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1.
Matern Child Health J ; 26(3): 623-631, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35015174

RESUMO

BACKGROUND: Little is understood about child welfare involvement (CWI) in cases where the birth mother has experienced human trafficking. OBJECTIVES: The aim of this study was to explore provider perceptions of the impact of CWI for the trafficked mother. METHODS: Participants were selected among providers caring for trafficked birth mothers. Semi-structured interviews were conducted with providers and qualitative content analysis was conducted. RESULTS: Interviewees reported reasons for CWI, positive and negative impacts of CWI and provided recommendations for systems improvement. CONCLUSION FOR PRACTICE: Recommendations from this exploratory study include mechanisms to support trafficked mothers, train hospital social workers, and systems change. During the prenatal period, strategies to support the trafficked mother may include addressing gaps in social determinants of health, ensuring appropriate medical and mental health care, early screening and referral to substance use treatment services, enhancing community support, and working to develop safety plans for survivors and their families. Enhanced engagement of social workers and all providers to improve understanding of the unique complexity of trafficked mothers is needed. Education should include an understanding that judgement of a caretaker's ability to parent should be current and holistic and not reflexive based on history in the electronic medical record. An exploration of the child welfare system itself should also be undertaken to identify and modify discriminatory laws and policies. Finally, efforts to address social determinants of health in the community and enhance the trauma-informed nature of child welfare referrals could improve the lives of trafficked mothers.


Assuntos
Atitude do Pessoal de Saúde , Proteção da Criança , Tráfico de Pessoas , Mães , Criança , Feminino , Humanos , Gravidez , Encaminhamento e Consulta
2.
J Card Surg ; 36(12): 4756-4758, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34523160

RESUMO

A 26-year-old pregnant woman, with multiple metastatic Ewing sarcoma, presented with a sternal mass that began enlarging during pregnancy. Due to high-risk pregnancy, the patient was discussed in a multidisciplinary meeting and intubation was considered too risky without cardiopulmonary support. Computed tomography showed extrinsic tumor compression of the right ventricle outflow tract. Veno-arterial (VA) extracorporeal membrane oxygenation (ECMO) was initiated before general anesthesia, followed by Cesarean section (C-section). VA ECMO was initiated with the patient in the awake position, ECMO support was discontinued when the patient had stable ventilation and hemodynamics. This case represents a unique indication of VA ECMO, during C-section, with maternal and fetal survival.


Assuntos
Oxigenação por Membrana Extracorpórea , Sarcoma de Ewing , Adulto , Cesárea , Feminino , Hemodinâmica , Humanos , Gravidez , Sarcoma de Ewing/terapia
3.
Fertil Steril ; 116(3): 801-808, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34210397

RESUMO

OBJECTIVE: To study the incidence and clinical significance of congenital heart defects (CHDs) detected by fetal echocardiography in pregnancies conceived by in vitro fertilization (IVF). DESIGN: Cohort study comparing a prospectively maintained database of all fetal echocardiograms from 2012 to 2018 and pooled data from the Connecticut Birth Defects Registry and statewide hospital discharge data. SETTING: Large tertiary care center. PATIENT(S): A total of 181,749 live births and 9,252 fetal echocardiograms were analyzed. Fetal echocardiograms in patients with a previous child with a CHD, a family history of CHD, medication exposure, diabetes, anomaly in previous pregnancy, cardiac or other abnormality noted on previous ultrasound, or monochorionic twins were excluded from the final analysis. INTERVENTION(S): Treatment with IVF. MAIN OUTCOME MEASURE(S): Incidence of CHD and odds ratios with 95% confidence intervals (CIs). Infant outcomes for cases of CHD were evaluated for clinically significant disease, defined a priori as disease requiring any medical or surgical intervention or continued follow-up with pediatric cardiology. RESULT(S): Fetal echocardiography was performed in 2,230 IVF pregnancies, of which 2,040 were without other known risk factors for CHD. The mean gestational age at the time of fetal echocardiography was 22.2 ± 1.4 weeks. The odds ratio for CHD in the IVF group compared with statewide population rates was 1.4 (95% CI 0.9-2.1). CHD was diagnosed in 26 fetuses, of which 21 were clinically insignificant ventricular septal defects. One fetal echocardiogram was concerning for pulmonary stenosis that was not present at birth. Four defects were clinically significant, indicating that 510 fetal echocardiograms were performed for every diagnosis of one clinically significant CHD in the IVF group. CONCLUSION(S): The incidence of CHD in IVF pregnancies without other risk factors is not significantly different from baseline population rates, and most CHDs diagnosed by fetal echocardiography in this group are clinically insignificant. Routine screening with fetal echocardiography in all IVF pregnancies provides limited utility beyond routine prenatal care and need not be recommended without the presence of other risk factors.


