Genome sequence analysis of Malayan pangolin (Manis javanica) forensic samples reveals the presence of Paraburkholderia fungorum sequences.

Background: The Malayan pangolin (Manis javanica) is a placental mammal and is listed as Critically Endangered on the IUCN Red List of Threatened Species. Most previous attempts to breed pangolins in captivity have met with little success because of dietary issues, infections, and other complications, although a previous study reported breeding pangolins in captivity to the third generation. In our previous pangolin genome sequencing data analysis, we obtained a considerable amount of bacterial DNA from a pregnant female Malayan pangolin (named "UM3"), which was likely infected by Paraburkholderia fungorum-an agent of biodegradation and bioremediation in agriculture. Methodology: Here, we further confirmed and characterized this bacterial species using PCR, histological staining, whole-genome sequencing, and bioinformatics approaches. PCR assays with in-house designed primer sets and 16S universal primers showed clear positive bands in the cerebrum, cerebellum, lung, and blood of UM3 suggesting that UM3 might have developed septicaemia. Histological staining showed the presence of Gram-negative rod-shaped bacteria in the pangolin brain and lungs, indicating the colonization of the bacteria in these two organs. In addition, PCR screening of UM3's fetal tissues revealed the presence of P. fungorum in the gastrocnemius muscle, but not in other tissues that we examined. We also sequenced and reconstructed the genome of pangolin P. fungorum, which has a genome size of 7.7 Mbps. Conclusion: Our study is the first to present detailed evidence of the presence of P. fungorum in a pangolin and her fetus (although preliminary results were presented in our previous article). Here, we raise the concern that P. fungorum may potentially infect humans, especially YOPI (young, old, pregnant, and immunocompromised) people. Therefore, caution should be exercised when using this bacterial species as biodegradation or bioremediation agents in agriculture.

Results of Routine Antenatal Screening for Cytomegalovirus at a Tertiary Center.

Objective: Cytomegalovirus (CMV) is the most common viral infection. In this study, we discussed the results of pregnant women who underwent antenatal CMV screening in a tertiary center and the value of CMV antenatal screening. Methods: For this retrospective study, the data of pregnant patients with antenatal CMV screening test results between 2019 and 2022 were obtained from hospital records. CMV immunoglobulin M (IgM), CMV IgG, anti-IgG avidity test results, amniocentesis, CMV polymerase chain reaction (PCR), and the outcome of the babies were recorded. Results: A total of 31,912 CMV IgM and 26,969 CMV IgG tests were performed. CMV IgG seropositivity was observed in 78.99% of pregnant women, and 0.09% of the pregnant women were confirmed to have a positive CMV IgM test result. Pregnant women with positive IgM accompanying low avidity were referred to perinatology clinics for detailed ultrasonography and amniocentesis. Only 3 of the 44 pregnant women who underwent amniocentesis were confirmed to have positive CMV PCR testing. Conclusions: CMV screening should be preserved for pregnant women with ultrasonographic findings at high risk of congenital CMV infection.

Mpox (Monkeypox) in Pregnancy: Viral Clade Differences and Their Associations with Varying Obstetrical and Fetal Outcomes.

In African countries where mpox (monkeypox) is endemic, infection is caused by two genetically related clades-Clade I (formerly Congo Basin), and Clade IIa (formerly West Africa), both of which are potentially life-threatening infections. Prior to the 2022-2023 global outbreak, mpox infections among pregnant women caused by Clade I were reported to have a 75% perinatal case fatality rate in the Democratic Republic of Congo, including the only documented case of placental infection and stillbirth from the Congenital Mpox Syndrome, and the Clade IIa mpox infection was associated with stillbirths in Nigeria. The 2022-2023 global mpox outbreak, caused by a genetically distinct strain, Clade IIb, has focused attention on the effects of mpox on pregnant women and fetal outcomes. There have been at least 58 cases of mpox infection occurring in pregnant women during the 2022-2023 outbreak. No confirmed cases of adverse perinatal outcome, including stillbirth, have been reported. The absence of perinatal morbidity and mortality from Clade IIb corresponds to the overall case fatality rate among non-pregnant women of <0.1%, as this clade has been demonstrated to produce a less-severe disease than the mpox Clade I or IIa variants. Thus, there are apparently important differences between mpox clades affecting pregnant women and perinatal outcomes.

Hyperechogenic fetal bowel: Current evidence-based prenatal diagnosis and management.

