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1.
Exp Neurol ; 347: 113917, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34748755

RESUMO

Perinatal brain injury is a multifactorial process. In utero placental physiology plays a major role in neuroprotection and the normal development of the fetal central nervous system. Advances in placental pathology have clarified several specific mechanisms of injury and the histologic lesions most strongly associated with them. This review provides an updated summary of the relevant placental anatomy and physiology, the specific placental pathways leading to brain injury, the revised Amsterdam classification system for placental pathology, and the known associations of specific placental lesions with subtypes of adverse neurologic outcomes.


Assuntos
Lesões Encefálicas/patologia , Feto/patologia , Placenta/patologia , Lesões Encefálicas/metabolismo , Corioamnionite/metabolismo , Corioamnionite/patologia , Feminino , Hipóxia Fetal/metabolismo , Hipóxia Fetal/patologia , Feto/metabolismo , Humanos , Placenta/metabolismo , Gravidez
2.
Exp Neurol ; 347: 113914, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34752783

RESUMO

Pregnancy is an inflammatory process that is carefully regulated by the placenta via immunomodulation and cell-to-cell communication of maternal and fetal tissues. Exosomes, types of extracellular vesicles, facilitate the intercellular communication and traffic biologically modifying cargo within the maternal-placental-fetal axis in normal and pathologic pregnancies. Chorioamnionitis is characterized by inflammation of chorioamniotic membranes that produces systemic maternal and fetal inflammatory responses of cytokine dysregulation and has been associated with brain injury and neurodevelopmental disorders. This review focuses on how pathologic placental exosomes propagate acute and chronic inflammation leading to brain injury. The evidence reviewed here highlights the need to investigate exosomes from pathologic pregnancies and those with known brain injury to identify new diagnostics, biomarkers, and potential therapeutic targets.


Assuntos
Lesões Encefálicas/metabolismo , Corioamnionite/metabolismo , Exossomos/metabolismo , Mediadores da Inflamação/metabolismo , Placenta/metabolismo , Lesões Encefálicas/patologia , Corioamnionite/patologia , Exossomos/patologia , Feminino , Humanos , Inflamação/metabolismo , Inflamação/patologia , Placenta/patologia , Gravidez
3.
Sci Rep ; 11(1): 10331, 2021 05 14.
Artigo em Inglês | MEDLINE | ID: mdl-33990635

RESUMO

Chorioamnionitis, inflammation of fetal membranes, is an important cause of preterm birth and a risk factor for the development of adverse neonatal outcomes including sepsis and intestinal pathologies. Intestinal bile acids (BAs) accumulation and hepatic cytokine production are involved in adverse intestinal outcomes. These findings triggered us to study the liver and enterohepatic circulation (EHC) following intra-amniotic (IA) lipopolysaccharide (LPS) exposure. An ovine chorioamnionitis model was used in which circulatory cytokines and outcomes of the liver and EHC of preterm lambs were longitudinally assessed following IA administration of 10 mg LPS at 5, 12 or 24h or 2, 4, 8 or 15d before preterm birth. Hepatic inflammation was observed, characterized by increased hepatic cytokine mRNA levels (5h - 2d post IA LPS exposure) and increased erythropoietic clusters (at 8 and 15 days post IA LPS exposure). Besides, 12h after IA LPS exposure, plasma BA levels were increased, whereas gene expression levels of several hepatic BA transporters were decreased. Initial EHC alterations normalized over time. Concluding, IA LPS exposure induces significant time-dependent changes in the fetal liver and EHC. These chorioamnionitis induced changes have potential postnatal consequences and the duration of IA LPS exposure might be essential herein.


Assuntos
Corioamnionite/imunologia , Circulação Êntero-Hepática/imunologia , Feto/irrigação sanguínea , Hepatite/imunologia , Nascimento Prematuro/imunologia , Animais , Ácidos e Sais Biliares/sangue , Ácidos e Sais Biliares/metabolismo , Proteínas de Transporte/genética , Proteínas de Transporte/metabolismo , Corioamnionite/sangue , Corioamnionite/patologia , Citocinas/sangue , Citocinas/metabolismo , Modelos Animais de Doenças , Feminino , Feto/imunologia , Regulação da Expressão Gênica/imunologia , Hepatite/sangue , Hepatite/patologia , Lipopolissacarídeos/administração & dosagem , Lipopolissacarídeos/imunologia , Fígado/imunologia , Fígado/patologia , Glicoproteínas de Membrana/genética , Glicoproteínas de Membrana/metabolismo , Gravidez , Nascimento Prematuro/sangue , Carneiro Doméstico , Fatores de Tempo
4.
Obstet Gynecol ; 137(6): 1007-1022, 2021 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-33957655

