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BACKGROUND: Functional placental niches are presumed to spatially separate maternal-fetal antigens and restrict the vertical transmission of pathogens. We hypothesized a high-resolution map of placental transcription could provide direct evidence for niche microenvironments with unique functions and transcription profiles. METHODS: We utilized Visium Spatial Transcriptomics paired with H&E staining to generate 17,927 spatial transcriptomes. By integrating these spatial transcriptomes with 273,944 placental single-cell and single-nuclei transcriptomes, we generated an atlas composed of at least 22 subpopulations in the maternal decidua, fetal chorionic villi, and chorioamniotic membranes. FINDINGS: Comparisons of placentae from uninfected healthy controls (n = 4) with COVID-19 asymptomatic (n = 4) and symptomatic (n = 5) infected participants demonstrated that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) detection in syncytiotrophoblasts occurred in both the presence and the absence of maternal clinical disease. With spatial transcriptomics, we found that the limit of detection for SARS-CoV-2 was 1/7,000 cells, and placental niches without detectable viral transcripts were unperturbed. In contrast, niches with high SARS-CoV-2 transcript levels were associated with significant upregulation in pro-inflammatory cytokines and interferon-stimulated genes, altered metallopeptidase signaling (TIMP1), with coordinated shifts in macrophage polarization, histiocytic intervillositis, and perivillous fibrin deposition. Fetal sex differences in gene expression responses to SARS-CoV-2 were limited, with confirmed mapping limited to the maternal decidua in males. CONCLUSIONS: High-resolution placental transcriptomics with spatial resolution revealed dynamic responses to SARS-CoV-2 in coordinate microenvironments in the absence and presence of clinically evident disease. FUNDING: This work was supported by the NIH (R01HD091731 and T32-HD098069), NSF (2208903), the Burroughs Welcome Fund and the March of Dimes Preterm Birth Research Initiatives, and a Career Development Award from the American Society of Gene and Cell Therapy.
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COVID-19 , Nascimento Prematuro , Recém-Nascido , Gravidez , Humanos , Feminino , Masculino , Placenta , SARS-CoV-2/genética , Transcriptoma/genética , COVID-19/genéticaRESUMO
OBJECTIVE: We aimed to evaluate whether there is a significant association between a placental pathology diagnosis basal plate myofibers (BPMF) in an index pregnancy with placenta accreta spectrum (PAS) in the subsequent pregnancy. STUDY DESIGN: We conducted a retrospective nested cohort study of all cases with a histopathological finding of BPMF between August 2012 and March 2020 at a single tertiary referral center. Data were collected for all subjects (cases and controls) with at least two consecutive pregnancies (the initial index pregnancy and at least one subsequent pregnancy) accompanied by a concomitant record of histopathological study of the placenta at our center. The primary outcome was pathologically confirmed PAS in the subsequent pregnancy. Data are presented as percentage or median, interquartile range accordingly. RESULTS: A total of n = 1,344 participants were included, of which n = 119 (index cases) carried a contemporaneous histopathological diagnosis of BPMF during the index pregnancy and n = 1,225 did not (index controls). Among the index cases, patients with BPMF were older (31.0 [20, 42] vs. 29.0 [15, 43], p < 0.001), more likely to have undergone in vitro fertilization (IVF) for conception (10.9 vs. 3.8%, p = 0.001) and were of a more advanced gestational age at delivery (39.0 [25, 41] vs. 38.0 [20, 42], p = 0.006). In the subsequent pregnancy, the rate of PAS was significantly higher among the BPMF index cases (6.7 vs. 1.1%, p < 0.001). After adjusting for maternal age and IVF, a histopathological diagnosis of BPMF in an index pregnancy was shown to be a significant risk factor for PAS in the subsequent gestation (hazard ratio: 5.67 [95% confidence interval: 2.28, 14.06], p < 0.001). CONCLUSION: Our findings support that a histopathological diagnosis of BPMF is an independent risk factor for PAS in the subsequent pregnancy. KEY POINTS: · BPMF may indicate morbid adherence of placenta.. · Patients with BPMF were older and more likely to have undergone IVF for conception.. · The BPMF in the current pregnancy is an independent risk factor for PAS in the subsequent pregnancy..