Echogenic fetal bowel (EB) is a prenatal ultrasound finding (0.2%-1.4% of all pregnancies) defined as bowel of similar or greater echogenicity than surrounding bone. In fact, the ultrasound assessment is strongly subjective with inter-observer variability. The pathophysiology depends on the underlying condition, apparently related with meconium stasis and hypercellularity. It is often an isolated finding, with possible association with other structural anomalies. About the origin, it was observed in fetuses with cystic fibrosis, congenital infections, thalassemia, intraamniotic bleeding, fetal growth restriction. Fetuses with EB are at increased risk of adverse perinatal outcome, such as intrauterine growth restriction, placental dysfunction and perinatal death, highlighting the need for a thorough antenatal management and post-natal follow-up. It seems to be associated with a plenty of conditions, such as a poor fetal outcome, fetal growth restriction and placental dysfunction. Therefore management requires a multidisciplinary approach with different specialties' involvement and the prognosis is influenced by the underlying pathophysiology. In this complex scenario, the present review aims to define the clinical pathway which should be offered to pregnant women in case of finding of fetal EB ultrasound marker, to rule out any suspected pathological cause.

Progressive inflammation reduces high-frequency EEG activity and cortical dendritic arborisation in late gestation fetal sheep.

BACKGROUND: Antenatal infection/inflammation is associated with disturbances in neuronal connectivity, impaired cortical growth and poor neurodevelopmental outcomes. The pathophysiological substrate that underpins these changes is poorly understood. We tested the hypothesis that progressive inflammation in late gestation fetal sheep would alter cortical neuronal microstructure and neural function assessed using electroencephalogram band power analysis. METHODS: Fetal sheep (0.85 of gestation) were surgically instrumented for continuous electroencephalogram (EEG) recording and randomly assigned to repeated saline (control; n = 9) or LPS (0 h = 300 ng, 24 h = 600 ng, 48 h = 1200 ng; n = 8) infusions to induce inflammation. Sheep were euthanised 4 days after the first LPS infusion for assessment of inflammatory gene expression, histopathology and neuronal dendritic morphology in the somatosensory cortex. RESULTS: LPS infusions increased delta power between 8 and 50 h, with reduced beta power from 18 to 96 h (P < 0.05 vs. control). Basal dendritic length, numbers of dendritic terminals, dendritic arborisation and numbers of dendritic spines were reduced in LPS-exposed fetuses (P < 0.05 vs. control) within the somatosensory cortex. Numbers of microglia and interleukin (IL)-1ß immunoreactivity were increased in LPS-exposed fetuses compared with controls (P < 0.05). There were no differences in total numbers of cortical NeuN + neurons or cortical area between the groups. CONCLUSIONS: Exposure to antenatal infection/inflammation was associated with impaired dendritic arborisation, spine number and loss of high-frequency EEG activity, despite normal numbers of neurons, that may contribute to disturbed cortical development and connectivity.

Intrauterine Blood Transfusion for Parvo B19-Induced Fetal Anemia: Neuroimaging Findings and Long-Term Neurological Outcomes.

INTRODUCTION: We aimed to evaluate the neuroimaging findings and long-term neurodevelopmental outcomes of fetuses and children following intrauterine blood transfusion (IUT) for parvo B19 infection-induced anemia compared to those with RBC alloimmunization. METHODS: We conducted a retrospective cohort study including women who underwent an IUT due to fetal anemia between 2006 and 2019 in a tertiary, university-affiliated medical center. The cohort was divided into two groups: a study group - fetuses affected by congenital parvo B19 infection; and a control group - fetuses affected by RBC alloimmunization. Retrospective data such as antenatal sonographic evaluations, fetal brain MRI results, and short-term fetal and neonatal outcomes were collected. All children underwent a neurodevelopmental evaluation after birth using a Vineland questionnaire. Primary outcome was defined as the presence or absence of neurodevelopmental delay. Secondary outcome was defined as the presence of abnormal fetal neuroimaging findings such as cerebellar hypoplasia, polymicrogyria, intracranial hemorrhage, or severe ventriculomegaly. RESULTS: Overall, 71 fetuses requiring at least one IUT were included in the study. Of these, 18 were affected by parvo B19 infection and 53 by RBC alloimmunization with various associated antibodies. Fetuses in the parvo B19 group presented at an earlier gestational age (22.91 ± 3.36 weeks vs. 27.37 ± 4.67 weeks, p = 0.002) and were more affected by hydrops (93.33% vs. 16.98%, p < 0.001). Three fetuses out of the 18 (16.67%) fetuses in the parvo B19 group died in utero following the IUT. Abnormal neuroimaging findings were detected in 4/15 (26.7%) of the parvo B19 survivors versus 2/53 (3.8%) of fetuses affected by RBC alloimmunization (p = 0.005). There was no difference in long-term neurodevelopmental delay rates between the children in the study and control groups, as assessed at the average age of 3.65 and 6.53 years, accordingly. CONCLUSION: Fetal anemia due to parvo B19, treated with IUT, might be associated with increased rates of abnormal neurosonographic findings. The correlation between those findings and long-term adverse neurodevelopmental outcomes requires further investigation.

