RESUMO
Preeclampsia is a risk factor for future cardiovascular diseases. However, the mechanisms underlying this association remain unclear, limiting effective prevention strategies. Blood pressure responses to acute stimuli may reveal cardiovascular dysfunction not apparent at rest, identifying individuals at elevated cardiovascular risk. Therefore, we compared blood pressure responsiveness with acute stimuli between previously preeclamptic (PPE) women (34 ± 5 yr old, 13 ± 6 mo postpartum) and women following healthy pregnancies (Ctrl; 29 ± 3 yr old, 15 ± 4 mo postpartum). Blood pressure (finger photoplethysmography calibrated to manual sphygmomanometry-derived values; PPE: n = 12, Ctrl: n = 12) was assessed during end-expiratory apnea, mental stress, and isometric handgrip exercise protocols. Integrated muscle sympathetic nerve activity (MSNA) was assessed in a subset of participants (peroneal nerve microneurography; PPE: n = 6, Ctrl: n = 8). Across all protocols, systolic blood pressure (SBP) was higher in PPE than Ctrl (main effects of group all P < 0.05). Peak changes in SBP were stressor specific: peak increases in SBP were not different between PPE and Ctrl during apnea (8 ± 6 vs. 6 ± 5 mmHg, P = 0.32) or mental stress (9 ± 5 vs. 4 ± 7 mmHg, P = 0.06). However, peak exercise-induced increases in SBP were greater in PPE than Ctrl (11 ± 5 vs. 7 ± 7 mmHg, P = 0.04). MSNA was higher in PPE than Ctrl across all protocols (main effects of group all P < 0.05), and increases in peak MSNA were greater in PPE than Ctrl during apnea (44 ± 6 vs. 27 ± 14 burst/100 hb, P = 0.04) and exercise (25 ± 8 vs. 13 ± 11 burst/100 hb, P = 0.01) but not different between groups during mental stress (2 ± 3 vs. 0 ± 5 burst/100 hb, P = 0.41). Exaggerated pressor and sympathetic responses to certain stimuli may contribute to the elevated long-term risk for cardiovascular disease in PPE.NEW & NOTEWORTHY Women with recent histories of preeclampsia demonstrated higher systolic blood pressures across sympathoexcitatory stressors relative to controls. Peak systolic blood pressure reactivity was exacerbated in previously preeclamptic women during small muscle-mass exercises, although not during apneic or mental stress stimuli. These findings underscore the importance of assessing blood pressure control during a variety of experimental conditions in previously preeclamptic women to elucidate mechanisms that may contribute to their elevated cardiovascular disease risk.
Assuntos
Apneia , Pressão Sanguínea , Força da Mão , Pré-Eclâmpsia , Estresse Psicológico , Sistema Nervoso Simpático , Humanos , Feminino , Pré-Eclâmpsia/fisiopatologia , Pré-Eclâmpsia/diagnóstico , Gravidez , Adulto , Estresse Psicológico/fisiopatologia , Apneia/fisiopatologia , Sistema Nervoso Simpático/fisiopatologia , Exercício Físico , Músculo Esquelético/inervação , Músculo Esquelético/fisiopatologia , Estudos de Casos e ControlesRESUMO
There is an immediate need to address long-standing questions about the reproductive health of girls and women with sickle cell disease (SCD). There are many SCD-related reproductive risks and uncertainties across girls' and women's reproductive life span, with particularly outstanding concerns about menstruation, contraception, fertility and pregnancy. Extant literature addressing women's reproductive health topics is mostly descriptive; there are few high-quality interventional studies. In 2020, the Centers for Disease Control and Prevention and the Foundation for Women and Girls with Blood Disorders convened an expert panel to assess the knowledge gaps in women's reproductive health in SCD. The panel identified significant limitations to clinical care due to the need for research. The panel also identified prominent barriers to research and care. In this report, we frame these issues, providing a roadmap for investigators, funding agencies, and policy makers to advance care for girls and women with SCD.