Assuntos
Ecocardiografia Doppler em Cores , Fertilização in vitro , Coração Fetal/diagnóstico por imagem , Cardiopatias Congênitas/diagnóstico por imagem , Infertilidade/terapia , Ultrassonografia Pré-Natal , Bases de Dados Factuais , Feminino , Fertilização in vitro/efeitos adversos , Coração Fetal/anormalidades , Cardiopatias Congênitas/epidemiologia , Humanos , Incidência , Infertilidade/diagnóstico , Infertilidade/fisiopatologia , Valor Preditivo dos Testes , Gravidez , Sistema de Registros , Medição de Risco , Fatores de Risco , Resultado do Tratamento
4.
Am J Perinatol ; 36(10): 1031-1038, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-30500963

RESUMO

OBJECTIVE: Placenta accreta is a feared pathology, in part, because prenatal diagnosis is imperfect. It is not known whether clinical risk factors or sonographic features equally predict the entire graded pathological spectrum of placental overinvasion disease nor whether clinical outcomes differ along the spectrum. STUDY DESIGN: We conducted a mixed methods retrospective study of a cohort of women screened sonographically for placenta accreta, cross-referenced against cases identified by pathological diagnosis (N = 416). Demographic, diagnostic, and outcome information were compared across the spectrum of invasive placentation: percreta, increta, accreta, and focal accreta not requiring hysterectomy. The t-test, chi-square, Mann-Whitney, and Kruskal-Wallis tests were used for statistical analysis across groups. RESULTS: As the depth of invasion decreased, risk factors for placental overinvasion were less common, especially placenta previa and previous cesarean. There was also reduced anticipation by sonographic examination of the placenta. Rates of adverse outcomes were lower among women with focal accreta compared with those with deeper invasion. CONCLUSION: As the depth of invasion decreases, clinical risk factors and sonographic evaluation are less reliable in the antenatal prediction of placenta accreta. The potential for unanticipated morbidity underscores the need for improved diagnostic tools for placenta accreta spectrum.


Assuntos
Placenta Acreta/diagnóstico por imagem , Ultrassonografia Pré-Natal , Adulto , Cesárea , Feminino , Humanos , Histerectomia , Idade Materna , Gravidade do Paciente , Placenta/diagnóstico por imagem , Placenta/patologia , Placenta Acreta/patologia , Placenta Acreta/cirurgia , Gravidez , Resultado da Gravidez , Nascimento Prematuro/epidemiologia , Estudos Retrospectivos , Fatores de Risco
5.
Obstet Gynecol ; 132(5): 1285-1295, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30303911

RESUMO

OBJECTIVE: To describe the treatment and subsequent pregnancy outcomes in patients with cesarean scar pregnancies at a single institution over 5 years. METHODS: This is a case series of all cesarean scar pregnancies diagnosed from May 2013 to March 2018 at Yale-New Haven Hospital. Data were collected on each patient using electronic medical record review and included patient demographics; medical, surgical, and obstetric history; pregnancy characteristics; treatment modalities used; response to therapy; complications; and subsequent pregnancy outcomes. RESULTS: Thirty cases of cesarean scar pregnancies were diagnosed in 26 patients, including one recurrence in one patient and three recurrences in another. Forty-six percent of cesarean scar pregnancies were in Hispanic women. The median number of prior cesarean deliveries was two. Mean gestational age at the time of diagnosis was 46 days (SD±10). Fetal cardiac activity was detected in 18 cases. Three patients initially were erroneously diagnosed with a viable intrauterine pregnancy and failed medical termination. Others opted for termination through systemic methotrexate alone (n=4), systemic and local methotrexate (n=12), systemic and local methotrexate with potassium chloride injected into the gestational sac (n=3), potassium chloride injection with laparotomy and wedge resection (n=1), methotrexate with bilateral uterine artery embolization (n=2), or intrauterine balloon (n=4). Five patients who underwent expectant management or methotrexate therapy had retained products of conception and required hysteroscopy and curettage. One patient opted for hysterectomy after failed curettage. After complete resolution of cesarean scar pregnancies, there were 10 subsequent spontaneous conceptions in eight patients, including four recurrent cesarean scar pregnancies, four term pregnancies, and one spontaneous abortion. One viable normally located pregnancy is ongoing. CONCLUSION: There is a wide array of treatment modalities available for cesarean scar pregnancies. Women with a cesarean scar pregnancy are at risk for its recurrence in the future, although normal pregnancy after a cesarean scar pregnancy is also possible. Safe outcomes depend on timely diagnosis and multidisciplinary care by skilled clinicians.