Expresión de ACE2 en cerebro durante el desarrollo y susceptibilidad de infección cerebral por SARS-COV-2 / ACE2 expression in the brain during development and susceptibility to brain infection by SARS-COV-2

Resumen La pandemia COVID-19 se extendió por todo por a la enorme capacidad del coronavirus SARS-CoV-2 para transmitirse entre humanos. El COVID-19 es una amenaza para la salud pública mundial. La entrada de este virus en las células se ve muy facilitada por la presencia de la enzima convertidora de angiotensina 2 (ACE2) en la membrana celular. Hoy en día no tenemos un conocimiento preciso de cómo se expresa este receptor en el cerebro durante el desarrollo humano y, como consecuencia, no sabemos si las células neurales en desarrollo son susceptibles de ser infectadas a través de la transmisión de madre a feto. Revisamos en este artículo los conocimientos sobre la expresión de ACE2 en el cerebro humano en desarrollo, con especial atención a la etapa fetal. Esta etapa corresponde al periodo de formación de la corteza cerebral. La posibilidad de infección por SARS-CoV-2 durante el periodo fetal puede alterar el desarrollo normal de la corteza cerebral. Así pues, aunque se han publicado pocos casos demostrando la transmisión vertical de la infección por SARS-CoV-2, el gran número de jóvenes infectados puede representar un problema sanitario que necesite seguimiento, por la posibilidad de que se originen alteraciones cognitivas y anomalías en el desarrollo de los circuitos corticales, que pueden representar predisposición a padecer problemas mentales a lo largo de la vida.

Abstract The COVID-19 pandemic spread around the world due to the enormous transmission of the SARS-CoV-2 among humans. COVID-19 represents a threat to global public health. The entry of this virus into cells is greatly facilitated by the presence of angiotensin-converting enzyme 2 (ACE2) in the cell membrane. Today we do not have a precise understanding of how this receptor expresses in the brain during human development and, as a consequence, we do not know whether neural cells in the developing brain are susceptible to infection. We review the knowledge about ACE2 expression in the developing human brain, with special attention to the fetal stage. This stage corresponds to the period of the cerebral cortex formation. Therefore, SARS-CoV-2 infection during the fetal period may alter the normal development of the cerebral cortex. Although few cases have been published demonstrating vertical transmission of SARS-CoV-2 infection, the large number of infected young people may represent a problem which requires health surveillance, due to the possibility of cognitive alterations and abnormalities in the development of cortical circuits that may represent a predisposition to mental problems later in life.

Abnormal fetal heart rate patterns caused by pathophysiologic processes other than fetal acidemia.

Fetal acidemia is a common final pathway to fetal death, and in many cases, to fetal central nervous system injury. However, certain fetal pathophysiological processes are associated with significant category II or category III fetal heart rate changes before the development of or in the absence of fetal acidemia. The most frequent of these processes include fetal infection and/or inflammation, anemia, fetal congenital heart disease, and fetal central nervous system injury. In the presence of significant category II or category III fetal heart rate patterns, clinicians should consider the possibility of the aforementioned fetal processes depending on the clinical circumstances. The common characteristic of these pathophysiological processes is that their associated fetal heart rate patterns are linked to increased adverse neonatal outcomes despite the absence of acidemia at birth. Therefore, in these cases, the fetal heart rate patterns may provide more insight about the fetal condition and pathophysiology than the acid-base status at birth. In addition, as successful timing of intrapartum interventions on the basis of evolution of fetal heart rate patterns aims to prevent fetal acidemia, it may not be logical to continue to use the fetal acid-base status at birth as the gold standard outcome to determine the predictive ability of category II or III fetal heart rate patterns. A more reasonable approach may be to use the umbilical cord blood acid-base status at birth as the gold standard for determining the appropriateness of the timing of our interventions.

