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1.
AIDS Behav ; 28(3): 805-810, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37843685

RESUMO

Alcohol use and HIV infection are prevalent in sub-Saharan Africa (sSA), and both are associated with low birth weight. Yet, few studies have evaluated the combined effects of maternal HIV infection and alcohol use on birth outcomes. We analyzed data from a prospective cohort study of HIV-related placental changes in Ugandan women. We defined alcohol use as self-reported alcohol use within the last year, using the AUDIT questionnaire and used linear and logistic regression to measure associations between maternal alcohol use, HIV serostatus, and birth weight. In a subsample, we measured alcohol exposure using phosphatidylethanol (PEth) in neonatal heelstick dried blood spots to confirm maternal alcohol use. Of 352 participants, 176 (50%) were women with HIV (WHIV). Three of 176 (2%) HIVuninfected women and 17/176 (10%) of WHIV self-reported alcohol use (P = 0.002). Maternal HIV infection was associated with lower birth weight (ß = -0.12, 95% CI [-0.20, -0.02], P = 0.02), but self-reported alcohol use was not (ß = 0.06, 95% CI [-0.15, 0.26], P = 0.54), and the interaction between HIV serostatus and alcohol use was not significant (P = 0.13). Among the PEth subsample, neither HIV status nor PEthconfirmed alcohol use were associated with low birth weight. Maternal HIV infection was associated with lower birth weight, but alcohol use was not, and there was no significant interaction between maternal HIV infection and alcohol use. Alcohol use was more prevalent in WHIV and under-reporting was common. A larger study of the effects of laboratory-confirmed alcohol and HIV exposure on birth outcomes is warranted.


Assuntos
Infecções por HIV , Recém-Nascido , Humanos , Feminino , Gravidez , Masculino , Infecções por HIV/epidemiologia , Peso ao Nascer , Uganda/epidemiologia , Estudos Prospectivos , Placenta
2.
Pediatr Dev Pathol ; 27(2): 123-131, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-37749054

RESUMO

OBJECTIVE: To elucidate particular placental pathology findings that are associated with hypoxic ischemic encephalopathy (HIE) and determine which patterns are associated with adverse fetal/neonatal outcomes. STUDY DESIGN: Multi-institutional retrospective case-control study of newborns with HIE (2002-2022) and controls. Four perinatal pathologists performed gross and histologic evaluation of placentas of cases and controls. RESULTS: A total of 265 placentas of neonates with HIE and 122 controls were examined. Infants with HIE were more likely to have anatomic umbilical cord abnormalities (19.7% vs 7.4%, P = .003), fetal inflammatory response in the setting of amniotic fluid infection (27.7% vs 13.9%, P = .004), and fetal vascular malperfusion (30.6% vs 9.0%, P = <.001) versus controls. Fetal vascular malperfusion with maternal vascular malperfusion was more common in those who died of disease (P = .01). CONCLUSION: Placental pathology examination of neonates with HIE may improve our understanding of this disorder and its adverse outcomes.


Assuntos
Hipóxia-Isquemia Encefálica , Doenças Placentárias , Lactente , Humanos , Gravidez , Recém-Nascido , Feminino , Placenta/patologia , Estudos Retrospectivos , Estudos de Casos e Controles , Hipóxia-Isquemia Encefálica/patologia , Doenças Placentárias/patologia , Líquido Amniótico
3.
Am J Obstet Gynecol ; 228(3): 261-269, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36243041

RESUMO

Stillbirth is a recognized complication of COVID-19 in pregnant women that has recently been demonstrated to be caused by SARS-CoV-2 infection of the placenta. Multiple global studies have found that the placental pathology present in cases of stillbirth consists of a combination of concurrent destructive findings that include increased fibrin deposition that typically reaches the level of massive perivillous fibrin deposition, chronic histiocytic intervillositis, and trophoblast necrosis. These 3 pathologic lesions, collectively termed SARS-CoV-2 placentitis, can cause severe and diffuse placental parenchymal destruction that can affect >75% of the placenta, effectively rendering it incapable of performing its function of oxygenating the fetus and leading to stillbirth and neonatal death via malperfusion and placental insufficiency. Placental infection and destruction can occur in the absence of demonstrable fetal infection. Development of SARS-CoV-2 placentitis is a complex process that may have both an infectious and immunologic basis. An important observation is that in all reported cases of SARS-CoV-2 placentitis causing stillbirth and neonatal death, the mothers were unvaccinated. SARS-CoV-2 placentitis is likely the result of an episode of SARS-CoV-2 viremia at some time during the pregnancy. This article discusses clinical and pathologic aspects of the relationship between maternal COVID-19 vaccination, SARS-CoV-2 placentitis, and perinatal death.


