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Acta Obstetricia Et Gynecologica... May 2023There has been increasing recognition of the association between various pregnancy complications and development of chronic disease in later life. Pregnancy has come to... (Review)
Review
There has been increasing recognition of the association between various pregnancy complications and development of chronic disease in later life. Pregnancy has come to be regarded as a physiological stress test, as the strain it places on a woman's body may reveal underlying predispositions to disease that would otherwise remain hidden for many years. Despite the increasing body of data, there is a lack of awareness among healthcare providers surrounding these risks. We performed a narrative literature review and have summarized the associations between the common pregnancy complications including gestational hypertension, pre-eclampsia, gestational diabetes, placental abruption, spontaneous preterm birth, stillbirth and miscarriage and subsequent development of chronic disease. Hypertensive disorders of pregnancy, spontaneous preterm birth, gestational diabetes, pregnancy loss and placental abruption are all associated with increased risk of various forms of cardiovascular disease. Gestational diabetes, pre-eclampsia, early miscarriage and recurrent miscarriage are associated with increased risk of diabetes mellitus. Pre-eclampsia, stillbirth and recurrent miscarriage are associated with increased risk of venous thromboembolism. Pre-eclampsia, gestational diabetes and stillbirth are associated with increased risk of chronic kidney disease. Gestational diabetes is associated with postnatal depression, and also with increased risk of thyroid and stomach cancers. Stillbirth, miscarriage and recurrent miscarriage are associated with increased risk of mental health disorders including depression, anxiety and post-traumatic stress disorders. Counseling in the postnatal period following a complicated pregnancy, and advice regarding risk reduction should be available for all women. Further studies are required to establish optimal screening intervals for cardiovascular disease and diabetes following complicated pregnancy.
Topics: Pregnancy; Female; Infant, Newborn; Humans; Pre-Eclampsia; Stillbirth; Abruptio Placentae; Diabetes, Gestational; Premature Birth; Cardiovascular Diseases; Placenta; Pregnancy Complications; Women's Health; Abortion, Habitual; Risk Factors
PubMed: 36799269
DOI: 10.1111/aogs.14523 -
Journal of Clinical Lipidology 2022Hypertensive disorders of pregnancy are among the leading causes of maternal morbidity and mortality in the US. Preeclampsia (PreE) which includes hypertension and... (Review)
Review
Hypertensive disorders of pregnancy are among the leading causes of maternal morbidity and mortality in the US. Preeclampsia (PreE) which includes hypertension and proteinuria during pregnancy, is thought to result from placental ischemia. Risk factors for PreE parallel those for cardiovascular disease, and recent studies point to hyperlipidemia specifically, hypertriglyceridemia, as a risk factor for PreE. Current practice does not routinely include lipid testing pre-conception or during pregnancy. Professional, societal recommendations should advocate for hyperlipidemia screening, followed by appropriate management, pre-conception and during pregnancy.
Topics: Female; Humans; Hyperlipidemias; Hypertension; Placenta; Pre-Eclampsia; Pregnancy; Proteinuria; Risk Factors
PubMed: 35260347
DOI: 10.1016/j.jacl.2022.02.005 -
American Journal of Physiology. Renal... Jun 2020Preeclampsia is defined as new-onset hypertension after the 20th wk of gestation along with evidence of maternal organ failure. Rates of preeclampsia have steadily... (Review)
Review
Preeclampsia is defined as new-onset hypertension after the 20th wk of gestation along with evidence of maternal organ failure. Rates of preeclampsia have steadily increased over the past 30 yr, affecting ∼4% of pregnancies in the United States and causing a high economic burden (22, 69). The pathogenesis is multifactorial, with acknowledged contributions by placental, vascular, renal, and immunological dysfunction. Treatment is limited, commonly using symptomatic management and/or early delivery of the fetus (6). Along with significant peripartum morbidity and mortality, current research continues to demonstrate that the consequences of preeclampsia extend far beyond preterm delivery. It has lasting effects for both mother and child, resulting in increased susceptibility to hypertension and chronic kidney disease (45, 54, 115, 116), yielding lifelong risk to both individuals. This review discusses recent guideline updates and recommendations along with current research on these long-term consequences of preeclampsia.