RESUMO

OBJECTIVE: To estimate the risk of maternal and neonatal sepsis associated with chorioamnionitis. DATA SOURCES: PubMed, BIOSIS, and ClinicalTrials.gov databases were systematically searched for full-text articles in English from inception until May 11, 2020. METHODS OF STUDY SELECTION: We screened 1,251 studies. Randomized controlled trials, case-control, or cohort studies quantifying a relationship between chorioamnionitis and sepsis in mothers (postpartum) or neonates born at greater than 22 weeks of gestation were eligible. Studies were grouped for meta-analyses according to exposures of histologic or clinical chorioamnionitis and outcomes of maternal or neonatal sepsis. TABULATION, INTEGRATION, AND RESULTS: One hundred three studies were included, and 55 met criteria for meta-analysis (39 studies of preterm neonates, 10 studies of general populations of preterm and term neonates, and six studies of late preterm and term neonates). Study details and quantitative data were abstracted. Random-effects models were used to generate pooled odds ratios (ORs); most studies only reported unadjusted results. Histologic chorioamnionitis was associated with confirmed and any early-onset neonatal sepsis (unadjusted pooled ORs 4.42 [95% CI 2.68-7.29] and 5.88 [95% CI 3.68-9.41], respectively). Clinical chorioamnionitis was also associated with confirmed and any early-onset neonatal sepsis (unadjusted pooled ORs 6.82 [95% CI 4.93-9.45] and 3.90 [95% CI 2.74-5.55], respectively). Additionally, histologic and clinical chorioamnionitis were each associated with higher odds of late-onset sepsis in preterm neonates. Confirmed sepsis incidence was 7% (early-onset) and 22% (late-onset) for histologic and 6% (early-onset) and 26% (late-onset) for clinical chorioamnionitis-exposed neonates. Three studies evaluated chorioamnionitis and maternal sepsis and were inconclusive. CONCLUSION: Both histologic and clinical chorioamnionitis were associated with early- and late-onset sepsis in neonates. Overall, our findings support current guidelines for preventative neonatal care. There was insufficient evidence to determine the association between chorioamnionitis and maternal sepsis. SYSTEMATIC REVIEW REGISTRATION: PROSPERO, CRD42020156812.


Assuntos
Corioamnionite/epidemiologia , Corioamnionite/patologia , Sepse Neonatal/epidemiologia , Nascimento Prematuro/epidemiologia , Feminino , Idade Gestacional , Humanos , Incidência , Recém-Nascido , Período Pós-Parto , Gravidez , Sepse/epidemiologia , Nascimento a Termo , Fatores de Tempo
5.
BMC Pregnancy Childbirth ; 21(1): 296, 2021 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-33845786

RESUMO

BACKGROUND: Necrotising funisitis (NF) is a rare, chronic stage of funisitis, a severe inflammation of the umbilical cord and an important risk factor for fetal adverse outcomes. NF is characterized by yellow-white bands running parallel to the umbilical blood vessels. These bands consist of inflammatory cells, necrotic debris, and calcium deposits. Calcification is visible in ultrasonography, which makes it possible to suspect NF when umbilical vascular wall calcification is detected by prenatal ultrasonography. CASE PRESENTATION: Ultrasonography revealed calcification of the umbilical venous wall in an expectant 31-year-old woman who was gravida 1, para 0. The woman required emergency cesarean section because of fetal distress and suspected umbilical cord torsion at 31 weeks gestation. The root of the umbilical cord was quite fragile and broke during the operation. The pathological results on the placenta showed histologic chorioamnionitis and NF. The infant was diagnosed to have neonatal sepsis and acidosis after delivery but was discharged without severe complications after a one-month hospitalization that included antibiotic and supportive therapy. CONCLUSION: NF is a rare and severe inflammation of the umbilical cord. Umbilical vascular wall calcification discovered in prenatal ultrasonography is diagnostically helpful.


Assuntos
Corioamnionite/diagnóstico , Cordão Umbilical/patologia , Calcificação Vascular/diagnóstico , Adulto , Cesárea , Corioamnionite/patologia , Corioamnionite/cirurgia , Feminino , Humanos , Imageamento Tridimensional , Recém-Nascido , Recém-Nascido de muito Baixo Peso , Masculino , Necrose/diagnóstico , Necrose/etiologia , Gravidez , Índice de Gravidade de Doença , Resultado do Tratamento , Ultrassonografia Doppler em Cores , Ultrassonografia Pré-Natal , Cordão Umbilical/irrigação sanguínea , Cordão Umbilical/diagnóstico por imagem , Veias Umbilicais/diagnóstico por imagem , Veias Umbilicais/patologia , Calcificação Vascular/complicações
6.
J Korean Med Sci ; 36(14): e93, 2021 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-33847083

RESUMO

BACKGROUND: In accordance with the guidelines for the expectant management of women exposed to previable preterm premature rupture of membrane, we compared neonatal outcomes according to the latent period from membrane rupture to delivery among extremely preterm infants exposed to maternal preterm premature rupture of membrane using the Korean Neonatal Network database. METHODS: Of the 3,305 extremely preterm infants born at 23-27 weeks' gestation between 2014 and 2017 who were registered in the Korean Neonatal Network, 1,464 infants were born to pregnant women who were exposed to preterm premature rupture of membrane. The short latency group was defined as infants born with a latent period between membrane rupture and delivery < 7 days (n = 450), whereas the prolonged latency group was defined as infants born with a latent period of ≥ 7 days (n = 434). Using well-established risk factors for adverse short-term outcomes, multivariate logistic regression analysis was performed to assess a prolonged latent period in preterm premature rupture of membrane as an independent risk factor for neonatal outcomes in extremely preterm infants exposed to preterm premature rupture of membrane. RESULTS: The mean gestational age at membrane rupture in the prolonged latency group was significantly lower than that in the short latency group (22.7 ± 2.5 vs. 25.4 ± 1.3 weeks, P < 0.001). Nevertheless, the mean gestational age at delivery and birth weight were not significantly different between the two groups. The incidence of oligohydramnios and histologic chorioamnionitis in the prolonged latency group was significantly higher than that in the short latency group (38.7 [155/401] vs. 26.1 [105/403], 69.8 [270/384] vs. 61.0 [242/397], respectively, P < 0.05). The survival rate in the prolonged latency group did not differ from that in the short latency group (71.2 [309/434] vs. 73.3 [330/450], P = 0.478). Although the prolonged latency group was not associated with mortality during hospitalization in the multivariate logistic regression analysis, the prolonged latency group's early pulmonary hypertension and bronchopulmonary dysplasia rates were increased by 1.8 and 1.5 times, respectively. CONCLUSION: A prolonged latent period of 7 days or more does not affect the survival rate but increases the risk of bronchopulmonary dysplasia occurrence among extremely preterm infants who are exposed to maternal preterm premature rupture of membrane.


