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International Journal of Molecular... Feb 2024Pre-eclampsia is a serious complication of pregnancy characterized by a state of multiorgan hypertensive disorders, with or without proteinuria and possible multiorgan... (Review)
Review
Pre-eclampsia is a serious complication of pregnancy characterized by a state of multiorgan hypertensive disorders, with or without proteinuria and possible multiorgan dysfunction. Chronic kidney disease is an established risk factor for the development of pre-eclampsia, as angiogenic homeostasis is altered and the maternal circulation is already hypertensive. Facing pre-eclampsia in the context of chronic kidney disease is a challenging emergency for both the mother and the fetus. The clinical features and the management of this multi-organ disorder are clearly defined in the modern literature but the underlying pathophysiologic mechanisms remain not fully elucidated. Understanding the pathophysiology that mediates the onset of pre-eclampsia itself and in synergy with chronic kidney disease is fundamental for developing prompt prevention strategies, treatment planning, and patient counseling. This review aims to summarize the main molecular mechanisms involved in the process of pre-eclampsia, with a particular focus on the role of the kidneys and hormonal pathways related to renal function in normal pregnancy and pre-eclamptic syndromes.
Topics: Pregnancy; Female; Humans; Placenta; Pre-Eclampsia; Kidney; Hypertension; Renal Insufficiency, Chronic
PubMed: 38473987
DOI: 10.3390/ijms25052741 -
Hipertension Y Riesgo Vascular 2024Hypertensive disorders in pregnancy (HDP) remain a leading cause of pregnancy-related maternal and foetal morbidity and mortality worldwide, including chronic... (Review)
Review
Hypertensive disorders in pregnancy (HDP) remain a leading cause of pregnancy-related maternal and foetal morbidity and mortality worldwide, including chronic hypertension, gestational hypertension, and pre-eclampsia. Affected women and newborns also have an increased risk of cardiovascular disease later in life, independent of traditional cardiovascular disease risks. Despite these risks, recommendations for optimal diagnosis and treatment have changed little in recent decades, probably due to fear of the foetal repercussions of decreased blood pressure and possible drug toxicity. In this document we review the diagnostic criteria and classification of (HDP), as well as important aspects regarding pathophysiology and early detection that allows early identification of women at risk, with the aim of preventing both immediate and long-term consequences. Prophylactic treatment with aspirin is also reviewed early and a therapeutic approach is carried out that involves close maternal and foetal monitoring, and if necessary, the use of safe drugs in each situation. This review aims to provide an updated vision for the prevention, diagnosis, and treatment of HDP that is useful in our usual clinical practice.
Topics: Pregnancy; Infant, Newborn; Female; Humans; Cardiovascular Diseases; Hypertension, Pregnancy-Induced; Pre-Eclampsia; Risk Assessment
PubMed: 38508878
DOI: 10.1016/j.hipert.2023.11.006 -
Indian Journal of Gastroenterology :... Apr 2024Liver function abnormalities are noted in a minority of pregnancies with multiple causes for the same. A small proportion of these develop severe liver injury and... (Review)
Review
Liver function abnormalities are noted in a minority of pregnancies with multiple causes for the same. A small proportion of these develop severe liver injury and progress to acute liver failure (ALF). There is a discrete set of etiology for ALF in pregnancy and comprehensive understanding will help in urgent evaluation. Certain diseases such as acute fatty liver of pregnancy, hemolysis, elevated liver enzyme, low platelet (HELLP) syndrome and pre-eclampsia are secondary to pregnant state and can present as ALF. Quick and targeted evaluation with urgent institution of etiology-specific management, especially urgent delivery in patients with pregnancy-associated liver diseases, is the key to avoiding maternal deaths. Pregnancy, as also the fetal life, imparts a further layer of complication in assessment, prognosis and management of these sick patients with ALF. Optimal management often requires a multidisciplinary approach in a well-equipped centre. In this review, we discuss evaluation, assessment and management of pregnant patients with ALF, focussing on approach to pregnancy-associated liver diseases.
Topics: Humans; Pregnancy; Female; Liver Failure, Acute; Pregnancy Complications; HELLP Syndrome; Fatty Liver; Prognosis; Pre-Eclampsia
PubMed: 38691240
DOI: 10.1007/s12664-024-01571-9 -
Science Advances Nov 2023Early-onset preeclampsia (EOPE) is a severe pregnancy complication associated with defective trophoblast differentiation and functions at implantation, but manifestation...
