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The American Journal of Emergency... Aug 2022Eclampsia is a rare partum and puerperal condition that carries a high rate of morbidity and mortality. (Review)
Review
INTRODUCTION
Eclampsia is a rare partum and puerperal condition that carries a high rate of morbidity and mortality.
OBJECTIVE
This review highlights the pearls and pitfalls of the care of patients with eclampsia, including presentation, evaluation, and evidence-based management in the emergency department (ED).
DISCUSSION
Eclampsia is a hypertensive disease of pregnancy defined by new onset tonic-clonic, focal, or multifocal seizures or unexplained altered mental status in a pregnant or postpartum patient in the absence of other causative etiologies. However, signs and symptoms of preeclampsia and prodromes of eclampsia are often subtle and non-specific, making the diagnosis difficult. Thus, it should be considered in pregnant and postpartum patients who present to the ED. Laboratory testing including complete blood cell count, renal and liver function panels, electrolytes, glucose, coagulation panel, fibrinogen, lactate dehydrogenase, uric acid, and urinalysis, as well as imaging to include head computed tomography, can assist, but these evaluations should not delay management. Components of treatment include emergent obstetric specialist consultation, magnesium administration, and blood pressure control in patients with hypertension. Definitive treatment of eclampsia requires emergent delivery in pregnant patients. If consultants are not in-house, emergent stabilization and immediate transfer are required.
CONCLUSIONS
An understanding of eclampsia can assist emergency clinicians in rapid recognition and timely management of this potentially deadly disease.
Topics: Eclampsia; Female; Humans; Hypertension; Postpartum Period; Pre-Eclampsia; Pregnancy; Prevalence; Seizures
PubMed: 35716535
DOI: 10.1016/j.ajem.2022.06.004 -
Medical Science Monitor : International... Jul 2023Eclampsia is the most serious pregnancy complication and one of the main causes of death of pregnant and delivering women. The mortality rate of young mothers is 5-20%,... (Review)
Review
Eclampsia is the most serious pregnancy complication and one of the main causes of death of pregnant and delivering women. The mortality rate of young mothers is 5-20%, emphasizing the severity of this pregnancy-related disorder. Today many centers have only rare opportunities to see and deal with eclampsia cases; therefore, it is very important to bring this emergency medical condition to the attention of attending physicians. All patients with eclampsia, and after eclamptic seizures, should be treated in an intensive care unit. However, taking into account clinical realities, especially in developing countries, this is not always possible. It is necessary for all gynecologists-obstetricians to be fully prepared for eclampsia, although its occurrence is very rare. Drug treatment aims to stop eclampsia seizures and prevent reoccurrence of convulsions and complications. Magnesium sulphate is the drug of first choice used in treatment of eclampsia seizure, whereas treatment with the use of antihypertensive drugs and proper blood pressure control is one of the most important factors effectively reducing the risk of deaths or acute complications and poor pregnancy outcomes. The most urgent part of the treatment is the lifesaving procedure involving airways patency assessment, maintenance of breathing and blood circulation of the mother, securing an adequate oxygen level of the mother and thereby of the fetus, and prevention of injuries. This review aims to present an overview of the current prevalence, diagnosis, and management of eclampsia and the need for improved maternal care.
Topics: Pregnancy; Female; Humans; Eclampsia; Magnesium Sulfate; Pregnancy Complications; Pregnancy Outcome; Seizures; Pre-Eclampsia
PubMed: 37415326
DOI: 10.12659/MSM.939919 -
Clinical Journal of the American... Sep 2020It is estimated that women with CKD are ten times more likely to develop preeclampsia than women without CKD, with preeclampsia affecting up to 40% of pregnancies in... (Review)
Review
It is estimated that women with CKD are ten times more likely to develop preeclampsia than women without CKD, with preeclampsia affecting up to 40% of pregnancies in women with CKD. However, the shared phenotype of hypertension, proteinuria, and impaired excretory kidney function complicates the diagnosis of superimposed preeclampsia in women with CKD who have hypertension and/or proteinuria that predates pregnancy. This article outlines the diagnoses of preeclampsia and superimposed preeclampsia. It discusses the pathogenesis of preeclampsia, including abnormal placentation and angiogenic dysfunction. The clinical use of angiogenic markers as diagnostic adjuncts for women with suspected preeclampsia is described, and the limited data on the use of these markers in women with CKD are presented. The role of kidney biopsy in pregnancy is examined. The management of preeclampsia is outlined, including important advances and controversies in aspirin prophylaxis, BP treatment targets, and the timing of delivery.
