Population-based study of eclampsia: Lessons learnt to improve maternity care.

BACKGROUND: Among hypertensive disorders of pregnancy (HDP), eclampsia is a rare but serious event, often considered avoidable. Detailed assessment of the adequacy of care for the women who have eclampsia can help identify opportunities for improvement and for prevention of the associated adverse maternal and neonatal outcomes. OBJECTIVE: 1/ To estimate the incidence and describe the characteristics of women with eclampsia and to compare them with those of women with non-eclamptic hypertensive disorders of pregnancy (HDP)-related severe maternal morbidity (SMM) and of control women without SMM 2/ To analyse the quality of management in women who had eclampsia, at various stages of their care pathway. METHODS: It was a planned ancillary analysis of the EPIMOMS population-based study, conducted in six French regions in 2012-2013. Among the 182,309 maternities of the source population, all women with eclampsia (n = 51), with non-eclamptic HDP-related SMM (n = 351) and a 2% representative sample of women without SMM (n = 3,651) were included. Main outcome was the quality of care for eclampsia assessed by an independent expert panel at three different stages of management: antenatal care, care for pre-eclampsia and care for eclampsia. RESULTS: The eclampsia incidence was 2.8 per 10,000 (95%CI 2.0-4.0). Antenatal care was considered completely inadequate or substandard in 39% of women, as was pre-eclampsia care in 76%. Care for eclampsia was judged completely inadequate or substandard in 50% (21/42), mainly due to inadequate use of magnesium sulphate. CONCLUSION: The high proportion of inadequate quality of care underlines the need for an evidence-based standardisation of care for HDP.

Co-creation of a toolkit to assist risk communication and clinical decision-making in severe preeclampsia: SPOT-Impact study design.

Globally, the incidence of hypertensive disorders of pregnancy, especially preeclampsia, remains high, particularly in low- and middle-income countries. The burden of adverse maternal and perinatal outcomes is particularly high for women who develop a hypertensive disorder remote from term (<34 weeks). In parallel, many women have a suboptimal experience of care. To improve the quality of care in terms of provision and experience, there is a need to support the communication of risks and making of treatment decision in ways that promote respectful maternity care. Our study objective is to co-create a tool(kit) to support clinical decision-making, communication of risks and shared decision-making in preeclampsia with relevant stakeholders, incorporating respectful maternity care, justice, and equity principles. This qualitative study detailing the exploratory phase of co-creation takes place over 17 months (Nov 2021-March 2024) in the Greater Accra and Eastern Regions of Ghana. Informed by ethnographic observations of care interactions, in-depth interviews and focus group and group discussions, the tool(kit) will be developed with survivors and women with hypertensive disorders of pregnancy and their families, health professionals, policy makers, and researchers. The tool(kit) will consist of three components: quantitative predicted risk (based on external validated risk models or absolute risk of adverse outcomes), risk communication, and shared decision-making support. We expect to co-create a user-friendly tool(kit) to improve the quality of care for women with preeclampsia remote from term which will contribute to better maternal and perinatal health outcomes as well as better maternity care experience for women in Ghana.

Adverse maternal and perinatal outcomes is high for women who develop preeclampsia remote from term (<34 weeks). To improve the quality of provision and experience of care, there is a need to support communication of risks and treatment decisions that promotes respectful maternity care.This article describes the methodology deployed to cocreate a user-friendly tool(kit) to support risk communication and shared decision-making in the context of severe preeclampsia in a low resource setting.

The Role of Regulatory T Cells and Their Therapeutic Potential in Hypertensive Disease of Pregnancy: A Literature Review.

