Materiały źródłowe

• #1 The etiology of preeclampsia

  https://pmc.ncbi.nlm.nih.gov/articles/PMC8988238/

  A fundamental task in medicine is the understanding of the causes of diseases. Preeclampsia and eclampsia, an enigmatic and elusive disorder, have been labeled the disease of theories. Preeclampsia is one of the great obstetrical syndromes in which multiple and sometimes overlapping pathologic processes activate a common pathway composed of endothelial cell activation, intravascular inflammation, and syncytiotrophoblast stress. This article addresses the potential etiologies, or causal explanations, for preeclampsia. The role of uteroplacental ischemia is well established, based upon a solid body of clinical and experimental evidence. […] A causal role for microorganisms has gained recognition through the realization that periodontal disease and maternal gut dysbiosis are linked to atherosclerosis, thus possibly to a subset of patients with preeclampsia.

• #1 Preeclampsia – Symptoms & causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/preeclampsia/symptoms-causes/syc-20355745

  Preeclampsia is a complication of pregnancy. […] The exact cause of preeclampsia likely involves several factors. Experts believe it begins in the placenta the organ that nourishes the fetus throughout pregnancy. Early in a pregnancy, new blood vessels develop and evolve to supply oxygen and nutrients to the placenta. […] In women with preeclampsia, these blood vessels don’t seem to develop or work properly. Problems with how well blood circulates in the placenta may lead to the irregular regulation of blood pressure in the mother.

• #1 Preeclampsia: Background, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/1476919-overview

  Placental implantation with abnormal trophoblastic invasion of uterine vessels is a major cause of hypertension associated with preeclampsia syndrome. […] The primary cause for the failure of these invasive cytotrophoblasts to undergo pseudovascularization and invade maternal blood vessels is not clear. However, immunologic and genetic factors have been proposed. […] Data show that an imbalance of proangiogenic and antiangiogenic factors produced by the placenta may play a major role in mediating endothelial dysfunction. […] Preeclampsia has been shown to involve multiple genes. Over 100 maternal and paternal genes have been studied for their association with preeclampsia, including those known to play a role in vascular diseases, BP regulation, diabetes, and immunologic functions. […] Other substances that have been proposed, but not proven, to contribute to preeclampsia include tumor necrosis factor, interleukins, various lipid molecules, and syncytial knots.

• #1 The etiology of preeclampsia

  https://pmc.ncbi.nlm.nih.gov/articles/PMC8988238/

  Particular etiological factors, such as the breakdown of maternal-fetal immune tolerance, thought to account for the excess of preeclampsia in primipaternity and egg donation may operate, in part, through uteroplacental ischemia, while another, such as placental aging, may operate largely through syncytiotrophoblast stress. […] The various roles of autoimmunity, fetal diseases, and endocrine disorders are also discussed. A greater understanding of the etiologic factors of preeclampsia is essential to improve treatment and prevention. […] The principal mechanism of disease implicated in the etiology of preeclampsia and eclampsia is uteroplacental ischemia. […] Additional evidence supporting a role for uteroplacental ischemia came from studies by Ogden, Hildebrand, and Page who reported that clamping of the abdominal aorta below the renal arteries (to avoid renovascular hypertension) in dogs reduced uteroplacental perfusion; furthermore, this response was followed by maternal hypertension that resolved after the clamp was released.

• #1 Cause Of Preeclampsia

  https://www.preeclampsia.org/cause-of-preeclampsia

  A promising area of recent research involves the role of proteins produced by the placenta that inhibit angiogenesis (the production of new blood vessels). Two of these “antiangiogenic factors” (soluble Fms-like tyrosine kinase-1, and soluble endoglin) have been shown to produce a preeclampsia-like disease in rodents. […] Preeclampsia may have multiple causes, and other leads are being investigated, including prostaglandins, digoxin-like molecules, immunological mechanisms, autoantibodies that trigger receptors that lead to vessel constriction (agonistic autoantibodies to the angiotensin-1 receptor), oxidative stress, mitochondrial pathology, the impact of hypertension and prehypertension on endovascular health, and genes sensitive to low-oxygen environments. […] While we are moving closer to historically elusive answers, the true cause of preeclampsia remains unknown. Successful ongoing research needs far more support and funding.

• #1 The etiology of preeclampsia

  https://pmc.ncbi.nlm.nih.gov/articles/PMC8988238/

  The mechanisms whereby insulin resistance predisposes to the development of preeclampsia are related to intravascular inflammation and endothelial cell dysfunction, which is the common pathway of the syndrome. […] The mechanisms whereby a breakdown of maternal-fetal immune tolerance leads to preeclampsia appear to involve defective placentation, an example of the convergence of an immune disorder with uteroplacental ischemia.

• #1 Pre-eclampsia – Wikipedia

  https://en.wikipedia.org/wiki/Pre-eclampsia

  Pre-eclampsia is a multi-system disorder specific to pregnancy, characterized by the new onset of high blood pressure and often a significant amount of protein in the urine or by the new onset of high blood pressure along with significant end-organ damage, with or without the proteinuria. […] Risk factors for pre-eclampsia include obesity, prior hypertension, older age, and diabetes mellitus. […] The underlying mechanisms are complex and involve abnormal formation of blood vessels in the placenta amongst other factors. […] While the exact cause of pre-eclampsia remains unclear, there is strong evidence that a major cause predisposing a susceptible woman to pre-eclampsia is an abnormally implanted placenta. […] This abnormally implanted placenta may result in poor uterine and placental perfusion, yielding a state of hypoxia and increased oxidative stress and the release of anti-angiogenic proteins along with inflammatory mediators into the maternal plasma.

• #1 Preeclampsia: Clinical features and diagnosis – UpToDate

  https://www.uptodate.com/contents/preeclampsia-clinical-features-and-diagnosis

  The reasons for this relationship are not clear but may include multiple mechanisms involving inflammation, microangiopathy, increased platelet turnover, complement dysregulation, and kidney dysfunction. […] A past history of preeclampsia increases the risk of developing preeclampsia in a subsequent pregnancy eightfold compared with patients without this history. […] The severity of preeclampsia in the first pregnancy strongly impacts the risk of developing preeclampsia in the next pregnancy. […] The clinical findings of preeclampsia result from the underlying pathophysiology of the disease: placental insufficiency, vasoconstriction, increased capillary permeability, and endothelial dysfunction.

