-
Medical Science Monitor : International... Jul 2023Eclampsia is the most serious pregnancy complication and one of the main causes of death of pregnant and delivering women. The mortality rate of young mothers is 5-20%,... (Review)
Review
Eclampsia is the most serious pregnancy complication and one of the main causes of death of pregnant and delivering women. The mortality rate of young mothers is 5-20%, emphasizing the severity of this pregnancy-related disorder. Today many centers have only rare opportunities to see and deal with eclampsia cases; therefore, it is very important to bring this emergency medical condition to the attention of attending physicians. All patients with eclampsia, and after eclamptic seizures, should be treated in an intensive care unit. However, taking into account clinical realities, especially in developing countries, this is not always possible. It is necessary for all gynecologists-obstetricians to be fully prepared for eclampsia, although its occurrence is very rare. Drug treatment aims to stop eclampsia seizures and prevent reoccurrence of convulsions and complications. Magnesium sulphate is the drug of first choice used in treatment of eclampsia seizure, whereas treatment with the use of antihypertensive drugs and proper blood pressure control is one of the most important factors effectively reducing the risk of deaths or acute complications and poor pregnancy outcomes. The most urgent part of the treatment is the lifesaving procedure involving airways patency assessment, maintenance of breathing and blood circulation of the mother, securing an adequate oxygen level of the mother and thereby of the fetus, and prevention of injuries. This review aims to present an overview of the current prevalence, diagnosis, and management of eclampsia and the need for improved maternal care.
Topics: Pregnancy; Female; Humans; Eclampsia; Magnesium Sulfate; Pregnancy Complications; Pregnancy Outcome; Seizures; Pre-Eclampsia
PubMed: 37415326
DOI: 10.12659/MSM.939919 -
JAMA Cardiology Jul 2023A genetic contribution to preeclampsia susceptibility has been established but is still incompletely understood.
IMPORTANCE
A genetic contribution to preeclampsia susceptibility has been established but is still incompletely understood.
OBJECTIVE
To disentangle the underlying genetic architecture of preeclampsia and preeclampsia or other maternal hypertension during pregnancy with a genome-wide association study (GWAS) of hypertensive disorders of pregnancy.
DESIGN, SETTING, AND PARTICIPANTS
This GWAS included meta-analyses in maternal preeclampsia and a combination phenotype encompassing maternal preeclampsia and preeclampsia or other maternal hypertensive disorders. Two overlapping phenotype groups were selected for examination, namely, preeclampsia and preeclampsia or other maternal hypertension during pregnancy. Data from the Finnish Genetics of Pre-eclampsia Consortium (FINNPEC, 1990-2011), Finnish FinnGen project (1964-2019), Estonian Biobank (1997-2019), and the previously published InterPregGen consortium GWAS were combined. Individuals with preeclampsia or other maternal hypertension during pregnancy and control individuals were selected from the cohorts based on relevant International Classification of Diseases codes. Data were analyzed from July 2020 to February 2023.
EXPOSURES
The association of a genome-wide set of genetic variants and clinical risk factors was analyzed for the 2 phenotypes.
RESULTS
A total of 16 743 women with prior preeclampsia and 15 200 with preeclampsia or other maternal hypertension during pregnancy were obtained from FINNPEC, FinnGen, Estonian Biobank, and the InterPregGen consortium study (respective mean [SD] ages at diagnosis: 30.3 [5.5], 28.7 [5.6], 29.7 [7.0], and 28 [not available] years). The analysis found 19 genome-wide significant associations, 13 of which were novel. Seven of the novel loci harbor genes previously associated with blood pressure traits (NPPA, NPR3, PLCE1, TNS2, FURIN, RGL3, and PREX1). In line with this, the 2 study phenotypes showed genetic correlation with blood pressure traits. In addition, novel risk loci were identified in the proximity of genes involved in the development of placenta (PGR, TRPC6, ACTN4, and PZP), remodeling of uterine spiral arteries (NPPA, NPPB, NPR3, and ACTN4), kidney function (PLCE1, TNS2, ACTN4, and TRPC6), and maintenance of proteostasis in pregnancy serum (PZP).
CONCLUSIONS AND RELEVANCE
The findings indicate that genes related to blood pressure traits are associated with preeclampsia, but many of these genes have additional pleiotropic effects on cardiometabolic, endothelial, and placental function. Furthermore, several of the associated loci have no known connection with cardiovascular disease but instead harbor genes contributing to maintenance of successful pregnancy, with dysfunctions leading to preeclampsialike symptoms.
Topics: Humans; Female; Pregnancy; Pre-Eclampsia; Hypertension, Pregnancy-Induced; Genome-Wide Association Study; TRPC6 Cation Channel; Placenta; Risk Factors
PubMed: 37285119
DOI: 10.1001/jamacardio.2023.1312 -
American Journal of Obstetrics and... Nov 2023Preeclampsia, especially preterm preeclampsia and early-onset preeclampsia, is a life-threating pregnancy disorder, and the heterogeneity and complexity of preeclampsia...
BACKGROUND
Preeclampsia, especially preterm preeclampsia and early-onset preeclampsia, is a life-threating pregnancy disorder, and the heterogeneity and complexity of preeclampsia make it difficult to predict risk and to develop treatments. Plasma cell-free RNA carries unique information from human tissue and may be useful for noninvasive monitoring of maternal, placental, and fetal dynamics during pregnancy.
OBJECTIVE
This study aimed to investigate various RNA biotypes associated with preeclampsia in plasma and to develop classifiers to predict preterm preeclampsia and early-onset preeclampsia before diagnosis.