Hypertensive disorders of pregnancy (HDP), including preeclampsia (PE) and gestational hypertension (GH), are major causes of maternal and foetal morbidity and mortality. This review elucidates the role of regulatory T cells (Tregs) in the immunological aspects of HDP and explores their therapeutic potential. Tregs, which play a critical role in maintaining immune homeostasis, are crucial in pregnancy to prevent immune-mediated rejection of the foetus. The review highlights that Tregs contribute to immunological adaptation in normal pregnancy, ensuring foetal acceptance. In contrast, HDP is associated with Treg dysfunction, which is marked by decreased numbers and impaired regulatory capacity, leading to inadequate immune tolerance and abnormal placental development. This dysfunction is particularly evident in PE, in which Tregs fail to adequately modulate the maternal immune response against foetal antigens, contributing to the pathophysiology of the disorder. Therapeutic interventions aiming to modulate Treg activity represent a promising avenue for HDP management. Studies in animal models and limited clinical trials suggest that enhancing Treg functionality could mitigate HDP symptoms and improve pregnancy outcomes. However, given the multifactorial nature of HDP and the intricate regulatory mechanisms of Tregs, the review explores the complexities of translating in vitro and animal model findings into effective clinical therapies. In conclusion, while the precise role of Tregs in HDP is still being unravelled, their central role in immune regulation during pregnancy is indisputable. Further research is needed to fully understand the mechanisms by which Tregs contribute to HDP and to develop targeted therapies that can safely and effectively harness their regulatory potential for treating hypertensive diseases of pregnancy.

Treating Mild Chronic Hypertension During Pregnancy: A Cost-Effectiveness Analysis.

OBJECTIVE: To assess the cost effectiveness of targeting a blood pressure of less than 140/90 mm Hg compared with 160/105 mm Hg. METHODS: A decision-analytic model was constructed to compare the treatment of chronic hypertension in pregnancy at mild-range blood pressures (140/90 mm Hg) with the treatment of chronic hypertension before 20 weeks of gestation at severe-range blood pressures (160/105 mm Hg) in a theoretical cohort of 180,000 patients with mild chronic hypertension. Probabilities, costs, and utilities were derived from literature and varied in sensitivity analyses. Primary outcomes included incremental cost per quality-adjusted life-year (QALY), cases of preeclampsia, preeclampsia with severe features, severe maternal morbidity (SMM), preterm birth, maternal death, neonatal death, and neurodevelopmental delay. The cost-effectiveness threshold was $100,000 per QALY. RESULTS: Treating chronic hypertension in a population of 180,000 pregnant persons at mild-range blood pressures, compared with severe-range blood pressures, resulted in 14,177 fewer cases of preeclampsia (43,953 vs 58,130), 11,835 of which were cases of preeclampsia with severe features (40,530 vs 52,365). This led to 817 fewer cases of SMM (4,375 vs 5,192), and 18 fewer cases of maternal death (102 vs 120). Treating at a lower threshold also resulted in 8,078 fewer cases of preterm birth (22,000 vs 30,078), which led to 26 fewer neonatal deaths (276 vs 302) and 157 fewer cases of neurodevelopmental delay (661 vs 818). Overall, treating chronic hypertension at a lower threshold was a dominant strategy that resulted in decreased costs of $600 million and increased effectiveness of 12,852 QALYs. CONCLUSION: Treating chronic hypertension at a threshold of mild-range blood pressures is a dominant (lower costs, better outcomes) and cost-effective strategy that results in fewer neonatal and maternal deaths compared with the standard treatment of treating at severe range blood pressures.

Mesenchymal stem cell-derived exosomes: a promising alternative in the therapy of preeclampsia.