• #1 Preeclampsia: Background, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/1476919-overview

  Preeclampsia is part of a spectrum of hypertensive disorders that complicate pregnancy. […] Although each of these disorders can appear in isolation, they are thought of as progressive manifestations of a single process and are believed to share a common etiology. […] The mechanisms by which preeclampsia occurs is not certain, and numerous maternal, paternal, and fetal factors have been implicated in its development. The factors considered to be the most important include the following: Maternal immunologic intolerance, Abnormal placental implantation, Genetic, nutritional, and environmental factors, Cardiovascular and inflammatory changes. […] Immunologic factors have long been considered to be key players in preeclampsia. One important component is a poorly understood dysregulation of maternal tolerance to paternally derived placental and fetal antigens.

• #1 Preeclampsia: Pathophysiology and the Maternal-Fetal Risk

  https://clinmedjournals.org/articles/jhm/journal-of-hypertension-and-management-jhm-3-024.php?jid=jhm

  Preeclampsia complicates about 5% of all pregnancies worldwide and is one of the leading causes of maternal and fetal morbidity and even mortality. […] The exact pathophysiology of preeclampsia remains unknown. However, there are several theories that have been put forth that may explain most of the abnormalities seen in this disease process. […] Preeclampsia is primarily a disease of the placenta as it may be encountered in molar pregnancies. One of the most accepted theories in preeclampsia revolves around abnormal placentation. […] Preeclampsia tends to affect the first pregnancy (naïve to the paternal/fetal antigens) and repeat exposure to paternal/fetal antigens tends to lower the risk of the disease. […] Signs of inflammation are seen in normal pregnancies at term, but these changes are exaggerated in women with preeclampsia.

• #1 Modern concepts of etiology, pathogenesis and risk factors for preeclampsia – Abramova – Journal of obstetrics and women’s diseases

  https://journals.eco-vector.com/jowd/article/view/77046

  With PE, these processes are disrupted, which ultimately leads to defective trophoblast invasion and impaired formation of uteroplacental blood flow. […] Not only hypoxia has a pathogenic effect, but also systematically repeated episodes of ischemia and reperfusion, which are accompanied by increased reactive oxygen species production, thereby creating a favorable environment for oxidative stress development. […] Evidence on the involvement of the renin-angiotensin-aldosterone system in PE pathogenesis has been obtained. […] Immune maladjustment of the mothers body also contributes to PE development. […] One of the components of the pathogenesis of PE is the deregulation of the complement system, which is most often associated with the presence of mutations in genes that control the biosynthesis of complement activation regulators.

• #1

  https://www.nhs.uk/conditions/pre-eclampsia/causes/

  Pre-eclampsia is thought to be caused by the placenta not developing properly due to a problem with the blood vessels supplying it. The exact cause isn’t fully understood. […] In pre-eclampsia, the placenta doesn’t get enough blood. This could be because the placenta didn’t develop properly as it was forming during the first half of the pregnancy. […] If the blood vessels don’t fully transform, it’s likely that the placenta won’t develop properly because it won’t get enough nutrients. This may lead to pre-eclampsia. […] It’s likely that inherited changes in your genes have some sort of role, as the condition often runs in families. But this only explains some cases.

• #1 Preeclampsia: MedlinePlus GeneticsLock

  https://medlineplus.gov/genetics/condition/preeclampsia/

  Preeclampsia is a complication of pregnancy in which affected women develop high blood pressure (hypertension); they can also have abnormally high levels of protein in their urine (proteinuria). […] The specific causes of preeclampsia are not well understood. In pregnancy, blood volume normally increases to support the fetus, and the mother’s body must adjust to handle this extra fluid. In some women the body does not react normally to the fluid changes of pregnancy, leading to the signs and symptoms of preeclampsia. […] Studies suggest that preeclampsia is related to a problem with the placenta, the link between the mother’s blood supply and the fetus. […] Researchers are studying whether variations in genes involved in fluid balance, the functioning of the vascular endothelium, or placental development affect the risk of developing preeclampsia or its severity.

• #1 Modern concepts of etiology, pathogenesis and risk factors for preeclampsia – Abramova – Journal of obstetrics and women’s diseases

  https://journals.eco-vector.com/jowd/article/view/77046

  The main component of the arterial hypertension pathophysiology in PE is the biologically imbalanced active substances produced by endothelial cells, which are involved in vascular tone regulation. […] To date, a large number of studies have been conducted that comprise the information about 130 possible PE risk factors, covering a large list of comorbidities, biomarkers, environmental factors, and genetic determinants. […] The most common modifiable risk factor for PE is overweight (BMI 25 kg/m2), as 10% of all pregnant women are obese. […] A hereditary predisposition is significant in PE formation. […] Therefore, as studied in the international and Russian literature, we can conclude that, firstly, despite numerous studies, no consensus was found on the molecular mechanisms of PE etiopathogenesis. Secondly, the key role in the development of this pregnancy complication is attributed to the processes of placentation disturbance, immune maladjustment of the mothers body, endothelial dysfunction, angiogenic imbalance, and others; however, their significance in the formation of early and late PE is considerably different. Thirdly, 130 different risk factors were identified for PE development (family history of PE, DM, CAH, hereditary thrombophilia, etc.), but the available data are often ambiguous and vary depending on the studied population. Thus, the existing contradictions and insufficient consensus of certain biological processes involved in PE development necessitate a further study of this pregnancy complication.

• #1 Pathophysiology of Pre-Eclampsia—Two Theories of the Development of the Disease

  https://www.mdpi.com/1422-0067/25/1/307

  The second theory of the development of PE is a cardiogenic one. According to this model, the primary cause of the disease is a pre-existing cardiac dysfunction, which is triggered or exacerbated by pregnancy. This cardiac dysfunction subsequently leads to reduced placental perfusion and the characteristic clinical consequences observed in PE. […] Impaired placental perfusion, recognized as the first step in the development of PE, may have etiologies other than impaired trophoblast invasion. The possible causes of impaired placental perfusion may include (1) primary pathologies of the vessel walls, characteristic for some autoimmune disorders, such as lupus or scleroderma or diabetes; (2) primary dyslipidemia affecting the quality of vascular perfusion; (3) hypercoagulability or thrombophilia, especially the anti-phospholipid syndrome; (4) obesity, which is associated with inflammation of the vessel walls; (5) enlarged, big placentas, which are associated with increased risk of hypoxia; (6) chronic hypertension; and (7) acute atherosis.