Topics: Angiogenic Proteins; Biomarkers; Blood Pressure; Female; Humans; Kidney; Neovascularization, Pathologic; Placentation; Pre-Eclampsia; Pregnancy; Renal Insufficiency, Chronic; Treatment Outcome
PubMed: 32241779
DOI: 10.2215/CJN.15121219 -
Frontiers in Immunology 2022Preeclampsia is a common and serious complication of pregnancy, posing a threat to maternal and fetal safety due to the lack of effective biomarkers and treatment...
OBJECTIVE
Preeclampsia is a common and serious complication of pregnancy, posing a threat to maternal and fetal safety due to the lack of effective biomarkers and treatment strategies. This study aimed to identify potential biomarkers that can be used to predict preeclampsia and identify the molecular mechanisms of preeclampsia pathogenesis and drug prediction at the transcriptome level.
METHODS
We analyzed differential expression genes (DEGs) in preeclampsia and non-preeclampsia groups in the GSE75010 dataset, cross-linking with extracted inflammatory response-related genes to obtain differentially expressed inflammation-related genes (DINRGs). Enrichment analysis and protein-protein interaction (PPI) networks were constructed to understand the functions and enrichment pathways. Machine learning models were used to identify key genes associated with preeclampsia and build a nomogram in the training set, which was validated in the validation set. The R package RcisTarget was used to predict transcription factors, and Cytoscape was used to construct miRNA-mRNA pathways, which could identify the molecular mechanisms. Then, we conducted molecular docking of the obtained key genes (inhibin subunit beta A), (opioid receptor kappa 1), and (trophoblast glycoprotein), as well as predicted transcription factors with drug molecules. Additionally, the CIBERSORT method explored the differences in immune cell infiltration between preeclampsia and non-preeclampsia samples based on the GSE75010 dataset.
RESULTS
A total of 69 DINRGs associated with preeclampsia patients were screened. , and were the key genes based on machine learning models. A nomogram for prediction was further constructed, and the receiver operating curves (ROCs) showed good performance. Based on the transcriptome level of key genes, we proposed that RELA-miR-548K/miR-1206-TPBG may be a potential RNA regulatory pathway regulating the progression of early preeclampsia. Molecular docking suggested the effectiveness of curcumin in the treatment of preeclampsia. Additionally, regulatory T cells (Tregs) and resting mast cells were significantly different between the two groups.
CONCLUSION
In summary, we identified three key inflammation-associated genes, namely , and , which can be used as potential genetic biomarkers for preeclampsia prediction and treatment, and established a nomogram as a predictive model. Additionally, we provided insights into the mechanisms of preeclampsia development at the transcriptome level and performed corresponding drug predictions.
Topics: Female; Gene Regulatory Networks; Genetic Markers; Humans; Inflammation; MicroRNAs; Molecular Docking Simulation; Pre-Eclampsia; Pregnancy; Transcription Factors
PubMed: 35880174
DOI: 10.3389/fimmu.2022.883404 -
Ultrasound in Obstetrics & Gynecology :... Jul 2019Primary studies and systematic reviews provide estimates of varying accuracy for different factors in the prediction of pre-eclampsia. The aim of this study was to...
OBJECTIVE
Primary studies and systematic reviews provide estimates of varying accuracy for different factors in the prediction of pre-eclampsia. The aim of this study was to review published systematic reviews to collate evidence on the ability of available tests to predict pre-eclampsia, to identify high-value avenues for future research and to minimize future research waste in this field.