Preeclampsia (PE) is a common morbid complication during pregnancy, affecting 2%-8% of pregnancies globally and posing serous risks to the health of both mother and fetus. Currently, the only effective treatment for PE is timely termination of pregnancy, which comes with increased perinatal risks. However, there is no effective way to delay pathological progress and improve maternal and fetal outcomes. In light of this, it is of great significance to seek effective therapeutic strategies for PE. Exosomes which are nanoparticles carrying bioactive substances such as proteins, lipids, and nucleic acids, have emerged as a novel vehicle for intercellular communication. Mesenchymal stem cell-derived exosomes (MSC-Exos) participate in various important physiological processes, including immune regulation, cell proliferation and migration, and angiogenesis, and have shown promising potential in tissue repair and disease treatment. Recently, MSC-Exos therapy has gained popularity in the treatment of ischaemic diseases, immune dysfunction, inflammatory diseases, and other fields due to their minimal immunogenicity, characteristics similar to donor cells, ease of storage, and low risk of tumor formation. This review elaborates on the potential therapeutic mechanism of MSC-Exos in treating preeclampsia, considering the main pathogenic factors of the condition, including placental vascular dysplasia, immunological disorders, and oxidative stress, based on the biological function of MSC-Exos. Additionally, we discuss in depth the advantages and challenges of MSC-Exos as a novel acellular therapeutic agent in preeclampsia treatment.

Informing Mobile Health Policy for Pregnant Women in Rural Populations in Canada, with a Focus on Pre-Eclampsia.

Canadian healthcare suffers rural disparities, especially in maternal and prenatal care. Drawing on a literature review, the paper highlights the potential of mobile health (mHealth) applications to bridge this gap and improve maternal care in rural communities. mHealth tools have great potential for knowledge and trust-building among healthcare workers and pregnant women. To support the success of these solutions, more funding and policy support are required. mHealth solutions have a great potential for great economic savings while addressing healthcare disparities and ensuring everyone has access to high quality care.

Gut microbiota-derived trimethylamine N-Oxide: a novel target for the treatment of preeclampsia.

Pre-eclampsia (PE) is the most common complication of pregnancy and seriously threatens the health and safety of the mother and child. Studies have shown that an imbalance in gut microbiota can affect the progression of PE. Trimethylamine N-oxide (TMAO) is an intestinal microbiota-derived metabolite that is thought to be involved in the occurrence of PE; however, its causal relationship and mechanism remain unclear. In this clinical cohort study, including 28 patients with eclampsia and 39 matched healthy controls, fecal samples were collected for 16S rRNA gene sequencing, and serum was collected for targeted metabolomics research. The results showed that the level of TMAO and the abundance of its source bacteria had significantly increased in patients with PE, and were positively correlated with the clinical progression of PE. Fecal microbiota transplantation (FMT) was applied to an antibiotic-depleted-treated mouse model and targeted inhibition of TMAO. The results of the FMT experiment revealed that mice that received fecal microbiota transplantation from patients with PE developed typical PE symptoms and increased oxidative stress and inflammatory damage, both of which were reversed by 3,3-Dimethyl-1-butanol (DMB), a TMAO inhibitor, which also improved pregnancy outcomes in the model mice. Similar results were obtained in the classical NG-Nitroarginine methyl ester (L-NAME) induced PE mouse model. Mechanistically, TMAO promotes the progression of PE by regulating inflammatory and oxidative stress-related signaling pathways, affecting the migration and angiogenesis of vascular endothelial cells, as well as the migration and invasion of trophoblast cells. Our results reveal the role and mechanism of gut microbiota and TMAO in the progression of PE, provides new ideas for exploring the pathogenesis and therapeutic targets of PE, and determines the potential application value of TMAO as a target for PE intervention.

Patients and health care workers perceived challenges in managing preeclampsia, in Malawi.

OBJECTIVES: This study investigated perceptions of the challenges for patients and health care workers (HCW) in dealing with preeclampsia in Blantyre, Malawi. METHODS: A descriptive cross-sectional formative study using semi-structured In-Depth Interviews (IDI) was conducted at Queen Elizabeth Central Hospital (QECH), Malawi. Data was analyzed using NVIVO™ software. Thematic content analysis was used to analyze and interpret the findings. Emerging themes were then developed inductively and deductively. Patients were interviewed who recently had preeclampsia. RESULTS: Stress, lack of information, physical symptoms, delay in receiving care were identified challenges to better care among patients as well as the impact of poor pregnancy outcomes. Late diagnosis, staff burn out, inadequate skills and lack of resources were expressed as challenge to provide better management by the interviewed HCWs. CONCLUSION: Our study showed that a diagnosis of preeclampsia is challenging to both patients and HCWs. These challenges need to be addressed carefully at all levels for optimal management of preeclampsia in Malawi, Africa and in order to improve outcomes.