Assuntos
Anemia Falciforme , Saúde Reprodutiva , Saúde Sexual , Anemia Falciforme/epidemiologia , Anemia Falciforme/fisiopatologia , Feminino , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Saúde da MulherRESUMO
Preeclampsia is associated with the development of cardiovascular diseases later in life. To investigate this phenomenon, we compared established markers of cardiovascular dysregulation between previously preeclamptic women (PPE; n = 12, 13 ± 6 mo postpartum, 34 ± 6 yr) and women who had previously had an uncomplicated pregnancy [control (CTRL); n = 12, 15 ± 4 mo postpartum; 29 ± 3 yr]. We hypothesized that PPE would present with elevated arterial stiffness (assessed as central and peripheral pulse wave velocity) and muscle sympathetic nerve activity (MSNA; microneurography) and blunted baroreflex sensitivity (BRS) relative to CTRL. Blood pressure (Finometer) was similar between PPE and CTRL (mean arterial pressure: 94 ± 11 vs. 89 ± 9, P = 0.16). Central (6.92 ± 0.21 vs. 6.24 ± 0.22 m/s, P = 0.04) but not peripheral arterial stiffness (7.52 ± 0.19 vs. 7.09 ± 0.19 m/s, P = 0.13) was elevated in PPE versus CTRL (values normalized to MAP). MSNA was also elevated in PPE versus CTRL (22 ± 7 vs. 13 ± 5 bursts/min, P = 0.01), although this was independent of arterial stiffness (central: r2 = 0.01, P = 0.74; peripheral: r2 = 0.01, P = 0.74). Cardiovagal BRS was blunted in PPE versus CTRL (15 ± 5 vs. 28 ± 1 ms/mmHg, P = 0.01), whereas sympathetic vascular BRS was similar (-3.2 ± 0.9 vs. -3.1 ± 1.4 bursts·100 hb-1·mmHg-1, P = 0.88). Cardiovagal and sympathetic BRS were inversely correlated in both CTRL (r2 = 0.43; P = 0.05) and PPE (r2 = 0.69; P = 0.04), supporting a compensatory mechanism resulting in normal blood pressures in both groups. Overall, these data indicate that PPE retain their ability to buffer elevated MSNA. We propose that the higher incidence of cardiovascular disease observed later in life in PPE results from this arterial stiffness, combined with the loss of protective vascular mechanisms and the "unmasking" of high MSNA.NEW & NOTEWORTHY We demonstrate that resting muscle sympathetic nerve activity is elevated in women with a recent history of preeclampsia relative to women who have recently had uncomplicated pregnancies and without a history of preeclampsia. Structural changes in the central arteries are associated with arterial stiffness following preeclampsia, independent of changes in the sympathetic nervous system. The structural changes are observed in these relatively young previously preeclamptic women, indicating elevated cardiovascular risk. Our data suggest that with aging (and the gradual loss of vascular protection for women, as established by others), this risk will become exaggerated compared with women who have had normal pregnancies.
Assuntos
Músculo Esquelético/inervação , Pré-Eclâmpsia/fisiopatologia , Sistema Nervoso Simpático/fisiopatologia , Rigidez Vascular/fisiologia , Adulto , Barorreflexo/fisiologia , Biomarcadores/sangue , Pressão Sanguínea/fisiologia , Feminino , Frequência Cardíaca/fisiologia , Hemodinâmica/fisiologia , Humanos , Músculo Esquelético/fisiopatologia , Gravidez , Análise de Onda de PulsoRESUMO
BACKGROUND: Despite expectant management, preeclampsia remote from term usually results in preterm delivery. Antithrombin, which displays antiinflammatory and anticoagulant properties, may have a therapeutic role in treating preterm preeclampsia, a disorder characterized by endothelial dysfunction, inflammation, and activation of the coagulation system. OBJECTIVE: This randomized, placebo-controlled clinical trial aimed to evaluate whether intravenous recombinant human antithrombin could prolong gestation and therefore improve maternal and fetal outcomes. STUDY DESIGN: We performed a double-blind, placebo-controlled trial at 23 hospitals. Women were eligible if they had a singleton pregnancy, early-onset or superimposed preeclampsia at 23 0/7 to 30 0/7 weeks' gestation, and planned expectant management. In addition to standard therapy, patients were randomized to receive either recombinant human antithrombin 250 mg loading dose followed by a continuous infusion of 2000 mg per 24 hours or an identical saline infusion until delivery. The primary outcome was days gained from randomization until delivery. The secondary outcome was composite neonatal morbidity score. A total of 120 women were randomized. RESULTS: There was no difference in median gestational age at enrollment (27.3 weeks' gestation for the recombinant human antithrombin group [range, 23.1-30.0] and 27.6 weeks' gestation for the placebo group [range, 23.0-30.0]; P=.67). There were no differences in median increase in days gained (5.0 in the recombinant human antithrombin group [range, 0-75] and 6.0 for the placebo group [range, 0-85]; P=.95). There were no differences between groups in composite neonatal morbidity scores or in maternal complications. No safety issues related to recombinant human antithrombin were noted in this study, despite the achievement of supraphysiological antithrombin concentrations. CONCLUSION: The administration of recombinant human antithrombin in preterm preeclampsia neither prolonged pregnancy nor improved neonatal or maternal outcomes.