METHODS
MEDLINE, EMBASE and The Cochrane Library including DARE (Database of Abstracts of Reviews of Effects) databases, from database inception to March 2017, and bibliographies of relevant articles were searched, without language restrictions, for systematic reviews and meta-analyses on the prediction of pre-eclampsia. The quality of the included reviews was assessed using the AMSTAR tool and a modified version of the QUIPS tool. We evaluated the comprehensiveness of search, sample size, tests and outcomes evaluated, data synthesis methods, predictive ability estimates, risk of bias related to the population studied, measurement of predictors and outcomes, study attrition and adjustment for confounding.
RESULTS
From 2444 citations identified, 126 reviews were included, reporting on over 90 predictors and 52 prediction models for pre-eclampsia. Around a third (n = 37 (29.4%)) of all reviews investigated solely biochemical markers for predicting pre-eclampsia, 31 (24.6%) investigated genetic associations with pre-eclampsia, 46 (36.5%) reported on clinical characteristics, four (3.2%) evaluated only ultrasound markers and six (4.8%) studied a combination of tests; two (1.6%) additional reviews evaluated primary studies investigating any screening test for pre-eclampsia. Reviews included between two and 265 primary studies, including up to 25 356 688 women in the largest review. Only approximately half (n = 67 (53.2%)) of the reviews assessed the quality of the included studies. There was a high risk of bias in many of the included reviews, particularly in relation to population representativeness and study attrition. Over 80% (n = 106 (84.1%)) summarized the findings using meta-analysis. Thirty-two (25.4%) studies lacked a formal statement on funding. The predictors with the best test performance were body mass index (BMI) > 35 kg/m , with a specificity of 92% (95% CI, 89-95%) and a sensitivity of 21% (95% CI, 12-31%); BMI > 25 kg/m , with a specificity of 73% (95% CI, 64-83%) and a sensitivity of 47% (95% CI, 33-61%); first-trimester uterine artery pulsatility index or resistance index > 90 centile (specificity 93% (95% CI, 90-96%) and sensitivity 26% (95% CI, 23-31%)); placental growth factor (specificity 89% (95% CI, 89-89%) and sensitivity 65% (95% CI, 63-67%)); and placental protein 13 (specificity 88% (95% CI, 87-89%) and sensitivity 37% (95% CI, 33-41%)). No single marker had a test performance suitable for routine clinical use. Models combining markers showed promise, but none had undergone external validation.
CONCLUSIONS
This review of reviews calls into question the need for further aggregate meta-analysis in this area given the large number of published reviews subject to the common limitations of primary predictive studies. Prospective, well-designed studies of predictive markers, preferably randomized intervention studies, and combined through individual-patient data meta-analysis are needed to develop and validate new prediction models to facilitate the prediction of pre-eclampsia and minimize further research waste in this field. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.
Topics: Adult; Biomarkers; Body Mass Index; Female; Humans; Mass Screening; Meta-Analysis as Topic; Placenta Growth Factor; Pre-Eclampsia; Predictive Value of Tests; Pregnancy; Pregnancy Complications; Prospective Studies; Pulsatile Flow; Risk Factors; Sensitivity and Specificity; Ultrasonography; Uterine Artery
PubMed: 30267475
DOI: 10.1002/uog.20117 -
Nature Reviews. Disease Primers Feb 2023
Topics: Pregnancy; Female; Humans; Pre-Eclampsia
PubMed: 36797280
DOI: 10.1038/s41572-023-00425-6 -
American Journal of Obstetrics &... Dec 2023Pregnancy involves an interplay between maternal and fetal factors affecting changes to maternal anatomy and physiology to support the developing fetus and ensure the... (Review)
Review