Assuntos
Cesárea/efeitos adversos , Cicatriz/complicações , Gravidez Ectópica/terapia , Abortivos não Esteroides/uso terapêutico , Adulto , Terapia Combinada , Curetagem , Feminino , Humanos , Histeroscopia , Metotrexato/uso terapêutico , Cloreto de Potássio/uso terapêutico , Gravidez , Taxa de Gravidez , Gravidez Ectópica/etiologia , Recidiva , Centros de Atenção Terciária , Embolização da Artéria Uterina , Tamponamento com Balão Uterino , Conduta Expectante , Adulto Jovem
6.
Obstet Gynecol ; 125(1): 157-159, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25560118

RESUMO

BACKGROUND: Müllerian anomalies are associated with adverse pregnancy outcomes. We discuss pregnancy in anomalous uteri, with a focus on uterine didelphys, in the setting of a prior cesarean delivery. CASE(S): A 30-year-old woman, gravida 2 para 1001, presented in latent labor at 40 1/7 weeks of gestation. Her first pregnancy was in the right horn of a didelphic uterus and resulted in a cesarean delivery in the setting of chorioamnionitis remote from delivery. The current pregnancy was in the left horn and resulted in a vacuum-assisted vaginal delivery after spontaneous labor. CONCLUSION: There is sparse literature on a trial of labor after cesarean delivery in a uterine didelphys.


Assuntos
Útero/anormalidades , Nascimento Vaginal Após Cesárea , Adulto , Feminino , Humanos , Gravidez , Prova de Trabalho de Parto , Vácuo-Extração
7.
Am J Reprod Immunol ; 73(3): 242-50, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25070806

RESUMO

PROBLEM: Women with antiphospholipid syndrome (APS) are at increased risk of recurrent pregnancy loss (RPL) and preeclampsia. Antiphospholipid antibodies (aPL) directly alter trophoblast function. Treatment with low molecular weight heparin (LMWH) reduces the risk of RPL but not preeclampsia. Moreover, LMWH stimulates trophoblast sFlt-1 release, an anti-angiogenic factor associated with preeclampsia. Since vitamin D deficiency is associated with APS and preeclampsia, this study sought to determine the effect of vitamin D on trophoblast function in the setting of aPL and LMWH. METHOD OF STUDY: A human first trimester trophoblast cell line (HTR8) and primary trophoblast cultures were treated with or without aPL in the presence and absence of vitamin D, LMWH or both. Trophoblast secretion of inflammatory cytokines and angiogenic factors were measured by ELISA. RESULTS: Vitamin D alone or in combination with LMWH attenuated the aPL-induced trophoblast inflammatory response in the HTR8 cells and primary cultures. While vitamin D did not have any impact on aPL-mediated modulation of angiogenic factors in the primary trophoblast, it significantly inhibited LMWH-induced sFlt-1 release. CONCLUSION: LMWH in combination with vitamin D may be more beneficial than single-agent therapy by preventing aPL-induced trophoblast inflammation and reversing LMWH-induced sFlt-1 secretion.


Assuntos
Anti-Inflamatórios/farmacologia , Anticorpos Antifosfolipídeos/imunologia , Calcitriol/farmacologia , Citocinas/metabolismo , Enoxaparina/farmacologia , Proteínas de Membrana/metabolismo , Trofoblastos/efeitos dos fármacos , Fator A de Crescimento do Endotélio Vascular/metabolismo , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/metabolismo , Animais , Linhagem Celular , Avaliação Pré-Clínica de Medicamentos , Feminino , Humanos , Imunoglobulina G/imunologia , Inflamação , Interleucina-8/metabolismo , Camundongos , Gravidez , Trofoblastos/metabolismo
8.
J Ultrasound Med ; 33(2): 337-41, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24449738

RESUMO

OBJECTIVES: Induction of fetal demise before second-trimester termination is performed for a number of reasons. One method for inducing fetal demise is via sonographically guided intracardiac potassium chloride (KCl) injection. We performed a retrospective cohort study to determine the efficacy and safety of intracardiac KCl injection as a method of second-trimester induced fetal demise. METHODS: We reviewed records from patients who were referred for induced fetal demise from October 2002 to October 2011. We excluded patients undergoing selective fetal reduction in multiple gestations. Procedural complications, the dose of KCl, and the number of failed procedures were determined. RESULTS: Of the 192 completed procedures, 191 were successful (99.5%). The median gestational age at termination was 22 weeks (range, 15.4-24.9 weeks), and most terminations were surgical (68.0%). Major indications for termination were fetal anomalies (41.6%), unwanted pregnancy (20.8%), and aneuploidy (15.7%). The median dose of KCl was 10 mL (range, 3-40 mL). We found a significant correlation between the dose of KCl and estimated fetal weight. There was no significant correlation between the dose of KCl and body mass index or gestational age. We had 1 maternal complication of a seizure after needle placement but before KCl injection. CONCLUSIONS: Intracardiac KCl injection is an effective and safe method for induced fetal demise.