Assuntos
Proteínas Antitrombina/uso terapêutico , Cesárea/estatística & dados numéricos , Idade Gestacional , Pré-Eclâmpsia/tratamento farmacológico , Administração Intravenosa , Adolescente , Adulto , Parto Obstétrico/estatística & dados numéricos , Método Duplo-Cego , Feminino , Sofrimento Fetal/epidemiologia , Humanos , Doenças do Prematuro/epidemiologia , Recém-Nascido Pequeno para a Idade Gestacional , Pessoa de Meia-Idade , Sepse Neonatal/epidemiologia , Mortalidade Perinatal , Pré-Eclâmpsia/sangue , Pré-Eclâmpsia/fisiopatologia , Gravidez , Segundo Trimestre da Gravidez , Terceiro Trimestre da Gravidez , Estudos Prospectivos , Proteínas Recombinantes , Adulto JovemRESUMO
BACKGROUND: Cardiovascular disease is the leading cause of pregnancy-related death in the United States. Identification of short-term indicators of cardiovascular morbidity has the potential to alter the course of this devastating disease among women. It has been established that hypertensive disorders of pregnancy are associated with increased risk of cardiovascular disease 10-30 years after delivery; however, little is known about the association of hypertensive disorders of pregnancy with cardiovascular morbidity during the delivery hospitalization. OBJECTIVE: We aimed to identify the immediate risk of cardiovascular morbidity during the delivery hospitalization among women who experienced a hypertensive disorder of pregnancy. MATERIALS AND METHODS: This retrospective cohort study of women, 15-55 years old with a singleton gestation between 2008 and 2012 in New York City, examined the risk of severe cardiovascular morbidity in women with hypertensive disorders of pregnancy compared with normotensive women during their delivery hospitalization. Women with a history of chronic hypertension, diabetes mellitus, or cardiovascular disease were excluded. Mortality and severe cardiovascular morbidity (myocardial infarction, cerebrovascular disease, acute heart failure, heart failure or arrest during labor or procedure, cardiomyopathy, cardiac arrest and ventricular fibrillation, or conversion of cardiac rhythm) during the delivery hospitalization were identified using birth certificates and discharge record coding. Using multivariable logistic regression, we assessed the association between hypertensive disorders of pregnancy and severe cardiovascular morbidity, adjusting for relevant sociodemographic and pregnancy-specific clinical risk factors. RESULTS: A total of 569,900 women met inclusion criteria. Of those women, 39,624 (6.9%) had a hypertensive disorder of pregnancy: 11,301 (1.9%) gestational hypertension; 16,117 (2.8%) preeclampsia without severe features; and 12,206 (2.1%) preeclampsia with severe features, of whom 319 (0.06%) had eclampsia. Among women with a hypertensive disorder of pregnancy, 431 experienced severe cardiovascular morbidity (10.9 per 1000 deliveries; 95% confidence interval, 9.9-11.9). Among normotensive women, 1780 women experienced severe cardiovascular morbidity (3.4 per 1000 deliveries; 95% confidence interval, 3.2-3.5). Compared with normotensive women, there was a progressively increased risk of cardiovascular morbidity with gestational hypertension (adjusted odds ratio, 1.18; 95% confidence interval, 0.92-1.52), preeclampsia without severe features (adjusted odds ratio, 1.96; 95% confidence interval, 1.66-2.32), preeclampsia with severe features (adjusted odds ratio, 3.46; 95% confidence interval, 2.99-4.00), and eclampsia (adjusted odds ratio, 12.46; 95% confidence interval, 7.69-20.22). Of the 39,624 women with hypertensive disorders of pregnancy, there were 15 maternal deaths, 14 of which involved 1 or more cases of severe cardiovascular morbidity. CONCLUSION: Hypertensive disorders of pregnancy, particularly preeclampsia with severe features and eclampsia, are significantly associated with cardiovascular morbidity during the delivery hospitalization. Increased vigilance, including diligent screening for cardiac pathology in patients with hypertensive disorders of pregnancy, may lead to decreased morbidity for mothers.
Assuntos
Doenças Cardiovasculares/epidemiologia , Hospitalização , Hipertensão Induzida pela Gravidez/epidemiologia , Adolescente , Adulto , Cardiomiopatias/epidemiologia , Transtornos Cerebrovasculares/epidemiologia , Estudos de Coortes , Eclampsia/epidemiologia , Escolaridade , Cardioversão Elétrica , Etnicidade/estatística & dados numéricos , Feminino , Parada Cardíaca/epidemiologia , Insuficiência Cardíaca/epidemiologia , Humanos , Armazenamento e Recuperação da Informação , Seguro Saúde/estatística & dados numéricos , Modelos Logísticos , Pessoa de Meia-Idade , Análise Multivariada , Infarto do Miocárdio/epidemiologia , Cidade de Nova Iorque/epidemiologia , Obesidade Materna/epidemiologia , Pobreza/estatística & dados numéricos , Pré-Eclâmpsia/epidemiologia , Gravidez , Estudos Retrospectivos , Índice de Gravidade de Doença , Fibrilação Ventricular/epidemiologia , Adulto JovemRESUMO
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 RiscoRESUMO
Cytomegalovirus (CMV) is the most common infectious cause of brain defects and neurological dysfunction in developing human babies. Due to the teratogenicity and toxicity of available CMV antiviral agents, treatment options during early development are markedly limited. Valnoctamide (VCD), a neuroactive mood stabilizer with no known teratogenic activity, was recently demonstrated to have anti-CMV potential. However, it is not known whether this can be translated into an efficacious therapeutic effect to improve CMV-induced adverse neurological outcomes. Using multiple models of CMV infection in the developing mouse brain, we show that subcutaneous low-dose VCD suppresses CMV by reducing the level of virus available for entry into the brain and by acting directly within the brain to block virus replication and dispersal. VCD during the first 3 weeks of life restored timely acquisition of neurological milestones in neonatal male and female mice and rescued long-term motor and behavioral outcomes in juvenile male mice. CMV-mediated brain defects, including decreased brain size, cerebellar hypoplasia, and neuronal loss, were substantially attenuated by VCD. No adverse side effects on neurodevelopment of uninfected control mice receiving VCD were detected. Treatment of CMV-infected human fetal astrocytes with VCD reduced both viral infectivity and replication by blocking viral particle attachment to the cell, a mechanism that differs from available anti-CMV drugs. These data suggest that VCD during critical periods of neurodevelopment can effectively suppress CMV replication in the brain and safely improve both immediate and long-term neurological outcomes.SIGNIFICANCE STATEMENT Cytomegalovirus (CMV) can irreversibly damage the developing brain. No anti-CMV drugs are available for use during fetal development, and treatment during the neonatal period has substantial limitations. We studied the anti-CMV actions of valnoctamide (VCD), a psychiatric sedative that appears to lack teratogenicity and toxicity, in the newborn mouse brain, a developmental period that parallels that of an early second-trimester human fetus. In infected mice, subcutaneous VCD reaches the brain and suppresses viral replication within the CNS, rescuing the animals from CMV-induced brain defects and neurological problems. Treatment of uninfected control animals exerts no detectable adverse effects. VCD also blocks CMV replication in human fetal brain cells.