[ACE2 expression in the brain during development and susceptibility to brain infection by SARS-CoV-2]. / Expresión de ACE2 en cerebro durante el desarrollo y susceptibilidad de infección cerebral por SARS-CoV-2.

The COVID-19 pandemic spread around the world due to the enormous transmission of the SARSCoV-2 among humans. COVID-19 represents a threat to global public health. The entry of this virus into cells is greatly facilitated by the presence of angiotensin-converting enzyme 2 (ACE2) in the cell membrane. Today we do not have a precise understanding of how this receptor expresses in the brain during human development and, as a consequence, we do not know whether neural cells in the developing brain are susceptible to infection. We review the knowledge about ACE2 expression in the developing human brain, with special attention to the fetal stage. This stage corresponds to the period of the cerebral cortex formation. Therefore, SARS-CoV-2 infection during the fetal period may alter the normal development of the cerebral cortex. Although few cases have been published demonstrating vertical transmission of SARS-CoV-2 infection, the large number of infected young people may represent a problem which requires health surveillance, due to the possibility of cognitive alterations and abnormalities in the development of cortical circuits that may represent a predisposition to mental problems later in life.

La pandemia COVID-19 se extendió por todo por a la enorme capacidad del coronavirus SARS-CoV-2 para transmitirse entre humanos. El COVID-19 es una amenaza para la salud pública mundial. La entrada de este virus en las células se ve muy facilitada por la presencia de la enzima convertidora de angiotensina 2 (ACE2) en la membrana celular. Hoy en día no tenemos un conocimiento preciso de cómo se expresa este receptor en el cerebro durante el desarrollo humano y, como consecuencia, no sabemos si las células neurales en desarrollo son susceptibles de ser infectadas a través de la transmisión de madre a feto. Revisamos en este artículo los conocimientos sobre la expresión de ACE2 en el cerebro humano en desarrollo, con especial atención a la etapa fetal. Esta etapa corresponde al periodo de formación de la corteza cerebral. La posibilidad de infección por SARS-CoV-2 durante el periodo fetal puede alterar el desarrollo normal de la corteza cerebral. Así pues, aunque se han publicado pocos casos demostrando la transmisión vertical de la infección por SARS-CoV-2, el gran número de jóvenes infectados puede representar un problema sanitario que necesite seguimiento, por la posibilidad de que se originen alteraciones cognitivas y anomalías en el desarrollo de los circuitos corticales, que pueden representar predisposición a padecer problemas mentales a lo largo de la vida.

Edwardsiella tarda is an Important Causative Agent of Maternal-Fetal Infections in Pregnant Women: a Case Report and Japanese Literature Review.

We present a case study of a 6-day-old male infant who was referred to our hospital for fever, jaundice, and poor suckling, and was diagnosed with meningitis due to Edwardsiella tarda. We were able to detect E. tarda DNA after performing broad-range polymerase chain reaction targeting the bacterial 16S rRNA gene followed by a Basic Local Alignment Search Tool analysis of the DNA extracted from the cerebrospinal fluid. Furthermore, Japanese literature review showed that E. tarda caused perinatal invasive infections in mothers and infants and that the risk of fetal meningitis might be related to the food preference of Japanese people for raw fish. It is crucial to disseminate the information that pregnant women should refrain from eating high-risk raw fish, including freshwater fish.

Intrauterine transfusion in 103 fetuses with severe anemia caused by parvovirus infection. A multicenter retrospective study.

PURPOSE: Evaluating procedure-related complications and perinatal outcomes after intrauterine transfusion (IUT) before or after 20+0 weeks of gestation in fetuses with severe anemia due to intrauterine human parvovirus B19 infection. METHODS: A retrospective study investigating fetuses requiring IUT for fetal Parvo B19 infection in two tertiary referral centers between December 2002 and December 2021. Procedure-related complications, intrauterine fetal death (IUFD), and perinatal outcome were correlated to gestational age (GA) at first IUT, the presence of hydrops and fetal blood sampling results. RESULTS: A total of 186 IUTs were performed in 103 fetuses. The median GA at first IUT was 19+3 (13+0-31+4) weeks of gestation. IUFD occurred in 16/103 fetuses (15.5%). Overall survival was 84.5% (87/103). Hydrops (p = 0.001), lower mean hemoglobin at first IUT (p = 0.001) and low platelets (p = 0.002) were strongly associated with IUFD. There was no difference observed in fetuses transfused before or after 20+0 weeks of gestation. CONCLUSION: IUT is a successful treatment option in fetuses affected by severe anemia due to parvovirus B19 infection in specialized centers. In experienced hands, IUT before 20 weeks is not related to worse perinatal outcome.