Mesenchymal stem cell-derived exosomes in preeclampsia: A next-generation therapeutic tool.

Preeclampsia (PE) is a major gestational disorder that causes both long- and short-term damage to both the mother and the fetus. Endometrium decidualization and the formation of the placenta are orchestrated by mesenchymal stem cells (MSCs). MSCs obtained from patients with PE exhibit an elevated rate of aging and apoptosis, which impairs the interplay between MSCs and endothelium, trophoblast, and immune cells in the placenta, accelerating the onset of PE. Preclinical and clinical evidence imply that the MSC-based therapy approach for PE is prospective. Importantly, as a novel cell-free approach, MSC-derived exosomes can improve symptoms and maternal-fetal survival in PE models by raising cell metabolism, encouraging angiogenesis balance, and regulating immune responses. Even following allogeneic administration, the likelihood of immune rejection is very limited as a result of the small quantity of exosome membrane-bound proteins. Furthermore, because exosomes do not expand, developing tumors is not probable. As a result, MSC-derived exosomes show superiority over MSCs in terms of safety. For the first time, we outline the properties of MSC-exosomes and highlight their functions and potential as a new paradigm for PE therapy in this review.

[Preeclampsia: Guidelines for clinical practice from the French College of Obstetricians and Gynecologists]. / La pré-éclampsie : recommandations pour la pratique clinique du Collège national des gynécologues obstétriciens français.

