Preeclampsia: Short- and Long-Term Effects.

Does our time inside the womb predict our future? Evidence suggests that the environment in the womb plays a powerful role in predicting specific adult diseases. The fetus is constantly responding and adapting to the intrauterine environment by a process called programming. Toxic exposures, such as nutritional deficits and hypoxia, can affect fetal development and increase the risk for specific diseases that manifest later in our adult life. Preeclampsia (PE) is one disorder that results in a less-than-optimal environment for the growing fetus. It is pregnancy-specific and defined as new-onset hypertension after 20 weeks' gestation in the presence of maternal multiorgan dysfunction. To the best of our understanding, the pathogenesis is multifactorial and involves dysfunction of the placenta and the vascular, renal, and immunological systems. Treatment options are limited and may result in adverse outcomes for the fetus and newborn. Preeclampsia is a major contributor to perinatal and maternal morbidity and mortality worldwide, thus generating a significant healthcare burden. Research continues to demonstrate that mothers and infants affected by PE are at increased susceptibility to chronic conditions such as cardiovascular, renal, metabolic, and neurological diseases. More efforts are needed to further understand this disease. Efforts to increase awareness will help improve clinical outcomes for both mothers and infants.

Midwifery experiences in rural Southern Aotearoa New Zealand: insights into pre-eclampsia management.

AIM: This study investigated the experiences of rural midwives in the Southern region of Aotearoa New Zealand, focussing on practices and challenges in caring for pregnant individuals displaying signs of pre-eclampsia (PE). METHOD: Conducted as part of the University of Otago's Trainee Intern Healthcare Evaluation Project, investigating the efficacy of the soluble FMS-like tyrosine kinase 1 (sFlt-1)/placental growth factor (PlGF) ratio test, this exploratory study employed qualitative research methods. Twenty-three midwives from nine locations across the Southern region were interviewed by trainee intern doctors (TIs) using a semi-structured interview protocol. Thematic analysis was applied to the data. RESULTS: The study highlighted the challenging context of rural midwifery, emphasising diverse working conditions, geographic complexities and the impact of the midwifery shortage. Midwives' decision making about PE depended on location, experience, scientific evidence, holistic model of care and the constant concern about PE. A model illustrating midwifery decision making in PE management was developed. CONCLUSION: Rural midwives in Aotearoa New Zealand's Southern region managing PE cases face complex challenges. The model derived from this study illustrates the delicate balance that rural midwives navigate, emphasising the need for strategies to support their practice and preserve Aotearoa New Zealand's distinctive maternity care model.

Pre-eclampsia challenges and care in low and middle-income countries: Understanding diagnosis, management, and health impacts in remote and developing regions.

As an example of a low- and middle-income country (LMIC), India ranks pre-eclampsia among the top three causes of maternal mortality, following haemorrhage and infections. It is one of the primary concerns for maternal and perinatal health in LMICs. Many LMICs lack clear consensus and guidelines for the prevention, diagnosis, and management of hypertensive disorders in pregnancy, including pre-eclampsia. The International Society for the Study of Hypertension in Pregnancy 2021 guidelines address LMIC applications, offering customisable solutions. Atypical presentations of pre-eclampsia contribute to diagnostic delays, resulting in additional adverse maternal and perinatal outcomes. Implementing management strategies faces challenges in both urban and rural settings. Adapting global research involving local populations is imperative, with the potential for cost-effective adoption of international guidelines. Prevention, early diagnosis, and education dissemination are essential, involving healthcare providers and advocacy initiatives. Encouraging government investment in pre-eclampsia management as a public health initiative is important. This article explores socio-economic, cultural, and legislative factors influencing the management of pre-eclampsia in LMICs, addressing emerging challenges and potential partnerships for healthcare provision.

Human amniotic epithelial cells improve uterine spiral artery remodeling to ameliorate preeclampsia in a rat model†.