Early-onset preeclampsia (EOPE) is a severe pregnancy complication associated with defective trophoblast differentiation and functions at implantation, but manifestation of its phenotypes is in late pregnancy. There is no reliable method for early prediction and treatment of EOPE. Adrenomedullin (ADM) is an abundant placental peptide in early pregnancy. Integrated single-cell sequencing and spatial transcriptomics confirm a high ADM expression in the human villous cytotrophoblast and syncytiotrophoblast. The levels of ADM in chorionic villi and serum were lower in first-trimester pregnant women who later developed EOPE than those with normotensive pregnancy. ADM stimulates differentiation of trophoblast stem cells and trophoblast organoids in vitro. In pregnant mice, placenta-specific ADM suppression led to EOPE-like phenotypes. The EOPE-like phenotypes in a mouse PE model were reduced by a placenta-specific nanoparticle-based forced expression of ADM. Our study reveals the roles of trophoblastic ADM in placental development, EOPE pathogenesis, and its potential clinical uses.
Topics: Pregnancy; Female; Mice; Humans; Animals; Pre-Eclampsia; Trophoblasts; Adrenomedullin; Placenta; Cell Differentiation
PubMed: 37922358
DOI: 10.1126/sciadv.adi4777 -
BJOG : An International Journal of... Nov 2023Although historically pre-eclampsia, preterm birth, abruption, fetal growth restriction and stillbirth have been viewed as clinically distinct entities, a growing body... (Review)
Review
Although historically pre-eclampsia, preterm birth, abruption, fetal growth restriction and stillbirth have been viewed as clinically distinct entities, a growing body of literature has demonstrated that the placenta and its development is the root cause of many cases of these conditions. This has led to the term 'the great obstetrical syndromes' being coined to reflect this common origin. Although these conditions mostly manifest in the second half of pregnancy, a failure to complete deep placentation (the transition from histiotrophic placentation to haemochorial placenta at 10-18 weeks of gestation via a second wave of extravillous trophoblast invasion), is understood to be key to the pathogenesis of the great obstetrical syndromes. While the reasons that the placenta fails to achieve deep placentation remain active areas of investigation, maternal inflammation and thrombosis have been clearly implicated. From a clinical standpoint these mechanisms provide a biological explanation of how low-dose aspirin, which affects the COX-1 receptor (thrombosis) and the COX-2 receptor (inflammation), prevents not just pre-eclampsia but all the components of the great obstetrical syndromes if initiated early in pregnancy. The optimal dose of low-dose aspirin that is maximally effective in pregnancy remains a question open for further research. Additionally, other candidate medications have been identified that may also prevent pre-eclampsia, and further study of them may offer therapeutic options beyond low-dose aspirin. Interestingly, three of the eight identified compounds (hydroxychloroquine, metformin and pravastatin) are known to decrease inflammation.
Topics: Pregnancy; Female; Infant, Newborn; Humans; Pre-Eclampsia; Premature Birth; Placenta; Aspirin; Inflammation; Thrombosis
PubMed: 37530495
DOI: 10.1111/1471-0528.17613 -
Tissue & Cell Jun 2024GATA3 plays critical roles in the development and function of various tissues and organs throughout the body. Likewise, TGF-β signaling is critical for placental...
GATA3 plays critical roles in the development and function of various tissues and organs throughout the body. Likewise, TGF-β signaling is critical for placental development and can interact with GATA3. We aimed to investigate the involvement of the multifunctional cytokine and transcription factor in trophoblast development. By using immunohistochemistry, we evaluated the localization and expression level of GATA3 and TGF-β in placentas at term of normal pregnancy and with pre-eclampsia. Up-regulation of both GATA3 and TGF-β was observed in pathological placentas, with localization in the villus epithelium (syncytiotrophoblast) stroma and decidua. Our data show altered expression of TGF-β and GATA3, which downstream could lead to a cascade of events that negatively influence trophoblast development and contribute to the pathogenesis of pre-eclampsia.
Topics: Pre-Eclampsia; Humans; Pregnancy; Female; GATA3 Transcription Factor; Placenta; Transforming Growth Factor beta; Adult; Trophoblasts
PubMed: 38759523
DOI: 10.1016/j.tice.2024.102402 -
BJOG : An International Journal of... Nov 2023To develop a model for predicting postpartum readmission for hypertension and pre-eclampsia at delivery discharge and assess external validation or model...
OBJECTIVE
To develop a model for predicting postpartum readmission for hypertension and pre-eclampsia at delivery discharge and assess external validation or model transportability across clinical sites.
DESIGN
Prediction model using data available in the electronic health record from two clinical sites.
SETTING
Two tertiary care health systems from the Southern (2014-2015) and Northeastern USA (2017-2019).
POPULATION
A total of 28 201 postpartum individuals: 10 100 in the South and 18 101 in the Northeast.