OBJECTIVE: To identify strategies to reduce maternal and neonatal morbidity related to preeclampsia. MATERIAL AND METHODS: The quality of evidence of the literature was assessed following the GRADE® method with questions formulated in the PICO format (Patients, Intervention, Comparison, Outcome) and outcomes defined a priori and classified according to their importance. An extensive bibliographic search was performed on PubMed, Cochrane, EMBASE and Google Scholar databases. The quality of the evidence was assessed (high, moderate, low, very low) and recommendations were formulated as a (i) strong, (ii) weak or (iii) no recommendation. The recommendations were reviewed in two rounds with external reviewers (Delphi survey) to select the consensus recommendations. RESULTS: Preeclampsia is defined by the association of gestational hypertension (systolic blood pressure≥140mmHg and/or diastolic blood pressure≥90mmHg) and proteinuria≥0.3g/24h or a Proteinuria/Creatininuria ratio≥30mg/mmol occurring after 20 weeks of gestation. Data from the literature do not show any benefit in terms of maternal or perinatal health from implementing a broader definition of preeclampsia. Of the 31 questions, there was agreement between the working group and the external reviewers on 31 (100%). In general population, physical activity during pregnancy should be encouraged to reduce the risk of preeclampsia (Strong recommendation, Quality of the evidence low) but an early screening based on algorithms (Weak recommendation, Quality of the evidence low) or aspirin administration (Weak recommendation, Quality of the evidence very low) is not recommended to reduce maternal and neonatal morbidity related to preeclampsia. In women with preexisting diabetes or hypertension or renal disease, or multiple pregnancy, the level of evidence is insufficient to determine whether aspirin administration during pregnancy is useful to reduce maternal and perinatal morbidity (No recommendation, Quality of the evidence low). In women with a history of vasculo-placental disease, low dose of aspirin (Strong recommendation, Quality of the evidence moderate) at a dosage of 100-160mg per day (Weak recommendation, Quality of the evidence low), ideally before 16 weeks of gestation and not after 20 weeks of gestation (Strong recommendation, Quality of the evidence low) until 36 weeks of gestation (Weak recommendation, Quality of the evidence very low) is recommended. In a high-risk population, additional administration of low molecular weight heparin is not recommended (Weak recommendation, Quality of the evidence moderate). In case of preeclampsia (Weak recommendation, Quality of the evidence low) or suspicion of preeclampsia (Weak recommendation, Quality of the evidence moderate, the assessment of PlGF concentration or sFLT-1/PlGF ratio is not routinely recommended) in the only goal to reduce maternal or perinatal morbidity. In women with non-severe preeclampsia antihypertensive agent should be administered orally when the systolic blood pressure is measured between 140 and 159mmHg or diastolic blood pressure is measured between 90 and 109mmHg (Weak recommendation, Quality of the evidence low). In women with non-severe preeclampsia, delivery between 34 and 36+6 weeks of gestation reduces severe maternal hypertension but increases the incidence of moderate prematurity. Taking into account the benefit/risk balance for the mother and the child, it is recommended not to systematically induce birth in women with non-severe preeclampsia between 34 and 36+6 weeks of gestation (Strong recommendation, Quality of evidence high). In women with non-severe preeclampsia diagnosed between 37+0 and 41 weeks of gestation, it is recommended to induce birth to reduce maternal morbidity (Strong recommendation, Low quality of evidence), and to perform a trial of labor in the absence of contraindication (Strong recommendation, Very low quality of evidence). In women with a history of preeclampsia, screening maternal thrombophilia is not recommended (Strong recommendation, Quality of the evidence moderate). Because women with a history of a preeclampsia have an increased lifelong risk of chronic hypertension and cardiovascular complications, they should be informed of the need for medical follow-up to monitor blood pressure and to manage other possible cardiovascular risk factors (Strong recommendation, Quality of the evidence moderate). CONCLUSION: The purpose of these recommendations was to reassess the definition of preeclampsia, and to determine the strategies to reduce maternal and perinatal morbidity related to preeclampsia, during pregnancy but also after childbirth. They aim to help health professionals in their daily clinical practice to inform or care for patients who have had or have preeclampsia. Synthetic information documents are also offered for professionals and patients.

Use of therapeutic apheresis methods during pregnancy.

This review will focus on the current application of TA in pregnancy and possible aspects for future studies. It seems that scientific interest and field for further research in pregnancy is lately focused in specific removal of pathogens implicated in the physiologic mechanism of pre-eclampsia/HELLP syndrome as well as recurrent pregnancy failure.

Midwives' experiences of providing pre-eclampsia care in a low- and middle-income country - A qualitative study.

PROBLEM: Like other low- and middle-income countries, Ghana has high maternal mortality stemming from pre-eclampsia. Ghanaian midwives are frontline service providers of emergency care in obstetric complications and have the greatest potential to maximise pre-eclampsia outcomes. Little is known about the potential barriers and challenges to midwives' capacity to provide quality care in pre-eclampsia in Ghana. Therefore, we aimed to explore and gain insights into midwives' experiences of pre-eclampsia care including their knowledge, skills, and psychological aspects such as midwives' resilience. BACKGROUND: There is a rising global incidence of pre-eclampsia. Quality midwifery care in inter-professional collaborative practice is crucial to reducing pre-eclampsia-related morbidity and mortality. METHODS: A qualitative descriptive exploratory study. In-depth semi-structured interviews (n = 35) were performed in 2021 and analysed by thematic analysis. FINDINGS: There were three main themes. 1) Competence and Confidence in care; midwives provided timely and appropriate care based on sound knowledge and skills; they explained how pre-eclampsia care was organised within a multidisciplinary context and described collaborative working amongst midwives for mutual learning and support. 2) Emotional concerns and empathy; midwives' described fulfillment in achieving positive pre-eclampsia outcomes. In contrast, maternal loss was distressing and traumatic. 3) Call for improved care resources for pre-eclampsia; midwives recommended expansion of continuing professional development opportunities, appropriate infrastructure, resources, tailored public education, and a review of pre-service education to support their participation in pre-eclampsia care. CONCLUSION: To improve the quality of care in pre-eclampsia, midwives should be capacitated, systems should promptly address barriers, and prioritise midwives' emotional well-being.