Assuntos
Amidas/administração & dosagem , Transtornos Cognitivos/prevenção & controle , Transtornos Cognitivos/fisiopatologia , Infecções por Citomegalovirus/tratamento farmacológico , Infecções por Citomegalovirus/fisiopatologia , Encefalite Viral/tratamento farmacológico , Encefalite Viral/fisiopatologia , Animais , Animais Recém-Nascidos , Antivirais/administração & dosagem , Transtornos Cognitivos/patologia , Infecções por Citomegalovirus/patologia , Relação Dose-Resposta a Droga , Encefalite Viral/patologia , Feminino , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Resultado do TratamentoRESUMO
Preeclampsia is a multisystem disorder affecting 2% to 8% of pregnancies and a leading cause of maternal and perinatal morbidity and mortality worldwide. Recent investigations have improved our understanding of the pathogenesis of this potentially life-threatening disease, especially in its early-onset form of manifestation. Despite these advances, therapeutic options are still limited and no effective pharmacologic interventions are currently available. Ongoing lines of research indicate some potential novel treatments targeting specific pathogenic steps. In this article we provide an updated overview of the multiple therapeutic approaches under preclinical and clinical assessment for the treatment of early-onset preeclampsia.
Assuntos
Desenho de Fármacos , Pré-Eclâmpsia/tratamento farmacológico , Feminino , Humanos , Mortalidade Materna , Pré-Eclâmpsia/fisiopatologia , GravidezRESUMO
Dysfunction and loss of neurons are the major characteristics of CNS disorders that include stroke, multiple sclerosis, and Alzheimer's disease. Activation of the Toll-like receptor 7 by extracellular microRNA let-7, a highly expressed microRNA in the CNS, induces neuronal cell death. Let-7 released from injured neurons and immune cells acts on neighboring cells, exacerbating CNS damage. Here we show that a synthetic peptide analogous to the mammalian PreImplantation factor (PIF) secreted by developing embryos and which is present in the maternal circulation during pregnancy inhibits the biogenesis of let-7 in both neuronal and immune cells of the mouse. The synthetic peptide, sPIF, destabilizes KH-type splicing regulatory protein (KSRP), a key microRNA-processing protein, in a Toll-like receptor 4 (TLR4)-dependent manner, leading to decreased production of let-7. Furthermore, s.c. administration of sPIF into neonatal rats following hypoxic-ischemic brain injury robustly rescued cortical volume and number of neurons and decreased the detrimental glial response, as is consistent with diminished levels of KSRP and let-7 in sPIF-treated brains. Our results reveal a previously unexpected mechanism of action of PIF and underscore the potential clinical utility of sPIF in treating hypoxic-ischemic brain damage. The newly identified PIF/TLR4/KSRP/let-7 regulatory axis also may operate during embryo implantation and development.
Assuntos
Blastocisto/metabolismo , Implantação do Embrião/fisiologia , MicroRNAs/metabolismo , Peptídeos/metabolismo , Animais , Blastocisto/citologia , Isquemia Encefálica/genética , Isquemia Encefálica/metabolismo , Feminino , Camundongos , MicroRNAs/genética , Peptídeos/genética , Gravidez , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismo , Ratos , Ratos Wistar , Receptor 4 Toll-Like/genética , Receptor 4 Toll-Like/metabolismo , Transativadores/genética , Transativadores/metabolismoRESUMO
The earliest stages of pregnancy are marked by countless changes in the maternal environment. A specific coordination of activity is required for a successful pregnancy, starting early in the menstrual cycle. Early establishment of maternal-fetal crosstalk is critical for the progression of pregnancy. Many factors, both maternal and fetal derived, play specific and important roles immediately following fertilization, through implantation and beyond. Here we present a review of some of the key factors involved with a focus on PreImplantation Factor (PIF), a small peptide secreted only by competent embryos, which carries an important role required for pregnancy progression.