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Pathologic examination of the placenta can provide insight into likely (and unlikely) causes of antepartum and intrapartum events, diagnoses with urgent clinical relevance, prognostic information for mother and infant, support for practice evaluation and improvement, and insight into advancing the sciences of obstetrics and neonatology. Although it is true that not all placentas require pathologic examination (although alternative opinions have been expressed), prioritization of placentas for pathologic examination should be based on vetted indications such as maternal comorbidities or pregnancy complications in which placental pathology is thought to be useful for maternal or infant care, understanding pathophysiology, or practice modifications. Herein we provide placental triage criteria for the obstetrical and neonatal provider based on publications and expert opinion of 16 placental pathologists and a pathologists' assistant, formulated using a modified Delphi approach. These criteria include indications in which placental pathology has clinical relevance, such as pregnancy loss, maternal infection, suspected abruption, fetal growth restriction, preterm birth, nonreassuring fetal heart testing requiring urgent delivery, preeclampsia with severe features, or neonates with early evidence of multiorgan system failure including neurologic compromise. We encourage a focused gross examination by the provider or an attendant at delivery for all placentas and provide guidance for this examination. We recommend that any placenta that is abnormal on gross examination undergo a complete pathology examination. In addition, we suggest practice criteria for placental pathology services, including a list of critical values to be used by the relevant provider. We hope that these sets of triage indications, criteria, and practice suggestions will facilitate appropriate submission of placentas for pathologic examination and improve its relevance to clinical care.
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Obstetrícia , Complicações na Gravidez , Nascimento Prematuro , Gravidez , Recém-Nascido , Feminino , Humanos , Placenta/patologia , Retardo do Crescimento Fetal/patologiaRESUMO
OBJECTIVE: Placenta accreta spectrum (PAS) covers a wide spectrum of placental adherence/invasion with varied clinical significance. Histopathologic examination is considered the confirmatory gold standard, but is only obtained sometime after definitive treatment. The International Federation of Gynecology and Obstetrics (FIGO) has published a new clinical classification that can be assigned at delivery, and we aimed to investigate the association between this new FIGO classification and histopathology and also to assess its correlation with maternal outcomes. STUDY DESIGN: We studied a retrospective cohort of 185 patients with histopathologically proven PAS managed at our referral center between September 2012 and January 2019. Two experienced surgeons retrospectively reviewed charts and assigned the FIGO grading based on findings reported at delivery. A third experienced reviewer adjudicated to determine the classification used for final analysis. Categorical outcomes were compared with the use of chi-squared and the Fisher exact test, as appropriate. A multivariate model was designed to adjust outcomes in different FIGO groups for the involvement of a formal multidisciplinary management team. RESULTS: Among 185 patients, there were 41 (22%) placenta accreta, 44 (24%) placenta increta, and 100 (54%) placenta percreta on histopathology. The inter-rater reliability was found to be substantial with Kappa = 0.661 (p < 0.001), and 95% confidence interval (CI): 0.449-0.872. There was a significant association between all histopathology groupings and the FIGO clinical classification (p < 0.001). However, we found no association between FIGO classifications and maternal complications. CONCLUSION: The new FIGO clinical classification is strongly associated with histopathologic findings. A better understanding of the depth and extent of invasion as afforded by the clinical classification system will help standardize reporting and future research. KEY POINTS: · PAS includes a wide spectrum of placental invasion with varied clinical significance.. · Histopathological examination is considered the confirmatory gold standard.. · The new FIGO clinical classification is strongly associated with histopathologic findings..