METHODS
An internal-external cross validation (IECV) approach was used to assess external validation or model transportability across the two sites. In IECV, data from each health system were first used to develop and internally validate a prediction model; each model was then externally validated using the other health system. Models were fit using penalised logistic regression, and accuracy was estimated using discrimination (concordance index), calibration curves and decision curves. Internal validation was performed using bootstrapping with bias-corrected performance measures. Decision curve analysis was used to display potential cut points where the model provided net benefit for clinical decision-making.
MAIN OUTCOME MEASURES
The outcome was postpartum readmission for either hypertension or pre-eclampsia <6 weeks after delivery.
RESULTS
The postpartum readmission rate for hypertension and pre-eclampsia overall was 0.9% (0.3% and 1.2% by site, respectively). The final model included six variables: age, parity, maximum postpartum diastolic blood pressure, birthweight, pre-eclampsia before discharge and delivery mode (and interaction between pre-eclampsia × delivery mode). Discrimination was adequate at both health systems on internal validation (c-statistic South: 0.88; 95% confidence interval [CI] 0.87-0.89; Northeast: 0.74; 95% CI 0.74-0.74). In IECV, discrimination was inconsistent across sites, with improved discrimination for the Northeastern model on the Southern cohort (c-statistic 0.61 and 0.86, respectively), but calibration was not adequate. Next, model updating was performed using the combined dataset to develop a new model. This final model had adequate discrimination (c-statistic: 0.80, 95% CI 0.80-0.80), moderate calibration (intercept -0.153, slope 0.960, E 0.042) and provided superior net benefit at clinical decision-making thresholds between 1% and 7% for interventions preventing readmission. An online calculator is provided here.
CONCLUSIONS
Postpartum readmission for hypertension and pre-eclampsia may be accurately predicted but further model validation is needed. Model updating using data from multiple sites will be needed before use across clinical settings.
Topics: Pregnancy; Female; Humans; Pre-Eclampsia; Patient Readmission; Logistic Models; Hypertension; Postpartum Period
PubMed: 37317035
DOI: 10.1111/1471-0528.17572 -
Obstetrics and Gynecology Apr 2024Preeclampsia contributes disproportionately to maternal and neonatal morbidity and mortality throughout the world. A critical driver of preeclampsia is angiogenic... (Review)
Review
Preeclampsia contributes disproportionately to maternal and neonatal morbidity and mortality throughout the world. A critical driver of preeclampsia is angiogenic imbalance, which is often present weeks to months before overt disease. Two placenta-derived angiogenic biomarkers, soluble fms-like tyrosine kinase 1 (sFlt-1) and placental growth factor (PlGF), have proved useful as diagnostic and prognostic tests for preeclampsia. Recently, the U.S. Food and Drug Administration approved the sFlt-1/PlGF assay to aid in the prediction of preeclampsia with severe features among women with hypertensive disorders of pregnancy at 24-34 weeks of gestation. In this narrative review, we summarize the body of work leading to this approval and describe how the sFlt-1/PlGF ratio may be implemented in clinical practice as an adjunctive measure to help optimize care and to reduce adverse outcomes in preeclampsia.
Topics: Pregnancy; Infant, Newborn; Female; Humans; Pre-Eclampsia; Placenta Growth Factor; Vascular Endothelial Growth Factor Receptor-1; Hypertension; Biomarkers
PubMed: 38350106
DOI: 10.1097/AOG.0000000000005532 -
The Cochrane Database of Systematic... Oct 2023Magnesium sulphate is the drug of choice for the prevention and treatment of women with eclampsia. Regimens for administration of this drug have evolved over the years,... (Review)
Review
BACKGROUND
Magnesium sulphate is the drug of choice for the prevention and treatment of women with eclampsia. Regimens for administration of this drug have evolved over the years, but there is no clarity on the comparative benefits or harm of alternative regimens. This is an update of a review first published in 2010.
OBJECTIVES
To assess if one magnesium sulphate regimen is better than another when used for the care of women with pre-eclampsia or eclampsia, or both, to reduce the risk of severe morbidity and mortality for the woman and her baby.
SEARCH METHODS
We searched Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform (29 April 2022), and reference lists of retrieved studies.
SELECTION CRITERIA
We included randomised trials and cluster-randomised trials comparing different regimens for administration of magnesium sulphate used in women with pre-eclampsia or eclampsia, or both. Comparisons included different dose regimens, intramuscular versus intravenous route for maintenance therapy, and different durations of therapy. We excluded studies with quasi-random or cross-over designs. We included abstracts of conference proceedings if compliant with the trustworthiness assessment.