Assuntos
Endocrinologia , Feminino , Humanos , Peptídeos , GravidezRESUMO
BACKGROUND: Preterm birth remains a major cause of neonatal morbidity and mortality worldwide. Short cervical length (CL) as measured by transvaginal ultrasound (TVU) in the second trimester represents the single most predictive risk factor for spontaneous preterm birth. Previous studies have addressed, in part, the limitations of TVU availability by utilizing a cervicometer to screen patients for short cervix, identifying those patients who may not benefit from TVU CL screening. In view of the prior studies indicating that a cervicometer measurement may have a high negative predictive value (NPV) for a sonographically short cervix, we sought to identify the ideal cervicometer threshold value in a prospective, multicenter study. OBJECTIVE: The primary objective was to determine the cervicometer CL measurement threshold that provides a high NPV for the identification of patients who are highly unlikely to have a TVU CL measurement ≤20 and ≤25 mm and, therefore, may forego TVU. STUDY DESIGN: This prospective study, executed in 5 US centers, included 401 women ≥18 years of age who provided written informed consent to undergo CL measurement in the mid trimester. All women underwent both cervicometer- and TVU-measured CLs by individuals blinded to results of the other measurement. Both measurements were performed at 17-23 weeks' gestation (visit 1) and repeated at 24-29 weeks' gestation (visit 2). All TVU measurement images were reviewed by a central reader. Test characteristics and receiver operating characteristic curves were created to determine and confirm the optimal cervicometer CL threshold, maximizing the NPV. RESULTS: In all, 358 subjects were evaluable at visit 1 and 267 at visit 2. At visit 1, the average TVU CL was 38.7 ± 7.6 mm and the average cervicometer CL was 30.3 ± 8.8 mm. Similar measurements were seen at visit 2. Receiver operating characteristic curves were utilized to graphically identify a cervicometer CL threshold of 30 mm that maximized sensitivity while minimizing the false-positive rate. The 30-mm cervicometer CL threshold provided a 98-100% NPV and 0.0 negative likelihood ratio for identification of women who have a low likelihood to have a sonographic short cervix (ie, transvaginal CL ≤20 mm or ≤25 mm). The 17-23 weeks' gestation 30-mm cervicometer CL threshold has 100% sensitivity, 45-46% specificity, and 1.8 and 0.0 positive and negative likelihood ratios to predict sonographic CL ≤20 and ≤25 mm. CONCLUSION: Cervicometer CL screening successfully identifies women at low risk for short transvaginal CL. Use of a 30-mm threshold by cervicometer CL measurement confers a 98-100% NPV, with high sensitivity and moderate specificity to predict a TVU short CL. Cervicometer measurement of CL may permit almost 50% of women to avoid TVU.
Assuntos
Medida do Comprimento Cervical/instrumentação , Medida do Comprimento Cervical/métodos , Colo do Útero/diagnóstico por imagem , Nascimento Prematuro/prevenção & controle , Ultrassonografia/métodos , Adolescente , Adulto , Feminino , Idade Gestacional , Humanos , Gravidez , Estudos Prospectivos , Medição de Risco , Sensibilidade e Especificidade , Adulto JovemRESUMO
Obstetric venous thromboembolism is a leading cause of severe maternal morbidity and mortality. Maternal death from thromboembolism is amenable to prevention, and thromboprophylaxis is the most readily implementable means of systematically reducing the maternal death rate. Observational data support the benefit of risk-factor-based prophylaxis in reducing obstetric thromboembolism. This bundle, developed by a multidisciplinary working group and published by the National Partnership for Maternal Safety under the guidance of the Council on Patient Safety in Women's Health Care, supports routine thromboembolism risk assessment for obstetric patients, with appropriate use of pharmacologic and mechanical thromboprophylaxis. Safety bundles outline critical clinical practices that should be implemented in every maternity unit. The safety bundle is organized into four domains: Readiness, Recognition, Response, and Reporting and Systems Learning. Although the bundle components may be adapted to meet the resources available in individual facilities, standardization within an institution is strongly encouraged.
