Mild COVID-19 in an APECED Patient with Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) and High Titer of Type 1 IFN-Abs: A Case Report.

Autoimmune-Poly-Endocrinopathy-Candidiasis-Ectodermal Dystrophy (APECED), caused by mutations in the Autoimmune Regulator (AIRE) gene, is an autosomal recessive multi-organ autoimmunity syndrome usually defined by high serum titers of type I Interferon Autoantibodies (Type 1 IFN-Abs). These antibodies have recently been found in individuals in the general population who develop life-threatening Coronavirus Disease 2019 (COVID-19), but the significance of pre-existing Type 1 IFN-Abs in APECED patients with COVID-19 remains unclear. Previous reports of COVID-19 outcomes in APECED patients have been divergent, and protective roles have been proposed for female sex, age <26 years, and immunomodulatory medications including intravenous immunoglobulin (IVIg). We report the case of a 30-year-old male APECED patient who experienced a Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection with mild symptoms of fatigue and headache without respiratory distress and did not require hospitalization. He received a stress dose of hydrocortisone for adrenal insufficiency and continued on his baseline medications, including subcutaneous administration of Immunoglobulins (SCIgs) for chronic inflammatory demyelinating polyneuropathy (CIDP). Mild COVID-19 in a 30-year-old male patient with APECED and pre-existing Type 1 IFN-Abs was unexpected. Younger age and management of autoimmunity may have played a role.

Echocardiographic features and outcome of restrictive foramen ovale in fetuses with and without cardiac malformations: Literature review.

Foramen ovale is a small communication between the left and the right atrium and its restriction is a rare congenital heart anomaly. There is no consensus on diagnosis and management of fetal restrictive foramen ovale (RFO). In our paper we included 11 studies about fetuses affected by isolated RFO, RFO with D-Transposition of the Great Arteries (dTGA) and RFO with hypoplastic left heart syndrome (HLHS). While fetuses affected from HLHS and dTGA with RFO have a poor prognosis, premature RFO in an otherwise structurally normal heart, if found in later gestation, have an overall good outcome.

Current protocols and clinical efficacy of human fetal liver cell therapy in patients with liver disease: A literature review.

The fetal liver is unique because of the coexistence of cells with endodermal and mesenchymal origins, making it a potential source of hepatic and pancreatic regenerative medicine. The liver appears at about the third week of gestation, growing rapidly from the fifth to the 10th week. We define fetal liver from 10 weeks of gestation, when hematopoietic progenitor cells gradually migrate from the aorta-mesonephros-gonad region to colonize the liver. Indeed, the fetal liver may be the most available source of cell therapy for liver disease. We conducted a review of the literature using Medline and EMBASE (up to May 2021) to identify clinical studies in which patients with liver disease had been given fetal liver cell therapy. This literature review highlighted the heterogeneity of cell isolation and selection protocols, which hinders the ability to pool data and perform a meta-analysis. A limitation of the studies analyzed was the scarcity of reports (n = 8) and the extremely small sample sizes (median sample size of treated patients was two), although there was a fairly long follow-up (median 12 months). The weeks after conception ranged from 16 to 34. There were no randomized controlled trials, and therefore no study was stratified as being of good methodological quality. Cryopreservation may help to circumvent the critical logistic issues that hamper the use of fetal liver cell therapy in clinical practice. To help consolidate the role of the fetal liver in regenerative medicine, good preclinical translational studies are necessary, whereas tracing strategies and biopsy-based endpoints are crucial in the clinic, along with well-designed, large, multicenter, randomized controlled trials using clinically applicable primary outcomes and refined imaging assessment.

Stillbirth and fetal capillary infection by SARS-CoV-2.

We presented the case of stillbirth in a paucisymptomatic mother affected by SARS-CoV-2. At gross examination, the placenta showed a diffuse marble appearance and a focal hemorrhagic area. Multiple areas of hemorrhagic or ischemic necrosis with central and peripheral villous infarctions and thrombosis of several maternal and fetal vessels with luminal fibrin and platelet deposition were observed. All lesions seemed to be synchronous. Virus particles were identified within the cytoplasm of endothelial cells using electron microscopy, whereas SARS-CoV-2 RNA was detected in the placental tissue using real-time reverse transcription-polymerase chain reaction. Here, fetal vascular malperfusion was associated with infection; in fact, electron microscopy images showed that marked SARS-CoV-2 endotheliotropism involved the intravillous fetal capillaries. Furthermore, we confirmed that syncytiotrophoblast is the major target cell type for SARS-CoV-2 infection of the placenta. In conclusion, the possible consequences of the action of the placentotropic SARS-CoV-2 included the occurrence of vertical transmission, as reported in the literature, and/or stillbirth: the latter possibility may be triggered by a hampered maternal and/or fetal perfusion of the placenta. The diffuse thrombosis and subsequent ischemia of fetal capillaries induced by COVID-19 cannot be predicted by standard clinical surveillance.