Assuntos
COVID-19 , Corioamnionite , Morte Perinatal , Complicações Infecciosas na Gravidez , Gravidez , Recém-Nascido , Feminino , Humanos , Natimorto/epidemiologia , SARS-CoV-2 , Placenta , Vacinas contra COVID-19 , Mães , Fibrina , Transmissão Vertical de Doenças Infecciosas
4.
Am J Obstet Gynecol ; 228(2): 187-202, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-35973475

RESUMO

The importance of a fully functioning placenta for a good pregnancy outcome is unquestioned. Loss of function can lead to pregnancy complications and is often detected by a thorough placental pathologic examination. Placental pathology has advanced the science and practice of obstetrics and neonatal-perinatal medicine by classifying diseases according to underlying biology and specific patterns of injury. Many past obstacles have limited the incorporation of placental findings into both clinical studies and day-to-day practice. Limitations have included variability in the nomenclature used to describe placental lesions, a shortage of perinatal pathologists fully competent to analyze placental specimens, and a troubling lack of understanding of placental diagnoses by clinicians. However, the potential use of placental pathology for phenotypic classification, improved understanding of the biology of adverse pregnancy outcomes, the development of treatment and prevention, and patient counseling has never been greater. This review, written partly in response to a recent critique published in a major obstetrics-gynecology journal, reexamines the role of placental pathology by reviewing current concepts of biology; explaining the most recent terminology; emphasizing the usefulness of specific diagnoses for obstetrician-gynecologists, neonatologists, and patients; previewing upcoming changes in recommendations for placental submission; and suggesting future improvements. These improvements should include further consideration of overall healthcare costs, cost-effectiveness, the clinical value added of placental assessment, improvements in placental pathology education and practice, and leveraging of placental pathology to identify new biomarkers of disease and evaluate novel therapies tailored to specific clinicopathologic phenotypes of both women and infants.


Assuntos
Placenta , Complicações na Gravidez , Humanos , Gravidez , Feminino , Placenta/patologia , Resultado da Gravidez
5.
Am J Obstet Gynecol ; 228(5): 497-508.e4, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36549567

RESUMO

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.


Assuntos
Obstetrícia , Complicações na Gravidez , Nascimento Prematuro , Gravidez , Recém-Nascido , Feminino , Humanos , Placenta/patologia , Retardo do Crescimento Fetal/patologia
6.
Eur J Nutr ; 62(2): 987-1001, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36344770

RESUMO

PURPOSE: Whether anemia type modifies the risk of pregnancy and newborn outcomes and the effectiveness of iron supplementation is unclear. We examined the association of iron deficiency anemia (IDA) and non-iron deficiency anemia (NIDA) on the risks of these outcomes and the extent to which anemia type modifies the impact of prenatal iron supplementation. METHODS: This was a secondary analysis of a placebo-controlled trial of iron supplementation among 1450 HIV-negative women in Tanzania. Eligibility criteria included gestational age < 27 weeks, hemoglobin > 85 g/L, and ferritin > 12 µg/L. Individuals were categorized as non-anemia, IDA or NIDA using hemoglobin, ferritin and CRP. Analyses were conducted using regression models and likelihood ratio tests. RESULTS: Compared to the non-anemia group, delivery hemoglobin was lower by 15 g/L (95% CI 10.9, 19.3) in the baseline IDA group, and 7.3 g/L (95% CI 3.1, 11.5) in the baseline NIDA group. The RRs of anemia severity, iron deficiency, placental malaria, stillbirths, perinatal mortality, birthweight, and preterm birth were not different among women in the baseline NIDA group (vs. non-anemia) compared to the baseline IDA group (vs. non-anemia). The difference in the mean delivery hemoglobin for iron supplementation and placebo arms was 8 g/L (95% CI 6, 11) in the non-anemia group, 7 g/L (95% CI 2, 13) in the NIDA group, and 16 g/L (95% CI 10, 22) in the IDA group. CONCLUSION: Iron supplementation is effective even among pregnant women with NIDA. TRIAL REGISTRATION: NCT01119612 (May 7, 2010).