Assuntos
Morte Materna/prevenção & controle , Segurança do Paciente , Complicações na Gravidez/epidemiologia , Complicações na Gravidez/prevenção & controle , Tromboembolia Venosa/epidemiologia , Tromboembolia Venosa/prevenção & controle , Parto Obstétrico/efeitos adversos , Parto Obstétrico/métodos , Parto Obstétrico/normas , Feminino , Humanos , Mortalidade Materna/tendências , Segurança do Paciente/normas , Hemorragia Pós-Parto/diagnóstico , Hemorragia Pós-Parto/epidemiologia , Hemorragia Pós-Parto/prevenção & controle , Gravidez , Complicações na Gravidez/diagnóstico , Fatores de Risco , Estados Unidos/epidemiologia , Tromboembolia Venosa/diagnósticoRESUMO
The challenging nature of recurrent pregnancy loss (RPL) is multifactorial, but largely begins with determining who meets diagnostic criteria for RPL as definitions vary and frequently change. Many patients seek obstetrical intervention after losses, even if they do not meet the criteria for RPL, and even those strictly meeting criteria often present a conundrum as to the etiology of their condition. The contribution of hereditary thrombophilia to RPL, the impact of each disorder on the clotting cascade, available evidence regarding pregnancy outcomes, and current recommendations for evaluation and treatment is presented.
Assuntos
Aborto Habitual/genética , Trombofilia/genética , Fator V/genética , Feminino , Humanos , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Mutação , Gravidez , Primeiro Trimestre da Gravidez , Deficiência de Proteína C/complicações , Deficiência de Proteína C/genética , Deficiência de Proteína S/complicações , Deficiência de Proteína S/genética , Protrombina/genética , Trombofilia/complicaçõesRESUMO
OBJECTIVE: Preeclampsia is one of the top six causes of maternal mortality in the United States (US) and is associated with considerable perinatal morbidity and mortality. Evidence suggests the US incidence of preeclampsia has increased dramatically over the past two decades. This study aims to compile, summarize, and critique the literature on the health and economic burden of preeclampsia and early-onset preeclampsia. STUDY DESIGN: We reviewed the literature for estimates of burden of preeclampsia and early-onset preeclampsia to both mother and child, summarized the evidence on economic and social burden, and highlighted current gaps in the literature. RESULTS: No recent studies comprehensively assess the costs and health consequences of preeclampsia or early-onset preeclampsia for both mother and child. Where it exists, the literature suggests preeclampsia and early-onset preeclampsia cause numerous adverse health consequences, but these conditions currently lack effective treatment. The need for preterm delivery from early-onset preeclampsia suggests its costs are substantial: very (28-31 weeks) and extremely (<28 weeks) preterm birth cost approximately 40 and 100 times a term pregnancy, respectively. CONCLUSION: Given the severity of outcomes from preeclampsia, further research on its health and economic consequences is essential to inform policy and resource allocation decisions in health care.
Assuntos
Efeitos Psicossociais da Doença , Mortalidade Infantil/tendências , Mortalidade Materna/tendências , Pré-Eclâmpsia/epidemiologia , Nascimento Prematuro/epidemiologia , Saúde da Criança , Feminino , Idade Gestacional , Humanos , Incidência , Lactente , Recém-Nascido , Saúde Materna , Gravidez , Resultado da Gravidez , Fatores de Risco , Estados UnidosRESUMO
OBJECTIVES: The purpose of this analysis was to evaluate the use of recombinant human antithrombin (rhAT) in preventing venous thromboembolism (VTE) in pregnant patients with hereditary AT deficiency (HATD). STUDY DESIGN: Data from two clinical trials were pooled. Dosing of rhAT was based on body weight and baseline AT activity, started up to 24 hours before scheduled induction or cesarean delivery, or at the onset of labor. RESULTS: A total of 21 pregnant HATD patients were enrolled. Mean rhAT therapy duration was 4.3 days and dose was 245.1 IU/kg/day. All patients achieved target mean AT activity (80-120% of normal) during rhAT therapy. There were no confirmed VTEs during rhAT treatment or within 7 ( ± 1) days after dosing. Two VTE events (one deep vein thrombosis and one pulmonary embolism) occurred 11 and 14 days after discontinuation of rhAT, in patients managed with prophylactic doses of heparin or low-molecular-weight heparin following delivery. CONCLUSION: rhAT was safe and effective in pregnant HATD patients when administered during the peripartum period, the period of highest VTE risk and a time when anticoagulation therapy is normally withheld. Pregnant HATD patients may benefit from therapeutic, rather than prophylactic, doses of anticoagulation after delivery to protect against postpartum VTE.
Assuntos
Anticoagulantes/administração & dosagem , Deficiência de Antitrombina III/tratamento farmacológico , Antitrombina III/administração & dosagem , Heparina de Baixo Peso Molecular/administração & dosagem , Trombose Venosa/prevenção & controle , Adulto , Feminino , Heparina de Baixo Peso Molecular/efeitos adversos , Humanos , Internacionalidade , Período Periparto , Gravidez , Proteínas Recombinantes/administração & dosagem , Trombose Venosa/epidemiologia , Adulto JovemRESUMO
Maternal thromboembolism and a spectrum of placenta-mediated complications including the pre-eclampsia syndromes, fetal growth restriction, fetal loss, and abruption manifest a shared etiopathogenesis and predisposing risk factors. Furthermore, these maternal and fetal complications are often linked to subsequent maternal health consequences that comprise the metabolic syndrome, namely, thromboembolism, chronic hypertension, and type II diabetes. Traditionally, several lines of evidence have linked vasoconstriction, excessive thrombosis and inflammation, and impaired trophoblast invasion at the uteroplacental interface as hallmark features of the placental complications. "Omic" technologies and biomarker development have been largely based upon advances in vascular biology, improved understanding of the molecular basis and biochemical pathways responsible for the clinically relevant diseases, and increasingly robust large cohort and/or registry based studies. Advances in understanding of innate and adaptive immunity appear to play an important role in several pregnancy complications. Strategies aimed at improving prediction of these pregnancy complications are often incorporating hemodynamic blood flow data using non-invasive imaging technologies of the utero-placental and maternal circulations early in pregnancy. Some evidence suggests that a multiple marker approach will yield the best performing prediction tools, which may then in turn offer the possibility of early intervention to prevent or ameliorate these pregnancy complications. Prediction of maternal cardiovascular and non-cardiovascular consequences following pregnancy represents an important area of future research, which may have significant public health consequences not only for cardiovascular disease, but also for a variety of other disorders, such as autoimmune and neurodegenerative diseases.