Labor and delivery: DIC, HELLP, preeclampsia.

Hematologists are often needed to assist with the management of microangiopathic emergencies in pregnancy. A firm understanding of the diagnosis and management of preeclampsia with severe features, hemolysis elevated liver enzyme and low platelet syndrome, and disseminated intravascular coagulation, which are the most common causes of microangiopathic emergencies, is critical. However, being able to consider when other microangiopathic emergencies (acute fatty liver of pregnancy, congenital and acquired thrombotic thrombocytopenic purpura, complement mediated microangiopathy, antiphospholipid syndrome) should be considered is imperative. The hematologist and obstetric team should work together to optimize the care of common as well as rare hematologic emergencies.

Research progress on the correlation between gut microbiota and preeclampsia: microbiome changes, mechanisms and treatments.

Preeclampsia is a specific disease during pregnancy and is a significant factor in the increased mortality in perinatal women. Gut microbiota, an intricate and abundant microbial community in the digestive tract, is crucial for host metabolism, immunity, and nutrient absorption. The onset and progression of preeclampsia are closely correlated with the changes in maternal gut microbiota. Research purpose was to compile the existing bits of present scientific data and to close the gap in the knowledge of changes in gut microbiota in preeclampsia and their association with preeclampsia. We searched studies from two electronic databases (PubMed and Web of Science) included from 2014 to 2023. This review is divided into three parts. In the first part, the author elaborates longitudinal differences of maternal gut microbiota during different gestation periods. In the second part, we discuss that gut microbiota can lead to the occurrence of preeclampsia by systemic immune response, influencing the release of active peptides, short-chain fatty acids, trimethylamine-N-oxide (TMAO) and other metabolites, vascular factors and Microorganism-immune axis. In the third part, we proposed that a high-fiber diet combined with drugs and microecological regulators may be therapeutic in enhancing or preventing the emergence and evolution of preeclampsia, which needs further exploration. Although the pathogenesis of preeclampsia is still nebulous and there is no clear and valid clinical treatment, our study provides new ideas for the pathogenesis, prevention and treatment of preeclampsia.

Perinatal outcomes and their determinants among women with eclampsia and severe preeclampsia in selected tertiary hospitals, Eastern Ethiopia.

BACKGROUND: Neonatal complications and deaths are still increasing worldwide. Therefore, this study aimed to assess perinatal outcomes and their determinants among women with eclampsia and severe preeclampsia admitted to selected tertiary hospitals Eastern Ethiopia. METHODS: The prospective observational study was conducted among 245 foetal born to women with eclampsia and severe preeclampsia admitted to selected Hospitals. Data were collected from patients' charts and maternal interviews using questionnaires and telephone follow-ups from April 01 to September 30, 2022. Then, Cox regression were used to determine the predictors of perinatal clinical outcomes by SPSS (version 21.0®). Hazard ratios with a two-sided P-value < 0.05 were considered statistically significant. RESULT: Of 245 deliveries, perinatal mortality was 26.1 % and about 57.4 % of newborns developed neonatal complications. Fifth-minute Apgar score (AHR: 10.3; 95 % C.I: 3.8-28.1; P: 0.0001) was statistically a determinant to perinatal mortality whereas maternal parity (AHR: 1.7; 95 % CI: 1.0-2.86; P: 0.05), maternal diagnosis (AHR: 2.1; 95 % C.I:1.17-3.66; P: 0.012), maternal complications (AHR: 1.96; 95 % C.I: 1.13-3.41; P: 0.018) and fifth-minute Apgar score (AHR: 2.0; 95 % C.I: 1.29-3.19; P: 0.002) were found to be determinants for neonatal complications. CONCLUSION: Despite the inclusion of magnesium sulphate into the national drug list of Ethiopia to reduce maternal and perinatal morbidity and mortality, the perinatal condition remained a severe concern and worse among patients with eclampsia. Interventions to reduce the incidence of eclampsia, better antenatal care, early recognition, prompt treatment of severe preeclampsia, and enhanced neonatal care have to be initiated for patients.