• #1 Preeclampsia in Pregnancy: Symptoms, Causes &Treatments | Ada

  https://ada.com/conditions/preeclampsia/

  There is some evidence that preeclampsia and heart disease share some risk factors, namely: endothelial dysfunction, obesity, hypertension, hyperglycemia, insulin resistance, and dyslipidemia. […] There also appears to be a genetic component that determines a person’s risk of developing preeclampsia. […] While the cause is uncertain, the risk factors for preeclampsia are well-known. […] Preeclampsia is slightly more common among pregnant women from poorer communities, which may suggest that there is a connection between nutrition and preeclampsia. […] A related theory is that overnutrition, especially obesity before and during pregnancy, as well as undernutrition, can both cause the risk of preeclampsia to rise. […] It has been suggested that low-protein diets, low-fat diets and low-energy diets may affect preeclampsia.

• #1 The etiology of preeclampsia

  https://pmc.ncbi.nlm.nih.gov/articles/PMC8988238/

  The role of placental ischemia in the pathogenesis of preeclampsia is now well established. […] What is the cause of placental ischemia in women with preeclampsia? The traditional explanation has been that a defect in placentation leads to ischemia but more recently, a dysfunctional maternal cardiovascular system has been implicated. […] The best evidence to support a relationship between microorganisms and preeclampsia derives from studies of periodontal disease, which increases the risk of developing this pregnancy-related syndrome. […] Maternal infection has been implicated in the etiology for preeclampsia and eclampsia since the beginning of the 20th century. […] A recent meta-analysis demonstrated that SARS-CoV-2 infection during pregnancy is associated with a significant increase in the odds of developing preeclampsia.

• #1 Pre-Eclampsia: From Etiology and Molecular Mechanisms to Clinical Tools—A Review of the Literature

  https://www.mdpi.com/1467-3045/45/8/391

  The development of high blood pressure, proteinuria, a low platelet count, and glomerular fibrinogen deposits occurs after intravenous low-dose endotoxin administration in pregnant rats on day 14 of gestation, according to experimental findings supporting a causal relationship between infection, systemic inflammation, and pre-eclampsia. […] The microbiota in the human gut is crucial for host nutrition, energy production, and immunological defenses against possible pathogens. […] Gut dysbiosis, or an imbalance in the microbial populations of the human gut, is currently thought to contribute to the onset of atherosclerosis, hypertension, proteinuria, cardiometabolic syndrome, and more recently, pre-eclampsia. […] Changes in the human gut flora have been linked to pre-eclampsia, which lasts until six weeks after delivery.

• #1 Preeclampsia: Background, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/1476919-overview

  Risk factors for preeclampsia include the following: Nulliparity, Multifetal gestations, Preeclampsia in a previous pregnancy, Chronic hypertension, Pregestational diabetes, Gestational diabetes, Thrombophilia, Systemic lupus erythematosus, Prepregnancy body mass index greater than 30, Antiphospholipid antibody syndrome, Maternal age 35 years or older, Kidney disease, Assisted reproductive technology, Obstructive sleep apnea.

• #1 Preeclampsia During Pregnancy: Types, Symptoms, Causes And Treatment | TheEMTSpot

  https://www.theemtspot.org/blood-pressure/preeclampsia/

  A 2023 study from the University of Western Ontario identified a toxic protein, cis P-tau, as a central driver of preeclampsia. […] A 2019 study published by Prof. Racheal Fox and her group in the Journal of Clinical Medicine, in fact, highlights this disparity and demands an evidence-based approach to figure out the right ways, timing, and how often we should evaluate this disease. […] The timing of the first delivery also plays a role. The risk of preeclampsia recurring is higher (38.6%) if the first delivery occurred at or before 28 weeks of gestation. This risk decreases with later deliveries. i.e., 29% for deliveries between 29-32 weeks, 22% for 33-36 weeks, and 13% for deliveries at 37 weeks or later. […] Further research is needed to elucidate the root cause of this disease and gain a better understanding of the underlying causes of preeclampsia.

• #1 Pre-Eclampsia: From Etiology and Molecular Mechanisms to Clinical Tools—A Review of the Literature

  https://www.mdpi.com/1467-3045/45/8/391

  Obesity worsens metabolic abnormalities such as insulin resistance, inflammation, and atherosclerosis disease, which raises the risk for PE in comparison to a normal-weight person. […] Gestational diabetes mellitus could be considered as an independent risk factor for pre-eclampsia. […] The finding that the risk of pre-eclampsia is decreased when gestational diabetes mellitus is treated with diet, insulin, and metformin reinforces the existence of a causal relationship. […] Pre-eclampsia is not traditionally considered an autoimmune disorder. However, patients with systemic autoimmune diseases, such as systemic lupus erythematosus (SLE) or antiphospholipid syndrome (APS), are at an increased risk for pre-eclampsia.

• #1 Eclampsia: Causes, symptoms, and treatment

  https://www.medicalnewstoday.com/articles/316255

  Eclampsia follows preeclampsia, which is a high blood pressure disorder during pregnancy. […] Researchers have not yet discovered a definitive cause for the condition. Each case of eclampsia is unique, and the pregnant woman may share few or no characteristics with other women who develop the condition. […] Risk factors for preeclampsia and eclampsia will vary from patient to patient. Factors that should be taken into consideration are: Pregnancy history: Most cases of preeclampsia happen in first pregnancies. Previous pregnancies with poor outcomes could also increase the risk of developing eclampsia. Patient age: Teen pregnancies and pregnancies in women over 35 have an increased risk of developing eclampsia. Family history: Cases of preeclampsia or eclampsia in family members could signal a genetic predisposition to the condition. Obesity: Women who are obese are at a higher risk of developing eclampsia than others. High blood pressure: Patients with long-term high blood pressure are at a higher risk of developing eclampsia than others. […] Other medical conditions, including lupus, gestational diabetes, and renal disease, also increase the chances of developing eclampsia.