Comparative Genomics of Listeria monocytogenes Isolates from Ruminant Listeriosis Cases in the Midwest United States.

Ruminants are a well-known reservoir for Listeria monocytogenes. In addition to asymptomatic carriage of the pathogen, ruminants can also acquire listeriosis and develop clinical manifestations in the form of neurologic or fetal infections, similar to those occurring in humans. Genomic characterization of ruminant listeriosis cases in Europe have identified lineage 1 and 2 strains associated with infection, as well as clonal complexes (CCs) that are commonly isolated from human cases of listeriosis; however, there is little information on the diversity of L. monocytogenes from ruminant listeriosis in the United States. In this study, we characterized and compared 73 L. monocytogenes isolates from ruminant listeriosis cases from the Midwest and the Upper Great Plains collected from 2015 to 2020. Using whole-genome sequence data, we classified the isolates and identified key virulence factors, stress-associated genes, and mobile genetic elements within our data set. Our isolates belonged to three different lineages: 31% to lineage 1, 53% to lineage 2, and 15% to lineage 3. Lineage 1 and 3 isolates were associated with neurologic infections, while lineage 2 showed a greater frequency of fetal infections. Additionally, the presence of mobile elements, virulence-associated genes, and stress and antimicrobial resistance genes was evaluated. These genetic elements are responsible for most of the subgroup-specific features and may play a key role in the spread of hypervirulent clones, including the spread of hypervirulent CC1 clone commonly associated with disease in humans, and may explain the increased frequency of certain clones in the area. IMPORTANCE Listeria monocytogenes affects humans and animals, causing encephalitis, septicemia, and abortions, among other clinical outcomes. Ruminants such as cattle, goats, and sheep are the main carriers contributing to the maintenance and dispersal of this pathogen in the farm environment. Contamination of food products from farms is of concern not only because many L. monocytogenes genotypes found there are associated with human listeriosis but also as a cause of significant economic losses when livestock and food products are affected. Ruminant listeriosis has been characterized extensively in Europe; however, there is limited information about the genetic diversity of these cases in the United States. Identification of subgroups with a greater ability to spread may facilitate surveillance and management of listeriosis and contribute to a better understanding of the genome diversity of this pathogen, providing insights into the molecular epidemiology of ruminant listeriosis in the region.

Detection of bovine gammaherpesvirus 6 in tissues of aborted fetuses from dairy cows concomitantly infected by Histophilus somni.