Fetoscopic laser ablation in twin-to-twin transfusion syndrome: tips for counselling.

Twin-to-twin transfusion syndrome (TTTS) is a serious complication that affects approximately 10-15% of monochorionic twin pregnancies. The most important role for the development of this condition is the presence of an unbalanced flow through the inter-twin vascular anastomoses. Depending on the number, type and direction of the connecting vessels, blood can be transfused disproportionately from one twin (the donor) to the other twin (the recipient). The diagnosis is defined prenatally by ultrasound and involves of two main criteria: the presence of a monochorionic diamniotic (MCDA) pregnancy; and the presence of oligohydramnios in the donor's sac- deep vertical pocket (DVP) 2 cm - and polyhydramnios in the recipient's sac- DVP>8 cm. Once diagnosed, TTTS is usually graded by using the Quintero staging system, that is composed by five stages, from oligohydramnios in the donor and polyhydramnios in the recipient twin to fetal demise in one or both twins. Photocoagulation of the anastomotic vessels, usually followed by equatorial dichorionization, it has currently become the most common fetoscopic operation today and is considered as the gold standard for stage II-IV TTTS. pPROM, chorioamniotic separation and iatrogenic preterm birth are among the most common complications of fetoscopic laser ablation, and the mean gestational age at delivery after laser procedure is about 31 weeks.

Hypoplasia of the Corpus Callosum: A Single Center Experience and a Concise Literature Review.

AimCorpus callosum hypoplasia is described as a fully formed corpus callosum with reduced thickness. Our purpose is to evaluate the current knowledge about this anomaly including it's effect on the neurodevelopmental outcome and to report our single center experience. Methods: PubMed, Medline and reference lists were searched using combinations of these terms: "Hypoplasia of corpus callosum and prenatal diagnosis" and "neurodevelopmental outcome". Results: Eleven studies were included, with a final population of 48 patients (45 cases from literature plus 3 of our own cases). Hypoplasia of the corpus callosum was detected by ultrasound scan alone in 77% of cases: magnetic resonance confirmed the ultrasound suspicion in the remaining 23% of cases. Isolated form was detected in 31% cases. Adverse fetal outcomes occurred in 62% of cases, while 38% of cases were born alive. The neurodevelopmental outcome was found to be normal in 33% of cases. Conclusion: Antenatal detection of corpus callosum hypoplasia remains challenging. Counseling is difficult because neurodevelopmental outcomes are variable.

Pregnant women's knowledge and behaviour to prevent cytomegalovirus infection: an observational study.

OBJECTIVES: Congenital cytomegalovirus (cCMV) infection can negatively affect pregnancy outcomes, but may be prevented by simple precautions. Literature suggests that gynaecologists do not always adequately inform about preventive behaviour and most pregnant women have a low-level knowledge regarding cCMV infection. The aim of this study is to evaluate knowledge and risk behaviours related to cCMV infection in an unselected group of pregnant women. METHODS: An institutional based cross-sectional study was conducted in three Maternal and Fetal Divisions in Rome between November and February 2019 on 296 pregnant women, their knowledge on cCMV was measured using six cytomegalovirus (CMV) related questions. RESULTS: Out of the 296 respondents, 59.1% had heard, read or seen information about cCMV infection. Regarding the way of transmission, 96/296 (32.4%) correctly recognize children as a potential source of the infection but only 25/296 (8.44%) knew all prevention practices, 28/296 (9.5%) of women reported that they have never performed cCMV test during pregnancy. CONCLUSIONS: The results of this survey show that knowledge on cCMV infection among pregnant women is poor. This highlights the need to improve counselling on all preventive practices for cCMV infection during perinatal care consultation.

Obstetrical and perinatal outcomes in fetuses with early versus late sonographic diagnosis of short femur length: A single-center, prospective, cohort study.