• #1 Preeclampsia During Pregnancy: Types, Symptoms, Causes And Treatment | TheEMTSpot

  https://www.theemtspot.org/blood-pressure/preeclampsia/

  Preeclampsia is a significant health concern in pregnancy. It is defined by the American College of Cardiology as a hypertensive disorder occurring in 2-8% of pregnancies worldwide, leading to substantial morbidity and mortality. […] The primary cause and risk factor for preeclampsia is not fully understood, but its believed to be related to issues with the placenta. […] Risk factors include a history of preeclampsia, first-time pregnancy, pre-existing conditions like hypertension or diabetes, obesity, and advanced maternal age. Genetic factors and immune system responses may also play a role. […] Preeclampsia is believed to result from a combination of genetic, nutritional, and environmental factors, with abnormal placental development playing a significant role. […] According to current medical understanding and research, stress does not directly cause preeclampsia. However, stress may lead to high blood pressure during pregnancy, which increases the risk of serious conditions such as preeclampsia, preterm birth, and having a low-birthweight infant.

• #1 Cause Of Preeclampsia

  https://www.preeclampsia.org/cause-of-preeclampsia

  Preeclampsia was once called “the disease of theories,” but research efforts this past decade have produced exciting breakthroughs that may bring us closer to causality, improve diagnosis and even prediction, and lead to prevention and/or specific treatments. Some speculation remains over different theories including: changes in biology of the placenta, the systemic inflammatory response, a variety of hormones and other proteins that are in the mother’s circulation, changes in immune factors, improper cardiovascular adaptations to the pregnant state, underlying maternal risks for cardiovascular disease, associations with insulin resistance and diabetes, and deficiencies in essential nutrients, minerals, and vitamins. […] The most plausible theories on the cause of preeclampsia focus on the placenta and describe the disorder in two stages. The first stage happens as the placenta first develops. The placenta produces factors (e.g., specific proteins, placental “debris”) that enter the maternal circulation and are believed responsible for producing the second stage.

• #1 Preeclampsia | Symptoms, Warning Signs and Causes

  https://www.birthinjuryhelpcenter.org/birth-injuries/prenatal-problems/preeclampsia/

  We do know is that placental factors are believed to be the cause of preeclampsia. How do we know this? Delivery of the placenta will resolve the maternal symptoms of the disease. […] Preeclampsia is likely caused by from abnormalities in the placenta that feeds the fetus with blood and oxygen. Adequate blood supply is critical for fetal health. […] The continuing uncertainty about the exact causes of preeclampsia makes it impossible to diagnose preeclampsia in advance. However, there are a number of well-known maternal risk factors which can be used to identify pregnant mothers who are more likely to suffer from preeclampsia than others. The most reliable risk-factors for preeclampsia are maternal obesity prior to and during pregnancy; older mothers (over 35 years); mothers with a prior history of hypertension; and diabetes. Preeclampsia is also more likely to occur if it is the mothers first pregnancy. Multiples (i.e., twins, triplets, etc.) also make preeclampsia more likely to occur.

• #1 Pre-Eclampsia | HealthLink BC

  https://www.healthlinkbc.ca/healthwise/pre-eclampsia

  Pre-eclampsia is high blood pressure after 20 weeks of pregnancy that may affect the mother’s organs or the baby. […] Experts don’t know the exact cause of pre-eclampsia. It seems to start because the placenta doesn’t grow the usual network of blood vessels deep in the uterine wall. This leads to poor blood flow in the placenta. It’s not clear what causes this placenta problem and why the mother then develops high blood pressure. […] Some things increase your risk of pre-eclampsia. For example, your risk is higher if you: Have chronic (ongoing) high blood pressure, chronic kidney disease, certain autoimmune diseases, or diabetes. […] Lowering your blood pressure helps to prevent pre-eclampsia. […] After you’ve had pre-eclampsia, you have a higher-than-average risk of heart disease, stroke, and kidney disease. This may be because the same things that cause pre-eclampsia also cause heart and kidney disease.

• #1 Preeclampsia: Clinical features and diagnosis – UpToDate

  https://www.uptodate.com/contents/preeclampsia-clinical-features-and-diagnosis

  Preeclampsia is a multisystem progressive disorder characterized by the new onset of hypertension and proteinuria or the new onset of hypertension plus significant end-organ dysfunction with or without proteinuria, typically presenting after 20 weeks of gestation or postpartum. The pathogenesis involves both abnormal placentation and maternal systemic vascular dysfunction. […] Several subtypes of preeclampsia may exist, with a variety of pathophysiological pathways leading to maternal and fetal mortality and morbidity. The most commonly described subtypes are early onset (<34 weeks of gestation) and late onset (≥34 weeks of gestation). [...] It has been hypothesized that the two phenotypes have different origins and pathophysiologies. [...] The pathogenesis of preeclampsia likely involves both placental and maternal factors. Abnormal development of the placental vasculature early in pregnancy (failure of normal spiral artery remodeling) is a key event that results in relative placental underperfusion, hypoxia, ischemia, and oxidative stress, leading to release of antiangiogenic factors into the maternal circulation.

• #1 Preeclampsia – Pregnancy-Related Hypertension – Pregnancy-Related Conditions – Diseases – McMaster Textbook of Internal Medicine

  https://empendium.com/mcmtextbook/chapter/B31.II.2.20.4.1.

  Specific angiogenic factors implicated in the pathogenesis of preeclampsia can be measured but are not yet widely available in North America. These include the antiangiogenic soluble fms-like tyrosine kinase-1 (sFlt-1) and angiogenic placental growth factor (PlGF). […] The syndrome of HELLP (hemolysis, elevated liver enzymes, low platelets) is most often seen in preeclampsia but can occur in other situations, for example, in placental abruption, amniotic fluid embolism, or septicemia. The exact pathophysiology of HELLP is unclear, but it is considered a subtype of severe preeclampsia. […] Evolving evidence has identified 2 different phenotypes of preeclampsia, with fetal growth restriction being the key distinguishing factor. These 2 phenotypes have opposite underlying cardiovascular hemodynamic profiles with regard to maternal cardiac output and peripheral vascular resistance.

