Decreased Fetal Movements: A Sign of Placental SARS-CoV-2 Infection with Perinatal Brain Injury.
Ontology highlight
ABSTRACT:
SUBMITTER: Favre G
PROVIDER: S-EPMC8706116 | biostudies-literature | 2021 Dec
REPOSITORIES: biostudies-literature
Publications
Decreased Fetal Movements: A Sign of Placental SARS-CoV-2 Infection with Perinatal Brain Injury.
Favre Guillaume G Mazzetti Sara S Gengler Carole C Bertelli Claire C Schneider Juliane J Laubscher Bernard B Capoccia Romina R Pakniyat Fatemeh F Ben Jazia Inès I Eggel-Hort Béatrice B de Leval Laurence L Pomar Léo L Greub Gilbert G Baud David D Giannoni Eric E
Viruses 20211215 12
Neonatal COVID-19 is rare and mainly results from postnatal transmission. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), however, can infect the placenta and compromise its function. We present two cases of decreased fetal movements and abnormal fetal heart rhythm 5 days after mild maternal COVID-19, requiring emergency caesarean section at 29 + 3 and 32 + 1 weeks of gestation, and leading to brain injury. Placental examination revealed extensive and multifocal chronic intervillos ...[more]
Similar Datasets
Project description:IntroductionWe demonstrate the nonlinear severity of symptoms of SARS-CoV-2 infection in the mother leading to fetal death after acute placental failure.MethodsCareful clinical evaluation, real-time RT-PCR molecular microbiologic testing, isolation of a viable virus, and autopsy with histologic results were used to investigate the possible vertical transmission of SARS-CoV-2 infection from mother to fetus.ResultsHistologic changes in the placenta correlate with SARS-CoV-2 infection. Total nucleic acid isolated from vaginal swabs, fresh placental tissue, and deparaffinized tissue showed a high viral load of SARS-CoV-2. Complete genome sequencing confirmed the presence of the SARS-CoV-2 Delta variant.DiscussionSeveral methods have been used to confirm SARS-CoV-2-mediated acute placental failure, all of which were conclusive. It should be noted that careful periodic fetal well-being checks are required in women infected with SARS-CoV-2, regardless of the severity of symptoms. Most of the cases described with fetal death occurred in the third trimester.
| S-EPMC10191722 | biostudies-literature
Project description:To date, mother-to-fetus transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), responsible for the coronavirus disease 2019 (COVID-19) pandemic, remains controversial. Although placental COVID-19 infection has been documented in some cases during the second- and third-trimesters, no reports are available for the first trimester of pregnancy, and no SARS-CoV-2 protein has been found in fetal tissues. We studied the placenta and fetal organs from an early pregnancy miscarriage in a COVID-19 maternal infection by immunohistochemical, reverse transcription quantitative real-time polymerase chain reaction, immunofluorescence, and electron microscopy methods. SARS-CoV-2 nucleocapsid protein, viral RNA, and particles consistent with coronavirus were found in the placenta and fetal tissues, accompanied by RNA replication revealed by double-stranded RNA (dsRNA) positive immunostain. Prominent damage of the placenta and fetal organs were associated with a hyperinflammatory process identified by histological examination and immunohistochemistry. The findings provided in this study document that congenital SARS-CoV-2 infection is possible during the first trimester of pregnancy and that fetal organs, such as lung and kidney, are targets for coronavirus. The infection and multi-organic fetal inflammation produced by SARS-CoV-2 during early pregnancy should alert clinicians in the assessment and management of pregnant women for possible fetal consequences and adverse perinatal outcomes.