Assuntos
Abortivos/administração & dosagem , Abortivos/efeitos adversos , Cloreto de Potássio/administração & dosagem , Cloreto de Potássio/efeitos adversos , Ultrassonografia Pré-Natal , Adolescente , Adulto , Estudos de Coortes , Feminino , Humanos , Injeções Intravenosas/efeitos adversos , Pessoa de Meia-Idade , Gravidez , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
9.
Rev Obstet Gynecol ; 5(2): 85-93, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22866187

RESUMO

Congenital cystic lesions of the lung in fetuses are rare. The most common malformations of the lower respiratory tract are congenital cystic adenomatoid malformation and bronchopulmonary sequestration. With the increased use of obstetric ultrasound, cystic lung lesions are detected more often antenatally, which allows for proper planning of peripartum and neonatal management. This article discusses a range of diagnostic and management options.

10.
Hum Reprod ; 27(10): 2933-40, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22888169

RESUMO

STUDY QUESTION: What is the effect of pravastatin on antiphospholipid antibody (aPL) modulation of human first trimester trophoblast function? SUMMARY ANSWER: Pravastatin does not prevent the effects of aPL on human first trimester trophoblast cell function. WHAT IS KNOWN ALREADY: Antiphospholipid syndrome (APS) is associated with recurrent pregnancy loss and late pregnancy complications, such as pre-eclampsia, owing to direct targeting of the placenta by aPL. While treatment with heparin reduces the rate of pregnancy loss, the risk for severe pre-eclampsia remains high. Thus, there is a need to find alternative treatments for the prenatal management of patients with APS. Statins have recently been shown to prevent aPL-mediated fetal loss in mice but their effects on a human pregnancy model of APS have not yet been studied. DESIGN, DATA COLLECTION, METHODS: The human first trimester trophoblast cell line, HTR8, and human first trimester trophoblast primary cultures were incubated with or without a mouse anti-human beta 2 glycoprotein I (ß(2)GPI) monoclonal antibody in the presence or absence of pravastatin. Cytokine and angiogenic factor secretion were measured by enzyme-linked immunosorbent assay and multiplex analysis. Cell migration was measured using a colorimetric two-chamber migration assay. MAIN FINDINGS: Using the human first trimester trophoblast cell line, HTR8, pravastatin significantly augmented, compared with no treatment, aPL-dependent secretion of interleukin (IL)-8 (P< 0.05), IL-1ß (P< 0.05) and soluble endoglin (P< 0.01) but had no effect on aPL-induced up-regulation of vascular endothelial growth factor, placenta growth factor or growth-related oncogene alpha secretion. Furthermore, pravastatin alone limited basal HTR8 cell migration (P< 0.01), and did not mitigate the adverse effect of aPL on trophoblast migration. Pravastatin also had no impact on the secretion of pro-inflammatory cytokines and angiogenic factors by primary human first trimester trophoblast cells exposed to aPL. LIMITATIONS AND WIDER IMPLICATIONS OF THE FINDINGS: While our in vitro findings suggest that pravastatin may not be effective in preventing pregnancy complications in patients with APS, the in vivo condition may be more complex, and thus, more studies are needed to determine the effectiveness of pravastatin in the prevention of aPL-associated pregnancy complications in humans. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by the American Heart Association.


Assuntos
Síndrome Antifosfolipídica/imunologia , Pravastatina/farmacologia , Trofoblastos/efeitos dos fármacos , Indutores da Angiogênese/metabolismo , Anticorpos Antifosfolipídeos/imunologia , Anticorpos Monoclonais , Síndrome Antifosfolipídica/tratamento farmacológico , Linhagem Celular , Movimento Celular/efeitos dos fármacos , Citocinas/metabolismo , Ensaio de Imunoadsorção Enzimática , Humanos , Reação em Cadeia da Polimerase Multiplex , Trofoblastos/imunologia , Trofoblastos/patologia , beta 2-Glicoproteína I/imunologia
11.
Obstet Gynecol ; 118(4): 913-20, 2011 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-21934456