Assuntos
Complicações Hematológicas na Gravidez/terapia , Trombose/terapia , Biomarcadores/metabolismo , Feminino , Genômica , Humanos , Metabolômica , Gravidez , Complicações Hematológicas na Gravidez/prevenção & controle , Proteômica , Fatores de Risco , Trombose/prevenção & controleRESUMO
BACKGROUND: Postpartum hemorrhage (PPH) remains one of the leading causes of maternal morbidity and mortality worldwide, although the lack of a precise definition precludes accurate data of the absolute prevalence of PPH. STUDY DESIGN AND METHODS: An international expert panel in obstetrics, gynecology, hematology, transfusion, and anesthesiology undertook a comprehensive review of the literature. At a meeting in November 2011, the panel agreed on a definition of severe PPH that would identify those women who were at a high risk of adverse clinical outcomes. RESULTS: The panel agreed on the following definition for severe persistent (ongoing) PPH: "Active bleeding >1000 mL within the 24 hours following birth that continues despite the use of initial measures including first-line uterotonic agents and uterine massage." A treatment algorithm for severe persistent PPH was subsequently developed. Initial evaluations include measurement of blood loss and clinical assessments of PPH severity. Coagulation screens should be performed as soon as persistent (ongoing) PPH is diagnosed, to guide subsequent therapy. If initial measures fail to stop bleeding and uterine atony persists, second- and third-line (if required) interventions should be instated. These include mechanical or surgical maneuvers, i.e., intrauterine balloon tamponade or hemostatic brace sutures with hysterectomy as the final surgical option for uncontrollable PPH. Pharmacologic options include hemostatic agents (tranexamic acid), with timely transfusion of blood and plasma products playing an important role in persistent and severe PPH. CONCLUSION: Early, aggressive, and coordinated intervention by health care professionals is critical in minimizing blood loss to ensure optimal clinical outcomes in management of women with severe, persistent PPH.
Assuntos
Hemorragia Pós-Parto/diagnóstico , Hemorragia Pós-Parto/terapia , Prática Profissional , Transtornos Herdados da Coagulação Sanguínea/complicações , Transtornos Herdados da Coagulação Sanguínea/diagnóstico , Transtornos Herdados da Coagulação Sanguínea/terapia , Transfusão de Componentes Sanguíneos/estatística & dados numéricos , Prova Pericial , Feminino , Hemostáticos/uso terapêutico , Humanos , Trabalho de Parto , Hemorragia Pós-Parto/etiologia , Guias de Prática Clínica como Assunto , Gravidez , Prática Profissional/normas , Prática Profissional/estatística & dados numéricos , Fatores de RiscoRESUMO
Unexplained postpartum hemorrhage (PPH) refractory to standard hemostatic measures should trigger a heightened clinical suspicion of an acquired bleeding disorder. When hemostatic medical interventions and surgical procedures fail to control the bleeding, then significant postoperative blood loss, debilitating morbidity, loss of fertility, and death may occur. In the setting of an autoantibody inhibitor to factor VIII (FVIII), control of life-threatening PPH and avoidance of subsequent bleeding episodes depends on a timely and accurate diagnosis, prompt hemostatic treatment and eradication of FVIII inhibitors, and appropriate long-term patient care and management. Acquired postpartum hemophilia due to a FVIII inhibitor is a rare cause of PPH; however, delayed treatment can lead to increased maternal morbidity and mortality. Acquired FVIII inhibitors also pose an emerging bleeding threat to the neonate as a result of possible transplacental transfer of FVIII autoantibodies to the fetus during the last trimester of pregnancy. The purpose of this review is to increase awareness among hematologists and obstetricians/gynecologists regarding the occurrence of FVIII neutralizing autoantibodies as a cause of PPH, and emphasize the importance of collaboration between obstetrician/gynecologists and hematology specialists to optimize the diagnostic evaluation, treatment, and long-term management of women who experience PPH due to an acquired FVIII inhibitor.
