Obstetrics and neonatal outcomes of Binder phenotype with antenatal diagnosis: a case report and literature review.

BACKGROUND: Binder phenotype (BP) is a term used to define a form of maxillo-nasal dysplasia defined by the presence of flattened nose, verticalized nasal bones, and retrusion of the maxilla (BP triad). This facial anomaly can be associated with other anomalies in both genetic and acquired conditions as well as in isolation. This systematic review aimed to summarize the antenatal findings, maternal and obstetrics characteristics as well as the obstetrics and neonatal outcomes of all cases of BP diagnosed in utero. METHODS: According to the PRISMA statement, we conducted a systematic review of the literatures to identify all the Binder phenotype cases diagnosed antenatally. We extracted and summarized obstetrics and neonatal characteristics of each study, including our case report. MAIN FINDINGS: We identified a total of 47 cases of BP. The median gestational age at diagnosis was 23 weeks. BP was associated with other skeletal or non-skeletal anomalies in all cases apart from six confirmed to be isolated. Respiratory distress syndrome was observed in 12 neonates and in 18 cases BP was one of the clinical findings of chondrodysplasia punctata X-linked. CONCLUSION: BP is often associated with other fetal defects; however, when isolated, BP seems to have good obstetrics and neonatal outcomes. In fetuses with apparent isolated BP at midtrimester, genetic testing with fluorescence in situ hybridization (FISH) for ARSE deletion can be offered for CDPX1 diagnosis while exome sequencing may be more informative in cases where a syndromic condition is suspected. Lastly, BP per se is associated with a higher risk of respiratory distress syndrome and feeding difficulties.

Placental and umbilical cord anomalies detected by ultrasound as clinical risk factors of adverse perinatal outcome: Case series review of selected conditions. Part 1: Placental abnormalities.

BACKGROUND: The aim of this extended review of multicenter case series is to describe the prenatal ultrasound features and pathogenetic mechanisms underlying placental and umbilical cord anomalies and their relationship with adverse perinatal outcome. From an educational point of view, the case series has been divided in three parts; Part 1 is dedicated to placental abnormalities. METHODS: Multicenter case series of women undergoing routine and extended prenatal ultrasound and perinatal obstetric care. RESULTS: Prenatal ultrasound findings, perinatal care, and pathology documentation in cases of placental pathology are presented. CONCLUSIONS: Our case series review and that of the medical literature confirms the ethiopathogenetic role and involvement of placenta abnormalities in a wide variety of obstetrics diseases that may jeopardize the fetal well-being. Some of these specific pathologies are strongly associated with a high risk of poor perinatal outcome.

Agenesis of the ductus venosus and fetal growth restriction: Is there a relation? A tertiary care center experience and systematic review of the literature.

An update on the antenatal diagnosis of agenesis of ductus venosus (ADV) by differentiating the various possible types of shunts, focusing on the associated fetal anomalies, and predicting neonatal outcomes. This study reviewed the experience of two tertiary referral centers and literature. An unfavorable outcome was detected in preterm fetuses (p = 0.017), fetuses with a genetic anomaly (p = 0.046) or other associated malformations (p < 0.001). 71% of ADVs with other anomalies had an extrahepatic ADV (p = 0.002). 76% of fetuses with Fetal Growth Restriction (FGR) had an extrahepatic ADV (p = 0.025). ADV may negatively influence fetal growth in cases with extrahepatic vein drainage.

3D ultrasound angioscan with MV-Flow™: Enhancing fetal brain low-flow microvascular neuroimaging.

MVFlow™ is a 3D algorithm that enhances the study of the microvasculature, useful in the study of tumoral lesions or in assessing the slow-flow of the placenta vessels and the developing fetal brain. It may improve the study of the corpus callosum in normal fetuses and be applied in the characterization of brain pathologies.

Simulator, machine learning, and artificial intelligence: Time has come to assist prenatal ultrasound diagnosis.