Assuntos
Ruptura Prematura de Membranas Fetais/patologia , Lactente Extremamente Prematuro , Adulto , Displasia Broncopulmonar/patologia , Corioamnionite/epidemiologia , Corioamnionite/patologia , Estudos de Coortes , Bases de Dados Factuais , Feminino , Ruptura Prematura de Membranas Fetais/mortalidade , Idade Gestacional , Humanos , Hipertensão Pulmonar/patologia , Incidência , Recém-Nascido , Modelos Logísticos , Masculino , Oligo-Hidrâmnio/epidemiologia , Oligo-Hidrâmnio/patologia , Gravidez , Nascimento Prematuro , Estudos Prospectivos , Taxa de Sobrevida
7.
BMC Pregnancy Childbirth ; 21(1): 263, 2021 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-33784970

RESUMO

BACKGROUND: Intrauterine inflammation affects short- and long-term neonatal outcomes. Histological chorioamnionitis and funisitis are acute inflammatory responses in the fetal membranes and umbilical cord, respectively. Although labor dystocia includes a potential risk of intrauterine inflammation, the risk of histological chorioamnionitis and funisitis of labor dystocia has not been evaluated yet. This study aimed to examine the association between labor dystocia and risk of histological chorioamnionitis and funisitis. METHODS: In this retrospective cohort study, the cases who underwent histopathological examinations of the placenta and umbilical cord at Fukushima Medical University Hospital, Japan, between 2015 and 2020, were included. From the dataset, the pathological findings of the patients with labor dystocia and spontaneous preterm birth were reviewed. Based on the location of leukocytes, the inflammation in the placenta (histological chorioamnionitis) and umbilical cord (funisitis) was staged as 0-3. Multiple logistic regression analysis was performed to evaluate the risk of histological chorioamnionitis, histological chorioamnionitis stage ≥2, funisitis, and funisitis stage ≥2. RESULT: Of 317 women who met the study criteria, 83 and 144 women had labor dystocia and spontaneous preterm birth, respectively, and 90 women were included as controls. Labor dystocia was a risk factor for histological chorioamnionitis (adjusted odds ratio, 6.3; 95% confidential interval, 1.9-20.5), histological chorioamnionitis stage ≥2 (adjusted odds ratio, 6.0; 95% confidence interval, 1.7-21.8), funisitis (adjusted odds ratio, 15.4; 95% confidence interval, 2.3-101.3), and funisitis stage ≥2 (adjusted odds ratio, 18.5; 95% confidence interval, 2.5-134.0). Spontaneous preterm birth was also a risk factor for histological chorioamnionitis (adjusted odds ratio, 3.7; 95% confidence interval, 1.7-7.8), histological chorioamnionitis stage ≥2 (adjusted odds ratio, 3.0; 95% confidence interval, 1.2-7.9), and funisitis (adjusted odds ratio, 6.6; 95% confidence interval, 1.4-30.6). However, the adjusted odds ratio was smaller in spontaneous preterm births than in labor dystocia. CONCLUSION: Labor dystocia is a risk factor for severe histological chorioamnionitis and funisitis. Further studies are required to evaluate the effects of histological chorioamnionitis and funisitis on long-term neonatal outcomes.


Assuntos
Corioamnionite/epidemiologia , Distocia/epidemiologia , Nascimento Prematuro/epidemiologia , Adulto , Corioamnionite/diagnóstico , Corioamnionite/patologia , Conjuntos de Dados como Assunto , Feminino , Humanos , Recém-Nascido , Japão/epidemiologia , Placenta/patologia , Gravidez , Estudos Retrospectivos , Fatores de Risco , Índice de Gravidade de Doença , Centros de Atenção Terciária/estatística & dados numéricos , Cordão Umbilical/patologia
8.
BMC Pregnancy Childbirth ; 21(1): 250, 2021 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-33765949