RESUMO

OBJECTIVE: To test the hypothesis that myometrial thickness predicts the success of external cephalic version. METHODS: Abdominal ultrasonographic scans were performed in 114 consecutive pregnant women with breech singletons before an external cephalic version maneuver. Myometrial thickness was measured by a standardized protocol at three sites: the lower segment, midanterior wall, and the fundal uterine wall. Independent variables analyzed in conjunction with myometrial thickness were: maternal age, parity, body mass index, abdominal wall thickness, estimated fetal weight, amniotic fluid index, placental thickness and location, fetal spine position, breech type, and delivery outcomes such as final mode of delivery and birth weight. RESULTS: Successful version was associated with a thicker ultrasonographic fundal myometrium (unsuccessful: 6.7 [5.5-8.4] compared with successful: 7.4 [6.6-9.7] mm, P=.037). Multivariate regression analysis showed that increased fundal myometrial thickness, high amniotic fluid index, and nonfrank breech presentation were the strongest independent predictors of external cephalic version success (P<.001). A fundal myometrial thickness greater than 6.75 mm and an amniotic fluid index greater than 12 cm were each associated with successful external cephalic versions (fundal myometrial thickness: odds ratio [OR] 2.4, 95% confidence interval [CI] 1.1-5.2, P=.029; amniotic fluid index: OR 2.8, 95% CI 1.3-6.0, P=.008). Combining the two variables resulted in an absolute risk reduction for a failed version of 27.6% (95% CI 7.1-48.1) and a number needed to treat of four (95% CI 2.1-14.2). CONCLUSION: Fundal myometrial thickness and amniotic fluid index contribute to success of external cephalic version and their evaluation can be easily incorporated in algorithms before the procedure. LEVEL OF EVIDENCE: III.


Assuntos
Miométrio/diagnóstico por imagem , Versão Fetal , Adulto , Líquido Amniótico/diagnóstico por imagem , Apresentação Pélvica/diagnóstico por imagem , Apresentação Pélvica/terapia , Parto Obstétrico , Feminino , Humanos , Miométrio/anatomia & histologia , Tamanho do Órgão , Gravidez , Complicações na Gravidez/diagnóstico por imagem , Resultado da Gravidez , Resultado do Tratamento , Ultrassonografia
12.
Obstet Gynecol ; 118(2 Pt 2): 497-500, 2011 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-21768866

RESUMO

BACKGROUND: The diagnosis of uterine dehiscence in the early second trimester by ultrasonography is rare and its effect on pregnancy outcome is unclear. CASE: An asymptomatic woman presented for anatomy survey in the 19th week of pregnancy. Uterine dehiscence at the site of previous hysterotomy was diagnosed by ultrasound scan. She was admitted to the hospital for expectant management and eventually opted for termination of pregnancy in the 22nd week of pregnancy. Termination was performed by classical hysterotomy without any complications. CONCLUSION: Given the increasing cesarean delivery rate and improvements in ultrasound technology, obstetricians should expect to face the management dilemma of antenatally diagnosed uterine dehiscence. The risks of expectant management compared with termination remain theoretical, and timing of delivery and methods of termination are important questions to consider.


Assuntos
Cesárea/efeitos adversos , Histerotomia/efeitos adversos , Complicações na Gravidez/diagnóstico por imagem , Deiscência da Ferida Operatória/diagnóstico por imagem , Ultrassonografia Pré-Natal , Aborto Induzido , Adulto , Feminino , Humanos , Gravidez , Segundo Trimestre da Gravidez , Resultado do Tratamento
13.
J Immunol ; 187(2): 980-6, 2011 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-21677137

RESUMO

There is a strong association between infection and prematurity; however, the underlying mechanisms remain largely unknown. Nod1 and Nod2 are intracellular pattern recognition receptors that are activated by bacterial peptides and mediate innate immunity. We previously demonstrated that human first-trimester trophoblasts express Nod1 and Nod2, which trigger inflammation upon stimulation. This study sought to determine the expression and function of Nod1 and Nod2 in third-trimester trophoblasts, and to characterize the in vivo effects of Nod1 activation on pregnancy outcome. Human term placental tissues and isolated term trophoblast expressed Nod1, but not Nod2. Activation of Nod1 by its agonist, bacterial γ-D-glutamyl-meso-diaminopimelic acid (iE-DAP), in term trophoblast cultures induced a proinflammatory cytokine profile, characterized by elevated levels of secreted IL-6, GRO-α, and MCP-1, when compared with the control. However, these cytokines were not upregulated in response to Nod2 stimulation with bacterial MDP. Administration of high-dose bacterial iE-DAP to pregnant C57BL/6J mice on embryonic day 14.5 triggered preterm delivery within 24 h. iE-DAP at a lower dose that did not induce prematurity, reduced fetal weight, altered the cytokine profile at the maternal-fetal interface, and induced fetal inflammation. Thus, functional Nod1 is expressed by trophoblast cells across gestation and may have a role in mediating infection-associated inflammation and prematurity. This study demonstrates that pattern recognition receptors, other than the TLRs, may be implicated or involved in infection-associated preterm labor.