Pregnancy involves an interplay between maternal and fetal factors affecting changes to maternal anatomy and physiology to support the developing fetus and ensure the well-being of both the mother and offspring. A century of research has provided evidence of the imperative role of the placenta in the development of preeclampsia. Recently, a growing body of evidence has supported the adaptations of the maternal cardiovascular system during normal pregnancy and its maladaptation in preeclampsia. Debate surrounds the roles of the placenta vs the maternal cardiovascular system in the pathophysiology of preeclampsia. We proposed an integrated model of the maternal cardiac-placental-fetal array and the development of preeclampsia, which reconciles the disease phenotypes and their proposed origins, whether placenta-dominant or maternal cardiovascular system-dominant. These phenotypes are sufficiently diverse to define 2 distinct types: preeclampsia Type I and Type II. Type I preeclampsia may present earlier, characterized by placental dysfunction or malperfusion, shallow trophoblast invasion, inadequate spiral artery conversion, profound syncytiotrophoblast stress, elevated soluble fms-like tyrosine kinase-1 levels, reduced placental growth factor levels, high peripheral vascular resistance, and low cardiac output. Type I is more often accompanied by fetal growth restriction, and low placental growth factor levels have a measurable impact on maternal cardiac remodeling and function. Type II preeclampsia typically occurs in the later stages of pregnancy and entails an evolving maternal cardiovascular intolerance to the demands of pregnancy, with a moderately dysfunctional placenta and inadequate blood supply. The soluble fms-like tyrosine kinase-1-placental growth factor ratio may be normal or slightly disturbed, peripheral vascular resistance is low, and cardiac output is high, but these adaptations still fail to meet demand. Emergent placental dysfunction, coupled with an increasing inability to meet demand, more often appears with fetal macrosomia, multiple pregnancies, or prolonged pregnancy. Support for the notion of 2 types of preeclampsia observable on the molecular level is provided by single-cell transcriptomic survey of gene expression patterns across different cell classes. This revealed widespread dysregulation of gene expression across all cell types, and significant imbalance in fms-like tyrosine kinase-1 (FLT1) and placental growth factor, particularly marked in the syncytium of early preeclampsia cases. Classification of preeclampsia into Type I and Type II can inform future research to develop targeted screening, prevention, and treatment approaches.
Topics: Pregnancy; Female; Humans; Placenta; Pre-Eclampsia; Placenta Growth Factor; Vascular Endothelial Growth Factor Receptor-1; Trophoblasts
PubMed: 37871693
DOI: 10.1016/j.ajogmf.2023.101203 -
Hypertension (Dallas, Tex. : 1979) Jun 2020Preeclampsia is a common pregnancy complication, affecting 2% to 8% of pregnancies worldwide, and is an important cause of both maternal and fetal morbidity and... (Review)
Review
Preeclampsia is a common pregnancy complication, affecting 2% to 8% of pregnancies worldwide, and is an important cause of both maternal and fetal morbidity and mortality. Importantly, although aspirin and calcium are able to prevent preeclampsia in some women, there is no cure apart from delivery of the placenta and fetus, often necessitating iatrogenic preterm birth. Preclinical models of preeclampsia are widely used to investigate the causes and consequences of preeclampsia and to evaluate safety and efficacy of potential preventative and therapeutic interventions. In this review, we provide a summary of the published preclinical models of preeclampsia that meet human diagnostic criteria, including the development of maternal hypertension, together with new-onset proteinuria, maternal organ dysfunction, and uteroplacental dysfunction. We then discuss evidence from preclinical models for multiple causal factors of preeclampsia, including those implicated in early-onset and late-onset preeclampsia. Next, we discuss the impact of exposure to a preeclampsia-like environment for later maternal and progeny health. The presence of long-term impairment, particularly cardiovascular outcomes, in mothers and progeny after an experimentally induced preeclampsia-like pregnancy, implies that later onset or reduced severity of preeclampsia will improve later maternal and progeny health. Finally, we summarize published intervention studies in preclinical models and identify gaps in knowledge that we consider should be targets for future research.