Assuntos
Anemia Ferropriva , Anemia , Nascimento Prematuro , Feminino , Humanos , Lactente , Recém-Nascido , Gravidez , Suplementos Nutricionais , Ferritinas , Hemoglobinas/uso terapêutico , Placenta , Gestantes , Tanzânia
7.
J Infect Dis ; 225(5): 754-758, 2022 03 02.
Artigo em Inglês | MEDLINE | ID: mdl-35024844

RESUMO

There is limited information on the specific impact of maternal infection with the SARS-CoV-2 B.1.617.2 (delta) variant on pregnancy outcomes. We present 2 cases of intrauterine fetal demise and 1 case of severe fetal distress in the setting of maternal infection with delta-variant SARS-CoV-2. In all cases, fetal demise or distress occurred within 14 days of COVID-19 diagnosis. Evaluation revealed maternal viremia, high nasopharyngeal viral load, evidence of placental infection with delta-variant SARS-CoV-2, and hallmark features of SARS-CoV-2 placentitis. We suggest that delta-variant SARS-CoV-2 infection during pregnancy warrants vigilance for placental dysfunction and fetal compromise regardless of disease severity.


Assuntos
COVID-19/diagnóstico , Morte Fetal , Sofrimento Fetal , Placenta/virologia , Complicações Infecciosas na Gravidez/virologia , SARS-CoV-2 , Adulto , COVID-19/complicações , COVID-19/mortalidade , Teste para COVID-19 , Corioamnionite , Feminino , Humanos , Transmissão Vertical de Doenças Infecciosas , Gravidez , Complicações Infecciosas na Gravidez/diagnóstico
8.
Clin Infect Dis ; 75(8): 1359-1369, 2022 10 12.
Artigo em Inglês | MEDLINE | ID: mdl-35245365

RESUMO

BACKGROUND: Human immunodeficiency virus (HIV)-exposed, uninfected (HEU) children have a higher risk of severe infection, but the causes are poorly understood. Emerging data point to altered antibody transfer in women with HIV (WHIV); however, specific perturbations and the influence of antiretroviral therapy (ART) and HIV viremia remain unclear. METHODS: We evaluated antigen-specific transplacental antibody transfer across 14 antigens in paired maternal and umbilical cord plasma from 352 Ugandan women; 176 were WHIV taking ART. We measured antigen-specific immunoglobulin G (IgG) sub-class (IgG1, 2, 3, 4) levels and antibody Fcγ receptor (FcγRn, 2a, 2b, 3a, 3b) binding profiles. We used partial least squares discrimi-nant analysis to define antigen-specific transplacental antibody transfer features. RESULTS: Global antibody transfer patterns were similar by maternal HIV serostatus, pointing to effective placental function in WHIV. However, HEU umbilical cord antibody profiles were altered, driven by perturbed WHIV seroprofiles, with higher levels of herpesvirus antibodies (P < .01 for Epstein-Barr virus, herpes simplex virus) and lower levels of classic vaccine-induced antibodies (P < .01 for tetanus, polio, Haemophilus influenzae type b), suggesting that umbilical cord antibody profile differences arise from imbalanced WHIV immunity. Abnormal WHIV antibody profiles were associated with HIV viremia, lower CD4 count, and postconception ART initiation (P = .01). CONCLUSIONS: Perturbed immune-dominance profiles in WHIV shift the balance of immunity delivered to neonates. Perturbed HIV-associated maternal antibody profiles are a key determinant of com-promised neonatal immunity. Maternal vaccination interventions may promote transfer of relevant, effective antibodies to protect HEU children against early-life infections.


Assuntos
Infecções por Vírus Epstein-Barr , Infecções por HIV , Anticorpos Antibacterianos , Anticorpos Antivirais , Criança , Feminino , HIV , Infecções por HIV/tratamento farmacológico , Herpesvirus Humano 4 , Humanos , Imunoglobulina G , Recém-Nascido , Placenta , Gravidez , Receptores de IgG , Toxoide Tetânico , Viremia
9.
Emerg Infect Dis ; 28(3): 510-517, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35138244

RESUMO

Severe coronavirus disease in neonates is rare. We analyzed clinical, laboratory, and autopsy findings from a neonate in the United States who was delivered at 25 weeks of gestation and died 4 days after birth; the mother had asymptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and preeclampsia. We observed severe diffuse alveolar damage and localized SARS-CoV-2 by immunohistochemistry, in situ hybridization, and electron microscopy of the lungs of the neonate. We localized SARS-CoV-2 RNA in neonatal heart and liver vascular endothelium by using in situ hybridization and detected SARS-CoV-2 RNA in neonatal and placental tissues by using reverse transcription PCR. Subgenomic reverse transcription PCR suggested viral replication in lung/airway, heart, and liver. These findings indicate that in utero SARS-CoV-2 transmission contributed to this neonatal death.