RESUMO

BACKGROUND: Chorioamnionitis may cause serious perinatal and neonatal adverse outcomes, and group B streptococcus (GBS) is one of the most common bacteria isolated from human chorioamnionitis. The present study analyzed the impact of GBS infection and histological chorioamnionitis (HCA) on pregnancy outcomes and the diagnostic value of various biomarkers. METHODS: Pregnant women were grouped according to GBS infection and HCA detection. Perinatal and neonatal adverse outcomes were recorded with a follow-up period of 6 weeks. The white blood cell count (WBC), neutrophil ratio, and C-reactive protein (CRP) level from peripheral blood and soluble intercellular adhesion molecule-1 (sICAM-1), interleukin 8 (IL-8), and tumor necrosis factor α (TNF-α) levels from cord blood were assessed. RESULTS: A total of 371 pregnant women were included. Pregnant women with GBS infection or HCA had a higher risk of pathological jaundice and premature rupture of membranes and higher levels of sICAM-1, IL-8, and TNF-α in umbilical cord blood. Univariate and multivariate regression analysis revealed that sICMA-1, IL-8, TNF-α, WBC, and CRP were significantly related to an increased HCA risk. For all included pregnant women, TNF-α had the largest receiver operating characteristic (ROC) area (area: 0.841; 95% CI: 0.778-0.904) of the biomarkers analyzed. TNF-α still had the largest area under the ROC curve (area: 0.898; 95% CI: 0.814-0.982) for non-GBS-infected pregnant women, who also exhibited a higher neutrophil ratio (area: 0.815; 95% CI: 0.645-0.985) and WBC (area: 0.849; 95% CI: 0.72-0.978), but all biomarkers had lower value in the diagnosis of HCA in GBS-infected pregnant women. CONCLUSION: GBS infection and HCA correlated with several perinatal and neonatal adverse outcomes. TNF-α in cord blood and WBCs in peripheral blood had diagnostic value for HCA in non-GBS-infected pregnant women but not GBS-infected pregnant women.


Assuntos
Corioamnionite/diagnóstico , Complicações Infecciosas na Gravidez/diagnóstico , Nascimento Prematuro/epidemiologia , Infecções Estreptocócicas/diagnóstico , Streptococcus agalactiae/isolamento & purificação , Adulto , Biomarcadores/sangue , Estudos de Casos e Controles , Corioamnionite/sangue , Corioamnionite/microbiologia , Corioamnionite/patologia , Feminino , Sangue Fetal/química , Seguimentos , Humanos , Recém-Nascido , Contagem de Leucócitos , Placenta/patologia , Gravidez , Complicações Infecciosas na Gravidez/sangue , Complicações Infecciosas na Gravidez/microbiologia , Complicações Infecciosas na Gravidez/patologia , Resultado da Gravidez , Curva ROC , Medição de Risco/métodos , Infecções Estreptocócicas/sangue , Infecções Estreptocócicas/microbiologia , Infecções Estreptocócicas/patologia , Fator de Necrose Tumoral alfa/sangue , Cordão Umbilical/patologia , Adulto Jovem
9.
Int J Mol Sci ; 22(4)2021 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-33669331

RESUMO

Chorioamnionitis, an important cause of preterm birth, is linked to necrotizing enterocolitis (NEC). NEC is characterized by a disrupted mucus barrier, goblet cell loss, and endoplasmic reticulum (ER) stress of the intestinal epithelium. These findings prompted us to investigate the mechanisms underlying goblet cell alterations over time in an ovine chorioamnionitis model. Fetal lambs were intra-amniotically (IA) exposed to lipopolysaccharides (LPS) for 5, 12, or 24 h, or 2, 4, 8, or 15 d before premature delivery at 125 d gestational age (GA). Gut inflammation, the number, distribution, and differentiation of goblet cells, ER stress, and apoptosis were measured. We found a biphasic reduction in goblet cell numbers 24 h-2 d after, and 15 d after IA LPS exposure. The second decrease of goblet cell numbers was preceded by intestinal inflammation, apoptosis, and crypt ER stress, and increased SAM-pointed domain-containing ETS transcription factor (SPDEF)-positive cell counts. Our combined findings indicated that ER stress drives apoptosis of maturating goblet cells during chorioamnionitis, ultimately reducing goblet cell numbers. As similar changes have been described in patients suffering from NEC, these findings are considered to be clinically important for understanding the predecessors of NEC, and targeting ER stress in this context is interesting for future therapeutics.


Assuntos
Corioamnionite/patologia , Corioamnionite/veterinária , Enterocolite Necrosante/patologia , Enterocolite Necrosante/reabilitação , Enterocolite Necrosante/veterinária , Feto/patologia , Células Caliciformes/patologia , Animais , Animais Recém-Nascidos , Apoptose , Contagem de Células , Diferenciação Celular , Corioamnionite/induzido quimicamente , Modelos Animais de Doenças , Estresse do Retículo Endoplasmático , Enterocolite Necrosante/induzido quimicamente , Feminino , Idade Gestacional , Humanos , Lipopolissacarídeos/efeitos adversos , Gravidez , Nascimento Prematuro , Ovinos
10.
Pediatr Dev Pathol ; 24(3): 246-251, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33617361

RESUMO

Optimal management of intrauterine infection to avoid serious adverse perinatal outcomes entails prompt administration of antibiotics and consideration of early delivery of the fetus to remove the focus of infection. We report an unusual case of preterm chorioamnionitis which did not improve with sensitive antibiotics, or delivery of the fetus, and ultimately required an emergency hysterectomy to save the mother's life. Interestingly, subsequent histopathological analysis of the post-hysterectomy specimen did not reveal myometrial necrosis or infectious microorganisms. The placental pathological examination, on the other hand, showed evidence of necrotising chorioamnionitis accompanied by a rarely reported lesion: acute villitis with abundant intravascular Escherichia coli, a finding which is strongly associated with fetal demise and adverse maternal outcomes.