Preeclampsia (PE) is a multisystem pregnancy disorder characterized by impaired remodeling of placental spiral arteries, which leads to the release of pro-inflammatory cytokines and anti-angiogenic agents. However, treatment options for PE are limited, with termination of pregnancy being the only curative option. In this work, we investigated the effects of human amniotic epithelial cells (hAECs) in PE rat model. The rats were induced with lipopolysaccharide (LPS) on gestational day 14.5 followed by injection of hAECs and human umbilical cord mesenchymal stem cells 24 h later. The hAECs treatment resulted in a reduction in blood pressure and proteinuria in the PE rat model. Furthermore, hAECs treatment decreased levels of pro-inflammatory cytokines, reduced inflammatory cells aggregation, and alleviated the damage to placental spiral arteries by downregulating the expression of anti-angiogenic factor and upregulating proangiogenic factor. In vitro experiments confirmed that hAECs treatment restored the proliferation, migration, and angiogenesis of LPS-damaged human umbilical vein endothelial cells. Additionally, hAECs treatment had positive effects on fetal weight and neurological development in the PE group, with no negative effects on the physical development or fertility of offspring rats. These results suggested that hAECs transplantation may be a novel adjuvant therapeutic strategy for PE by reducing the inflammatory and enhancing placental spiral artery angiogenesis.

Pathophysiology and pregnancy outcomes of ascites in preeclampsia-a scoping review.

Preeclampsia is a multisystem disorder associated with defective trophoblast invasion, maternal syndrome, and capillary endothelial leak. The presence of ascites/third space fluid accumulation increases the risk of maternal morbidity and mortality. The current criteria/guidelines of preeclampsia do not establish the presence of ascites as a marker of severity or recognize the timing and need for early delivery despite associated complications. Medline and Embase databases were searched to identify relevant literature, reported up to December 2023, regarding the pathophysiology, pregnancy outcome, and management of preeclampsia complicated with ascites. A total of 5 studies on pathophysiology and eight on pregnancy outcomes met the inclusion criteria, with 41 case reports on ascites in preeclampsia. The etiopathogenesis for the development of ascites in preeclampsia includes endothelial damage, capillary hyperpermeability, release of vasoconstrictive agents, reduced intravascular oncotic pressure, and raised intraabdominal pressure. The presence of ascites represents the extreme form of microvascular damage, which also correlates with the raised sFlt-1 levels in this condition. The adverse pregnancy outcomes include increased risk of congestive heart failure, eclampsia, renal failure, disseminated intravascular coagulation, acute respiratory distress syndrome, and maternal death. The presence of ascites in preeclampsia is associated with the deterioration of the maternal condition. Hence, it is indicative of preeclampsia with severe features and requires vigilant monitoring, and prompt delivery may be considered.

Update on Preeclampsia and Hypertensive Disorders of Pregnancy.

There have been recent advances in the prevention, diagnosis, and management of hypertensive disorders of pregnancy which complicate approximately 16% of pregnancies in the United States. Initiation of low-dose aspirin by 16 weeks' gestation reduces preeclampsia in high-risk women. The Food and Drug Administration approved the use of the soluble fms-like tyrosine kinase 1/placental growth factor ratio for the short-term prediction of preeclampsia. Pregnancy outcomes are improved in women with chronic hypertension when antihypertensives are initiated at a threshold blood pressure of 140/90 mm Hg. Women with prior preeclampsia have increased cardiovascular disease risk and should receive risk reduction counseling.

[Obstetric Antiphospholipid Syndrome: Insights on the Diagnosis, Treatment, and Hot Issues]. / 产科抗磷脂综合征的诊治原则与热点问题述评.