Bovine gammaherpesvirus 6 (BoGHV6), formerly known as bovine lymphotropic virus, is a member of the Macavirus genus, subfamily Gammaherpesvirinae, family Herpesviridae, that was initially associated with proliferative diseases in cattle. While the Macavirus genus contains agents, including alcelaphine gammaherpesvirus 1 (AlGHV1), ovine gammaherpesvirus 2 (OvGHV2), and caprine gammaherpesvirus-2 (CpGHV2), known to cause malignant catarrhal fever (MCF), and are collectively referred to as MCF virus (MCFV) group of organisms, diseases and/or clinical syndromes have not been associated with BoGHV6 and porcine lymphotropic herpesvirus (PLHV). This report investigated the occurrence of BoGHV6 in tissues of aborted dairy fetuses known to be infected by Histophilus somni to identify possible disease patterns associated with infection by this Macavirus. A nested-PCR (nPCR) assay was used to amplify the BoGHV6 polymerase gene from multiple tissues of 13 fetuses and the cow of one of these which were derived from seven dairy herds located in three geographical regions of Brazil. Direct sequencing confirmed the results of the nPCR assays. Additionally, all fetal tissues were previously investigated for the presence of H. somni, Listeria monocytogenes, Neospora caninum, Brucella abortus, Leptospira spp., bovine alphaherpesvirus 1, and bovine viral diarrhea virus (BVDV) by PCR and/or RT-PCR assays. The nPCR assay amplified BoGHV6 DNA from fetuses of most dairy herds (85.7%; 6/7) investigated, resulting in the amplification of BoGHV6 from 76.9% (10/13) of all fetuses evaluated from two geographical and important cattle-producing regions of Brazil. Furthermore, only BoGHV6 was identified in the spleen (n = 3), myocardium, and kidney (n = 2) of five fetuses, and BoGHV6 was the only agent associated with myocarditis in one of these. Nevertheless, dual, triple, and quadruple infections (including BVDV, B. abortus, and N. caninum) were identified in fetuses that were concomitantly infected by H. somni. Phylogenetic analysis revealed that the strain herein identified has 100% nucleotide (nt) sequence identity with wild type strains of BoGHV6 circulating in ruminants from Brazil and 99.8% nt identity with the reference strain of BoGHV6 but was 72.2-73.3% and 67.4-68.2% different from members of the MCFV group and PLHV, respectively. These results demonstrated that 76.9% of the fetuses evaluated were infected by BoGHV6, most likely via vertical infection resulting in transplacental transmission. Considering that most fetuses were concomitantly infected by BoGHV6 and H. somni the real impact of this viral infection cannot be efficiently determined. However, since BoGHV6 was the only pathogen identified in the myocardium of one fetus with myocarditis by histopathology, the possible participation of this Macavirus in the etiopathogenesis of the myocardial disease observed in this fetus cannot be ignored or discarded. However, the mere amplification of BoGHV6 DNA from the myocardium is not enough to establish a definite association between cause and effect, since in situ evaluations and experimental studies would be needed to confirm this agent in the etiopathogenesis of fetal diseases and/or abortions in cattle. Consequently, additional studies are needed to determine the exact role, if any, of BoGHV6 in the development of fetal disease, and possibly fetal mortality.

Amniocentesis to diagnose congenital cytomegalovirus infection following maternal primary infection.

BACKGROUND: Congenital cytomegalovirus infection following maternal primary cytomegalovirus infection affects approximately 0.4% of newborns in the United States but may be hard to diagnose prenatally. OBJECTIVE: To evaluate the current sensitivity and specificity of amniocentesis in detecting congenital cytomegalovirus infection. STUDY DESIGN: Secondary analysis of a multicenter randomized placebo-controlled trial designed to evaluate whether cytomegalovirus hyperimmune globulin reduces congenital cytomegalovirus infection in neonates of individuals diagnosed with primary cytomegalovirus infection before 24 weeks of gestation. At randomization, subjects had no clinical evidence of fetal infection. Eligible subjects were randomized to monthly infusions of cytomegalovirus hyperimmune globulin or placebo until delivery. Although not required by the trial protocol, amniocentesis following randomization was permitted. The fetuses and neonates were tested for the presence of cytomegalovirus at delivery. Comparisons were made between those with and without amniocentesis and between those with cytomegalovirus-positive and negative results, using chi-square or Fisher exact test for categorical variables and the Wilcoxon rank sum test or t test for continuous variables. A P value of <.05 was considered significant. RESULTS: From 2012 to 2018, 397 subjects were included, of whom 55 (14%) underwent amniocentesis. Cytomegalovirus results were available for 53 fetuses and neonates. Fourteen amniocenteses were positive (25%). Gestational age at amniocentesis was similar between those with and without cytomegalovirus present, as was the interval between maternal diagnosis and amniocentesis. The prevalence of fetal or neonatal infection was 26% (14/53). The neonates of all 12 subjects with a positive amniocentesis and available results had cytomegalovirus infection confirmed at delivery, as did 2 neonates from the group of 41 subjects with a negative amniocentesis, with a sensitivity of 86% (95% confidence interval, 57-98), specificity of 100% (95% confidence interval, 91-100), positive predictive value of 100% (95% confidence interval, 74-100), and negative predictive value of 95% (95% confidence interval, 83-99). Amniocentesis-positive pregnancies were delivered at an earlier gestational age (37.4 vs 39.6 weeks; P<.001) and had lower birthweights (2583±749 vs 3428±608 g, P=.004) than amniocentesis-negative pregnancies. CONCLUSION: Amniocentesis results are an accurate predictor of congenital cytomegalovirus infection.

Clinical factors associated with cytomegalovirus shedding among seropositive pregnant women.