Assuntos
Ácido Diaminopimélico/análogos & derivados , Recém-Nascido Prematuro/imunologia , Troca Materno-Fetal/imunologia , Proteína Adaptadora de Sinalização NOD1/metabolismo , Trabalho de Parto Prematuro/microbiologia , Trabalho de Parto Prematuro/patologia , Animais , Animais Recém-Nascidos , Linhagem Celular , Ácido Diaminopimélico/toxicidade , Modelos Animais de Doenças , Feminino , Humanos , Recém-Nascido , Inflamação/imunologia , Inflamação/metabolismo , Inflamação/microbiologia , Troca Materno-Fetal/efeitos dos fármacos , Troca Materno-Fetal/genética , Camundongos , Camundongos Endogâmicos C57BL , Proteína Adaptadora de Sinalização NOD1/biossíntese , Proteína Adaptadora de Sinalização NOD1/genética , Proteína Adaptadora de Sinalização NOD1/fisiologia , Trabalho de Parto Prematuro/imunologia , Gravidez , Resultado da Gravidez , Técnicas de Cultura de Tecidos , Trofoblastos/efeitos dos fármacos , Trofoblastos/imunologia , Trofoblastos/patologia
14.
Am J Reprod Immunol ; 66(4): 286-96, 2011 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-21545366

RESUMO

PROBLEM Women with antiphospholipid antibodies (aPL) are at risk of miscarriage and pre-eclampsia, obstetrical disorders associated with reduced trophoblast invasion and spiral artery transformation. aPL target the placenta by binding beta(2) -glycoprotein I (ß(2) GPI) on the trophoblast. In this study, we determined whether aPL alter the trophoblast secretion of angiogenic factors and evaluated the effect of low molecular weight heparin (LMWH) on this response. METHOD OF STUDY First-trimester trophoblast was treated with anti-ß(2) GPI antibodies with or without LMWH. Angiogenic factor secretion was measured by enzyme-linked immunosorbent assay. RESULTS Trophoblast cells produced more vascular endothelial growth factor (VEGF), placenta growth factor (PlGF), and soluble endoglin following exposure to anti-ß(2) GPI Abs, and this occurred in both a MyD88-dependent and MyD88-independent manner. LMWH was unable to reverse the effects of the anti-ß(2) GPI Abs on trophoblast VEGF secretion, but enhanced PlGF. Strikingly, LMWH upregulated soluble fms-like tyrosine kinase receptor-1 (sFlt-1) secretion independently of aPL. CONCLUSION This study demonstrates that aPL perturb the secretion of trophoblast angiogenic factors. LMWH does not reverse this effect but exacerbates sFlt-1 secretion, a potent anti-angiogenic factor. These findings may help to explain why women with antiphospholipid syndrome, who are treated with heparin to prevent early pregnancy loss, remain at increased risk of developing late obstetrical complications, such as pre-eclampsia.


Assuntos
Indutores da Angiogênese/imunologia , Anticorpos Antifosfolipídeos/farmacologia , Síndrome Antifosfolipídica/imunologia , Heparina de Baixo Peso Molecular/farmacologia , Primeiro Trimestre da Gravidez/efeitos dos fármacos , Trofoblastos/imunologia , beta 2-Glicoproteína I/antagonistas & inibidores , Adulto , Indutores da Angiogênese/metabolismo , Anticorpos Antifosfolipídeos/efeitos adversos , Anticorpos Antifosfolipídeos/imunologia , Síndrome Antifosfolipídica/metabolismo , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Técnicas In Vitro , Fator 88 de Diferenciação Mieloide/análise , Fator 88 de Diferenciação Mieloide/imunologia , Neovascularização Patológica/imunologia , Neovascularização Patológica/metabolismo , Fator de Crescimento Placentário , Pré-Eclâmpsia/imunologia , Pré-Eclâmpsia/metabolismo , Pré-Eclâmpsia/fisiopatologia , Gravidez , Proteínas da Gravidez/biossíntese , Proteínas da Gravidez/imunologia , Primeiro Trimestre da Gravidez/imunologia , Trofoblastos/efeitos dos fármacos , Trofoblastos/metabolismo , Fator A de Crescimento do Endotélio Vascular/biossíntese , Fator A de Crescimento do Endotélio Vascular/imunologia , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/biossíntese , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/imunologia , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/metabolismo , beta 2-Glicoproteína I/imunologia , beta 2-Glicoproteína I/metabolismo
15.
Am J Reprod Immunol ; 65(6): 542-8, 2011 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21352397