Obstetric antiphospholipid syndrome (OAPS) is an autoimmune disorder associated with various pathological pregnancies, such as recurrent miscarriage, stillbirth, severe pre-eclampsia and severe placental insufficiency. The persistent presence of antiphospholipid antibodies (aPLs) is the most important laboratory characteristic of OAPS. OAPS severely affects the reproductive health of women of childbearing age in China. Reports indicate that approximately 9.6% stillbirths, 11.5% severe pre-eclampsia, and 54% recurrent miscarriages are associated with OAPS or aPLs. However, the pathogenesis of OAPS remains unclear. Previously, thrombosis at the maternal-fetal interface (MFI) was considered the main mechanism of OAPS-related pathological pregnancies. Consequently, the use of low molecular weight heparin and aspirin throughout pregnancy was recommended to improve outcomes in OAPS patient. In recent years, many studies have found that thrombosis in MFI is uncommon, but various inflammatory factors are significantly increased in the MFI of OAPS patients. Based on these findings, some clinicians have started using anti-inflammatory treatments for OAPS, which have preliminarily improved the pregnancy outcomes. Nevertheless, there is no consensus on these second-line treatments of OAPS. Another troubling issue is the clinical diagnosis of OAPS. Similar to other autoimmune diseases, there are only classification criteria for OAPS, and clinical diagnosis of OAPS depends on the clinicians' experience. The present classification criteria of OAPS were established for clinical and basic research purposes, not for patient clinical management. In clinical practice, many patients with both positive aPLs and pathological pregnancy histories do not meet the strict OAPS criteria. This has led to widespread issues of incorrect diagnosis and treatment. Timely and accurate diagnosis of OAPS is crucial for effective treatment. In this article, we reviewed the epidemiological research progress on OAPS and summarized its classification principles, including: 1) the persistent presence of aPLs in circulation; 2) manifestations of OAPS, excluding other possible causes. For the first point, accurate assessment of aPLs is crucial; for the latter, previous studies regarded only placenta-related pregnancy complications as characteristic manifestations of OAPS. However, recent studies have indicated that adverse pregnancy outcomes related to trophoblast damage, such as recurrent miscarriage and stillbirth, also need to be considered in OAPS. We also discussed several key issues in the diagnosis and treatment of OAPS. First, we addressed the definition of non-standard OAPS and offered our opinion on defining non-standard OAPS within the framework of the 2023 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) APS criteria. Then, we discussed the advantages and disadvantages of different aPL testing methods, emphasizing that harmonizing results across platforms and establishing specific reference values are keys to resolving controversies in aPL testing results. We also introduced the application of non-criteria aPLs, especially anti-phosphatidylserine/prothrombin antibody (aPS/PT) and anti-ß2 glycoprotein Ⅰ domain Ⅰ antibody (aß2GPⅠDⅠ). Additionally, we discussed aPL-based OAPS risk classification strategies. Finally, we proposed potential treatment methods for refractory OAPS. The goal is to provide a reference for the clinical management of OAPS.

Integrated group antenatal and pediatric care in Haiti: A comprehensive care accompaniment model.

INTRODUCTION: The J9 Plus (J9) maternal-child accompaniment program is based on four pillars: group antenatal care (GANC), group pediatric care, psychosocial support, and community-based care. We aimed to evaluate the impact of the J9 model of care on perinatal outcomes. METHODOLOGY: We conducted a convergent mixed methods study of maternal-newborn dyads born in 2019 at Hôpital Universitaire de Mirebalais. Quantitative data was collected retrospectively to compare dyads receiving J9 care to usual care. A secondary analysis of qualitative data described patient perspectives of J9 care. RESULTS: Antenatal care attendance was significantly higher among women in J9 (n = 524) compared to usual care (n = 523), with 490(93%) and 189(36%) having >4 visits, respectively; p <0.001, as was post-partum visit attendance [271(52%) compared to 84(16%), p<0.001] and use of post-partum family planning methods [98(19%) compared to 47(9%), p = 0.003]. Incidence of pre-eclampsia with severe features was significantly lower in the J9 group [44(9%)] compared to the usual care group [73(14%)], p <0.001. Maternal and neonatal mortality and low birth weight did not differ across groups. Cesarean delivery [103(20%) and 82(16%), p<0.001] and preterm birth [118 (24%)] and 80 (17%), p <0.001] were higher in the J9 group compared to usual care, respectively. In the qualitative analysis, ease of access to high-quality care, meaningful social support, and maternal empowerment through education were identified as key contributors to these outcomes. CONCLUSION: Compared to usual care, the J9 Plus maternal-child accompaniment model of care is associated with increased engagement in antenatal and postpartum care, increased utilization of post-partum family planning, and lower incidence of pre-eclampsia with severe features, which remains a leading cause of maternal mortality in Haiti. The J9 accompaniment approach to care is an empowering model that has the potential to be replicated in similar settings to improve quality of care and outcomes globally.