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Placenta Acreta , Placenta Prévia , Gravidez , Humanos , Feminino , Placenta Acreta/cirurgia , Estudos Retrospectivos , Placenta , Reprodutibilidade dos TestesRESUMO
We aimed to perform a meta-analysis of the literature concerning histopathologic findings in the placentas of women with SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) infection during pregnancy. Searches for articles in English included PubMed, Web of Science, Google Scholar, and reference lists (up to April 2021). Studies presenting data on placental histopathology according to the Amsterdam Consensus Group criteria in SARS-CoV-2 positive and negative pregnancies were identified. Lesions were categorized into: maternal and fetal vascular malperfusion (MVM and FVM, respectively), acute placental inflammation with maternal and fetal inflammatory response (MIR and FIR, respectively), chronic inflammatory lesions (CILs), and increased perivillous fibrin deposition (PVFD). A total of 15 studies reporting on 19,025 placentas, n = 699 of which were derived from women who were identified as being infected with SARS-CoV-2 and 18,326 as SARS-CoV-2-negative controls, were eligible for analysis. No significant difference in incidence of MVM (odds ratio [OR]: 1.18, 95% confidence interval [CI]: 0.73-1.90), FVM (OR: 1.23, 95% CI: 0.63-2.42), MIR (OR: 0.66, 95% CI: 0.29-1.52) or FIR (OR: 0.85, 95% CI: 0.44-1.63), and CILs (OR: 0.97, 95% CI: 0.55-1.72) was found between placentae from gravida identified as being SARS-CoV-2 infected. However, placenta from gravida identified as being infected with SARS-CoV-2 were associated with significantly increased occurrence of PVFD (OR: 2.77, 95% CI: 1.06-7.27). After subgroup analyses based on clinical severity of COVID-19 infection, no significant difference was observed in terms of reported placental pathology between symptomatic or asymptomatic SARS-CoV-2 gravidae placenta. Current evidence based on the available literature suggests that the only pathologic finding in the placentae of women who are pregnant identified as having been infected with SARS-CoV-2 was an increased prevalence of PVFD. KEY POINTS: · No association between SARS-CoV-2 and maternal or fetal placental malperfusion.. · No association between SARS-CoV-2 and maternal or fetal inflammatory response.. · SARS-CoV-2 is associated with increased perivillous fibrin deposition in placenta..
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COVID-19 , Complicações Infecciosas na Gravidez , Feminino , Humanos , Gravidez , COVID-19/epidemiologia , Fibrina , Inflamação/patologia , Placenta/patologia , Complicações Infecciosas na Gravidez/epidemiologia , Complicações Infecciosas na Gravidez/virologia , SARS-CoV-2RESUMO
BACKGROUND: The terminology and diagnostic criteria presently used by pathologists to report placenta accreta spectrum is inconsistent and does not reflect current knowledge of the pathogenesis of this disease. OBJECTIVE: In 2020, the perinatal subcommittee of the Society for Pediatric Pathology Placenta Accreta Task Force proposed a new pathologic grading system for placenta accreta spectrum. We sought to correlate the clinical outcomes with the classification into each group in the new placenta accreta spectrum grading system. STUDY DESIGN: The pathology reports of patients with histopathologic confirmation of placenta accreta spectrum were reviewed in 2 academic referral centers by placental pathologists. Pathologic grading was assigned based on the new grading system according to which placenta accreta spectrum is categorized into 5 groups depending on the depth of invasion, from grade p1 with no invasion into the uterine wall to grade p3E with invasion beyond the uterine wall to the adjacent organs. Patient characteristics and clinical outcomes were compared among these groups. A univariate analysis was performed, and a multivariate linear or binomial regression was employed when needed. RESULTS: A total of 683 patients with placenta accreta spectrum were identified. Of those, 407 were included for histology review. There were 92 patients (23%) categorized into the grade p1 group, 74 (18%) in the grade p2 group, 84 (20%) in the grade p3A group, 121 (30%) in the grade p3D group, and 36 (9%) in the grade p3E group. There was a significant association between the pathology grading and the number of red blood cells transfused (ß=1.14; 95% confidence interval, 0.48-1.79) and the postoperative complications including the rate of readmission (risk ratio, 1.93; 95% confidence interval, 1.26-2.94) and bladder injury (risk ratio, 1.81; 95% confidence interval, 1.23-2.68) after adjustment for antenatal diagnosis and other variables. The pathology grading was not associated with the estimated blood loss (P=.072). CONCLUSION: The new pathology grading system accurately reflects maternal outcomes and complications of placenta accreta spectrum. We encourage the utilization of this new pathologic grading system because it is designed to omit discrepancies in placenta accreta spectrum reporting and to standardize communication.