Assuntos
COVID-19 , Complicações Infecciosas na Gravidez , Autopsia , Feminino , Humanos , Recém-Nascido , Transmissão Vertical de Doenças Infecciosas , Pulmão , Placenta , Gravidez , RNA Viral/genética , SARS-CoV-2
10.
Mod Pathol ; 35(9): 1175-1180, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35361888

RESUMO

Current public health initiatives to contain the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) global pandemic focus on expanding vaccination efforts to include vulnerable populations such as pregnant people. Vaccines using messenger ribonucleic acid (mRNA) technology rely on translation by immune cells, primarily at the injection site. Hesitancy remains among the general population regarding the safety of mRNA vaccines during gestation, and it remains unknown whether the SARS-CoV-2 Spike protein (the product of mRNA vaccines available) accumulates in the placenta after vaccination. Objective: To determine whether Spike protein translation and accumulation occurs in placental tissue in the context of recent mRNA SARC-CoV-2 vaccination during pregnancy. We identified 48 patients receiving one or two doses of mRNA SARS-CoV-2 vaccine during gestation and used immunohistochemistry against SARS-CoV-2 Spike protein in formalin-fixed, paraffin-embedded placental tissue. One placenta, positive for SARS-CoV-2 RNA by in situ hybridization (ISH) was used as positive control. Seven term placentas collected prior to the emergence of SARS-CoV-2 served as negative controls. Eighty one percent of patients in the study group underwent third-trimester delivery; remaining had a first-trimester spontaneous abortion or elective second-trimester termination. Patients received two (52%) or one (48%) vaccine doses during pregnancy, with a median interval between latest dose and delivery of 13 days (range 2-79 days). Most (63%) cases had their latest dose within 15 days prior to delivery. All the placentas in the study and negative control groups were negative for SARS-CoV-2 immunohistochemistry. Six study cases with short vaccine-delivery intervals (2-7 days) were subjected to SARS-CoV-2 ISH and were negative. Our findings suggest that mRNA vaccines do not reach significant concentrations in the placenta given the absence of definitive SARS-CoV-2 Spike protein accumulation in placental tissue. This observation provides evidence supporting the safety of mRNA vaccines to the placental-fetal unit.


Assuntos
Vacinas contra COVID-19 , COVID-19 , Placenta , Complicações Infecciosas na Gravidez , Glicoproteína da Espícula de Coronavírus , COVID-19/prevenção & controle , Vacinas contra COVID-19/administração & dosagem , Feminino , Humanos , Placenta/virologia , Gravidez , Complicações Infecciosas na Gravidez/prevenção & controle , Complicações Infecciosas na Gravidez/virologia , SARS-CoV-2 , Glicoproteína da Espícula de Coronavírus/análise , Vacinação
11.
J Infect Dis ; 224(Supplement_6): S642-S646, 2021 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-33880519

RESUMO

We previously demonstrated that the late gestation placental expression pattern of ACE2 (the primary severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2] receptor) is localized to the villous syncytiotrophoblast (ST), usually in a polarized membranous pattern at the ST base sparing the apical surface (that directly exposed to maternal blood). We found that the late gestation placental expression pattern of TMPRSS2 (the spike proteinase required for SARS-CoV-2 cellular infection), is usually absent in the trophoblast but is rarely, weakly expressed in the placental endothelium. We now show the developmental protein expression patterns of ACE2 and TMPRSS2 by immunohistochemistry throughout gestation, from the first through third trimester. We found that TMPRSS2 expression was rarely detectable in villous endothelium and very rarely detectable in the ST across gestation. We found that ACE2 expression varied during gestation with circumferential ST expression more common in early gestations and polarized expression more common in later gestation. Although this study is small, these preliminary results suggest that earlier gestation pregnancies may be more vulnerable to infection than later gestation pregnancies.


