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Nature Reviews. Nephrology May 2019Pre-eclampsia is a complication of pregnancy that is associated with substantial maternal and fetal morbidity and mortality. The disease presents with new-onset... (Review)
Review
Pre-eclampsia is a complication of pregnancy that is associated with substantial maternal and fetal morbidity and mortality. The disease presents with new-onset hypertension and often proteinuria in the mother, which can progress to multi-organ dysfunction, including hepatic, renal and cerebral disease, if the fetus and placenta are not delivered. Maternal endothelial dysfunction due to circulating factors of fetal origin from the placenta is a hallmark of pre-eclampsia. Risk factors for the disease include maternal comorbidities, such as chronic kidney disease, hypertension and obesity; a family history of pre-eclampsia, nulliparity or multiple pregnancies; and previous pre-eclampsia or intrauterine fetal growth restriction. In the past decade, the discovery and characterization of novel antiangiogenic pathways have been particularly impactful both in increasing understanding of the disease pathophysiology and in directing predictive and therapeutic efforts. In this Review, we discuss the pathogenic role of antiangiogenic proteins released by the placenta in the development of pre-eclampsia and review novel therapeutic strategies directed at restoring the angiogenic imbalance observed during pre-eclampsia. We also highlight other notable advances in the field, including the identification of long-term maternal and fetal risks conferred by pre-eclampsia.
Topics: Angiogenesis Inhibitors; Biomarkers; Female; Humans; Placenta; Pre-Eclampsia; Pregnancy; Risk Factors
PubMed: 30792480
DOI: 10.1038/s41581-019-0119-6 -
Nature Reviews. Disease Primers Feb 2023Pre-eclampsia is a life-threatening disease of pregnancy unique to humans and a leading cause of maternal and neonatal morbidity and mortality. Women who survive... (Review)
Review
Pre-eclampsia is a life-threatening disease of pregnancy unique to humans and a leading cause of maternal and neonatal morbidity and mortality. Women who survive pre-eclampsia have reduced life expectancy, with increased risks of stroke, cardiovascular disease and diabetes, while babies from a pre-eclamptic pregnancy have increased risks of preterm birth, perinatal death and neurodevelopmental disability and cardiovascular and metabolic disease later in life. Pre-eclampsia is a complex multisystem disease, diagnosed by sudden-onset hypertension (>20 weeks of gestation) and at least one other associated complication, including proteinuria, maternal organ dysfunction or uteroplacental dysfunction. Pre-eclampsia is found only when a placenta is or was recently present and is classified as preterm (delivery <37 weeks of gestation), term (delivery ≥37 weeks of gestation) and postpartum pre-eclampsia. The maternal syndrome of pre-eclampsia is driven by a dysfunctional placenta, which releases factors into maternal blood causing systemic inflammation and widespread maternal endothelial dysfunction. Available treatments target maternal hypertension and seizures, but the only 'cure' for pre-eclampsia is delivery of the dysfunctional placenta and baby, often prematurely. Despite decades of research, the aetiology of pre-eclampsia, particularly of term and postpartum pre-eclampsia, remains poorly defined. Significant advances have been made in the prediction and prevention of preterm pre-eclampsia, which is predicted in early pregnancy through combined screening and is prevented with daily low-dose aspirin, starting before 16 weeks of gestation. By contrast, the prediction of term and postpartum pre-eclampsia is limited and there are no preventive treatments. Future research must investigate the pathogenesis of pre-eclampsia, in particular of term and postpartum pre-eclampsia, and evaluate new prognostic tests and treatments in adequately powered clinical trials.
Topics: Pregnancy; Infant, Newborn; Female; Humans; Pre-Eclampsia; Premature Birth; Hypertension; Aspirin; Perinatal Death
PubMed: 36797292
DOI: 10.1038/s41572-023-00417-6 -
Lancet (London, England) Jul 2021Pre-eclampsia is a multisystem pregnancy disorder characterised by variable degrees of placental malperfusion, with release of soluble factors into the circulation.... (Review)
Review
Pre-eclampsia is a multisystem pregnancy disorder characterised by variable degrees of placental malperfusion, with release of soluble factors into the circulation. These factors cause maternal vascular endothelial injury, which leads to hypertension and multi-organ injury. The placental disease can cause fetal growth restriction and stillbirth. Pre-eclampsia is a major cause of maternal and perinatal mortality and morbidity, especially in low-income and middle-income countries. Prophylactic low-dose aspirin can reduce the risk of preterm pre-eclampsia, but once pre-eclampsia has been diagnosed there are no curative treatments except for delivery, and no drugs have been shown to influence disease progression. Timing of delivery is planned to optimise fetal and maternal outcomes. Clinical trials have reported diagnostic and prognostic strategies that could improve fetal and maternal outcomes and have evaluated the optimal timing of birth in women with late preterm pre-eclampsia. Ongoing studies are evaluating the efficacy, dose, and timing of aspirin and calcium to prevent pre-eclampsia and are evaluating other drugs to control hypertension or ameliorate disease progression.
