing neurosonography is lower than that reported previously. The large majority of these anomalies are difficult to detect on ultrasound. The findings from this study support the practice of MRI assessment in every fetus with a prenatal diagnosis of VM, although parents can be reassured of the low risk of an associated anomaly when VM is isolated on neurosonography. Copyright © 2020 ISUOG. Published by John Wiley & Sons Ltd.

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.

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.

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.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.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.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.

Aim: To evaluate an innovative sonopelvimetry method for early prediction of obstructed labour. Methods: A prospective study was conducted in two centers.GPS-based sonopelvimetry, laborProTM (Trig Medical Inc., Yoqneam Ilit, Israel) devise, was used prior to labour in nulliparous women at 39 - 42 weeks gestation remote from labor. Maternal pelvic parameters, including inter-iliac transverse diameter, obstetric conjugate and interspinous diameter were evaluated. Fetal parameters included head station, biparietal diameter and occipitofrontal diameter. Data on delivery and outcome were collected from the electronic files. Results: The innovative use of sonopelvimetry was applied to 154 consecutive women, none of the participants complained of discomfort or complications observed. The mean time of examination was 15 + 2 minutes. Mean time of examination to delivery interval was 4.8 days (range 0 - 16 days). Small interspinous diameter and high head station were the best predictors for obstructed labour. Analysis indicated 87% sensitivity and 61% specificity for birth weight fetal head station and ISD combined in predicting obstructed labour with an area under the curve of 0.77. Conclusions: Our results indicate that GPS-based sonopelvimetry combined with fetal estimated weight is a valuable tool in the risk assessment of obstructed labour. Parameters obtained by sonopelvimetry combined with birth weight may be useful.

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.

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. Copyright  2007 John Wiley & Sons, Ltd.

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.

BACKGROUND AND PURPOSE: Normal biometry of the fetal posterior fossa rules out most major anomalies of the cerebellum and vermis. Our aim was to provide new reference data of the fetal vermis in 4 biometric parameters by using 3 imaging modalities, 2D ultrasound, 3D ultrasound, and MR imaging, and to assess the relation among these modalities. MATERIALS AND METHODS: A retrospective study was conducted between June 2011 and June 2013. Three different imaging modalities were used to measure vermis biometry: 2D ultrasound, 3D ultrasound, and MR imaging. The vermian parameters evaluated were the maximum superoinferior diameter, maximum anteroposterior diameter, the perimeter, and the surface area. Statistical analysis was performed to calculate centiles for gestational age and to assess the agreement among the 3 imaging modalities. RESULTS: The number of fetuses in the study group was 193, 172, and 151 for 2D ultrasound, 3D ultrasound, and MR imaging, respectively. The mean and median gestational ages were 29.1 weeks, 29.5 weeks (range, 21–35 weeks); 28.2 weeks, 29.05 weeks (range, 21–35 weeks); and 32.1 weeks, 32.6 weeks (range, 27–35 weeks) for 2D ultrasound, 3D ultrasound, and MR imaging, respectively. In all 3 modalities, the biometric measurements of the vermis have shown a linear growth with gestational age. For all 4 biometric parameters, the lowest results were those measured by MR imaging, while the highest results were measured by 3D ultrasound. The inter- and intraobserver agreement was excellent for all measures and all imaging modalities. Limits of agreement were considered acceptable for clinical purposes for all parameters, with excellent or substantial agreement defined by the intraclass correlation coefficient. CONCLUSIONS: Imaging technique–specific reference data should be used for the assessment of the fetal vermis in pregnancy.

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.

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 5α-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.

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.

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.