Assuntos
Enzima de Conversão de Angiotensina 2/metabolismo , COVID-19 , Placenta/metabolismo , Complicações Infecciosas na Gravidez/virologia , SARS-CoV-2/metabolismo , Serina Endopeptidases/metabolismo , Adulto , Enzima de Conversão de Angiotensina 2/genética , Feminino , Idade Gestacional , Humanos , Placenta/virologia , Gravidez , Complicações Infecciosas na Gravidez/metabolismo , Complicações Infecciosas na Gravidez/patologia , Serina Endopeptidases/genética , Trofoblastos
12.
J Infect Dis ; 224(12 Suppl 2): S694-S700, 2021 12 08.
Artigo em Inglês | MEDLINE | ID: mdl-33880547

RESUMO

BACKGROUND: Women with human immunodeficiency virus (HIV) (WHIV) are at higher risk of adverse birth outcomes. Proposed mechanisms for the increased risk include placental arteriopathy (vasculopathy) and maternal vascular malperfusion (MVM) due to antiretroviral therapy and medical comorbid conditions. However, these features and their underlying pathophysiologic mechanisms have not been well characterized in WHIV. METHODS: We performed gross and histologic examination and immunohistochemistry staining for vascular endothelial growth factor A (VEGF-A), a key angiogenic factor, on placentas from women with ≥1 MVM risk factors including: weight below the fifth percentile, histologic infarct or distal villous hypoplasia, nevirapine-based antiretroviral therapy, hypertension, and preeclampsia/eclampsia during pregnancy. We compared pathologic characteristics by maternal HIV serostatus. RESULTS: Twenty-seven of 41 (placentas 66%) assessed for VEGF-A were from WHIV. Mean maternal age was 27 years. Among WHIV, median CD4 T-cell count was 440/µL, and the HIV viral load was undetectable in 74%. Of VEGF-A-stained placentas, both decidua and villous endothelium tissue layers were present in 36 (88%). VEGF-A was detected in 31 of 36 (86%) with decidua present, and 39 of 40 (98%) with villous endothelium present. There were no differences in VEGF-A presence in any tissue type by maternal HIV serostatus (P = .28 to >.99). MVM was more common in placentas selected for VEGF-A staining (51 vs 8%; P < .001). CONCLUSIONS: VEGF-A immunostaining was highly prevalent, and staining patterns did not differ by maternal HIV serostatus among those with MVM risk factors, indicating that the role of VEGF-A in placental vasculopathy may not differ by maternal HIV serostatus.


Assuntos
Infecções por HIV/complicações , Doenças Placentárias/patologia , Placenta/irrigação sanguínea , Doenças Vasculares , Adulto , Feminino , Retardo do Crescimento Fetal , HIV , Infecções por HIV/tratamento farmacológico , Humanos , Recém-Nascido Pequeno para a Idade Gestacional , Gravidez , Fator A de Crescimento do Endotélio Vascular
13.
J Infect Dis ; 224(Suppl 6): S647-S659, 2021 12 08.
Artigo em Inglês | MEDLINE | ID: mdl-34293137

RESUMO

BACKGROUND: Expression of angiotensin-converting enzyme 2 (ACE2) and type II transmembrane serine protease (TMPRSS2), host molecules required for viral entry, may underlie sex differences in vulnerability to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We investigated whether placental ACE2 and TMPRSS2 expression vary by fetal sex in the presence of maternal SARS-CoV-2 infection. METHODS: Placental ACE2 and TMPRSS2 expression was quantified by quantitative reverse transcription polymerase chain reaction (RT-PCR) and by Western blot in 68 pregnant women (38 SARS-CoV-2 positive, 30 SARS-CoV-2 negative) delivering at Mass General Brigham from April to June 2020. The impact of fetal sex and maternal SARS-CoV-2 exposure on ACE2 and TMPRSS2 was analyzed by 2-way analysis of variance (ANOVA). RESULTS: Maternal SARS-CoV-2 infection impacted placental TMPRSS2 expression in a sexually dimorphic fashion (2-way ANOVA interaction, P = .002). We observed no impact of fetal sex or maternal SARS-CoV-2 status on ACE2. TMPRSS2 expression was significantly correlated with ACE2 expression in males (Spearman ρ = 0.54, P = .02) but not females (ρ = 0.23, P = .34) exposed to maternal SARS-CoV-2. CONCLUSIONS: Sex differences in placental TMPRSS2 but not ACE2 were observed in the setting of maternal SARS-CoV-2 infection, which may have implications for offspring vulnerability to placental infection.