Assuntos
Hemofilia A/complicações , Hemorragia Pós-Parto/etiologia , Complicações Hematológicas na Gravidez/diagnóstico , Autoanticorpos/imunologia , Fator VIII/imunologia , Feminino , Hemofilia A/diagnóstico , Hemofilia A/terapia , Humanos , Gravidez , Complicações Hematológicas na Gravidez/imunologia , Complicações Hematológicas na Gravidez/terapiaRESUMO
The coronavirus disease-19 (COVID-19) pandemic, declared in early 2020, has left an indelible mark on global health, with over 7.0 million deaths and persistent challenges. While the pharmaceutical industry raced to develop vaccines, the emergence of mutant severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) strains continues to pose a significant threat. Beyond the immediate concerns, the long-term health repercussions of COVID-19 survivors are garnering attention, particularly due to documented cases of cardiovascular issues, liver dysfunction, pulmonary complications, kidney impairments, and notable neurocognitive deficits. Recent studies have delved into the pathophysiological changes in various organs following post-acute infection with murine hepatitis virus-1 (MHV-1), a coronavirus, in mice. One aspect that stands out is the impact on the skin, a previously underexplored facet of long-term COVID-19 effects. The research reveals significant cutaneous findings during both the acute and long-term phases post-MHV-1 infection, mirroring certain alterations observed in humans post-SARS-CoV-2 infection. In the acute stages, mice exhibited destruction of the epidermal layer, increased hair follicles, extensive collagen deposition in the dermal layer, and hyperplasticity of sebaceous glands. Moreover, the thinning of the panniculus carnosus and adventitial layer was noted, consistent with human studies. A long-term investigation revealed the absence of hair follicles, destruction of adipose tissues, and further damage to the epidermal layer. Remarkably, treatment with a synthetic peptide, SPIKENET (SPK), designed to prevent Spike glycoprotein-1 binding with host receptors and elicit a potent anti-inflammatory response, showed protection against MHV-1 infection. Precisely, SPK treatment restored hair follicle loss in MHV-1 infection, re-architected the epidermal and dermal layers, and successfully overhauled fatty tissue destruction. These promising findings underscore the potential of SPK as a therapeutic intervention to prevent long-term skin alterations initiated by SARS-CoV-2, providing a glimmer of hope in the battle against the lingering effects of the pandemic.
RESUMO
PROBLEM: Although endometrial receptivity is a key factor in influencing implantation in both naturally conceived and assisted reproductive technology (ART) cycles, very little is known about the endometrium milieu around the time of implantation. Previous studies have demonstrated the presence of several cytokines in the endometrium that affect implantation. However, there is lacking data about the presence of immune cell subtypes within the endometrium and in the uterine cavity at the time of implantation. METHOD OF STUDY: This study was approved by the Institutional Review Board (# 225589). The study was designed as a prospective observational cohort study between May 2021 and December 2022 at a single academic-based fertility center. All patients underwent at least one In Vitro Fertilization (IVF) cycle and have frozen embryos. Twenty-four participants were recruited for this study which was conducted during the frozen embryo transfer (FET) cycle regardless of the outcome of previous cycles. Two samples were acquired from each subject, denoted as lower and upper. A trial transfer catheter was introduced under ultrasound guidance into the lower uterine segment. Upon removal, the tip was rinsed in IMDM medium containing 10% FBS (lower uterus). A transfer catheter was then loaded with the embryo that was placed in the upper uterus under ultrasound guidance. The tip of the transfer catheter was rinsed in separate aliquot of the above media (upper uterus). After centrifugation, pelleted cells were stained for the following surface markers: CD45, CD3, CD19, CD4, CD8, gamma delta TCR, CD25, CD127, CD66b, CD14, CD16, CD56 and acquired on Sony SP6800 Spectral Analyzer. RESULTS: Upon staining the pelleted cells, we were able to identify viable leukocytes from samples obtained from both, upper and lower uterus (0.125 × 106 cells ± SD 0.32), (0.123 × 106 cells ± SD 0.12), respectively. Among total viable cells, there was no significant difference in both percent and number of CD45+ cells between the upper and lower uterus (9.88% ± 6.98 SD, 13.67% ± 9.79 SD, p = .198) respectively. However, there was significantly higher expression of CD3+ (p = .006), CD19+ (p = .032) and CD14+ (p = .019) cells in samples collected from upper compared to lower uterus. Within all CD3+ cells, we found that gamma delta T cells (GDT) were the major population of T cells in both upper and lower uterus. In contrast, CD8+ T cells were significantly higher in the lower uterus when compared to the upper uterus (p = .009). There was no statistically significant difference in the expression of CD4+ T cells, T regulatory cells (CD4+CD25+CD127-), NK cells (CD56+), neutrophils (CD66b+) and FcγRIII+ cells (CD16+) between upper and lower uterus. CONCLUSIONS: We believe the immune milieu at the time of embryo transfer will affect implantation. Understanding the composition of immune cells will guide further research in identifying optimal immune milieus that favor implantation. Comprehensive analysis of endometrium is expected to lead to new diagnostic and therapeutic approaches to improve IVF outcomes.