Transcutaneous Auricular Vagus Nerve Stimulation Ameliorates Preeclampsia-Induced Apoptosis of Placental Trophoblastic Cells Via Inhibiting the Mitochondrial Unfolded Protein Response.

Preeclampsia is a serious obstetric complication. Currently, there is a lack of effective preventive approaches for this disease. Recent studies have identified transcutaneous auricular vagus nerve stimulation (taVNS) as a potential novel non-pharmaceutical therapeutic modality for preeclampsia. In this study, we investigated whether taVNS inhibits apoptosis of placental trophoblastic cells through ROS-induced UPRmt. Our results showed that taVNS promoted the release of acetylcholine (ACh). ACh decreased the expression of UPRmt by inhibiting the formation of mitochondrial ROS (mtROS), presumably through M3AChR. This reduced the release of pro-apoptotic proteins (cleaved caspase-3, NF-κB-p65, and cytochrome C) and helped preserve the morphological and functional integrity of mitochondria, thus reducing the apoptosis of placental trophoblasts, improving placental function, and relieving preeclampsia. Our study unravels the potential pathophysiological mechanism of preeclampsia. In-depth characterization of the UPRmt is essential for developing more effective therapeutic strategies for preeclampsia targeting mitochondrial function.

Machine learning, advanced data analysis, and a role in pregnancy care? How can we help improve preeclampsia outcomes?

The value of machine learning capacity in maternal health, and in particular prediction of preeclampsia will only be realised when there are high quality clinical data provided, representative populations included, different health systems and models of care compared, and a culture of rapid use and application of real-time data and outcomes. This review has been undertaken to provide an overview of the language, and early results of machine learning in a pregnancy and preeclampsia context. Clinicians of all backgrounds are encouraged to learn the language of Machine Learning (ML) and Artificial intelligence (AI) to better understand their potential and utility to improve outcomes for women and their families. This review will outline some definitions and features of ML that will benefit clinician's knowledge in the preeclampsia discipline, and also outline some of the future possibilities for preeclampsia-focussed clinicians via understanding AI. It will further explore the criticality of defining the risk, and outcome being determined.

Well-Child Visits for Early Detection and Management of Maternal Postpartum Hypertensive Disorders.

Importance: Innovative approaches are needed to address the increasing rate of postpartum morbidity and mortality associated with hypertensive disorders. Objective: To determine whether assessing maternal blood pressure (BP) and associated symptoms at time of well-child visits is associated with increased detection of postpartum preeclampsia and need for hospitalization for medical management. Design, Setting, and Participants: This is a pre-post quality improvement (QI) study. Individuals who attended the well-child visits between preimplementation (December 2017 to December 2018) were compared with individuals who enrolled after the implementation of the QI program (March 2019 to December 2019). Individuals were enrolled at an academic pediatric clinic. Eligible participants included birth mothers who delivered at the hospital and brought their newborn for well-child check at 2 days, 2 weeks, and 2 months. A total of 620 individuals were screened in the preintervention cohort and 680 individuals were screened in the QI program. Data was analyzed from March to July 2022. Exposures: BP evaluation and preeclampsia symptoms screening were performed at the time of the well-child visit. A management algorithm-with criteria for routine or early postpartum visits, or prompt referral to the obstetric emergency department-was followed. Main Outcome and Measures: Readmission due to postpartum preeclampsia. Comparisons across groups were performed using a Fisher exact test for categorical variables, and t tests or Mann-Whitney tests for continuous variables. Results: A total of 595 individuals (mean [SD] age, 27.2 [6.1] years) were eligible for analysis in the preintervention cohort and 565 individuals (mean [SD] age, 27.0 [5.8] years) were eligible in the postintervention cohort. Baseline demographic information including age, race and ethnicity, body mass index, nulliparity, and factors associated with increased risk for preeclampsia were not significantly different in the preintervention cohort and postintervention QI program. The rate of readmission for postpartum preeclampsia differed significantly in the preintervention cohort (13 individuals [2.1%]) and the postintervention cohort (29 individuals [5.6%]) (P = .007). In the postintervention QI cohort, there was a significantly earlier time frame of readmission (median [IQR] 10.0 [10.0-11.0] days post partum for preintervention vs 7.0 [6.0-10.5] days post partum for postintervention; P = .001). In both time periods, a total of 42 patients were readmitted due to postpartum preeclampsia, of which 21 (50%) had de novo postpartum preeclampsia. Conclusions and Relevance: This QI program allowed for increased and earlier readmission due to postpartum preeclampsia. Further studies confirming generalizability and mitigating associated adverse outcomes are needed.