• #1 Pre-eclampsia | Nature Reviews Disease Primers

  https://www.nature.com/articles/s41572-023-00417-6

  Pre-eclampsia is a life-threatening disease of pregnancy unique to humans and a leading cause of maternal and neonatal morbidity and mortality. […] Despite decades of research, the aetiology of pre-eclampsia, particularly of term and postpartum pre-eclampsia, remains poorly defined. […] A comprehensive review of our understanding of the aetiology of pre-eclampsia that encompasses both preterm and term physiology. […] This publication identified that spiral artery remodelling was impaired in preterm pre-eclampsia. […] Publication demonstrating the importance of sFLT1 in the aetiology of pre-eclampsia.

• #1 Diagnosis and Management of Preeclampsia | AAFP

  https://www.aafp.org/pubs/afp/issues/2004/1215/p2317.html

  Risk factors for preeclampsia include medical conditions with the potential to cause microvascular disease (e.g., diabetes mellitus, chronic hypertension, vascular and connective tissue disorders), antiphospholipid antibody syndrome, and nephropathy. […] Some evidence does support the use of low-dose aspirin therapy and daily calcium supplementation in certain high-risk women. […] Research on the use of antioxidants in the prevention of preeclampsia is promising. […] Although preeclampsia is not preventable, many deaths from the disorder can be prevented.

• #1 ‘Mini-placentas’ help scientists understand the causes of pre-eclampsia and pregnancy disorders | University of Cambridge

  https://www.cam.ac.uk/research/news/mini-placentas-help-scientists-understand-the-causes-of-pre-eclampsia-and-pregnancy-disorders

  Scientists have grown mini-placentas in the lab and used them to shed light on how the placenta develops and interacts with the inner lining of the womb findings that could help scientists better understand and, in future, potentially treat pre-eclampsia. […] Most of the major disorders of pregnancy pre-eclampsia, still birth, growth restriction, for example depend on failings in the way the placenta develops in the first few weeks. […] When these interactions do not work properly, they can lead to complications, such as pre-eclampsia, a condition that causes high blood pressure during pregnancy. Pre-eclampsia occurs in around six in 100 first pregnancies and can put at risk the health of both the mother and the baby. […] Professor Moffett and colleagues identified genes that increase the risk of or protect against conditions such as pre-eclampsia.

• #1 Pre-Eclampsia: From Etiology and Molecular Mechanisms to Clinical Tools—A Review of the Literature

  https://www.mdpi.com/1467-3045/45/8/391

  Pre-eclampsia is a severe pregnancy-related complication that manifests as a syndrome with multisystem involvement and damage. […] However, the specific etiology and molecular mechanisms of pre-eclampsia are still poorly known and could have a variety of causes, such as altered angiogenesis, inflammations, maternal infections, obesity, metabolic disorders, gestational diabetes, and autoimmune diseases. […] The specific etiology and pathophysiology of pre-eclampsia are still poorly known and could have a variety of causes. […] To determine the relative importance of each cause and the impact of actions to stop this illness, more research is needed. […] Pre-eclampsia is linked to fetal complications including intrauterine growth restriction and premature birth as well as uterine and placental abnormalities.

• #1 What doctors wish patients knew about preeclampsia | American Medical Association

  https://www.ama-assn.org/delivering-care/population-care/what-doctors-wish-patients-knew-about-preeclampsia

  Preeclampsia is a disorder that occurs only during pregnancy and the postpartum period and affects both the mother and the unborn baby, Dr. Hoppe said, noting it is characterized by high blood pressure and usually the presence of protein in the urine. […] We dont exactly know what causes preeclampsia. Its likely a result of multiple, interacting things, Dr. Hoppe said. We think theres a large component of the placenta or abnormal placentation and then other underlying risk factors such as mental health, genetics, immune response and lifestyle. […] Women whove had a hypertension related diagnosis in a prior pregnancy are at risk of developing hypertension during a subsequent pregnancy, Dr. Hoppe said. The earlier, more severe the hypertension disorder was increases that risk. […] Preeclampsia is very rare before 20 to 24 weeks of the pregnancy and entry to prenatal care is typically between eight and 12 weeks of pregnancy. […] Once pregnant, we think aspirin can help lower ones risk of getting preeclampsia, said Dr. Hoppe.

• #1 Preeclampsia Information | Mount Sinai – New York

  https://www.mountsinai.org/health-library/diseases-conditions/preeclampsia

  Preeclampsia is high blood pressure and signs of liver or kidney damage that occur in women after the 20th week of pregnancy. […] The exact cause of preeclampsia is unknown. It occurs in 3% to 7% of all pregnancies. The condition is thought to start in the placenta. Factors that may lead to preeclampsia developing include: […] Risk factors for the condition include: […] Having a history of preeclampsia makes a woman a higher risk for future problems such as: […] There is no sure way to prevent preeclampsia.

• #1 What Is Preeclampsia

  https://www.preeclampsia.org/what-is-preeclampsia

  The amount of protein in the urine does not predict how severely the disease will progress. […] Most healthcare providers traditionally adhered to a rigid diagnosis of preeclampsia based on blood pressure and protein in the urine prior to these new guidelines. […] Preeclampsia can cause your blood pressure to rise and put you at risk of brain injury. […] It can impair kidney and liver function, and cause blood clotting problems, pulmonary edema (fluid on the lungs), seizures and, in severe forms or left untreated, maternal and infant death. […] Preeclampsia affects the blood flow to the placenta, often leading to smaller or prematurely born babies. […] While maternal death from preeclampsia is rare in the developed world, it is a leading cause of illness and death globally for mothers and infants.

• #1 Preeclampsia: Toxemia, Causes, Symptoms & Risk Factors

  https://my.clevelandclinic.org/health/diseases/17952-preeclampsia

  Preeclampsia is a serious blood pressure condition that develops during pregnancy. […] No one is entirely sure. Some researchers believe preeclampsia may happen due to a problem with blood supply to the placenta. […] Preeclampsia typically occurs after 20 weeks of pregnancy. […] If left untreated, preeclampsia can be potentially fatal to both you and the fetus. […] Preeclampsia can cause HELLP syndrome (hemolysis, elevated liver enzymes and low platelet count). […] Preeclampsia can also come after delivery (postpartum preeclampsia), which usually occurs between the first few days to one week after delivery. […] The only cure for preeclampsia is delivery.