Topics: Animals; Blood Pressure; Disease Models, Animal; Female; Humans; Hypertension; Maternal Health; Pre-Eclampsia; Pregnancy; Prenatal Exposure Delayed Effects; Prognosis; Renal Insufficiency, Chronic; Risk Assessment; Risk Factors; Time Factors
PubMed: 32249616
DOI: 10.1152/ajprenal.00071.2020 -
Hypertension (Dallas, Tex. : 1979) May 2021The concept that preeclampsia is a multisystemic syndrome is appreciated in both research and clinical care. Our understanding of pathophysiology recognizes the role of... (Review)
Review
The concept that preeclampsia is a multisystemic syndrome is appreciated in both research and clinical care. Our understanding of pathophysiology recognizes the role of inflammation, oxidative and endoplasm reticulum stress, and angiogenic dysfunction. Yet, we have not progressed greatly toward clinically useful prediction nor had substantial success in prevention or treatment. One possibility is that the maternal syndrome may be reached through different pathophysiological pathways, that is, subtypes of preeclampsia, that in their specificity yield more clinical utility. For example, early and late onset preeclampsia are increasingly acknowledged as different pathophysiological processes leading to a common presentation. Other subtypes of preeclampsia are supported by disparate clinical outcomes, long-range prognosis, organ systems involved, and risk factors. These insights have been supplemented by discovery-driven methods, which cluster preeclampsia cases into groups indicating different pathophysiologies. In this presentation, we review likely subtypes based on current knowledge and suggest others. We present a consideration of the requirements for a clinically meaningful preeclampsia subtype. A useful subtype should (1) identify a specific pathophysiological pathway or (2) specifically indicate maternal or fetal outcome, (3) be recognizable in a clinically useful time frame, and (4) these results should be reproducible and generalizable (but at varying frequency) including in low resource settings. We recommend that the default consideration be that preeclampsia includes several subtypes rather than trying to force all cases into a single pathophysiological pathway. The recognition of subtypes and deciphering their different pathophysiologies will provide specific targets for prevention, prediction, and treatment directing personalized care.
Topics: Female; Humans; Inflammation; Pre-Eclampsia; Pregnancy; Prognosis; Risk Factors
PubMed: 33775113
DOI: 10.1161/HYPERTENSIONAHA.120.14781 -
Clinical Journal of the American... Jun 2016Preeclampsia is becoming an increasingly common diagnosis in the developed world and remains a high cause of maternal and fetal morbidity and mortality in the developing... (Review)
Review
Preeclampsia is becoming an increasingly common diagnosis in the developed world and remains a high cause of maternal and fetal morbidity and mortality in the developing world. Delay in childbearing in the developed world feeds into the risk factors associated with preeclampsia, which include older maternal age, obesity, and/or vascular diseases. Inadequate prenatal care partially explains the persistent high prevalence in the developing world. In this review, we begin by presenting the most recent concepts in the pathogenesis of preeclampsia. Upstream triggers of the well described angiogenic pathways, such as the heme oxygenase and hydrogen sulfide pathways, as well as the roles of autoantibodies, misfolded proteins, nitric oxide, and oxidative stress will be described. We also detail updated definitions, classification schema, and treatment targets of hypertensive disorders of pregnancy put forth by obstetric and hypertensive societies throughout the world. The shift has been made to view preeclampsia as a systemic disease with widespread endothelial damage and the potential to affect future cardiovascular diseases rather than a self-limited occurrence. At the very least, we now know that preeclampsia does not end with delivery of the placenta. We conclude by summarizing the latest strategies for prevention and treatment of preeclampsia. A better understanding of this entity will help in the care of at-risk women before delivery and for decades after.
Topics: Autoantibodies; Endoglin; Female; Heme Oxygenase (Decyclizing); Humans; Hydrogen Sulfide; Nitric Oxide; Oxidative Stress; Postnatal Care; Practice Guidelines as Topic; Pre-Eclampsia; Preconception Care; Pregnancy; Protein Folding; Receptor, Angiotensin, Type 1; Vascular Endothelial Growth Factor Receptor-1
PubMed: 27094609
DOI: 10.2215/CJN.12081115 -
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 -
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 -
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