| S-EPMC8250563 | biostudies-literature
Project description:Whether or not SARS-CoV-2 can cross from mother to fetus during a prenatal infection has been controversial; however, recent evidence such as viral RNA detection in umbilical cord blood and amniotic fluid, as well as the discovery of additional entry receptors in fetal tissues suggests a potential for viral transmission to and infection of the fetus. Furthermore, neonates exposed to maternal COVID-19 during later development have displayed neurodevelopmental and motor skill deficiencies, suggesting the potential for consequential neurological infection or inflammation in utero. Thus, we investigated transmission potential of SARS-CoV-2 and the consequences of infection on the developing brain using human ACE2 knock-in mice. In this model, we found that viral transmission to the fetal tissues, including the brain, occurred at later developmental stages, and that infection primarily targeted male fetuses. In the brain, SARS-CoV-2 infection largely occurred within the vasculature, but also within other cells such as neurons, glia, and choroid plexus cells; however, viral replication and increased cell death were not observed in fetal tissues. Interestingly, early gross developmental differences were observed between infected and mock-infected offspring, and high levels of gliosis were seen in the infected brains 7 days post initial infection despite viral clearance at this time point. In the pregnant mice, we also observed more severe COVID-19 infections, with greater weight loss and viral dissemination to the brain, compared to non-pregnant mice. Surprisingly, we did not observe an increase in maternal inflammation or the antiviral IFN response in these infected mice, despite showing clinical signs of disease. Overall, these findings have concerning implications regarding neurodevelopment and pregnancy complications of the mother following prenatal COVID-19 exposure.
| S-EPMC10270733 | biostudies-literature
Project description:The association between maternal COVID-19 infection, placental histomorphology and perinatal outcomes is uncertain. The published studies on how placental structure is affected after SARS-CoV-2 virus in COVID-19-infected pregnant women are lacking. We investigated the effects of maternal SARS-CoV-2 infection on placental histomorphology and pregnancy outcomes. A retrospective cohort study on 47 pregnant women with confirmed SARS-CoV-2 infection, matched with non-infected controls, was conducted. Relevant clinicopathological data and primary birth outcomes were recorded. Histomorphology and SARS-CoV-2 immunohistochemistry analyses of placental tissues were performed. Only 1 of 47 cases showed SARS-CoV-2 immunoreactivity in the syncytiotrophoblasts. Histologically, decidual vasculopathy (n = 22/47, p = 0.004), maternal vascular thrombosis (n = 9/47, p = 0.015) and chronic histiocytic intervillositis (n = 10/47, p = 0.027) were significantly higher in the COVID-19-infected placentas when compared to the control group. Maternal vascular thrombosis was a significant feature in the active COVID-19 group. A significant lower gestational age (p < 0.001)) at delivery and a higher caesarean section rate (p = 0.007) were observed in the active SARS-CoV-2-infected cases, resulting in a significant lower fetal-placental weight ratio (p = 0.022) and poorer Apgar score (p < 0.001). Notably, active (p = 0.027), symptomatic (p = 0.039), severe-critical (p = 0.002) maternal COVID-19 infection and placental inflammation (p = 0.011) were associated with an increased risk of preterm delivery. Altered placental villous maturation and severe-critical maternal COVID-19 infection were associated with an elevated risk of poor Apgar scores at birth (p = 0.018) and maternal mortality (p = 0.023), respectively.