Assuntos
Enzima de Conversão de Angiotensina 2/metabolismo , COVID-19/diagnóstico , Sangue Fetal/imunologia , Placenta/metabolismo , SARS-CoV-2/imunologia , Serina Endopeptidases/metabolismo , Fatores Sexuais , Adulto , COVID-19/sangue , Feminino , Sangue Fetal/virologia , Feto/virologia , Expressão Gênica , Humanos , Transmissão Vertical de Doenças Infecciosas , Masculino , Gravidez , Complicações Infecciosas na Gravidez/virologia
14.
Am J Obstet Gynecol ; 225(6): 593.e1-593.e9, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34364845

RESUMO

Pregnant individuals infected with SARS-CoV-2 have higher rates of intensive care unit admission, oxygen requirement, need for mechanical ventilation, and death than nonpregnant individuals. Increased COVID-19 disease severity may be associated with an increased risk of viremia and placental infection. Maternal SARS-CoV-2 infection is also associated with pregnancy complications such as preeclampsia and preterm birth, which can be either placentally mediated or reflected in the placenta. Maternal viremia followed by placental infection may lead to maternal-fetal transmission (vertical), which affects 1% to 3% of exposed newborns. However, there is no agreed-upon or standard definition of placental infection. The National Institutes of Health/Eunice Kennedy Shriver National Institute of Child Health and Human Development convened a group of experts to propose a working definition of placental infection to inform ongoing studies of SARS-CoV-2 during pregnancy. Experts recommended that placental infection be defined using techniques that allow virus detection and localization in placental tissue by one or more of the following methods: in situ hybridization with antisense probe (detects replication) or a sense probe (detects viral messenger RNA) or immunohistochemistry to detect viral nucleocapsid or spike proteins. If the abovementioned methods are not possible, reverse transcription polymerase chain reaction detection or quantification of viral RNA in placental homogenates, or electron microscopy are alternative approaches. A graded classification for the likelihood of placental infection as definitive, probable, possible, and unlikely was proposed. Manuscripts reporting placental infection should describe the sampling method (location and number of samples collected), method of preservation of tissue, and detection technique. Recommendations were made for the handling of the placenta, examination, and sampling and the use of validated reagents and sample protocols (included as appendices).


Assuntos
Teste para COVID-19/métodos , COVID-19/diagnóstico , Doenças Placentárias/diagnóstico , Doenças Placentárias/virologia , Complicações Infecciosas na Gravidez/diagnóstico , Complicações Infecciosas na Gravidez/virologia , SARS-CoV-2 , Teste de Ácido Nucleico para COVID-19 , Consenso , Feminino , Guias como Assunto , Humanos , Imuno-Histoquímica , Hibridização In Situ , Microscopia Eletrônica , National Institute of Child Health and Human Development (U.S.) , Gravidez , Estados Unidos/epidemiologia
15.
Mod Pathol ; 33(11): 2092-2103, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32741970

RESUMO

Congenital infection of SARS-CoV-2 appears to be exceptionally rare despite many cases of COVID-19 during pregnancy. Robust proof of placental infection requires demonstration of viral localization within placental tissue. Only two of the few cases of possible vertical transmission have demonstrated placental infection. None have shown placental expression of the ACE2 or TMPRSS2 protein, both required for viral infection. We examined 19 COVID-19 exposed placentas for histopathologic findings, and for expression of ACE2, and TMPRSS2 by immunohistochemistry. Direct placental SARS-CoV-2 expression was studied by two methods-nucleocapsid protein expression by immunohistochemistry, and RNA expression by in situ hybridization. ACE2 membranous expression in the syncytiotrophoblast (ST) of the chorionic villi is predominantly in a polarized pattern with expression highest on the stromal side of the ST. In addition, cytotrophoblast and extravillous trophoblast express ACE2. No ACE2 expression was detected in villous stroma, Hofbauer cells, or endothelial cells. TMPRSS2 expression was only present weakly in the villous endothelium and rarely in the ST. In 2 of 19 cases, SARS-CoV-2 RNA was present in the placenta focally in the ST and cytotrophoblast. There was no characteristic histopathology present in our cases including the two placental infections. We found that the placenta is capable of being infected but that this event is rare. We propose one explanation could be the polarized expression of ACE2 away from the maternal blood and pronounced paucity of TMPRSS2 expression in trophoblast.