Adrenomedullin has a pivotal role in trophoblast differentiation: A promising nanotechnology-based therapeutic target for early-onset preeclampsia.

Early-onset preeclampsia (EOPE) is a severe pregnancy complication associated with defective trophoblast differentiation and functions at implantation, but manifestation of its phenotypes is in late pregnancy. There is no reliable method for early prediction and treatment of EOPE. Adrenomedullin (ADM) is an abundant placental peptide in early pregnancy. Integrated single-cell sequencing and spatial transcriptomics confirm a high ADM expression in the human villous cytotrophoblast and syncytiotrophoblast. The levels of ADM in chorionic villi and serum were lower in first-trimester pregnant women who later developed EOPE than those with normotensive pregnancy. ADM stimulates differentiation of trophoblast stem cells and trophoblast organoids in vitro. In pregnant mice, placenta-specific ADM suppression led to EOPE-like phenotypes. The EOPE-like phenotypes in a mouse PE model were reduced by a placenta-specific nanoparticle-based forced expression of ADM. Our study reveals the roles of trophoblastic ADM in placental development, EOPE pathogenesis, and its potential clinical uses.

Extracellular Vesicles Derived from Human Umbilical Cord MSC Improve Vascular Endothelial Function in In Vitro and In Vivo Models of Preeclampsia through Activating Arginine Metabolism.

Endothelial cell damage is an important feature of preeclampsia (PE). Human umbilical mesenchymal stem-cell-derived extracellular vesicles (HUMSCs-derived EVs) have been shown to have therapeutic effects on a variety of diseases and tissue damage. However, the therapeutic effect of HUMSCs-derived EVs on endothelial injury in PE remains unclear. This study explored the possible mechanism of HUMSCs-derived EVs in the treatment of endothelial cell injury. Tumor necrosis factor α- and lipopolysaccharide-induced endothelial dysfunction models were used to evaluate the therapeutic effect of HUMSCs-derived EVs on endothelial injury. We further constructed PE mouse models to explore the function of HUMSCs-derived EVs in vivo. The changes of metabolites in endothelial cells after HUMSCs-derived EVs treatment were analyzed by metabolomics analysis and further validated by cell experiments. HUMSCs-derived EVs treatment can alleviate endothelial cell injury in PE, involving cell proliferation, migration, angiogenesis, and anti-inflammatory. Importantly, administration of HUMSCs-derived EVs improves hypertension and proteinuria in PE mice, alleviates kidney damage, and promotes vascularization in the placenta. Furthermore, metabolomics analysis found that the arginine metabolic pathway is activated after HUMSCs-derived EVs treatment. We also observed increased arginine level, nitric oxide content, and nitric oxide synthase activity, and further experiments proved that activating the arginine metabolic pathway could alleviate endothelial dysfunction. Our results reveal that HUMSCs-derived EVs could ameliorate PE endothelial dysfunction by activating the arginine metabolic pathway and may serve as a therapeutic method for treating PE.

Hypertension in Women and Pregnancy.

Hypertension has been shown to have long-term cardiovascular effects if left untreated. Hypertension also has been shown to affect women during pregnancy, which can be detrimental not only to the patient but also to the fetus. Early identification and treatment are paramount to prevent adverse outcomes. This article details the epidemiology, clinical presentation, diagnosis, and treatment of essential hypertension in women, gestational hypertension, preeclampsia, and eclampsia.