BACKGROUND: Both neighborhood disadvantage and close contact with children have been associated with seroprevalence of cytomegalovirus in pregnancy. However, it is unknown which individual factors influence whether seropositive women are likely to have ongoing viral shedding. OBJECTIVE: This study aimed to define the frequency of and risk factors for ongoing maternal cytomegalovirus shedding across gestation among seropositive pregnant women. STUDY DESIGN: This was a prospective cohort study of women who were cytomegalovirus seropositive at a single tertiary care hospital between September 1, 2018, and September 1, 2020. The participants were eligible if positive for cytomegalovirus immunoglobulin G during the first trimester of pregnancy. Urine samples were planned to be collected from each trimester. DNA was isolated in urine samples to detect and quantitate cytomegalovirus immediate-early 1 gene. Participants were classified as "ever shedder" if cytomegalovirus was detected in any urine sample and "never shedder" if cytomegalovirus was never detected. Patient demographics and characteristics were compared between groups. Stochastic search variable selection (with a posterior probability of inclusion of >0.5) was used to identify predictors of cytomegalovirus shedding at any time point. Forward selection modeling was used as a sensitivity check for independent risks. RESULTS: A total of 240 participants who were cytomegalovirus immunoglobulin G seropositive were enrolled, with 567 urine samples analyzed across gestation. Fifty-eight participants (24.2%) were "never shedders", and 182 participants (75.8%) were "ever shedders." The characteristics and demographics were similar between cohorts. With stochastic search variable selection, nulliparity was the only variable selected (odds ratio, 1.82; 95% credible interval, 1.00-4.09; Bayes factor, 2.22). Furthermore, nulliparity was selected with standard logistic regression, with an odds ratio and 95% confidence interval of 1.89 (1.00-3.58). Sociodemographic characteristics, such as age, race, education level, occupation, children at home, children in daycare, housing type, insurance type, income, and concurrent infections, were not associated with shedding. The only positive neonatal sample (0.42%) was detected from a participant who had cytomegalovirus detected in all 3 time points. CONCLUSION: Approximately 75% of women who were positive for cytomegalovirus immunoglobulin G shed virus at some point during gestation. Nulliparity was the only variable selected that was associated with shedding.

Occurrence of malformed calves in April-May 2021 indicates an unnoticed 2020 emergence of Schmallenberg virus in Denmark.

During the European emergence of Schmallenberg virus (SBV) in 2011, examination of Culicoides spp. showed that SBV-infected midges were present across Denmark. However, SBV-associated malformations in ruminant species have not been reported in Denmark. In April 2021, seven calves with severe congenital generalized arthrogryposis and reduced body weight originating from a narrow region of the Jutlandic peninsula were submitted for examination. Analysis of fetal brain tissue for SBV viral RNA and pleural effusion for fetal anti-SBV antibodies identified SBV as the cause of the congenital syndrome. Backwards calculation from the calving dates indicated the occurrence of an unnoticed emergence of SBV in Denmark from early August 2020 and during the late summer and autumn. As SBV-associated malformations may lead to severe dystocia requiring fetotomy or caesarean section, veterinarians performing obstetric intervention are first-line personnel in recognition of SBV emergence in domestic ruminants.

Considerations on COVID-19 pregnancy: a cases series during outbreak in Bergamo Province, North Italy.

BACKGROUND: COVID-19 has rapidly spread worldwide, with severe complications affecting particularly elderly and compromised subjects. Less information about COVID-19 in pregnancy has been reported so far in the literature. METHODS: Case series on pregnancies complicated by COVID-19. All cases were diagnosed at Bolognini Hospital, Seriate, Italy. These cases are presented to clarify the features of COVID-19 occurring in pregnancy. RESULTS: Four women had symptoms of COVID-19 during pregnancy or immediately after delivery. All cases were confirmed by oropharyngeal swab. All patients presented with fever and low saturation levels at the diagnosis. One case was transferred after diagnosis to a tertiary referral center and delivered the day after for worsening clinical conditions. In the other three cases, bilateral pneumonia was documented at the admission. Antithrombotic therapy was used in most cases. No cases of the infected neonate was reported. At 2 month follow-up, all patients were alive, three were asymptomatic while one presented neurological complication. One more case was described because suspicious for COVID-19, however, it was not confirmed by oropharyngeal swab. CONCLUSIONS: In pregnant women, the peripheral nervous system could be affected. No case of trans-placental passage was reported. The swab could be helpful in diagnosis. The antithrombotic therapy could play a role in the positive course of COVID-19 also in pregnant women.