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.

A summary of the 2023 Society of Obstetric Medicine of Australia and New Zealand (SOMANZ) hypertension in pregnancy guideline.

INTRODUCTION: Hypertensive disorders of pregnancy (HDP) affect up to 10% of all pregnancies annually and are associated with an increased risk of maternal and fetal morbidity and mortality. This guideline represents an update of the Society of Obstetric Medicine of Australia and New Zealand (SOMANZ) guidelines for the management of hypertensive disorders of pregnancy 2014 and has been approved by the National Health and Medical Research Council (NHMRC) under section 14A of the National Health and Medical Research Council Act 1992. In approving the guideline recommendations, NHMRC considers that the guideline meets NHMRC's standard for clinical practice guidelines. MAIN RECOMMENDATIONS: A total of 39 recommendations on screening, preventing, diagnosing and managing HDP, especially preeclampsia, are presented in this guideline. Recommendations are presented as either evidence-based recommendations or practice points. Evidence-based recommendations are presented with the strength of recommendation and quality of evidence. Practice points were generated where there was inadequate evidence to develop specific recommendations and are based on the expertise of the working group. CHANGES IN MANAGEMENT RESULTING FROM THE GUIDELINE: This version of the SOMANZ guideline was developed in an academically robust and rigorous manner and includes recommendations on the use of combined first trimester screening to identify women at risk of developing preeclampsia, 14 pharmacological and two non-pharmacological preventive interventions, clinical use of angiogenic biomarkers and the long term care of women who experience HDP. The guideline also includes six multilingual patient infographics which can be accessed through the main website of the guideline. All measures were taken to ensure that this guideline is applicable and relevant to clinicians and multicultural women in regional and metropolitan settings in Australia and New Zealand.

Acute liver failure in pregnancy.

Liver function abnormalities are noted in a minority of pregnancies with multiple causes for the same. A small proportion of these develop severe liver injury and progress to acute liver failure (ALF). There is a discrete set of etiology for ALF in pregnancy and comprehensive understanding will help in urgent evaluation. Certain diseases such as acute fatty liver of pregnancy, hemolysis, elevated liver enzyme, low platelet (HELLP) syndrome and pre-eclampsia are secondary to pregnant state and can present as ALF. Quick and targeted evaluation with urgent institution of etiology-specific management, especially urgent delivery in patients with pregnancy-associated liver diseases, is the key to avoiding maternal deaths. Pregnancy, as also the fetal life, imparts a further layer of complication in assessment, prognosis and management of these sick patients with ALF. Optimal management often requires a multidisciplinary approach in a well-equipped centre. In this review, we discuss evaluation, assessment and management of pregnant patients with ALF, focussing on approach to pregnancy-associated liver diseases.

Maternal "mirror" syndrome: Evaluating the benefits of fetal therapy.