Assuntos
Corioamnionite/microbiologia , Vilosidades Coriônicas/microbiologia , Infecções por Escherichia coli/complicações , Sepse/microbiologia , Corioamnionite/patologia , Vilosidades Coriônicas/patologia , Feminino , Morte Fetal/etiologia , Humanos , Gravidez , Complicações Infecciosas na Gravidez/microbiologia , Complicações Infecciosas na Gravidez/patologia
11.
BMC Pregnancy Childbirth ; 21(1): 99, 2021 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-33516193

RESUMO

BACKGROUND: Chorangiosis is a vascular change involving the terminal chorionic villi in the placenta. It results from longstanding, low-grade hypoxia in the placental tissue, and is associated with such conditions as intrauterine growth restriction (IUGR), diabetes, and gestational hypertension in pregnancy. Chorangiosis rarely occurs in normal pregnancies. However, its prevalence is 5-7% of all placentas from infants admitted to newborn intensive care units. The present study was aimed at determining the association of chorangiosis with pregnancy complications and perinatal outcomes. METHODS: In this case-control study, 308 chorangiosis cases were compared with 308 controls (with other diagnoses in pathology) in terms of maternal, placental, prenatal, and neonatal characteristics derived from the medical records of participants retrospectively. R and SPSS version 22 software tools were used, and the statistical significance level was considered 0.05 for all the tests. RESULTS: Preeclampsia, diabetes mellitus, maternal hemoglobin, maternal hematocrit, C/S, oligohydramnios, fetal anomaly, dead neonates, NICU admissions were significantly higher in the chorangiosis group OR = 1.6, 3.98, 1.68, 1.92, 2.1, 4.47, 4.22, 2.9, 2.46, respectively (p-value< 0.05 for all). Amniotic fluid index, birth weight, cord PH amount, 1st, and 5th Apgar score was lower in the chorangiosis group OR = 0.31, 1, 0.097, 0.83, 0.85, respectively (p-value< 0.05 for all). Moreover, fundal placenta, retro placental hemorrhage, perivillous fibrin deposition, calcification, and acute chorioamnionitis were higher in the chorangiosis group OR = 2.1, 11.8, 19.96, 4.05, and 6.38 respectively, (p-value< 0.05). There was a high agreement between the two pathologists, and the power of the study was estimated at 99%. CONCLUSION: Although chorangiosis is an uncommon condition, it is associated with a higher incidence of perinatal and neonatal morbidity and mortality. Therefore, it should be considered an important clinical sign of adverse pregnancy outcomes and should be reported in the pathology evaluation.


Assuntos
Corioamnionite/patologia , Vilosidades Coriônicas/patologia , Doenças Placentárias/patologia , Placenta/patologia , Complicações na Gravidez/patologia , Resultado da Gravidez , Adulto , Índice de Apgar , Estudos de Casos e Controles , Feminino , Humanos , Lactente , Mortalidade Infantil/tendências , Recém-Nascido , Gravidez , Adulto Jovem
12.
J Reprod Immunol ; 144: 103268, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33454392

RESUMO

Ascending placentitis is a leading cause of abortion in the horse, but adaptive immune response to this disease is unknown. To evaluate this, sub-acute placentitis was experimentally-induced via trans-cervical inoculation of S. zooepidemicus, and endometrium and chorioallantois was collected 8 days later (n = 6 inoculated/n = 6 control). The expression of transcripts relating to Th1, Th2, Th17, and Treg maturation was assessed via RNASeq. IHC of transcription factors relating to each subtype in the same tissues (Th1: TBX21, Th2: GATA3, Th17: IRF4, Treg: FOXp3). An immunoassay was utilized to assess circulating cytokines (Th1: IFNg, IL-2; Th2: IL-4, IL-5; Th17: IL-17, IL-6; Treg: IL-10, GM-CSF). An increase in Th1 and Th17-related transcripts were noted in the chorioallantois, although no alterations were seen in the endometrium. Th2 and Treg-related transcripts altered in a dysregulated manner, as some transcripts increased in expression while others decreased. Immunolocalization of Th1, Th2, and Th17 cells was increased in diseased chorioallantois, while no Treg cells were noted in the diseased tissue. Secreted cytokines relating to Th1 (IFNg, IL-2), Th17 (IL-6), Th2 (IL-5), and Treg (IL-10) populations increased in maternal circulation eight days after inoculation. In conclusion, the Th1/Th17 response to ascending placentitis occurs primarily in the chorioallantois, indicating the adaptive immune response to occur in fetal derived placental tissue. Additionally, ascending placentitis leads to an increase in the helper T cell populations (Th1/Th17/Th2) while decreasing the Treg response. This increase in Th17-related responses alongside a diminishing Treg-related response may precede or contribute to fetal demise, abortion, or preterm labor.


Assuntos
Aborto Animal/imunologia , Corioamnionite/veterinária , Cavalos/imunologia , Linfócitos T Reguladores/imunologia , Células Th17/imunologia , Aborto Animal/patologia , Animais , Corioamnionite/imunologia , Corioamnionite/patologia , Citocinas/metabolismo , Feminino , Gravidez , Linfócitos T Reguladores/metabolismo , Células Th1/imunologia , Células Th1/metabolismo , Células Th17/metabolismo , Células Th2/imunologia , Células Th2/metabolismo
13.
J Obstet Gynaecol ; 41(5): 721-725, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33045849