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Placenta Acreta , Cesárea , Criança , Feminino , Humanos , Histerectomia , Placenta/patologia , Placenta Acreta/cirurgia , Gravidez , Estudos RetrospectivosRESUMO
Background: Multiple studies have shown both induction and inhibition of autophagy during Zika virus (ZIKV) infection. While some have proposed mechanisms by which autophagic dysregulation might facilitate ZIKV vertical transmission, there is a lack of in situ data in human and non-human primate models. This is an especially pertinent question as autophagy-inhibitors, such as hydroxychloroquine, have been proposed as potential therapeutic agents aimed at preventing vertical transmission of ZIKV and other RNA viruses. Objectives: Given the paucity of pre-clinical data in support of either autophagic enhancement or inhibition of placental ZIKV viral infection, we sought to assess cellular, spatial, and temporal associations between placental ZIKV infection and measures of autophagy in human primary cell culture and congenital infection cases, as well as an experimental non-human primate (marmoset, Callithrix jacchus) model. Study Design: Primary trophoblast cells were isolated from human placentae (n = 10) and infected in vitro with ZIKV. Autophagy-associated gene expression (ULK-1, BECN1, ATG5, ATG7, ATG12, ATG16L1, MAP1LC3A, MAP1LC3B, p62/SQSTM1) was then determined by TaqMan qPCR to determine fold-change with ZIKV-infection. In in vivo validation experiments, autophagy genes LC3B and p62/SQSTM1 were probed using in situ hybridization (ISH) in the placentae of human Congenital Zika Syndrome (CZS) cases (n = 3) and ZIKV-infected marmoset placenta (n = 1) and fetal tissue (n = 1). Infected and uninfected villi were compared for mean density and co-localization of autophagic protein markers. Results: Studies of primary cultured human trophoblasts revealed decreased expression of autophagy genes ATG5 and p62/SQSTM1 in ZIKV-infected trophoblasts [ATG5 fold change (±SD) 0.734-fold (±0.722), p = 0.036; p62/SQSTM1 0.661-fold (±0.666), p = 0.029]. Histologic examination by ISH and immunohistochemistry confirmed spatial association of autophagy and ZIKV infection in human congenital infection cases, as well as marmoset placental and fetal tissue samples. When quantified by densitometric data, autophagic protein LC3B, and p62/SQSTM1 expression in marmoset placenta were significantly decreased in in situ ZIKV-infected villi compared to less-infected areas [LC3B mean 0.951 (95% CI, 0.930-0.971), p = 0.018; p62/SQSTM1 mean 0.863 (95% CI, 0.810-0.916), p = 0.024]. Conclusion: In the current study, we observed that in the non-transformed human and non-human primate placenta, disruption (specifically down-regulation) of autophagy accompanies later ZIKV replication in vitro, in vivo, and in situ. The findings collectively suggest that dysregulated autophagy spatially and temporally accompanies placental ZIKV replication, providing the first in situ evidence in relevant primate pre-clinical and clinical models for the importance of timing of human therapeutic strategies aimed at agonizing/antagonizing autophagy. These studies have likely further implications for other congenitally transmitted viruses, particularly the RNA viruses, given the ubiquitous nature of autophagic disruption and dysregulation in host responses to viral infection during pregnancy.
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BACKGROUND AND AIMS: Alagille syndrome (ALGS) is a multisystem developmental disorder characterized by bile duct (BD) paucity, caused primarily by haploinsufficiency of the Notch ligand jagged1. The course of the liver disease is highly variable in ALGS. However, the genetic basis for ALGS phenotypic variability is unknown. Previous studies have reported decreased expression of the transcription factor SOX9 (sex determining region Y-box 9) in late embryonic and neonatal livers of Jag1-deficient mice. Here, we investigated the effects of altering the Sox9 gene dosage on the severity of liver disease in an ALGS mouse model. APPROACH AND RESULTS: Conditional removal of one copy of Sox9 in Jag1+/- livers impairs the biliary commitment of cholangiocytes and enhances the inflammatory reaction and liver fibrosis. Loss of both copies of Sox9 in Jag1+/- livers further worsens the phenotypes and results in partial lethality. Ink injection experiments reveal impaired biliary tree formation in the periphery of P30 Jag1+/- livers, which is improved by 5 months of age. Sox9 heterozygosity worsens the P30 biliary tree phenotype and impairs the partial recovery in 5-month-old animals. Notably, Sox9 overexpression improves BD paucity and liver phenotypes in Jag1+/- mice without ectopic hepatocyte-to-cholangiocyte transdifferentiation or long-term liver abnormalities. Notch2 expression in the liver is increased following Sox9 overexpression, and SOX9 binds the Notch2 regulatory region in the liver. Histological analysis shows a correlation between the level and pattern of SOX9 expression in the liver and outcome of the liver disease in patients with ALGS. CONCLUSIONS: Our results establish Sox9 as a dosage-sensitive modifier of Jag1+/- liver phenotypes with a permissive role in biliary development. Our data further suggest that liver-specific increase in SOX9 levels is a potential therapeutic approach for BD paucity in ALGS.