• #1

  https://myhealth.alberta.ca/Health/pages/conditions.aspx?hwid=hw2834

  Vision problems, a headache that won’t go away, and seizures (eclampsia) can develop. […] Low platelet levels in the blood are common with preeclampsia. […] A newborn affected by preeclampsia may also be smaller than normal. This is because the baby may not get enough nutrition due to poor blood flow through the placenta. […] Your healthcare provider or midwife may prescribe blood pressure medicine if your blood pressure reaches high levels that may be dangerous to you or your baby. But lowering high blood pressure doesn’t prevent preeclampsia from getting worse. High blood pressure is only a symptom of preeclampsia. It’s not a cause. […] Magnesium sulfate may be started before delivery and continued after delivery if you have moderate to severe preeclampsia. It can help prevent seizures (eclampsia).

• #2 Preeclampsia – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK570611/

  Although there is an extensive understanding of the clinical presentation, diagnostic criteria, and management of preeclampsia currently routinely utilized, the underlying etiology of preeclampsia is poorly understood. The principal mechanism of disease implicated in the etiology of preeclampsia and eclampsia is uteroplacental ischemia. This theory was based on the observation of placental infarctions in patients with eclampsia and on animal studies showing that subcutaneous injections of autolyzed human placental extracts into guinea pigs elicited convulsions, hepatic focal necrosis, and renal lesions, similar to those observed in women who died of eclampsia. […] The pathophysiology of preeclampsia, therefore, can be likened to the release and progression of a particular toxin, leading to a diffuse vasculopathy, which, if sustained, ultimately leads to severe complications such as the development of seizures seen in eclampsia. […] While there is a certain consensus on this proposed main etiology, further research aims to clarify this primary mechanism of uteroplacental ischemia implicated in PIH and preeclampsia.

• #2

  https://www.nhs.uk/conditions/pre-eclampsia/causes/

  Pre-eclampsia is thought to be caused by the placenta not developing properly due to a problem with the blood vessels supplying it. The exact cause isn’t fully understood. […] In pre-eclampsia, the placenta doesn’t get enough blood. This could be because the placenta didn’t develop properly as it was forming during the first half of the pregnancy. […] If the blood vessels don’t fully transform, it’s likely that the placenta won’t develop properly because it won’t get enough nutrients. This may lead to pre-eclampsia. […] It’s likely that inherited changes in your genes have some sort of role, as the condition often runs in families. But this only explains some cases.

• #2 The etiology of preeclampsia

  https://pmc.ncbi.nlm.nih.gov/articles/PMC8988238/

  Particular etiological factors, such as the breakdown of maternal-fetal immune tolerance, thought to account for the excess of preeclampsia in primipaternity and egg donation may operate, in part, through uteroplacental ischemia, while another, such as placental aging, may operate largely through syncytiotrophoblast stress. […] The various roles of autoimmunity, fetal diseases, and endocrine disorders are also discussed. A greater understanding of the etiologic factors of preeclampsia is essential to improve treatment and prevention. […] The principal mechanism of disease implicated in the etiology of preeclampsia and eclampsia is uteroplacental ischemia. […] Additional evidence supporting a role for uteroplacental ischemia came from studies by Ogden, Hildebrand, and Page who reported that clamping of the abdominal aorta below the renal arteries (to avoid renovascular hypertension) in dogs reduced uteroplacental perfusion; furthermore, this response was followed by maternal hypertension that resolved after the clamp was released.

• #2 Preeclampsia: Clinical features and diagnosis – UpToDate

  https://www.uptodate.com/contents/preeclampsia-clinical-features-and-diagnosis

  Preeclampsia is a multisystem progressive disorder characterized by the new onset of hypertension and proteinuria or the new onset of hypertension plus significant end-organ dysfunction with or without proteinuria, typically presenting after 20 weeks of gestation or postpartum. The pathogenesis involves both abnormal placentation and maternal systemic vascular dysfunction. […] Several subtypes of preeclampsia may exist, with a variety of pathophysiological pathways leading to maternal and fetal mortality and morbidity. The most commonly described subtypes are early onset (<34 weeks of gestation) and late onset (≥34 weeks of gestation). [...] It has been hypothesized that the two phenotypes have different origins and pathophysiologies. [...] The pathogenesis of preeclampsia likely involves both placental and maternal factors. Abnormal development of the placental vasculature early in pregnancy (failure of normal spiral artery remodeling) is a key event that results in relative placental underperfusion, hypoxia, ischemia, and oxidative stress, leading to release of antiangiogenic factors into the maternal circulation.

• #2 Pre-eclampsia – Wikipedia

  https://en.wikipedia.org/wiki/Pre-eclampsia

  A major consequence of this sequence of events is generalized endothelial dysfunction. […] The abnormal implantation may stem from the maternal immune system’s response to the placenta, specifically a lack of established immunological tolerance in pregnancy. […] The cause of preeclampsia is not fully understood. It is likely related factors such as abnormal placentation (formation and development of the placenta), immunologic factors, prior or existing maternal pathology pre-eclampsia is seen more at a higher incidence in individuals with pre-existing hypertension, obesity, or antiphospholipid antibody syndrome or those with a history of pre-eclampsia. […] Environmental factors, e.g. air pollution. […] Infection (for which there is much evidence), including at the time of conception.