RESUMO

The objective was to determine the relationship of histological chorioamnionitis (HCA) with genital tract cultures in preterm birth. Among two hundred women recruited for the study, 100 were taken as cases with gestational age between ≥28 and <37 weeks and 100 women with gestational age >37 weeks were taken as controls. Vaginal swabs were taken for culture sensitivity and vaginal smears were made for performing whiff test and heat dry gram stained smear was examined for growth of microorganisms. Histopathologic examination of the placenta was done after delivery. 49 cases and 26 controls had evidence of histological chorioamnionitis. A significant difference was observed in relation to the presence of E. coli, presence of clue cells, positive whiff test and occurrence of bacterial vaginosis in subjects with and without histological chorioamnionitis. Thus, we conclude that the presence of histological chorioamnionitis is closely related to the presence of pathogenic microorganisms in the cervicovaginal region.IMPACT STATEMENTWhat is already known on the subject? Histologic chorioamnionitis has been regarded to reflect amniotic fluid infection and there are studies showing an association between histologic chorioamnionitis, amniotic fluid, and subchorionic plate cultures. Nevertheless, studies of the correlation of the cervical swab cultures with intrauterine infection in preterm birth remain inconclusive.What do the results of this study add? Histologic chorioamnionitis is closely related to the presence of pathogenic microorganisms in the cervicovaginal region.What are the implications of these findings for clinical practice and/or further research? High vaginal swab cultures and gram staining of vaginal smear is useful in detecting antenatal patients who are at a higher risk for preterm labour. After detection, early intervention may be done to avoid preterm deliveries in these high-risk pregnancies.


Assuntos
Corioamnionite/microbiologia , Trabalho de Parto Prematuro/microbiologia , Complicações Infecciosas na Gravidez/microbiologia , Vaginose Bacteriana/complicações , Adulto , Colo do Útero/microbiologia , Corioamnionite/patologia , Escherichia coli , Feminino , Idade Gestacional , Humanos , Recém-Nascido , Trabalho de Parto Prematuro/patologia , Placenta/microbiologia , Placenta/patologia , Gravidez , Vagina/microbiologia , Esfregaço Vaginal , Vaginose Bacteriana/microbiologia
14.
Am J Perinatol ; 38(4): 377-382, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-31600792

RESUMO

OBJECTIVE: This study was aimed to assess the utility of diagnostic tests of maternal and fetal infection in the evaluation of stillbirth. STUDY DESIGN: A single-center retrospective study from January 2011 to December 2016 of all women presenting to the hospital with intrauterine fetal death at or after 20 weeks of gestation. Standard evaluation included review of medical records, clinical and laboratory inflammatory workup, maternal serologies, fetal autopsy, placental pathology, and fetal and placental cultures. A suspected infectious etiology was defined as meeting at least two diagnostic criteria, and only after exclusion of any other identifiable stillbirth cause. RESULTS: During the 7-year study period, 228 cases of stillbirth were diagnosed at our center. An infectious etiology was the suspected cause of stillbirth in 35 cases (15.3%). The mean gestational age of infection-related stillbirth was 28 1/7 (range: 22-37) weeks, while for a noninfectious etiology, it was 34 0/7 (range: 25-38) weeks (p = 0.005). Placental histological findings diagnostic of overt chorioamnionitis and funisitis were observed in 31 (88.5%) cases. In 16 (45.7%) cases the placental and fetal cultures were positive for the same pathogen. Serology of acute infection was positive in three (8.5%) of the cases. CONCLUSION: Maternal and fetal infectious workup is valuable in the investigation of stillbirth, particularly before 30 weeks of gestation and should be considered a part of standard evaluation.


Assuntos
Corioamnionite/epidemiologia , Morte Fetal/etiologia , Infecções/complicações , Complicações Infecciosas na Gravidez/epidemiologia , Natimorto/epidemiologia , Adulto , Autopsia , Corioamnionite/patologia , Feminino , Idade Gestacional , Humanos , Recém-Nascido , Israel/epidemiologia , Modelos Logísticos , Placenta/patologia , Gravidez , Estudos Retrospectivos
15.
Int J Surg Pathol ; 29(4): 438-442, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32844693

RESUMO

Placental intervillous hematomas have not previously been reported to undergo any sort of change, maturation, or healing. In this article, we present the first 2 case reports of recanalization-like neovascularization within placental hematomas: a 0.15 cm focus in an intervillous fibrin thrombus and a 0.2 cm focus in a subchorionic hematoma. Increased recognition and further studies are needed to gain a better understanding of this seemingly rare phenomenon and the factors that govern the lack of typical organization in placental hematomas. This might lead to a deeper knowledge of the repair process in general and shed light on how to control it in diseases caused by excessive repair.


Assuntos
Corioamnionite/diagnóstico , Hematoma/diagnóstico , Neovascularização Patológica/diagnóstico , Placenta/patologia , Cesárea , Corioamnionite/etiologia , Corioamnionite/patologia , Feminino , Hematoma/complicações , Hematoma/patologia , Humanos , Recém-Nascido , Neovascularização Patológica/complicações , Neovascularização Patológica/patologia , Placenta/irrigação sanguínea , Gravidez , Adulto Jovem
16.
PLoS One ; 15(12): e0243455, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33382728