Topics: Aspirin; Calcium; Calcium-Regulating Hormones and Agents; Female; Humans; Platelet Aggregation Inhibitors; Pre-Eclampsia; Pregnancy; Risk Factors
PubMed: 34051884
DOI: 10.1016/S0140-6736(20)32335-7 -
Circulation Research Mar 2019Hypertensive disorders of pregnancy-chronic hypertension, gestational hypertension, and preeclampsia-are uniquely challenging as the pathology and its therapeutic... (Review)
Review
Hypertensive disorders of pregnancy-chronic hypertension, gestational hypertension, and preeclampsia-are uniquely challenging as the pathology and its therapeutic management simultaneously affect mother and fetus, sometimes putting their well-being at odds with each other. Preeclampsia, in particular, is one of the most feared complications of pregnancy. Often presenting as new-onset hypertension and proteinuria during the third trimester, preeclampsia can progress rapidly to serious complications, including death of both mother and fetus. While the cause of preeclampsia is still debated, clinical and pathological studies suggest that the placenta is central to the pathogenesis of this syndrome. In this review, we will discuss the current evidence for the role of abnormal placentation and the role of placental factors such as the antiangiogenic factor, sFLT1 (soluble fms-like tyrosine kinase 1) in the pathogenesis of the maternal syndrome of preeclampsia. We will discuss angiogenic biomarker assays for disease-risk stratification and for the development of therapeutic strategies targeting the angiogenic pathway. Finally, we will review the substantial long-term cardiovascular and metabolic risks to mothers and children associated with gestational hypertensive disorders, in particular, preterm preeclampsia, and the need for an increased focus on interventional studies during the asymptomatic phase to delay the onset of cardiovascular disease in women.
Topics: Angiogenic Proteins; Animals; Biomarkers; Blood Pressure; Female; Humans; Intercellular Signaling Peptides and Proteins; Oxidative Stress; Placenta; Placentation; Pre-Eclampsia; Pregnancy; Pregnancy Outcome; Prognosis; Risk Factors
PubMed: 30920918
DOI: 10.1161/CIRCRESAHA.118.313276 -
Journal of the American College of... Oct 2020Preeclampsia is a hypertensive disorder of pregnancy. It affects 2% to 8% of pregnancies worldwide and causes significant maternal and perinatal morbidity and mortality.... (Review)
Review
Preeclampsia is a hypertensive disorder of pregnancy. It affects 2% to 8% of pregnancies worldwide and causes significant maternal and perinatal morbidity and mortality. Hypertension and proteinuria are the cornerstone of the disease, though systemic organ dysfunction may ensue. The clinical syndrome begins with abnormal placentation with subsequent release of antiangiogenic markers, mediated primarily by soluble fms-like tyrosine kinase-1 (sFlt-1) and soluble endoglin (sEng). High levels of sFlt-1 and sEng result in endothelial dysfunction, vasoconstriction, and immune dysregulation, which can negatively impact every maternal organ system and the fetus. This review comprehensively examines the pathogenesis of preeclampsia with a specific focus on the mechanisms underlying the clinical features. Delivery is the only definitive treatment. Low-dose aspirin is recommended for prophylaxis in high-risk populations. Other treatment options are limited. Additional research is needed to clarify the pathophysiology, and thus, identify potential therapeutic targets for improved treatment and, ultimately, outcomes of this prevalent disease.
Topics: Female; Humans; Hypertension; Nervous System Diseases; Pre-Eclampsia; Pregnancy; Review Literature as Topic
PubMed: 33004135
DOI: 10.1016/j.jacc.2020.08.014 -
Lancet (London, England) Mar 2016Pre-eclampsia affects 3-5% of pregnancies and is traditionally diagnosed by the combined presentation of high blood pressure and proteinuria. New definitions also... (Review)
Review
Pre-eclampsia affects 3-5% of pregnancies and is traditionally diagnosed by the combined presentation of high blood pressure and proteinuria. New definitions also include maternal organ dysfunction, such as renal insufficiency, liver involvement, neurological or haematological complications, uteroplacental dysfunction, or fetal growth restriction. When left untreated, pre-eclampsia can be lethal, and in low-resource settings, this disorder is one of the main causes of maternal and child mortality. In the absence of curative treatment, the management of pre-eclampsia involves stabilisation of the mother and fetus, followed by delivery at an optimal time. Although algorithms to predict pre-eclampsia are promising, they have yet to become validated. Simple preventive measures, such as low-dose aspirin, calcium, and diet and lifestyle interventions, show potential but small benefit. Because pre-eclampsia predisposes mothers to cardiovascular disease later in life, pregnancy is also a window for future health. A collaborative approach to discovery and assessment of the available treatments will hasten our understanding of pre-eclampsia and is an effort much needed by the women and babies affected by its complications.