In this Commentary authors investigated and extended the role of simulator in assisting obstetric sonographers in training program. The interconnection of different digitalized technologies such as digital data, artificial neuronal and convolutional networks, machine and deep learning, telemedicine, and output are discussed and contribute to the generation of artificial intelligence.

Clinical Presentations and Diagnostic Imaging of VACTERL Association.

Background: VACTERL association consists of Vertebral, Anorectal, Cardiac, Tracheo-Esophageal, Renal, and Limb defects. The diagnosis depends on the presence of at least three of these structural abnormalities. Methods: The clinical presentation and diagnostic prenatal imaging of VACTERL association are comprehensively reviewed. Results: The most common feature is a vertebral anomaly, found in 60-80% of cases. Tracheo-esophageal fistula is seen in 50-80% of cases and renal malformations in 30% of patients. Limb defects including thumb aplasia/hypoplasia, polydactyly, and radial agenesis/hypoplasia are present in 40-50% of cases. Anorectal defects, like imperforate anus/anal atresia, are challenging to detect prenatally. Conclusion: The diagnosis of VACTERL association mostly relies on imaging techniques such as ultrasound, computed tomography, and magnetic resonance. Differential diagnosis should exclude similar diseases such as CHARGE and Townes-Brocks syndromes and Fanconi anemia. New insights into genetic etiology have led to recommendations of chromosomal breakage investigation for optimal diagnosis and counseling.

Ultrasound and fetal magnetic resonance imaging: Clinical performance in the prenatal diagnosis of orofacial clefts and mandibular abnormalities.

Cleft lip, with or without cleft palate, is the most common congenital craniofacial anomaly and the second most common birth defect worldwide. Micrognathia is a rare facial malformation characterized by small, underdeveloped mandible and frequently associated with retrognathia. Second- and third-trimester prenatal ultrasound is the standard modality for screening and identification of fetal orofacial abnormalities, with a detection rate in the low-risk population ranging from 0% to 73% for all types of cleft. The prenatal ultrasonography detection can also be performed during the first trimester of pregnancy. Given the potential limitations of obstetric ultrasound for examining the fetal face, such as suboptimal fetal position, shadowing from the surrounding bones, reduce amniotic fluid around the face, interposition of fetal limbs, umbilical cord and placenta, and maternal habitus/abdominal scars, the use of adjunct imaging modalities can enhance prenatal diagnosis of craniofacial anomalies in at-risk pregnancies. Fetal magnetic resonance imaging (MRI) is a potentially useful second-line investigation for the prenatal diagnosis of orofacial malformations with a pooled sensitivity of 97%. In this review, we discuss the role of ultrasound and fetal MRI in the prenatal assessment of abnormalities of the upper lip, palate, and mandible.

Basic sonographic examination of the fetal brain at 11-13 weeks' gestation: Rationale for a simple and reliable four-step technique.

The widespread incorporation of first-trimester scanning between 11 and 13 weeks' gestation has shifted from the screening of chromosomal abnormalities, mainly by measuring nuchal translucency thickness and visualization of the nasal bone, to a more detailed study of the fetal anatomy leading to early detection of several structural congenital anomalies. This goal can be improved by the routine and focused sonographic assessment of specific anatomic planes and the identification of distinctive landmarks that can help disclosing a particular, non-evident condition. In this article we present the basis for a basic, early examination of the fetal brain during screening using a four-step technique, which can be readily incorporated during the first-trimester scan. The technique includes the focused visualization of the cranial contour, choroid plexuses of the lateral ventricles and midline, aqueduct of Sylvius, brainstem, fourth ventricle, and the choroid plexus of the fourth ventricle. The rationale for this approach is presented and discussed.

Fetal Hands: A Comprehensive Review of Prenatal Assessment and Diagnosis Over the Past 40 Years.