RESUMO

OBJECTIVE: To determine the placental pathologies and maternal factors associated with stillbirth at Kilimanjaro Christian Medical Centre, a tertiary referral hospital in Northern Tanzania. METHODS: A 1:2 unmatched case-control study was carried out among deliveries over an 8-month period. Stillbirths were a case group and live births were the control group. Respective placentas of the newborns from both groups were histopathologically analyzed. Maternal information was collected via chart review. Mean and standard deviation were used to summarize the numerical variables while frequency and percentage were used to summarize categorical variables. Crude and adjusted logistic regressions were done to test the association between each variable and the risk of stillbirth. RESULTS: A total of 2305 women delivered during the study period. Their mean age was 30 ± 5.9 years. Of all deliveries, 2207 (95.8%) were live births while 98 (4.2%) were stillbirths. Of these, 96 stillbirths (cases) and 192 live births (controls) were enrolled. The average gestational age for the enrolled cases was 33.8 ±3.2 weeks while that of the controls was 36.3±3.6 weeks, (p-value 0.244). Of all stillbirths, nearly two thirds 61(63.5%) were males while the females were 35(36.5%). Of the stillbirth, 41were fresh stillbirths while 55 were macerated. The risk of stillbirth was significantly associated with lower maternal education [aOR (95% CI): 5.22(2.01-13.58)], history of stillbirth [aOR (95%CI): 3.17(1.20-8.36)], lower number of antenatal visits [aOR (95%CI): 6.68(2.71-16.48), pre/eclampsia [aOR (95%CI): 4.06(2.03-8.13)], and ante partum haemorrhage [OR (95%CI): 2.39(1.04-5.53)]. Placental pathology associated with stillbirth included utero-placental vascular pathology and acute chorioamnionitis. CONCLUSIONS: Educating the mothers on the importance of regular antenatal clinic attendance, monitoring and managing maternal conditions during antenatal periods should be emphasized. Placentas from stillbirths should be histo-pathologically evaluated to better understand the possible aetiology of stillbirths.


Assuntos
Placenta/patologia , Natimorto , Adolescente , Adulto , Estudos de Casos e Controles , Corioamnionite/diagnóstico , Corioamnionite/patologia , Escolaridade , Feminino , Idade Gestacional , Humanos , Recém-Nascido , Modelos Logísticos , Masculino , Pré-Eclâmpsia/patologia , Gravidez , Complicações na Gravidez , Cuidado Pré-Natal/estatística & dados numéricos , Fatores de Risco , Tanzânia , Adulto Jovem
17.
Artigo em Inglês | MEDLINE | ID: mdl-33137520

RESUMO

OBJECTIVE: Prostaglandins (PGs) are considered universal mediators for the process of physiological parturition. This is based on observations that amniotic fluid concentrations of PGs are elevated prior to and during the onset of labor (mostly utilizing immunoassays). Distinguishing PGs from similarly structured molecules (i.e. prostamides; PG-EA) is difficult given the cross-reactivity of available antibodies and the chemical similarity between these compounds. Herein, this limitation was overcome by utilizing mass spectrometry to determine PG and PG-EA concentrations in amniotic fluid of women with spontaneous labor at term and in those with clinical chorioamnionitis (CHAM), the most common infection-related diagnosis made in labor and delivery units worldwide. STUDY DESIGN: Liquid chromatography-tandem mass spectrometry (LC MS/MS) was used to determine the PG and PG-EA content in amniotic fluid samples of women with spontaneous labor at term with (n = 14) or without (n = 28) CHAM. Controls included women who delivered at term without labor (n = 10). RESULTS: PGE2, PGF2α, and 13,14-dihydro-15-keto-PGF2α (PGFM) were higher in amniotic fluid of women with spontaneous labor at term than in those without labor. PGE2, PGF2α, and PGFM were also higher in amniotic fluid of women with CHAM than in those without labor. However, PGE2-EA and PGF2α-EA were lower in amniotic fluid of women with CHAM than in those without CHAM. The ratios of PGE2 to PGE2-EA and PGF2α to PGF2α-EA were higher in amniotic fluid of women with spontaneous labor at term with or without CHAM than in those without labor; yet, the ratio of PGF2α to PGF2α-EA was greater in women with CHAM than in those without this clinical condition. CONCLUSIONS: Spontaneous labor at term with or without CHAM is characterized by elevated amniotic fluid concentrations of prostaglandins (PGE2, PGF2α, and PGFM) but not prostamides. Quantification of these products by LC MS/MSlc==may potentially be of utility in identifying their physiological functions relevant to parturition. SUMMARY: Prostaglandins (PGs) are critical for the onset and progression of labor. Structural similarities of PGs and prostamides (PG-EA) prevents their specific identification by immunoassay. We utilized LC MS/MS to determine PG and PG-EA content in amniotic fluid (AF) of women with spontaneous labor at term with or without CHAM and women who delivered at term without labor. Higher aamniotic ffluid PG levels were observed in women with spontaneous labor with and without CHAM compared to women delivering without labor. PG-EA levels in amniotic fluid of women with spontaneous labor and CHAM were lower than in women with spontaneous labor without CHAM but not those without labor. Ratios of PGs to PG-EAs were higher in AF of women with labor and CHAM compared to those without labor. Delineation of these products by LC MS/MS may potentially be of utility in identifying their physiological functions relevant to parturition.