Assuntos
Infecções por Coronavirus/virologia , Placenta/patologia , Placenta/virologia , Pneumonia Viral/virologia , Complicações Infecciosas na Gravidez/virologia , Adulto , Enzima de Conversão de Angiotensina 2 , Betacoronavirus , COVID-19 , Infecções por Coronavirus/patologia , Feminino , Humanos , Pandemias , Peptidil Dipeptidase A/biossíntese , Placenta/metabolismo , Pneumonia Viral/patologia , Gravidez , Complicações Infecciosas na Gravidez/metabolismo , Complicações Infecciosas na Gravidez/patologia , RNA Viral/análise , SARS-CoV-2 , Serina Endopeptidases/biossíntese
16.
Mod Pathol ; 33(12): 2382-2396, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32415266

RESUMO

The terminology and diagnostic criteria presently used by pathologists to report invasive placentation is inconsistent and does not reflect current knowledge of the pathogenesis of the disease or the needs of the clinical care team. A consensus panel was convened to recommend terminology and reporting elements unified across the spectrum of PAS specimens (i.e., delivered placenta, total or partial hysterectomy with or without extrauterine tissues, curetting for retained products of conception). The proposed nomenclature under the umbrella diagnosis of placenta accreta spectrum (PAS) replaces the traditional categorical terminology (placenta accreta, increta, percreta) with a descriptive grading system that parallels the guidelines endorsed by the International Federation of Gynaecology and Obstetrics (FIGO). In addition, the nomenclature for hysterectomy specimens is separated from that for delivered placentas. The goal for each element in the system of nomenclature was to provide diagnostic criteria and guidelines for expected use in clinical practice.


Assuntos
Prontuários Médicos/normas , Patologia Clínica/normas , Placenta Acreta/patologia , Placenta/patologia , Placentação , Terminologia como Assunto , Biópsia , Consenso , Documentação/normas , Feminino , Controle de Formulários e Registros/normas , Humanos , Histerectomia , Placenta/cirurgia , Placenta Acreta/classificação , Placenta Acreta/cirurgia , Valor Preditivo dos Testes , Gravidez , Índice de Gravidade de Doença
17.
Am J Obstet Gynecol ; 222(4): 360.e1-360.e16, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31589863

RESUMO

BACKGROUND: The availability and use of frozen embryos after ovarian hyperstimulation for assisted reproduction has increased with improvement in vitrification techniques and the rise of preimplantation genetic testing. However, there are conflicting data regarding whether obstetric outcomes differ between fresh and frozen embryo transfer cycles. OBJECTIVE: To compare placental pathology from live births arising from fresh and frozen embryo transfer cycles. MATERIALS AND METHODS: A cohort of 1140 live births with placental pathology arising from autologous in vitro fertilization cycles with fresh or frozen programmed transfer performed at MGH Fertility Center between 2004 and 2017 was retrospectively reviewed. An experienced placental pathologist categorized the reported placental pathology as anatomic, infectious, inflammatory, or vascular/thrombotic. Our primary outcomes were differences in these placental pathologies between the 2 groups. Patient demographic, cycle, and birth outcomes were compared with the use of χ2 tests, Student t test, or nonparametric tests, as appropriate. Multivariate logistic regression models were used to compare placental pathology between the fresh and frozen transfer groups. RESULTS: Of the 1140 cycles included in our analysis, 929 arose from fresh embryo transfers (81.3%) and 211 arose from programmed frozen embryo transfers (18.5%). For both transfer types, the average age of the women at time of treatment was 35 years; mean body mass indices were within the normal range (23.6 kg/m2 for fresh transfers and 23.2 kg/m2 for frozen transfers, P = .26), and mean day 3 follicle-stimulating hormone values were 7.1 and 7.0 IU/L (P = .44), respectively. Deliveries occurred on average at 37.5 and 38.0 weeks' gestational age (P = .04) in the fresh versus frozen transfer group, with similar rates of obstetric complications. However, frozen transfers were more likely to be associated with marginal cord insertion (adjusted odds ratio, 1.87; confidence interval, 1.21, 2.91; P = .01), accessory lobe formation (adjusted odds ratio, 2.96; confidence interval, 1.12, 7.79; P = 0.03), subchorionic thrombi (adjusted odds ratio, 3.72; confidence interval, 1.80, 7.71; P < .001), and fetal vascular malperfusion characteristics with cord anomalies (adjusted odds ratio, 2.34; confidence interval, 1.22, 4.46; P = .01). These trends persisted when we analyzed day 5 transfers alone, and single frozen embryo transfers remained associated with increased rates of subchorionic thrombi compared to single fresh embryo transfers. CONCLUSION: Pregnancies arising from frozen embryo transfers demonstrated more anatomic and vascular placental pathology than those from fresh transfers in our cohort of patients, despite similar maternal outcomes. More research is needed to explore how these differences in pathology may influence obstetric and perinatal outcomes.