RESUMO

PROBLEM: Preeclampsia is associated with hyperuricemia, which correlates with the disease severity. Levels of circulating uric acid increase before the clinical manifestations, suggesting that they may be causally related. Uric acid, or monosodium urate (MSU), activates the Nod-like receptor, Nalp3, leading to inflammasome activation and IL-1ß processing. Because preeclampsia is associated with placental immune/ inflammatory dysregulation, we sought to determine in the trophoblast, the presence of the Nalp3 inflammasome, and the effect of MSU on its activation. METHOD OF STUDY: Isolated first- and third-trimester trophoblasts were assessed for expression of the inflammasome components, Nalp1, Nalp3, and ASC. First-trimester trophoblast cells were incubated with or without MSU, and after which, IL-1ß secretion and processing and caspase-1 activation were determined. RESULTS: Trophoblast cells expressed Nalp1, Nalp3, and ASC under basal conditions. Following incubation with MSU, first-trimester trophoblast IL-1ß secretion was upregulated. This correlated with increased expression levels of active IL-1ß and active caspase-1. ASC knockdown reduced MSU-induced IL-1ß secretion. CONCLUSION: These findings demonstrate that uric acid activates the inflammasome in the trophoblast, leading to IL-1ß production. This may provide a novel mechanism for the induction of inflammation at the maternal­fetal interface leading to placental dysfunction and adverse pregnancy outcome, including preeclampsia.


Assuntos
Inflamassomos/efeitos dos fármacos , Interleucina-1beta/metabolismo , Pré-Eclâmpsia/imunologia , Trofoblastos/efeitos dos fármacos , Ácido Úrico/farmacologia , Proteínas Adaptadoras de Transdução de Sinal/imunologia , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Proteínas Reguladoras de Apoptose/imunologia , Proteínas Reguladoras de Apoptose/metabolismo , Proteínas Adaptadoras de Sinalização CARD , Proteínas de Transporte/imunologia , Proteínas de Transporte/metabolismo , Caspase 1/imunologia , Caspase 1/metabolismo , Linhagem Celular , Proteínas do Citoesqueleto/imunologia , Proteínas do Citoesqueleto/metabolismo , Progressão da Doença , Ativação Enzimática/efeitos dos fármacos , Feminino , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Humanos , Hiperuricemia , Inflamassomos/imunologia , Inflamassomos/metabolismo , Relações Materno-Fetais , Proteína 3 que Contém Domínio de Pirina da Família NLR , Proteínas NLR , Pré-Eclâmpsia/sangue , Pré-Eclâmpsia/fisiopatologia , Gravidez , Trofoblastos/metabolismo , Trofoblastos/patologia , Ácido Úrico/sangue
16.
Am J Obstet Gynecol ; 204(5): 411.e1-411.e11, 2011 May.
Artigo em Inglês | MEDLINE | ID: mdl-21316642

RESUMO

OBJECTIVE: We sought to characterize serum angiogenic factor profile of women with complete placenta previa and determine if invasive trophoblast differentiation characteristic of accreta, increta, or percreta shares features of epithelial-to-mesenchymal transition. STUDY DESIGN: We analyzed gestational age-matched serum samples from 90 pregnant women with either complete placenta previa (n = 45) or uncomplicated pregnancies (n = 45). Vascular endothelial growth factor (VEGF), placental growth factor, and soluble form of fms-like-tyrosine-kinase-1 were immunoassayed. VEGF and phosphotyrosine immunoreactivity was surveyed in histological specimens relative to expression of vimentin and cytokeratin-7. RESULTS: Women with previa and invasive placentation (accreta, n = 5; increta, n = 6; percreta, n = 2) had lower systemic VEGF (invasive previa: median 0.8 [0.02-3.4] vs control 6.5 [2.7-10.5] pg/mL, P = .02). VEGF and phosphotyrosine immunostaining predominated in the invasive extravillous trophoblasts that coexpressed vimentin and cytokeratin-7, an epithelial-to-mesenchymal transition feature and tumorlike cell phenotype. CONCLUSION: Lower systemic free VEGF and a switch of the interstitial extravillous trophoblasts to a metastable cell phenotype characterize placenta previa with excessive myometrial invasion.


Assuntos
Placenta Acreta/metabolismo , Placenta Prévia/metabolismo , Trofoblastos/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Adulto , Estudos de Casos e Controles , Transição Epitelial-Mesenquimal , Feminino , Humanos , Queratina-7/metabolismo , Fosfotirosina/metabolismo , Placenta Acreta/patologia , Fator de Crescimento Placentário , Placenta Prévia/patologia , Gravidez , Proteínas da Gravidez/sangue , Trofoblastos/patologia , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/sangue , Vimentina/metabolismo
17.
Obstet Gynecol ; 116 Suppl 2: 477-479, 2010 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-20664424

RESUMO

BACKGROUND: The occurrence of a psoas abscess after a spontaneous vaginal delivery is a rare postpartum complication with a significant mortality risk. CASE: A 17-year-old primiparous patient presented 3 weeks after an uncomplicated spontaneous vaginal delivery with fever refractory to antibiotics. Imaging revealed the patient to have a 4x4-cm abscess of the right iliopsoas muscle. The patient underwent drainage of the abscess along with the administration of intravenous antibiotics. CONCLUSION: Prompt recognition of and subsequent effective treatment for a psoas abscess are crucial to avoid potential long-term morbidity and even mortality.