COVID-19 and vertical transmission: assessing the expression of ACE2/TMPRSS2 in the human fetus and placenta to assess the risk of SARS-CoV-2 infection.

BACKGROUND: Pregnant women have been identified as a potentially at-risk group concerning COVID-19 infection, but little is known regarding the susceptibility of the fetus to infection. Co-expression of ACE2 and TMPRSS2 has been identified as a prerequisite for infection, and expression across different tissues is known to vary between children and adults. However, the expression of these proteins in the fetus is unknown. METHODS: We performed a retrospective analysis of a single cell data repository. The data were then validated at both gene and protein level by performing RT-qPCR and two-colour immunohistochemistry on a library of second-trimester human fetal tissues. FINDINGS: TMPRSS2 is present at both gene and protein level in the predominantly epithelial fetal tissues analysed. ACE2 is present at significant levels only in the fetal intestine and kidney, and is not expressed in the fetal lung. The placenta also does not co-express the two proteins across the second trimester or at term. INTERPRETATION: This dataset indicates that the lungs are unlikely to be a viable route of SARS-CoV2 fetal infection. The fetal kidney, despite presenting both the proteins required for the infection, is anatomically protected from the exposure to the virus. However, the gastrointestinal tract is likely to be susceptible to infection due to its high co-expression of both proteins, as well as its exposure to potentially infected amniotic fluid. TWEETABLE ABSTRACT: This work provides detailed mechanistic insight into the relative protection & vulnerabilities of the fetus & placenta to SARS-CoV-2 infection by scRNAseq & protein expression analysis for ACE2 & TMPRSS2. The findings help to explain the low rate of vertical transmission.

Effects of intrauterine exposure to hepatitis B virus in foetuses.

Foetal response to hepatitis B viral infection is still unknown. The mechanisms of persistent infection that occurs more often in mother-to-child transmission than adult transmission are also unclear. Various aspects of the environmental factors that accelerate or inhibit infection and the cytokine responses are associated with the persistence of infection. Several studies showed that the cytokine poor immune response in immaturity causes the persistence of the infection. However, some reports suggested that a mature immune response was the cause of this persistent infection. This review comprehensively summarized the reports from in vitro, in vivo as well as clinical reports regarding the responses of the foetuses of hepatitis B infected mothers to the micro-organism. The mechanism of more opportunities to be persistently infected via the mother-to-child transmission route is also summarized and discussed. Since there are limited clinical reports at this time, this review will provide evidence for future studies regarding the intrauterine infection mechanism and foetal response to hepatitis B virus to elucidate the mechanisms responsible for mother-to-child transmission. This understanding may lead to effective interventions to control mother-to-child hepatitis B infection in the future.

Identification and Genetic Characterization of Viral Pathogens in Ruminant Gestation Abnormalities, Israel, 2015-2019.

Infectious agents including viruses are important abortifacients and can cause fetal abnormalities in livestock animals. Here, samples that had been collected in Israel from aborted or malformed ruminant fetuses between 2015 and 2019 were investigated for the presence of the following viruses: the reoviruses bluetongue virus (BTV) and epizootic hemorrhagic disease virus (EHDV), the flaviviruses bovine viral diarrhea virus (BVDV) and border disease virus (BDV), the peribunyaviruses Shuni virus (SHUV) and Akabane virus (AKAV), bovine herpesvirus type 1 (BoHV-1) and bovine ephemeral fever virus (BEFV). Domestic (cattle, sheep, goat) and wild/zoo ruminants were included in the study. The presence of viral nucleic acid or antigen could be confirmed in 21.8 % of abnormal pregnancies (213 out of 976 investigated cases), with peribunyaviruses, reoviruses and pestiviruses being the most prevalent. At least four different BTV serotypes were involved in abnormal courses of pregnancy in Israel. The subtyping of pestiviruses revealed the presence of two BDV and several distinct BVDV type 1 strains. The peribunyaviruses AKAV and SHUV were identified annually throughout the study period, however, variation in the extent of virus circulation could be observed between the years. In 2018, AKAV even represented the most detected pathogen in cases of small domestic ruminant gestation abnormalities. In conclusion, it was shown that various viruses are involved in abnormal courses of pregnancy in ruminants in Israel.