Assuntos
Criopreservação , Transferência Embrionária/métodos , Embrião de Mamíferos , Fertilização in vitro/métodos , Doenças Placentárias/epidemiologia , Trombose/epidemiologia , Adulto , Peso ao Nascer , Feminino , Humanos , Recém-Nascido , Nascido Vivo , Placenta/anormalidades , Doenças Placentárias/patologia , Gravidez , Estudos Retrospectivos
18.
BMC Pregnancy Childbirth ; 20(1): 365, 2020 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-32539690

RESUMO

BACKGROUND: Thrombotic thrombocytopenic purpura (TTP) is a rare but serious complication in pregnancy that places the mother and fetus at high risk for morbidity and mortality. This case illustrates novel pregnancy complications associated with this rare medical condition. CASE PRESENTATION: A 31-year-old G3P0020 at 28 weeks and 1 day was admitted with severe thrombocytopenia and was ultimately diagnosed with TTP. With therapeutic plasma exchange (TPE), maternal status improved. At 28 weeks 6 days, however, non-reassuring fetal testing prompted cesarean delivery with placental abruption noted intraoperatively. Pathology examination confirmed placental abruption and also revealed multiple placental infarcts. CONCLUSION: While medical management of TTP can significantly improve the health of the mother, this case highlights the potential role of TTP in abruption and other placental pathology and thus, the need for close fetal surveillance throughout an affected pregnancy.


Assuntos
Descolamento Prematuro da Placenta/etiologia , Complicações Hematológicas na Gravidez/diagnóstico , Púrpura Trombocitopênica Trombótica/complicações , Adulto , Cesárea , Feminino , Humanos , Placenta/patologia , Troca Plasmática , Gravidez , Complicações Hematológicas na Gravidez/terapia
19.
Pediatr Dev Pathol ; 22(3): 229-235, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30334666

RESUMO

Fetal bacterial infections are a common cause of fetal/neonatal morbidity and mortality. The pathologic correlates of congenital bacterial infection include acute chorioamnionitis, acute villitis, and acute intervillositis. The strength of the association of congenital bacterial infection differs among these pathologies. Acute chorioamnionitis results usually from an ascending infection, and damage to the fetus is thought to be cytokine driven rather than damage secondary to bacteremia. Acute villitis is strongly associated with fetal sepsis due to congenital infections. A much less common variant on acute villitis pattern has been described with additional presence of bacteria in the fetal capillaries of the chorionic villi. We describe the spectrum of bacteria that would induce this unique pattern. The histological archives were searched from 2 institutions for cases with intravascular bacteria present in the villous capillaries of the placenta. Thirteen cases were identified, of which 11 cases had acute chorioamnionitis and all cases showed an acute villitis. Eight cases had Escherichia coli identified and 3 cases had Group B Streptococcus. All cases were associated with fetal death. In 9 cases, the mother showed signs of a significant infection including 1 maternal death. We conclude that finding intravascular bacteria is a serious complication of congenital infection with serious fetal and maternal sequela.


Assuntos
Corioamnionite/patologia , Infecções por Escherichia coli/patologia , Doenças Placentárias/patologia , Sepse/patologia , Infecções Estreptocócicas/patologia , Doença Aguda , Adolescente , Adulto , Corioamnionite/microbiologia , Vilosidades Coriônicas/microbiologia , Vilosidades Coriônicas/patologia , Escherichia coli/isolamento & purificação , Infecções por Escherichia coli/microbiologia , Feminino , Morte Fetal , Feto/patologia , Idade Gestacional , Humanos , Morte Materna , Placenta/microbiologia , Placenta/patologia , Doenças Placentárias/microbiologia , Gravidez , Sepse/microbiologia , Infecções Estreptocócicas/microbiologia , Streptococcus agalactiae/isolamento & purificação , Adulto Jovem
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