OBJECTIVE: To evaluate maternal and perinatal outcomes following fetal intervention in the context of maternal "mirror" syndrome. STUDY DESIGN: A multicenter retrospective study of all cases of fetal hydrops complicated by maternal "mirror" syndrome and treated by any form of fetal therapy between 1995 and 2022. Medical records and ultrasound images of all cases were reviewed. "Mirror" syndrome was defined as fetal hydrops and/or placentomegaly associated with the maternal development of pronounced edema, with or without pre-eclampsia. Fetal hydrops was defined as the presence of abnormal fluid collections in ≥2 body cavities. RESULTS: Twenty-one pregnancies met the inclusion criteria. Causes of fetal hydrops and/or placentomegaly included fetal lung lesions (n = 9), twin-twin transfusion syndrome (n = 6), severe fetal anemia (n = 4), and others (n = 2). Mean gestational age at "mirror" presentation was 27.0 ± 3.8 weeks. Maternal "mirror" syndrome was identified following fetal therapeutic intervention in 14 cases (66.6%). "Mirror" symptoms resolved or significantly improved before delivery in 8 (38.1%) cases with a mean interval from fetal intervention to maternal recovery of 13.1 days (range 4-35). Three women needed to be delivered because of worsening "mirror" syndrome. Of the 21 pregnancies treated (27 fetuses), there were 15 (55.5%) livebirths, 7 (25.9%) neonatal deaths and 5 (18.5%) intra-uterine deaths. CONCLUSION: Following successful treatment and resolution of fetal hydrops, maternal "mirror" syndrome can improve or sometimes completely resolve before delivery. Furthermore, the recognition that "mirror" syndrome may arise only after fetal intervention necessitates hightened patient maternal surveillance in cases of fetal hydrops.

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.

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.

Comparison of double-filtration plasmapheresis (DFPP) versus heparin-mediated extracorporeal LDL-precipitation (HELP)-apheresis in early-onset preeclampsia.

OBJECTIVES: Preeclampsia (PE) is a major cause of maternal and fetal mortality, and preterm birth. Previous studies indicate that lipid-apheresis may prolong pregnancy, namely heparin-mediated extracorporeal LDL-precipitation (HELP)- and dextran sulfate cellulose (DSC)-apheresis. We now report on double membrane plasmapheresis (DFPP) in early-onset preeclampsia (eoPE). STUDY DESIGN: Open pilot study assessing the prolongation of pregnancy in PE by lipoprotein-apheresis (DRKS00004527). Two women with eoPE were treated by DFPP and compared to a historical cohort of 6 patients with eoPE treated by HELP-apheresis (NCT01967355). MAIN OUTCOME MEASURES: Clinical outcome of mothers and babies and prolongation of pregnancies (time of admission to birth). RESULTS: Patient 1 (33y; 22 + 5/7GW) received 4 DFPP. Delivery day 19; birthweight 270 g; weight at discharge 2134 g on day 132. Patient 2 (35y; 21 + 4/7GW) received 2 DFPP. Delivery day 19; birthweight 465 g; weight at discharge 2540 g on day 104. DFPP was well tolerated by both patients. CONCLUSIONS: DFPP proved to be save and pregnancies remained stable as long as 19 days. Although babies were born very preterm both babies could finally be dismissed from hospital. No relevant clinical differences between DFPP and HELP-apheresis could be observed. Therefore, DFPP may extend the range of available apheresis techniques to prolong pregnancies in early-onset preeclampsia. However, further studies are necessary to gain more information. REGISTER: (DRKS00004527).

Gene therapy in preeclampsia: the dawn of a new era.

Preeclampsia is a severe complication of pregnancy, affecting an estimated 4 million women annually. It is one of the leading causes of maternal and fetal mortality worldwide, and it has life-long consequences. The maternal multisystemic symptoms are driven by poor placentation, which causes syncytiotrophoblastic stress and the release of factors into the maternal bloodstream. Amongst them, the soluble fms-like tyrosine kinase-1 (sFLT-1) triggers extensive endothelial dysfunction by acting as a decoy receptor for the vascular endothelial growth factor (VEGF) and the placental growth factor (PGF). Current interventions aim to mitigate hypertension and seizures, but the only definite treatment remains induced delivery. Thus, there is a pressing need for novel therapies to remedy this situation. Notably, CBP-4888, a siRNA drug delivered subcutaneously to knock down sFLT1 expression in the placenta, has recently obtained Fast Track approval from the Food and Drug Administration (FDA) and is undergoing a phase 1 clinical trial. Such advance highlights a growing interest and significant potential in gene therapy to manage preeclampsia. This review summarizes the advances and prospects of gene therapy in treating placental dysfunction and illustrates crucial challenges and considerations for these emerging treatments.