Topics: Animals; Disease Models, Animal; Female; Pre-Eclampsia; Pregnancy
PubMed: 32248704
DOI: 10.1161/HYPERTENSIONAHA.119.14598 -
Biomolecules Jun 2020Preeclampsia (PE) is a serious pregnancy complication, affecting about 5-7% of pregnancies worldwide and is characterized by hypertension and damage to multiple maternal... (Review)
Review
Preeclampsia (PE) is a serious pregnancy complication, affecting about 5-7% of pregnancies worldwide and is characterized by hypertension and damage to multiple maternal organs, primarily the liver and kidneys. PE usually begins after 20 weeks' gestation and, if left untreated, can lead to serious complications and lifelong disabilities-even death-in both the mother and the infant. As delivery is the only cure for the disease, treatment is primarily focused on the management of blood pressure and other clinical symptoms. The pathogenesis of PE is still not clear. Abnormal spiral artery remodeling, placental ischemia and a resulting increase in the circulating levels of vascular endothelial growth factor receptor-1 (VEGFR-1), also called soluble fms-like tyrosine kinase-1 (sFlt-1), are believed to be among the primary pathologies associated with PE. sFlt-1 is produced mainly in the placenta during pregnancy and acts as a decoy receptor, binding to free VEGF (VEGF-A) and placental growth factor (PlGF), resulting in the decreased bioavailability of each to target cells. Despite the pathogenic effects of increased sFlt-1 on the maternal vasculature, recent studies from our laboratory and others have strongly indicated that the increase in sFlt-1 in PE may fulfill critical protective functions in preeclamptic pregnancies. Thus, further studies on the roles of sFlt-1 in normal and preeclamptic pregnancies are warranted for the development of therapeutic strategies targeting VEGF signaling for the treatment of PE. Another impediment to the treatment of PE is the lack of suitable methods for delivery of cargo to placental cells, as PE is believed to be of placental origin and most available therapies for PE adversely impact both the mother and the fetus. The present review discusses the pathogenesis of PE, the complex role of sFlt-1 in maternal disease and fetal protection, and the recently developed placenta-targeted drug delivery system for the potential treatment of PE with candidate therapeutic agents.
Topics: Female; Humans; Placenta; Pre-Eclampsia; Pregnancy; Vascular Endothelial Growth Factor Receptor-1
PubMed: 32599856
DOI: 10.3390/biom10060953 -
American Journal of Obstetrics and... Feb 2022Animal models have been critical in investigating the pathogenesis, mediators, and even therapeutic options for a number of diseases, including preeclampsia.... (Review)
Review
Animal models have been critical in investigating the pathogenesis, mediators, and even therapeutic options for a number of diseases, including preeclampsia. Preeclampsia is the leading cause of maternal and fetal morbidity and mortality worldwide. The placenta is thought to play a central role in the pathogenesis of this disease because it releases antiangiogenic and proinflammatory factors into the maternal circulation, resulting in the maternal syndrome. Despite the deleterious effects preeclampsia has been shown to have on the mother and baby during pregnancy and postpartum, there is still no effective treatment for this disease. Although clinical studies in patients are crucial to identify the involvement of pathogenic factors in preeclampsia, there are obvious limitations that prevent detailed investigation of the quantitative importance of time-dependent mechanisms involved in this syndrome. Animal models allow investigators to perform proof-of-concept studies and examine whether certain factors found in women with preeclampsia mediate hypertension and other manifestations of this disease. In this brief review, we summarize some of the more widely studied models used to investigate pathophysiological mechanisms that are thought to be involved in preeclampsia. These include models of placental ischemia, angiogenic imbalance, and maternal immune activation. Infusion of preeclampsia-related factors into animals has been widely studied to understand the specific mediators of this disease. These models have been included, in addition to a number of genetic models involved in overexpression of the renin-angiotensin system, complement activation, and trophoblast differentiation. Together, these models cover multiple mechanisms of preeclampsia from trophoblast dysfunction and impaired placental vascularization to the excess circulating placental factors and clinical manifestation of this disease. Most animal studies have been performed in rats and mice; however, we have also incorporated nonhuman primate models in this review. Preclinical animal models not only have been instrumental in understanding the pathophysiology of preeclampsia but also continue to be important tools in the search for novel therapeutic options for the treatment of this disease.
Topics: Animals; Disease Models, Animal; Female; Models, Genetic; Pre-Eclampsia; Pregnancy
PubMed: 33722383
DOI: 10.1016/j.ajog.2020.10.025