Assuntos
Líquido Amniótico/metabolismo , Corioamnionite/metabolismo , Nascimento Prematuro/metabolismo , Prostaglandinas/metabolismo , Adulto , Corioamnionite/patologia , Feminino , Humanos , Gravidez , Estudos Retrospectivos , Espectrometria de Massas em Tandem
18.
PLoS One ; 15(11): e0242579, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33253176

RESUMO

An opaque fetal membrane based on gross appearance is traditionally indicative of histological chorioamnionitis; however, to the best of our knowledge, there is currently no supportive evidence, and its diagnostic efficiency has not yet been scientifically demonstrated. The present study aimed to provide scientific insights into the traditional concept of an opaque fetal membrane based on gross appearance being an indicator of histological chorioamnionitis. We examined the placental pathology after screening of the placental gross appearance and perinatal complications and did not examine uncomplicated deliveries. We investigated the relationship between the presence of an opaque fetal membrane and histological chorioamnionitis (Cohort 1, 571 placentas) or the outcomes of neonates delivered at term (Cohort 2, 409 placentas) at Hamamatsu University School of Medicine between 2010 and 2017. The judgment of a positive opaque fetal membrane based on gross appearance correlated with histological chorioamnionitis (Cohort 1). Its sensitivity and specificity were 66.7 and 89.9%, respectively, while positive and negative predictive values were 86.8 and 73.0%, respectively. The judgment of a positive opaque fetal membrane based on gross appearance significantly correlated with chorioamnionitis-related complications in term newborns after adjustments for confounding factors (OR;1.82 [1.07-3.11], P<0.05) (Cohort 2). A correlation was observed even after adjustments for confounding factors. The present study is the first to demonstrate that the judgment of a positive opaque fetal membrane based on gross appearance correlated with histological chorioamnionitis as well as chorioamnionitis-related complications in newborns delivered at term. The present results provide support for the traditionally-described importance of gross inspections for an opaque fetal membrane soon after birth.


Assuntos
Corioamnionite/etiologia , Membranas Extraembrionárias/patologia , Doenças do Recém-Nascido/etiologia , Doenças Respiratórias/etiologia , Adolescente , Adulto , Corioamnionite/patologia , Feminino , Humanos , Recém-Nascido , Doenças do Recém-Nascido/patologia , Placenta/patologia , Gravidez , Nascimento Prematuro , Doenças Respiratórias/patologia , Adulto Jovem
19.
J Cell Mol Med ; 24(22): 13397-13407, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-33025767

RESUMO

Chorioamnionitis (CAM), as a common intrauterine infectious disease, is the leading cause of premature birth, stillbirth, neonatal infection and sepsis. The formyl peptide receptor 2 (FPR2) is a member of GPCRs widely distributed in a variety of tissues and is associated with many inflammatory diseases. With the discovery of FPR2 in human placenta, the possibility of exploring the function of FPR2 in obstetrics is evolving. The Resolvin D1 (RvD1) plays an important role in the resolution of inflammation by combining with FPR2. In this study, we evaluated the role of FPR2 and RvD1 in CAM, not only in the human placenta but also in mouse models. The expression of FPR2 increased in the placenta of CAM patients and the downstream PPARγ/NF-κB signalling changed accordingly. Moreover, Fpr2-/- mice were highly susceptible to LPS, displaying a worse CAM symptom, compared with WT mice. By establishing a model of trophoblast inflammation in vitro, it was confirmed that RvD1 rescued the effect of LPS on inflammation by combining with FPR2 and its downstream PPARγ/NF-κB pathway. Otherwise, RvD1 improved the preterm labour in a mouse model of CAM induced by LPS. Altogether, these findings show that RvD1 alleviated the inflammation of trophoblast in vivo and in vitro through FPR2/PPARγ/NF-κB pathway, suggesting RvD1/FPR2 might be a novel therapeutic strategy to alleviate CAM.


Assuntos
Corioamnionite/etiologia , Corioamnionite/metabolismo , Ácidos Docosa-Hexaenoicos/farmacologia , Receptores de Formil Peptídeo/metabolismo , Animais , Anti-Inflamatórios/farmacologia , Corioamnionite/tratamento farmacológico , Corioamnionite/patologia , Modelos Animais de Doenças , Suscetibilidade a Doenças , Feminino , Expressão Gênica , Humanos , Imuno-Histoquímica , Lipopolissacarídeos/efeitos adversos , Camundongos , Camundongos Knockout , NF-kappa B/metabolismo , PPAR gama/metabolismo , Placenta/metabolismo , Gravidez , Receptores de Formil Peptídeo/genética , Transdução de Sinais , Trofoblastos/efeitos dos fármacos , Trofoblastos/imunologia , Trofoblastos/metabolismo
20.
Semin Fetal Neonatal Med ; 25(4): 101142, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32912755

RESUMO

Fetal Inflammatory Response Syndrome (FIRS) is the fetal counterpart of systemic inflammatory response syndrome (SIRS) described in adults. When the fetus is directly exposed to inflammation of the fetal membranes or the placental-fetal circulation, and organs are adversely affected, the disorder is known as FIRS. This syndrome can significantly affect multiple organs with significant short and long term implications for the newborn. In cases of neonatal encephalopathy when no obvious etiology is identified, FIRS needs to be considered. Based on the significant incidence of chorioamnionitis and its potential effects on the newborn, any evidence of maternal, fetal, or neonatal infection should mandate further evaluation of the placenta and membrane histopathology.


Assuntos
Corioamnionite/patologia , Sangue Fetal , Síndrome de Resposta Inflamatória Sistêmica/patologia , Adulto , Corioamnionite/epidemiologia , Feminino , Humanos , Recém-Nascido , Placenta/patologia , Gravidez , Síndrome de Resposta Inflamatória Sistêmica/epidemiologia
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