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Síndrome de Alagille/genética , Síndrome de Alagille/patologia , Fígado/patologia , Fatores de Transcrição SOX9/genética , Animais , Ductos Biliares/anormalidades , Transdiferenciação Celular/genética , Criança , Pré-Escolar , Modelos Animais de Doenças , Hepatócitos/citologia , Heterozigoto , Humanos , Lactente , Proteína Jagged-1/genética , Fígado/anormalidades , Fígado/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Receptores Notch/genética , Receptores Notch/metabolismo , Índice de Gravidade de Doença , Transdução de SinaisRESUMO
BACKGROUND: Numerous reports have documented bacteria in the placental membranes and basal plate decidua in the absence of immunopathology using histologic techniques. Similarly, independent metagenomic characterizations have identified an altered taxonomic makeup in association with spontaneous preterm birth. Here we sought to corroborate these findings by localizing presumptive intact bacteria using molecular histology within the placental microanatomy. OBJECTIVE: Here we examined for microbes in term and preterm gestations using a signal-amplified 16S universal in situ hybridization probe set for bacterial rRNA, alongside traditional histologic methods of Warthin-Starry and Gram stains, as well as clinical culture methodologies. We further sought to differentiate accompanying 16S gene sequencing taxonomic profiles from germ-free (gnotobiotic) mouse and extraction and amplicon contamination controls. STUDY DESIGN: Placentas were collected from a total of 53 subjects, composed of term labored (n = 4) and unlabored cesarean deliveries (n = 22) and preterm vaginal (n = 18) and cesarean deliveries (n = 8); a placenta from a single subject with clinical and histologic evident choriomanionitis was employed as a positive control (n = 1). The preterm cohort included spontaneous preterm birth with (n = 6) and without (n = 10) preterm premature rupture of membranes, as well as medically indicated preterm births (n = 10). Placental microbes were visualized using an in situ hybridization probe set designed against highly conserved regions of the bacterial 16S ribosome, which produces an amplified stable signal using branched DNA probes. Extracted bacterial nucleic acids from these same samples were subjected to 16S rRNA metagenomic sequencing (Illumina, V4) for course taxonomic analysis, alongside environmental and kit contaminant controls. A subset of unlabored, cesarean-delivered term pregnancies were also assessed with clinical culture for readily cultivatable pathogenic microbes. RESULTS: Molecular in situ hybridization of bacterial rRNA enabled visualization and localization of low-abundance microbes after systematic high-power scanning. Despite the absence of clinical or histologic chorioamnionitis in 52 of 53 subjects, instances of 16S rRNA signal were confidently observed in 13 of 16 spontaneous preterm birth placentas, which was not significantly different from term unlabored cesarean specimens (18 of 22; P > .05). 16S rRNA signal was largely localized to the villous parenchyma and/or syncytiotrophoblast, and less commonly the chorion and the maternal intervillous space. In all term and unlabored cesarean deliveries, visualization of evident placental microbes by in situ hybridization occurred in the absence of clinical or histologic detection using conventional clinical cultivation, hematoxylin-eosin, and Gram staining. In 1 subject, appreciable villous bacteria localized to an infarction, where 16S microbial detection was confirmed by Warthin-Starry stain. In all instances, parallel sample principle coordinate analysis using Bray-Cutis distances of 16S rRNA gene sequencing data demonstrated consistent taxonomic distinction from all negative or potential contamination controls (P = .024, PERMANOVA). Classification from contaminant filtered data identified a distinct taxonomic makeup among term and preterm cohorts when compared with contaminant controls (false discovery rate <0.05). CONCLUSION: Presumptively intact placental microbes are visualized as low-abundance, low-biomass and sparse populations within the placenta regardless of gestational age and mode of delivery. Their taxonomic makeup is distinct from contamination controls. These findings further support several previously published findings, including our own, which have used metagenomics to characterize low-abundance and low-biomass microbial communities in the placenta.