• #2 Modern concepts of etiology, pathogenesis and risk factors for preeclampsia – Abramova – Journal of obstetrics and women’s diseases

  https://journals.eco-vector.com/jowd/article/view/77046

  The main component of the arterial hypertension pathophysiology in PE is the biologically imbalanced active substances produced by endothelial cells, which are involved in vascular tone regulation. […] To date, a large number of studies have been conducted that comprise the information about 130 possible PE risk factors, covering a large list of comorbidities, biomarkers, environmental factors, and genetic determinants. […] The most common modifiable risk factor for PE is overweight (BMI 25 kg/m2), as 10% of all pregnant women are obese. […] A hereditary predisposition is significant in PE formation. […] Therefore, as studied in the international and Russian literature, we can conclude that, firstly, despite numerous studies, no consensus was found on the molecular mechanisms of PE etiopathogenesis. Secondly, the key role in the development of this pregnancy complication is attributed to the processes of placentation disturbance, immune maladjustment of the mothers body, endothelial dysfunction, angiogenic imbalance, and others; however, their significance in the formation of early and late PE is considerably different. Thirdly, 130 different risk factors were identified for PE development (family history of PE, DM, CAH, hereditary thrombophilia, etc.), but the available data are often ambiguous and vary depending on the studied population. Thus, the existing contradictions and insufficient consensus of certain biological processes involved in PE development necessitate a further study of this pregnancy complication.

• #2 Preeclampsia – Pregnancy-Related Hypertension – Pregnancy-Related Conditions – Diseases – McMaster Textbook of Internal Medicine

  https://empendium.com/mcmtextbook/chapter/B31.II.2.20.4.1.

  Risk factors for preeclampsia: Preeclampsia likely involves a genetic predisposition. Individuals with a family history (mother or sister) of preeclampsia are at a heightened risk. Other risk factors include a previous history of preeclampsia, obesity (body mass index 30), age 40 years, multiple pregnancy, autoimmune disease, preexisting kidney disease, chronic hypertension, diabetes mellitus, assisted reproduction, and antiphospholipid antibodies. […] The maternal syndrome of preeclampsia is a systemic syndrome associated with endothelial injury, which can result in vasoconstriction, capillary leak, and activation of the coagulation system. […] The fetal syndrome can be characterized by intrauterine growth restriction (IUGR), oligohydramnios, asymmetric growth, or abnormalities in the uterine and umbilical arteries on ultrasonography.

• #2 Pathophysiology of Pre-Eclampsia—Two Theories of the Development of the Disease

  https://www.mdpi.com/1422-0067/25/1/307

  The most probable pathophysiological connection between the first stage of PE, characterized by impaired placental perfusion, and the subsequent second stage, marked by maternal endothelial dysfunction, is the increased production of anti-angiogenic factors by poorly perfused placentas in women who later develop PE. These anti-angiogenic factors, if produced in excess, have a negative influence both on the integrity and function of the maternal endothelium, ultimately leading to its damage and dysfunction. […] Although the two-stage model of PE is the most popular theory of the disease, the cardiac origin of PE must also be taken into consideration as a potential pathomechanism. A common element in both theories is impaired placental perfusion. It is possible that primary impaired placentation—as well as a reduced perfusion due to cardiac and cardiovascular system maladaptation and malfunction—may predispose to angiogenic imbalance, a phenomenon characteristic of PE.

• #2 Preeclampsia And Eclampsia – Harvard Health

  https://www.health.harvard.edu/a_to_z/preeclampsia-and-eclampsia-a-to-z

  The following conditions increase the chance that a woman will develop preeclampsia: chronic (long-lasting) high blood pressure, obesity, diabetes, kidney disease, being under 15 years old or over 35 years old, being a woman’s first pregnancy, having had preeclampsia in a previous pregnancy, multiple gestations: twins, triplets, or a greater number of multiples, certain autoimmune conditions, including antiphospholipid antibody syndrome and some autoimmune arthritis conditions, African American or Hispanic ethnicity, having a sister, mother, or daughter who had preeclampsia or high blood pressure during pregnancy, having a male partner whose previous partner had preeclampsia, having a male partner with whom you were sexually active for only a short length of time prior to becoming pregnant.

• #2 Preeclampsia and Eclampsia – Gynecology and Obstetrics – MSD Manual Professional Edition

  https://www.msdmanuals.com/professional/gynecology-and-obstetrics/antenatal-complications/preeclampsia-and-eclampsia

  Etiology of preeclampsia is unknown. […] However, high-risk and moderate-risk factors have been identified. […] High-risk factors include Previous pregnancy with preeclampsia, Multiple gestation, Kidney disorders, Autoimmune disorders, Type 1 or type 2 diabetes mellitus, Chronic hypertension. […] Moderate-risk factors include First pregnancy, Maternal age 35 years, Prepregnancy body mass index 30, Family history of preeclampsia (in a first-degree relative), Non-Hispanic Black and American Indian or Alaskan Native women, Lower income.

• #2 Preeclampsia – Causes, Symptoms, Treatment, Diagnosis – MedBroadcast.com

  https://medbroadcast.com/condition/getcondition/preeclampsia

  The known risk factors for preeclampsia are: being over the age of 35 to 40, or under 20; first pregnancy; preeclampsia in previous pregnancies; multiple fetuses (e.g., twins, triplets); non-Hispanic Black ancestry or Indigenous ancestry; family history of preeclampsia; diabetes; preexisting high blood pressure, kidney disease, or blood disorders; being overweight before pregnancy.

• #2 Pre-eclampsia | healthdirect

  https://www.healthdirect.gov.au/pre-eclampsia

  Pre-eclampsia is a complication of pregnancy. […] Pre-eclampsia causes high blood pressure and can affect your kidneys, liver and brain. […] The cause of pre-eclampsia is not completely clear, but there are factors that are known to increase the risk. […] Your risk of getting pre-eclampsia is increased if you: had pre-eclampsia with a previous pregnancy, have long-standing high blood pressure, have diabetes or kidney disease, have an autoimmune condition such as lupus, you are pregnant with twins or more. […] Your risk of pre-eclampsia is also increased if: it is your first pregnancy, you are 40 years old or older, it has been more than 10 years since your last pregnancy, you were very overweight at the beginning of your pregnancy, you have a family history of pre-eclampsia. […] There is no evidence that preeclampsia is caused by emotional stress, working too hard or not getting enough rest.

• #2 Pathophysiology of Pre-Eclampsia—Two Theories of the Development of the Disease

  https://www.mdpi.com/1422-0067/25/1/307

  Pre-eclampsia (PE) continues to be a leading cause of maternal and fetal mortality and morbidity. While substantial progress has been made in understanding the pathomechanisms of PE, the pathophysiology of the disease is still not fully understood. While the “two-stage model” of the development of PE is the most widely accepted theory, stating that the placenta is the main source of the disease, there are some other pathophysiological models of PE. Among these other theories, the one considering heart dysfunction as serving as the primary cause of PE seems to be gaining increasing prominence. […] Currently, the prevailing and most plausible theory regarding the development of PE is the two-stage theory. In this model, the first stage of the disease involves impaired placentation and reduced placental perfusion, while the second stage encompasses general maternal endothelial damage and dysfunction.