Fetal skeletal dysplasias involving limbs and hands are rare congenital malformations. Prenatal two-dimensional ultrasound diagnosis of fetal limb defects has a sensitivity of about 30%; however, an increased detection rate may be obtained using three-dimensional (3-D) ultrasound in the rendering mode. 3-D ultrasound may be used as a complementary method providing additional information. Currently, magnetic resonance imaging (MRI), with the emergence of ultrafast imaging techniques and new sequences, allows for better diagnosis of several fetal skeletal dysplasias such as limb reduction defects and neuromuscular disorders. 3-D volumetric images from ultrasound or MRI scan data allow 3-D ultrasound reconstructions of virtual/physical models, and virtual reality can help researchers to improve our understanding of both normal and abnormal fetal limb/hand anatomy. In this article, we review the embryological development of fetal hands and their main anomalies including prenatal diagnostic methods, genetic counseling, the role of orthopedic and plastic surgery reconstruction, and new perspectives in fetal surgery.

Placental and Umbilical Cord Anomalies Diagnosed by Two- and Three-Dimensional Ultrasound.

The aim of this review is to present a wide spectrum of placental and umbilical cord pathologies affecting the pregnancy. Placental and umbilical cord anomalies are highly associated with high-risk pregnancies and may jeopardize fetal well-being in utero as well as causing a predisposition towards poor perinatal outcome with increased fetal and neonatal mortality and morbidity. The permanent, computerized perinatology databases of different international centers have been searched and investigated to fulfil the aim of this manuscript. An extended gallery of prenatal imaging with autopsy correlation in specific cases will help to provide readers with a useful iconographic tool and will assist with the understanding and definition of this critical obstetrical and perinatological issue.

Congenital Syphilis Presenting with Brain Abnormalities at Neuroscan: A Case Report and a Brief Literature Review.

A case of vertical transmission in a 35-year-old pregnant woman, gravida 4, para 2 with an unknown medical history of carrying primary syphilis is described. A routine 3rd trimester scan was performed at 30 + 5 weeks of pregnancy, which revealed fetal growth restriction (FGR) associated with absent fetal movement, a pathologic neuroscan characterized by cortical calcifications and ominous Doppler waveform analysis of the umbilical artery and ductus venosus. Computerized electronic fetal monitoring (EFM) showed a Class III tracing, according to the American College of Obstetricians and Gynecologists (ACOG) guidelines. An emergency C-section was performed and a female newborn weighing 1470 g was delivered. The Apgar scores were 5 and 8 at the first and fifth min, respectively. Besides the prompted obstetrical and neonatal interventions, the neonate died after 7 days. A histologic examination of the placenta revealed a chorioamnionitis at stage 1/2 and grade 2/3. The parenchyma showed diffuse delayed villous maturation, focal infarcts, and intraparenchymal hemorrhages. The decidua presented with chronic deciduitis with plasma cells. The parents declined the autopsy. Congenital syphilis is an emerging worldwide phenomenon and the multidisciplinary management of the mother and the fetus should be mandatory.

Convalescent Plasma for Hospitalized COVID-19 Patients: A Single-Center Experience.

In Winter 2020, Italy, and in particular the Lombardy region, was the first country in the Western hemisphere to be hit by the COVID-19 pandemic. Plasma from individuals recovered from COVID-19 (COVID-19 convalescent plasma, CCP) was the first therapeutic tool adopted to counteract the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). In this retrospective cohort study, we report the experience of the city hospital of Mantua, Lombardy region, on the compassionate use of CCP in patients hospitalized for severe COVID-19. Between April 2020 and April 2021, 405 consecutive COVID-19 patients received 657 CCP units with a median anti-SARS-CoV-2 neutralizing antibody (nAb) titer of 160 (interquartile range (IQR), 80−320). Their median age was 68 years (IQR, 56−78 years), and 62% were males. At enrollment, 55% of patients had an increased body mass index (BMI), and 25.6% had at least three comorbidities. The 28-day crude mortality rate was 12.6% (51/405). Young age (<68 years), mild disease (admission to low-intensity departments) and early treatment (<7 days from symptoms onset) with high nAb titer (≥320) CCP were found as independently associated with a favorable response to CCP treatment. No safety concerns were recorded, with a rate of CCP-related adverse reactions (all of mild intensity) of 1.3%. In our real-life experience, the first in the western world, early administration of high-titer CCP was a safe and effective treatment for hospitalized COVID-19 patients.