Assuntos
Parto Obstétrico/efeitos adversos , Abscesso do Psoas/diagnóstico , Abscesso do Psoas/terapia , Adolescente , Feminino , Humanos , Gravidez , Abscesso do Psoas/etiologia
19.
Am J Perinatol ; 25(3): 175-87, 2008 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-18425720

RESUMO

Premature birth before 37 weeks of gestation is a significant public health problem. Each year, 4.5 million premature infants are born worldwide. Despite extensive research and a variety of interventions, the rate of preterm birth has steadily increased over the past 20 years and reached a high of 12.8% in 2006. The etiology of most preterm births remains elusive and is likely multifactorial, with many pathophysiological pathways involved, such as excessive stretching, oxidative stress, decidual hemorrhage, and infection. Genomics and proteomics have emerged to provide a better comprehension of the pathophysiological conditions leading to preterm birth, thereby providing a perspective for improving neonatal outcome.


Assuntos
Marcadores Genéticos , Resultado da Gravidez/genética , Nascimento Prematuro/genética , Biologia de Sistemas/métodos , Muco do Colo Uterino/fisiologia , Corioamnionite/genética , Decídua/fisiologia , Feminino , Ruptura Prematura de Membranas Fetais/genética , Redes Reguladoras de Genes , Homeostase/genética , Humanos , Polimorfismo Genético , Gravidez , Proteômica , Vagina/metabolismo
20.
Am J Obstet Gynecol ; 198(5): 530.e1-10, 2008 May.
Artigo em Inglês | MEDLINE | ID: mdl-18279826

RESUMO

OBJECTIVE: The objective of the study was to evaluate longitudinally the in vivo changes in myometrial thickness (MT) during gestation in patients carrying twin gestations in relation to pregnancy outcome. STUDY DESIGN: Serial abdominal ultrasounds were performed prospectively in 92 patients carrying twin gestations through each trimester. Ninety-seven patients pregnant with singletons served as controls. For twins, the primary endpoint was spontaneous delivery at less than 35 weeks' gestational age (GA). The myometrium was defined sonographically as the echohomogeneous layer between the serosa and the decidua and was measured at the anterior, fundal, and lower uterine segment (LUS) walls. The estimated fetal weight, maximum vertical pocket of amniotic fluid, and placental thickness were also assessed ultrasonographically at the same time as the MT and served as estimates for the contribution of each to the uterine volume. In twins, cervical length measurements were performed transvaginally, as clinically indicated. Data analysis included 2-way analysis of variance and linear, nonlinear, and multivariate regression. RESULTS: A total of 41.3% of twin pregnancies (38 of 92) delivered preterm (< 35 weeks). There were no significant changes in measurements at the anterior and fundal site over time throughout pregnancy and no differences in these sites between twin and singleton gestations. Conversely, in both twins and singletons, there was a significant and gradual thinning of the LUS myometrium during gestation. In the absence of uterine contractions or symptoms of preterm labor, twins that delivered preterm had a significantly thinner LUS at an earlier gestation, compared with twins that delivered at term (P < .001), suggesting that LUS thinning occurred earlier in these cases. There was a significant correlation between cervical length and LUS thinning during gestation in twins that delivered 35 weeks GA or later (r = 0.352; P < .001) but not in those that delivered preterm (< 35 weeks GA; r = 0.125; P = .326). CONCLUSION: Twin pregnancy is characterized by a significant, selective, and gradual thinning of the LUS during gestation, which does not occur in the anterior and fundal myometrium. Thinning of the LUS occurs earlier in twin pregnancies destined to deliver preterm. These observations suggest that similar to the cervix, the LUS changes dynamically during twin pregnancy and that this too may be assessed through ultrasound imaging.


Assuntos
Miométrio/diagnóstico por imagem , Miométrio/fisiopatologia , Resultado da Gravidez , Gravidez Múltipla/fisiologia , Ultrassonografia Pré-Natal , Parede Abdominal/diagnóstico por imagem , Adaptação Fisiológica , Adulto , Feminino , Idade Gestacional , Humanos , Análise Multivariada , Miométrio/fisiologia , Trabalho de Parto Prematuro/fisiopatologia , Placenta/fisiologia , Gravidez , Terceiro Trimestre da Gravidez/fisiologia , Pressão
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