OBJECTIVES: The aim of this study was to evaluate obstetrical and perinatal outcomes in fetuses with short femur length diagnosed before or after 24 weeks of gestation. STUDY DESIGN: This was a prospective cohort study on singleton pregnancies with a diagnosis of fetal femur < 5 centile. Included patients were divided into two groups: patients with a first diagnosis of femur length < 5th percentile at 14-24 weeks (group A) and those with the first diagnosis made at > 24 weeks (group B). RESULTS: 147 patients were included for the analysis. Group A and group B included 66 (44.9%) and 81 (55.1%) cases. Abnormal fetal karyotype and skeletal dysplasia rates were significantly higher (27.3% vs 3.7%,P < 0.001 and 19.7% vs 3.7%, P = 0.002) in group A. Women in group B had a higher incidence of small for gestational age and intrauterine growth restriction (7.6% vs 24.7%, P = 0.007 and 19.7% vs 44.4%, P = 0.002). There was a significant higher incidence of live births in group B (34.9% vs 97.5%, P < 0.001), while the rate of termination of pregnancy was increased in group A (56.1% vs 1.2%, P < 0.001). No significant difference was found in perinatal outcomes of live births, when comparing group A and B. CONCLUSIONS: The incidence of abnormal karyotype and skeletal dysplasia is higher when short femur length diagnosed earlier in gestation, while the incidence of small for gestational age, intrauterine growth restriction and the rate of live births are significantly increased when short femur length is diagnosed later during pregnancy.

An observational study to assess Italian obstetrics providers' knowledge about preventive practices and diagnosis of congenital cytomegalovirus.

OBJECTIVES: Congenital cytomegalovirus (cCMV) infection can be easily prevented by hygienic measures. Up to date the majority of the studies in literature highlighted a reduction in cCMV antenatal counseling and its prevention. Our purpose was to evaluate obstetrics providers' knowledge about cCMV infection, management and the behavioral practices to avoid it. METHODS: This is a cross-sectional survey carried out in Umberto I Hospital, "Sapienza" University of Rome between November 2019 and January 2020. We recruited 148 specialists and residents in Obstetrics and Gynecology through online anonymous multiple-choice 13-questions, 10 min-survey comparing responses between the two groups. RESULTS: A total of 94.6% of all participants said they always prescribe cytomegalovirus (CMV) serum screening: 73.6% of them regularly counsel about preventive practices, with specialists recording higher percentages (85.4 vs. 65.1%, p<0.005). We identified a good knowledge about the diagnostic pathway, but only 58.1% of our population knows the correct time of late amniocentesis. 12.2% of providers do not consider magnetic resonance (MRI) as a complementary exam. CONCLUSIONS: Prevention of maternal seroconversion is crucial: even if our data show an acceptable knowledge about antenatal counseling, we encourage clinicians to firmly inform and educate women about behavioral measures.

Congenital jugular vein phlebectasia or aneurysma: A rare entity in prenatal diagnosis.

Vascular malformations arising from the wall of the external jugular vein are rare and appeared most commonly in pediatric population. Here, we present a case of vascular malformation in the left external jugular vein diagnosed in a fetus during third trimester ultrasound. This is the first described case in prenatal diagnosis.

Functions and the Emerging Role of the Foetal Liver into Regenerative Medicine.

During foetal life, the liver plays the important roles of connection and transient hematopoietic function. Foetal liver cells develop in an environment called a hematopoietic stem cell niche composed of several cell types, where stem cells can proliferate and give rise to mature blood cells. Embryologically, at about the third week of gestation, the liver appears, and it grows rapidly from the fifth to 10th week under WNT/ß-Catenin signaling pathway stimulation, which induces hepatic progenitor cells proliferation and differentiation into hepatocytes. Development of new strategies and identification of new cell sources should represent the main aim in liver regenerative medicine and cell therapy. Cells isolated from organs with endodermal origin, like the liver, bile ducts, and pancreas, could be preferable cell sources. Furthermore, stem cells isolated from these organs could be more susceptible to differentiate into mature liver cells after transplantation with respect to stem cells isolated from organs or tissues with a different embryological origin. The foetal liver possesses unique features given the co-existence of cells having endodermal and mesenchymal origin, and it could be highly available source candidate for regenerative medicine in both the liver and pancreas. Taking into account these advantages, the foetal liver can be the highest potential and available cell source for cell therapy regarding liver diseases and diabetes.

Update in non-invasive prenatal testing.

Non-invasive prenatal testing (NIPT) has revolutionized the approach to prenatal diagnosis and, to date, it is the most superior screening method for the common autosomal aneuploidies, mostly trisomy 21. This screening is having a significant population-wide impact on the uptake of conventional screening and diagnostic testing. In recent years, emerging genomic technologies, largely based around next generation sequencing, have expanded the analyses to the sub-chromosomal aneuploidies. However, further clinical validation studies are needed to better characterize this technology. These tests bring advantage through providing a higher diagnostic yield, without risks of miscarriage than previously available diagnostic test, but also raise the question of harms related to an increase in uncertain and unknown results. In view of the revolution brought about by the NIPT, numerous scientific societies have published recommendations regarding the appropriate application of cell-free DNA screening in pregnancy. In this review, we discuss the progress that has been made to date in NIPT.