Early Prenatal Ultrasound and Molecular Diagnosis of Apert Syndrome: Case Report with Postmortem CT-Scan and Chondral Plate Histology.

Background Apert syndrome is characterized by craniosynostosis, midface hypoplasia and symmetric syndactyly. Case report: A 36-year-old mother, G2P1 underwent an ultrasound scan at 19 week's gestation. There was craniosynostosis, brachi-turricephaly and bilateral hand syndactyly. Genomic DNA from amniocentesis revealed the mutation C758C>Gp. (Pro to Arg substitution) at 252 of the exon 8 of the FGFR2 encoding for Apert syndrome. The pregnancy was terminated. Femoral chondral plate histology showed an increased interstitial matrix between bony trabeculae. Compared with normal, the trabeculae were thinner, more irregular with numerous osteoclasts suggesting abnormal bone remodeling. Hands and feet had an abrupt transition between resting and proliferating cartilage. Conclusion: Apert syndrome has increased intertrabecular matrix, thin trabeculae, increased remodeling, and irregular transition between the maturing and mineralization zones in the femur, and abnormal abrupt transition between the resting and proliferating cartilage in the fingers and toes.

Heterotaxy Syndrome with Increased Nuchal Translucency and Normal Karyotype Associated with Complex Systemic Venous Return. Ultrasound Diagnosis with Autopsy Correlation.

Background: Prenatal ultrasound (US) detection of heterotaxy syndrome can be challenging, especially in identifying cardiovascular and associated anomalies. We present a new case of heterotaxy syndrome with anomalous systemic venous return (ASVR) fully displayed at autopsy. Case report: Left heterotaxy syndrome was diagnosed in a 19 weeks' of gestation fetus with right-sided stomach. The heart showed both ventricles with left morphology, a large ventricular septal defect, persistent left superior vena cava draining into the coronary sinus, ASVR with interrupted inferior vena cava (IVC) and azygous continuation. Autopsy dissection further identified the azygous draining into the left lower pulmonary vein (LLPV). Prenatal a-CGH on villous sampling showed 22q13.1 microduplication inherited from the father, not contributory to the phenotype. Conclusion/discussion: Heterotaxy syndrome requires US accuracy for anomaly identification, as they allow legal termination of pregnancy. Our case is unusual as IVC drained into the azygous vein and then into the LLPV.

Convalescent Plasma for Pregnant Women with COVID-19: A Systematic Literature Review.

The treatment of COVID-19 is particularly critical in pregnant women, considering the potential teratogenic effects of antiviral agents and the immune-depression related with pregnancy. The aim of this review is to systematically examine the current evidence on the clinical use of convalescent plasma during pregnancy. The electronic databases Medline PubMed Advanced Search Builder, Scopus, Web Of Science and Google Scholar were searched (until 1 January 2021). Inclusion criteria were pregnant women with COVID-19 (or SARS-CoV-2 infection), in whom convalescent plasma (or hyperimmune plasma) was used as treatment. We searched clinical trial registries (censored 5 January 2021) for eligible studies under way. After elimination of duplications, the initial search yielded 79 potentially relevant records, of which 67 were subsequently excluded. The 12 remaining records were case reports involving 12 pregnancies. Six of the mothers were reported to be well, two were reported to have preeclampsia, and in one case each the maternal outcome was described as survival, clinical improvement, discharged with oxygen and rehabilitation. With regard to the neonates, two were declared to be well, four had transient morbidity, two were critically ill and one died; normal ongoing pregnancies, but no post-delivery information, were reported for the remaining three cases. Clinical trials under way or planned to investigate the use of convalescent plasma for COVID-19 during pregnancy are lacking. This is the first systematic review of the literature regarding the treatment of COVID-19 in pregnancy. The published literature data seem to indicate that convalescent plasma administered to pregnant women with severe COVID-19 provides benefits for both the mother and the fetus. The quality of the available studies is, however, very limited since they are all case reports and thus suffer from relevant reporting bias.