DATA COLLECTION AND ANALYSIS
For this update, two review authors assessed trials for inclusion, performed risk of bias assessment, and extracted data. We checked data for accuracy. We assessed the certainty of the evidence using the GRADE approach.
MAIN RESULTS
For this update, a total of 16 trials (3020 women) met our inclusion criteria: four trials (409 women) compared regimens for women with eclampsia, and 12 trials (2611 women) compared regimens for women with pre-eclampsia. Most of the included trials had small sample sizes and were conducted in low- and middle-income countries. Eleven trials reported adequate randomisation and allocation concealment. Blinding of participants and clinicians was not possible in most trials. The included studies were for the most part at low risk of attrition and reporting bias. Treatment of women with eclampsia (four comparisons) One trial compared a loading dose-alone regimen with a loading dose plus maintenance dose regimen (80 women). It is uncertain whether either regimen has an effect on the risk of recurrence of convulsions or maternal death (very low-certainty evidence). One trial compared a lower-dose regimen with standard-dose regimen over 24 hours (72 women). It is uncertain whether either regimen has an effect on the risk of recurrence of convulsion, severe morbidity, perinatal death, or maternal death (very low-certainty evidence). One trial (137 women) compared intravenous (IV) versus standard intramuscular (IM) maintenance regimen. It is uncertain whether either route has an effect on recurrence of convulsions, death of the baby before discharge (stillbirth and neonatal death), or maternal death (very low-certainty evidence). One trial (120 women) compared a short maintenance regimen with a standard (24 hours after birth) maintenance regimen. It is uncertain whether the duration of the maintenance regimen has an effect on recurrence of convulsions, severe morbidity, or side effects such as nausea and respiratory failure. A short maintenance regimen may reduce the risk of flushing when compared to a standard 24 hours maintenance regimen (risk ratio (RR) 0.27, 95% confidence interval (CI) 0.08 to 0.93; 1 trial, 120 women; low-certainty evidence). Many of our prespecified critical outcomes were not reported in the included trials. Prevention of eclampsia for women with pre-eclampsia (five comparisons) Two trials (462 women) compared loading dose alone with loading dose plus maintenance therapy. Low-certainty evidence suggests an uncertain effect with either regimen on the risk of eclampsia (RR 2.00, 95% CI 0.61 to 6.54; 2 trials, 462 women) or perinatal death (RR 0.50, 95% CI 0.19 to 1.36; 2 trials, 462 women). One small trial (17 women) compared an IV versus IM maintenance regimen for 24 hours. It is uncertain whether IV or IM maintenance regimen has an effect on eclampsia or stillbirth (very low-certainty evidence). Four trials (1713 women) compared short postpartum maintenance regimens with continuing for 24 hours after birth. Low-certainty evidence suggests there may be a wide range of benefit or harm between groups regarding eclampsia (RR 1.99, 95% CI 0.18 to 21.87; 4 trials, 1713 women). Low-certainty evidence suggests there may be little or no effect on severe morbidity (RR 0.96, 95% CI 0.71 to 1.29; 2 trials, 1233 women) or side effects such as respiratory depression (RR 0.80, 95% CI 0.25 to 2.61; 2 trials, 1424 women). Three trials (185 women) compared a higher-dose maintenance regimen versus a lower-dose maintenance regimen. It is uncertain whether either regimen has an effect on eclampsia (very low-certainty evidence). Low-certainty evidence suggests that a higher-dose maintenance regimen has little or no effect on side effects when compared to a lower-dose regimen (RR 0.79, 95% CI 0.61 to 1.01; 1 trial 62 women). One trial (200 women) compared a maintenance regimen by continuous infusion versus a serial IV bolus regimen. It is uncertain whether the duration of the maintenance regimen has an effect on eclampsia, side effects, perinatal death, maternal death, or other neonatal morbidity (very low-certainty evidence). Many of our prespecified critical outcomes were not reported in the included trials.
AUTHORS' CONCLUSIONS
Despite the number of trials evaluating various magnesium sulphate regimens for eclampsia prophylaxis and treatment, there is still no compelling evidence that one particular regimen is more effective than another. Well-designed randomised controlled trials are needed to answer this question.
Topics: Humans; Pregnancy; Infant, Newborn; Female; Pre-Eclampsia; Magnesium Sulfate; Eclampsia; Perinatal Death; Stillbirth; Maternal Death; Seizures
PubMed: 37815037
DOI: 10.1002/14651858.CD007388.pub3 -
Frontiers in Immunology 2024
Topics: Humans; Pre-Eclampsia; Pregnancy; Female; Inflammation; Fetal Development; Animals; Neurodevelopmental Disorders
PubMed: 38868765
DOI: 10.3389/fimmu.2024.1434260