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Placenta/microbiologia , RNA Ribossômico 16S , Adulto , Código de Barras de DNA Taxonômico , Feminino , Humanos , Hibridização In Situ , Metagenômica , Microbiota , Gravidez , Nascimento Prematuro , RNA Bacteriano/análise , Análise de Sequência de RNA , Nascimento a TermoRESUMO
BACKGROUND: The ex utero intrapartum treatment (EXIT) is utilized to transition fetuses with prenatally diagnosed airway obstruction to postnatal life. We describe the unique clinical course, diagnosis, treatment, and outcomes of patients with cervical lymphatic malformation (CLM) managed with EXIT. METHODS: Review of fetuses with diagnosed CLM was delivered by EXIT (2001-2018) in a tertiary referral fetal center. Outcomes included survival, tracheostomy at discharge, neonatal course after delivery, and pulmonary hypoplasia. Data are reported as median [range] and rate (%). RESULTS: Out of 45 patients delivered by EXIT, 10 were delivered for CLM: seven had polyhydramnios, one had nonimmune hydrops, five delivered preterm, and three were emergency EXITs. The EXIT time and estimated blood loss were 125 minutes (95, 158) and 900 mL (500, 1500), respectively. Airway was secured in all. There was one neonatal death (day 8) with prematurity, sepsis, and pulmonary hypoplasia. Three out of nine were discharged with a tracheostomy. CONCLUSION: In CLM, close monitoring for structural neck involvement and development of polyhydramnios are important and may be an indication for EXIT as the optimal delivery mode. An experienced multidisciplinary team is a key factor for an effective approach to the obstructed airway in CLM.
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Anormalidades Linfáticas/diagnóstico , Anormalidades Linfáticas/terapia , Vasos Linfáticos/anormalidades , Pescoço/anormalidades , Assistência Perinatal/métodos , Diagnóstico Pré-Natal , Adolescente , Adulto , Feminino , Doenças Fetais/diagnóstico , Doenças Fetais/mortalidade , Doenças Fetais/terapia , Humanos , Lactente , Cuidado do Lactente/métodos , Mortalidade Infantil , Recém-Nascido , Anormalidades Linfáticas/mortalidade , Vasos Linfáticos/cirurgia , Masculino , Pescoço/patologia , Parto/fisiologia , Gravidez , Diagnóstico Pré-Natal/métodos , Estudos Retrospectivos , Adulto JovemRESUMO
Contemporaneous Zika virus (ZIKV) strains can cause congenital Zika syndrome (CZS). Current ZIKV clinical laboratory testing strategies are limited and include IgM serology (which may wane 12 weeks after initial exposure) and nucleic acid testing (NAT) of maternal serum, urine, and placenta for (+) strand ZIKV RNA (which is often transient). The objectives of this study were to determine if use of additional molecular tools, such as quantitative PCR and microscopy, would add to the diagnostic value of current standard placental ZIKV testing in cases with maternal endemic exposure and indeterminate testing. ZIKV RNA was quantified from dissected sections of placental villi, chorioamnion sections, and full cross-sections of umbilical cord in all cases examined. Quantitation with high-resolution automated electrophoresis determined relative amounts of precisely verified ZIKV (74-nt amplicons). In order to localize and visualize stable and actively replicating placental ZIKV in situ, labeling of flaviviridae glycoprotein, RNA ISH against both (+) and (â») ZIKV-specific ssRNA strands, and independent histologic examination for significant pathologic changes were employed. We demonstrate that the use of these molecular tools added to the diagnostic value of placental ZIKV testing among suspected cases of congenital Zika syndrome with poorly ascribed maternal endemic exposure.