| S-EPMC9368100 | biostudies-literature
Project description:ImportanceStillbirth is a devastating pregnancy outcome with far-reaching economic and psychosocial consequences, but despite significant investment, a screening tool for identifying those fetuses at risk for stillbirth remains elusive. Maternal reporting of decreased fetal movements (DFM) has been found to be associated with stillbirth and other adverse perinatal outcomes.ObjectiveTo examine pregnancy outcomes of women presenting with DFM in the third trimester at a tertiary Australian center with a clear clinical management algorithm.Design, setting, and participantsThis cohort study used data on all births meeting the inclusion criteria from 2009 through 2019 at Mater Mothers' Hospital in Brisbane, Australia. This is a tertiary center and Australia's largest maternity hospital. All singleton births without a known congenital anomaly after 28 weeks' gestation were included. Among 203 071 potential participants identified from the hospital database, 101 597 individuals met the eligibility criteria. Data analysis was performed from May through September 2020.ExposurePresentation to hospital with DFM after 28 weeks gestation.Main outcomes and measuresThe primary outcome of this study was the incidence of stillbirth. Multivariate analysis was undertaken to determine the association between DFM and stillbirth, obstetric intervention, and other adverse outcomes, including being born small for gestational age (SGA) and a composite adverse perinatal outcome (at least 1 of the following: neonatal intensive care unit admission, severe acidosis [ie, umbilical artery pH <7.0 or base excess -12.0 mmol/L or less], 5-minute Apgar score <4, or stillbirth or neonatal death). The hypothesis being tested was formulated prior to data collection.ResultsAmong 101 597 women with pregnancies that met the inclusion criteria, 8821 (8.7%) presented at least once with DFM and 92 776 women (91.3%) did not present with DFM (ie, the control population). Women presenting with DFM, compared with those presenting without DFM, were younger (mean [SD] age, 30.4 [5.4] years vs 31.5 [5.2] years; P < .001), more likely to be nulliparous (4845 women [54.9%] vs 42 210 women [45.5%]; P < .001) and have a previous stillbirth (189 women [2.1%] vs 1156 women [1.2%]; P < .001), and less likely to have a previous cesarean delivery (1199 women [13.6%] vs 17 444 women [18.8%]; P < .001). During the study period, the stillbirth rate was 2.0 per 1000 births after 28 weeks' gestation. Presenting with DFM was not associated with higher odds of stillbirth (9 women [0.1%] vs 185 women [0.2%]; adjusted odds ratio [aOR], 0.54; 95% CI, 0.23-1.26, P = .16). However, presenting with DFM was associated with higher odds of a fetus being born SGA (aOR, 1.14; 95% CI, 1.03-1.27; P = .01) and the composite adverse perinatal outcome (aOR, 1.14; 95% CI, 1.02-1.27; P = .02). Presenting with DFM was also associated with higher odds of planned early term birth (aOR, 1.26; 95% CI, 1.15-1.38; P < .001), induction of labor (aOR, 1.63; 95% CI, 1.53-1.74; P < .001), and emergency cesarean delivery (aOR, 1.18; 95% CI, 1.09-1.28; P < .001).Conclusions and relevanceThe presence of DFM is a marker associated with increased risk for a fetus. This study's findings of a nonsignificantly lower rate of stillbirth among women with DFM may be reflective of increased community awareness of timely presentation to their obstetric care clinician when concerned about fetal movements and the benefits of tertiary level care guided by a clear clinical management protocol. However, DFM was associated with increased odds of an infant being born SGA, obstetric intervention, early term birth, and a composite of adverse perinatal outcomes.
| S-EPMC8033440 | biostudies-literature
Project description: Not available
| S-EPMC7700914 | biostudies-literature
Project description:Key pointsFetal glucagon concentrations are elevated in the setting of placental insufficiency, hypoxia and elevated stress hormones. Chronically elevated glucagon concentrations in the adult result in profound decreases in amino acid concentrations and lean body mass. Experimental elevation of fetal glucagon concentrations in a late-gestation pregnant sheep results in lower fetal amino acid concentrations, lower protein accretion and lower fetal weight, in addition to decreased placental function. This study demonstrates a negative effect of glucagon on fetal protein accretion and growth, and also provides the first example of a fetal hormone that negatively regulates placental nutrient transport and blood flow.AbstractFetal glucagon concentrations are elevated in the setting of placental insufficiency and fetal stress. Postnatal studies have demonstrated the importance of glucagon in amino acid metabolism, and limited fetal studies have suggested that glucagon inhibits umbilical uptake of certain amino acids. We hypothesized that chronic fetal hyperglucagonaemia would decrease amino acid transfer and increase amino acid oxidation by the fetus. Late gestation singleton fetal sheep received a direct intravenous infusion of glucagon (GCG; 5 or 50 ng/kg/min; n = 7 and 5, respectively) or a vehicle control (n = 10) for 8-10 days. Fetal and maternal nutrient concentrations, uterine and umbilical blood flows, fetal leucine flux, nutrient uptake rates, placental secretion of chorionic somatomammotropin (CSH), and targeted placental gene expression were measured. GCG fetuses had 13% lower fetal weight compared to controls (P = 0.0239) and >28% lower concentrations of 16 out of 21 amino acids (P < 0.02). Additionally, protein synthesis was 49% lower (P = 0.0005), and protein accretion was 92% lower in GCG fetuses (P = 0.0006). Uterine blood flow was 33% lower in ewes with GCG fetuses (P = 0.0154), while umbilical blood flow was similar. Fetal hyperglucagonaemia lowered uterine uptake of 10 amino acids by >48% (P < 0.05) and umbilical uptake of seven amino acids by >29% (P < 0.04). Placental secretion of CSH into maternal circulation was reduced by 80% compared to controls (P = 0.0080). This study demonstrates a negative effect of glucagon on fetal protein accretion and growth. It also demonstrates that glucagon, a hormone of fetal origin, negatively regulates maternal placental nutrient transport function, placental CSH production and uterine blood flow.