• #2 Preeclampsia | March of Dimes

  https://www.marchofdimes.org/find-support/topics/pregnancy/preeclampsia

  There are other factors that can put you at risk for preeclampsia. […] Without treatment, preeclampsia can cause serious health problems for you and your baby, and can even cause seizures or death. […] Having preeclampsia can also make you more likely to have heart disease, diabetes and kidney disease later in life. […] We dont know exactly what causes postpartum preeclampsia, but these may be risk factors: […] Complications from postpartum preeclampsia include these life-threatening conditions:

• #2 Pre-eclampsia | Nature Reviews Disease Primers

  https://www.nature.com/articles/s41572-023-00417-6

  Pre-eclampsia is a life-threatening disease of pregnancy unique to humans and a leading cause of maternal and neonatal morbidity and mortality. […] Despite decades of research, the aetiology of pre-eclampsia, particularly of term and postpartum pre-eclampsia, remains poorly defined. […] A comprehensive review of our understanding of the aetiology of pre-eclampsia that encompasses both preterm and term physiology. […] This publication identified that spiral artery remodelling was impaired in preterm pre-eclampsia. […] Publication demonstrating the importance of sFLT1 in the aetiology of pre-eclampsia.

• #2 ‘Mini-placentas’ help scientists understand the causes of pre-eclampsia and pregnancy disorders | University of Cambridge

  https://www.cam.ac.uk/research/news/mini-placentas-help-scientists-understand-the-causes-of-pre-eclampsia-and-pregnancy-disorders

  The researchers also found several genes that regulate blood flow and help with this implantation, which Professor Moffett says provide pointers for future research to better understand pre-eclampsia and similar disorders. […] Despite affecting millions of women a year worldwide, we still understand very little about pre-eclampsia. Women usually present with pre-eclampsia at the end of pregnancy, but really to understand it to predict it and prevent it we have to look at what’s happening in the first few weeks. […] Using mini-placentas, we can do just that, providing clues as to how and why pre-eclampsia occurs.

• #2 What Causes Preeclampsia?

  https://mydoctor.kaiserpermanente.org/mas/news/what-causes-preeclampsia-2477755

  Preeclampsia is a serious condition that can affect mom and baby. The condition affects approximately 5 percent of pregnancies in the United States. […] Preeclampsia is a serious blood pressure disorder that, if it develops, occurs after the 20th week of pregnancy (it can also develop soon after delivery). With preeclampsia, the placenta doesn’t work properly, which can interfere with baby getting enough nutrients and oxygen. This can affect the baby’s growth and development in the uterus. […] Some people are at moderate risk for developing preeclampsia; others are at high risk. […] People who have at least one of the high-risk factors for preeclampsia or at least two of the moderate-risk factors for preeclampsia can take a low-dose aspirin every day starting at 12-16 weeks and continuing through delivery.

• #2 Video: Overview of Preeclampsia and Eclampsia-Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/multimedia/video/overview-of-preeclampsia-and-eclampsia

  Endothelial injury also leads to the formation of lots of tiny thrombi in the microvasculature, which is a process that uses up massive amounts of platelets. […] Because all of the problems of preeclampsia and eclampsia stem from placental dysfunction, the ultimate treatment is delivery of the fetus and placenta.

• #2 Pre-Eclampsia: From Etiology and Molecular Mechanisms to Clinical Tools—A Review of the Literature

  https://www.mdpi.com/1467-3045/45/8/391

  Pre-eclampsia is a severe pregnancy-related complication that manifests as a syndrome with multisystem involvement and damage. […] However, the specific etiology and molecular mechanisms of pre-eclampsia are still poorly known and could have a variety of causes, such as altered angiogenesis, inflammations, maternal infections, obesity, metabolic disorders, gestational diabetes, and autoimmune diseases. […] The specific etiology and pathophysiology of pre-eclampsia are still poorly known and could have a variety of causes. […] To determine the relative importance of each cause and the impact of actions to stop this illness, more research is needed. […] Pre-eclampsia is linked to fetal complications including intrauterine growth restriction and premature birth as well as uterine and placental abnormalities.

• #2 Preeclampsia During Pregnancy: Types, Symptoms, Causes And Treatment | TheEMTSpot

  https://www.theemtspot.org/blood-pressure/preeclampsia/

  A 2023 study from the University of Western Ontario identified a toxic protein, cis P-tau, as a central driver of preeclampsia. […] A 2019 study published by Prof. Racheal Fox and her group in the Journal of Clinical Medicine, in fact, highlights this disparity and demands an evidence-based approach to figure out the right ways, timing, and how often we should evaluate this disease. […] The timing of the first delivery also plays a role. The risk of preeclampsia recurring is higher (38.6%) if the first delivery occurred at or before 28 weeks of gestation. This risk decreases with later deliveries. i.e., 29% for deliveries between 29-32 weeks, 22% for 33-36 weeks, and 13% for deliveries at 37 weeks or later. […] Further research is needed to elucidate the root cause of this disease and gain a better understanding of the underlying causes of preeclampsia.

• #3 Preeclampsia And Eclampsia – Harvard Health

  https://www.health.harvard.edu/a_to_z/preeclampsia-and-eclampsia-a-to-z

  The following conditions increase the chance that a woman will develop preeclampsia: chronic (long-lasting) high blood pressure, obesity, diabetes, kidney disease, being under 15 years old or over 35 years old, being a woman’s first pregnancy, having had preeclampsia in a previous pregnancy, multiple gestations: twins, triplets, or a greater number of multiples, certain autoimmune conditions, including antiphospholipid antibody syndrome and some autoimmune arthritis conditions, African American or Hispanic ethnicity, having a sister, mother, or daughter who had preeclampsia or high blood pressure during pregnancy, having a male partner whose previous partner had preeclampsia, having a male partner with whom you were sexually active for only a short length of time prior to becoming pregnant.

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