Topics: Female; Humans; Pre-Eclampsia; Pregnancy
PubMed: 26342729
DOI: 10.1016/S0140-6736(15)00070-7 -
Seminars in Fetal & Neonatal Medicine Oct 2020Preeclampsia is an obstetric disorder that affects 3-8% of pregnant women and remains a leading cause of short- and long-term neonatal and maternal morbidity and... (Review)
Review
Preeclampsia is an obstetric disorder that affects 3-8% of pregnant women and remains a leading cause of short- and long-term neonatal and maternal morbidity and mortality. Professional societies recommend the use of low dose aspirin to prevent preeclampsia in high-risk women. However, interest in prevention of this disease and better understanding of its pathophysiology have led to growing research on other agents. This review focuses on the main therapeutic agents evaluated or in use for preeclampsia prevention.
Topics: Aspirin; Female; Fibrinolytic Agents; Humans; Hypertension; Pre-Eclampsia; Pregnancy
PubMed: 32513597
DOI: 10.1016/j.siny.2020.101123 -
Pregnancy Hypertension Mar 2022All units managing hypertensive pregnant women should maintain and review uniform departmental management protocols and conduct regular audits of maternal & fetal...
All units managing hypertensive pregnant women should maintain and review uniform departmental management protocols and conduct regular audits of maternal & fetal outcomes. The cause(s) of pre-eclampsia and the optimal clinical management of the hypertensive disorders of pregnancy remain uncertain; therefore, we recommend that every hypertensive pregnant woman be offered an opportunity to participate in research, clinical trials and follow-up studies.
Topics: Antihypertensive Agents; Blood Pressure Determination; Exercise; Female; Humans; Postnatal Care; Pre-Eclampsia; Pregnancy; Proteinuria; Risk Factors; Societies, Medical
PubMed: 35066406
DOI: 10.1016/j.preghy.2021.09.008 -
Cardiology Clinics Feb 2021Hypertension is the most common medical disorder occurring during pregnancy and a leading cause of maternal and perinatal morbidity and mortality. Accurate blood... (Review)
Review
Hypertension is the most common medical disorder occurring during pregnancy and a leading cause of maternal and perinatal morbidity and mortality. Accurate blood pressure measurement and the diagnosis and treatment of hypertensive disorders during pregnancy and in the postpartum period are pivotal to improve outcomes. This article details hemodynamic adaptations to pregnancy and provides an approach to the prevention, diagnosis, and management of hypertensive disorders of pregnancy (HDP) and hypertensive emergencies. In addition, it reviews optimal strategies for the care of women with hypertension during the fourth trimester and beyond to minimize future cardiovascular risk.
Topics: Antihypertensive Agents; Female; Heart Disease Risk Factors; Humans; Hypertension, Pregnancy-Induced; Pre-Eclampsia; Pregnancy; Preventive Health Services; Prognosis; Risk Assessment
PubMed: 33222817
DOI: 10.1016/j.ccl.2020.09.005 -
Journal of Human Hypertension Dec 2017Placental growth factor (PlGF) is an increasingly important molecule in the prediction, diagnosis and treatment of pre-eclampsia. It has pro-angiogenic effects on the... (Review)
Review
Placental growth factor (PlGF) is an increasingly important molecule in the prediction, diagnosis and treatment of pre-eclampsia. It has pro-angiogenic effects on the feto-placental circulation and supports trophoblast growth. Mechanisms by which PlGF expression is regulated continue to be investigated. Low circulating PlGF precedes the manifestation of clinical disease in pre-eclamptic pregnancies and intrauterine growth restriction. This suggests that low PlGF is a marker of abnormal placentation, but it remains uncertain whether this is a cause or consequence. Prediction of pre-eclampsia using PlGF is promising and may assist in the targeting of resources to women at highest risk of adverse pregnancy outcomes. Promisingly, experimental animal models of pre-eclampsia have been successfully treated with supplemental PlGF. Treatment of pre-eclampsia with PlGF is a potential therapeutic option requiring further exploration. This review focuses specifically on the role of PlGF in normal and pathological placental development and in the clinical management of pre-eclampsia.
Topics: Animals; Female; Humans; Neovascularization, Physiologic; Placenta Growth Factor; Placentation; Pre-Eclampsia; Pregnancy
PubMed: 29115294
DOI: 10.1038/jhh.2017.61