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Placenta/patologia , Placenta/virologia , Complicações Infecciosas na Gravidez/diagnóstico , Complicações Infecciosas na Gravidez/virologia , Infecção por Zika virus/diagnóstico , Infecção por Zika virus/virologia , Zika virus , Adulto , Encéfalo/anormalidades , Encéfalo/diagnóstico por imagem , Feminino , Humanos , Imuno-Histoquímica , Transmissão Vertical de Doenças Infecciosas , Imageamento por Ressonância Magnética , Microcefalia/diagnóstico , Microcefalia/etiologia , Fenótipo , Gravidez , Avaliação de Sintomas , Síndrome , Ultrassonografia Pré-Natal , Adulto Jovem , Infecção por Zika virus/transmissãoRESUMO
Superb Microvascular Imaging (SMI; Canon Medical Systems, Tustin, CA) uses clutter suppression to extract flow signals at rapid frame rates, which provides high-resolution vessel-branching details without the need for contrast agents. The potential diagnostic benefits of SMI, as described in other areas of medicine, requires further exploration during pregnancy. In this pictorial essay, we demonstrate the complementary use of SMI compared to conventional Doppler ultrasound and how it may improve our ability to characterize placental microvascular patterns without the need for ultrasound contrast agents.
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Microvasos/diagnóstico por imagem , Doenças Placentárias/diagnóstico por imagem , Placenta/irrigação sanguínea , Ultrassonografia Doppler/métodos , Ultrassonografia Pré-Natal/métodos , Feminino , Humanos , GravidezRESUMO
A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.
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During its most recent outbreak across the Americas, Zika virus (ZIKV) was surprisingly shown to cause fetal loss and congenital malformations in acutely and chronically infected pregnant women. However, understanding the underlying pathogenesis of ZIKV congenital disease has been hampered by a lack of relevant in vivo experimental models. Here we present a candidate New World monkey model of ZIKV infection in pregnant marmosets that faithfully recapitulates human disease. ZIKV inoculation at the human-equivalent of early gestation caused an asymptomatic seroconversion, induction of type I/II interferon-associated genes and proinflammatory cytokines, and persistent viremia and viruria. Spontaneous pregnancy loss was observed 16-18 days post-infection, with extensive active placental viral replication and fetal neurocellular disorganization similar to that seen in humans. These findings underscore the key role of the placenta as a conduit for fetal infection, and demonstrate the utility of marmosets as a highly relevant model for studying congenital ZIKV disease and pregnancy loss.
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Aborto Espontâneo/virologia , Perda do Embrião/virologia , Feto/anormalidades , Malformações do Sistema Nervoso/virologia , Placenta/virologia , Complicações Infecciosas na Gravidez/virologia , Infecção por Zika virus/complicações , Zika virus , Animais , Callithrix , Citocinas/imunologia , Modelos Animais de Doenças , Feminino , Idade Gestacional , Humanos , Interferon Tipo I/imunologia , Interferon gama/imunologia , Gravidez , Complicações Infecciosas na Gravidez/imunologia , Viremia , Replicação ViralRESUMO
BACKGROUND: Ureaplasma spp. is a known risk factor for bronchopulmonary dysplasia in premature infants. Emerging research suggests treatment with azithromycin or clarithromycin in the first days of life (DOLs) reduces bronchopulmonary dysplasia in Ureaplasma spp. positive infants. Side effects of these antibiotics make it imperative to optimize reliable noninvasive screening procedures to identify infants who would benefit from treatment. METHODS: The aim of this study was to determine the best site and time to screen for Ureaplasma spp. in 24- to 34-week premature infants. Oral, nasal, gastric and tracheal cultures were collected and placed immediately in 10B broth media. Polymerase chain reaction verified culture results and identified the Ureaplasma spp. RESULTS: Cultures yielded a Ureaplasma spp. incidence of 80/168 = 47.6% [95% confidence interval (CI): 40-56]. Nasal cultures had greater sensitivity to detect Ureaplasma spp. than oral cultures (P = 0.008): however, a significant proportion of infants with Ureaplasma spp. would have been missed (12/79 = 15.2%, 95% CI: 8%-25%, P < 0.001) if oral cultures were not obtained. For all sites, the collection at DOL 7-10 were more likely to be positive than the collection at DOL 1-2: however, a significant proportion (5/77 = 6.5%, 95% CI: 2-15, P < 0.001) of infants with Ureaplasma spp. would have been missed if the DOL 1-2 cultures were not obtained. CONCLUSIONS: For optimal Ureaplasma spp. detection in 24- to 34-week premature infants, cultures need to be taken both early and late in the first 10 DOLs both from nasal and oral secretions.