| S-EPMC8249343 | biostudies-literature
Project description:BackgroundThe SARS-CoV-2 virus activates maternal and placental immune responses. Such activation in the setting of other infections during pregnancy is known to impact fetal brain development. The effects of maternal immune activation on neurodevelopment are mediated at least in part by fetal brain microglia. However, microglia are inaccessible for direct analysis, and there are no validated non-invasive surrogate models to evaluate in utero microglial priming and function. We have previously demonstrated shared transcriptional programs between microglia and Hofbauer cells (HBCs, or fetal placental macrophages) in mouse models.Methods and resultsWe assessed the impact of maternal SARS-CoV-2 on HBCs isolated from 24 term placentas (N = 10 SARS-CoV-2 positive cases, 14 negative controls). Using single-cell RNA-sequencing, we demonstrated that HBC subpopulations exhibit distinct cellular programs, with specific subpopulations differentially impacted by SARS-CoV-2. Assessment of differentially expressed genes implied impaired phagocytosis, a key function of both HBCs and microglia, in some subclusters. Leveraging previously validated models of microglial synaptic pruning, we showed that HBCs isolated from placentas of SARS-CoV-2 positive pregnancies can be transdifferentiated into microglia-like cells (HBC-iMGs), with impaired synaptic pruning behavior compared to HBC models from negative controls.ConclusionThese findings suggest that HBCs isolated at birth can be used to create personalized cellular models of offspring microglial programming.
| S-EPMC11197235 | biostudies-literature
Project description:Few studies have addressed the impact of maternal mild/asymptomatic SARS-CoV-2 infection on the developing neonatal immune system. In this study, we analyzed umbilical cord blood and placental chorionic villi from newborns of unvaccinated mothers with mild/asymptomatic SARSCoV-2 infection during pregnancy using flow cytometry, single-cell transcriptomics, and functional assays. Despite the lack of vertical transmission, levels of inflammatory mediators were altered in cord blood. Maternal infection was also associated with increased memory T, B cells, and non-classical monocytes as well as increased activation. However, ex vivo responses to stimulation were attenuated. Finally, within the placental villi, we report an expansion of fetal Hofbauer cells and infiltrating maternal macrophages and rewiring towards a heightened inflammatory state. In contrast to cord blood monocytes, placental myeloid cells were primed for heightened antiviral responses. Taken together, this study highlights dysregulated fetal immune cell responses in response to mild maternal SARS-CoV-2 infection during pregnancy.
| S-EPMC10197637 | biostudies-literature
Project description:SARS-CoV-2 infection during pregnancy is not usually associated with significant adverse effects. However, in this study, we report a fetal death associated with mild COVID-19 in a 34-week-pregnant woman. The virus was detected in the placenta and in an unprecedented way in several fetal tissues. Placental abnormalities (MRI and anatomopathological study) were consistent with intense vascular malperfusion, probably the cause of fetal death. Lung histopathology also showed signs of inflammation, which could have been a contributory factor. Monitoring inflammatory response and coagulation in high-risk pregnant women with COVID-19 may prevent unfavorable outcomes, as shown in this case.
| S-EPMC8415358 | biostudies-literature