STUDY DESIGN
We performed a novel, cell-free RNA sequencing method termed polyadenylation ligation-mediated sequencing to investigate the cell-free RNA characteristics of 715 healthy pregnancies and 202 pregnancies affected by preeclampsia before symptom onset. We explored differences in the abundance of different RNA biotypes in plasma between healthy and preeclampsia samples and built preterm preeclampsia and early-onset preeclampsia prediction classifiers using machine learning methods. Furthermore, we validated the performance of the classifiers using the external and internal validation cohorts and assessed the area under the curve and positive predictive value.
RESULTS
We detected 77 genes, including messenger RNA (44%) and microRNA (26%), that were differentially expressed in healthy mothers and mothers with preterm preeclampsia before symptom onset, which could separate participants with preterm preeclampsia from healthy samples and that played critical functional roles in preeclampsia physiology. We developed 2 classifiers for predicting preterm preeclampsia and early-onset preeclampsia before diagnosis based on 13 cell-free RNA signatures and 2 clinical features (in vitro fertilization and mean arterial pressure), respectively. Notably, both classifiers showed enhanced performance when compared with the existing methods. The preterm preeclampsia prediction model achieved 81% area under the curve and 68% positive predictive value in an independent validation cohort (preterm, n=46; control, n=151); the early-onset preeclampsia prediction model had an area under the curve of 88% and a positive predictive value of 73% in an external validation cohort (early-onset preeclampsia, n=28; control, n=234). Furthermore, we demonstrated that downregulation of microRNAs may play vital roles in preeclampsia through the upregulation of preeclampsia-relevant target genes.
CONCLUSION
In this cohort study, a comprehensive transcriptomic landscape of different RNA biotypes in preeclampsia was presented and 2 advanced classifiers with substantial clinical importance for preterm preeclampsia and early-onset preeclampsia prediction before symptom onset were developed. We demonstrated that messenger RNA, microRNA, and long noncoding RNA can simultaneously serve as potential biomarkers of preeclampsia, holding the promise of prevention of preeclampsia in the future. Abnormal cell-free messenger RNA, microRNA, and long noncoding RNA molecular changes may help to elucidate the pathogenic determinants of preeclampsia and open new therapeutic windows to effectively reduce pregnancy complications and fetal morbidity.
Topics: Infant, Newborn; Pregnancy; Female; Humans; Pre-Eclampsia; Cohort Studies; Placenta; RNA, Long Noncoding; MicroRNAs; RNA, Messenger; Biomarkers
PubMed: 37211139
DOI: 10.1016/j.ajog.2023.05.015 -
Frontiers in Immunology 2023Hypertensive disorders of pregnancy (HDP) pose a significant risk to maternal and fetal well-being; however, the etiology and pathogenesis of HDP remain ambiguous. It is...
BACKGROUND
Hypertensive disorders of pregnancy (HDP) pose a significant risk to maternal and fetal well-being; however, the etiology and pathogenesis of HDP remain ambiguous. It is now widely acknowledged that inflammatory response and the immune system are closely related to HDP. Previous research has identified several inflammatory cytokines are associated with HDP. This study applied Mendelian randomization (MR) analysis to further assess causality.
METHODS
Patients with HDP who participated in the MR analysis presented with four types of HDP: pre-eclampsia or eclampsia (PE); gestational hypertension (GH); pre-existing hypertension complicating pregnancy, childbirth and the puerperium (EH); and pre-eclampsia or poor fetal growth (PF). A two-sample MR analysis was used to analyze the data in the study. The causal relationship between exposure and outcome was analyzed with inverse variance weighting (IVW), MR Egger, weighted median, weighted mode, and simple mode methods, where IVW was the primary method employed.
RESULTS
Our MR analysis demonstrated a reliable causative effect of Interleukin-9 (IL-9) and macrophage migration inhibitory factor (MIF) on reducing HDP risk, while macrophage inflammatory protein 1-beta (MIP1b), Interleukin-13 (IL-13), and Interleukin-16 (IL-16) were associated with promoting HDP risk.
CONCLUSIONS
This study demonstrated that IL-9, MIF, MIP1b, IL-13, and IL-16 may be cytokines associated with the etiology of HDP, and that a number of inflammatory cytokines are probably involved in the progression of HDP. Additionally, our study revealed that these inflammatory cytokines have causal associations with HDP and may likely be potential therapeutic targets for HDP.
Topics: Female; Pregnancy; Humans; Interleukin-9; Hypertension, Pregnancy-Induced; Interleukin-13; Pre-Eclampsia; Interleukin-16; Mendelian Randomization Analysis
PubMed: 38035087
DOI: 10.3389/fimmu.2023.1297929 -
International Journal of Molecular... May 2024This Special Issue comprises original articles in the field of clinical studies whose major topics concern the genetic and immunological aspects of miscarriage and...
This Special Issue comprises original articles in the field of clinical studies whose major topics concern the genetic and immunological aspects of miscarriage and pre-eclampsia, the isolation of decidua macrophages and Hofbauer cells in the placenta for diagnostic purposes, and epigenetic mechanisms that trigger labor [...].
Topics: Humans; Pregnancy; Female; Placenta; Abortion, Spontaneous; Reproduction; Pre-Eclampsia; Macrophages; Decidua
PubMed: 38791171
DOI: 10.3390/ijms25105132 -
International Journal of Molecular... Jul 2023Preeclampsia (PE) is a pregnancy-specific disorder affecting 4-10% of all expectant women. It greatly increases the risk of maternal and foetal death. Although the main... (Review)
Review
Preeclampsia (PE) is a pregnancy-specific disorder affecting 4-10% of all expectant women. It greatly increases the risk of maternal and foetal death. Although the main symptoms generally appear after week 20 of gestation, scientific studies indicate that the mechanism underpinning PE is initiated at the beginning of gestation. It is known that the pathomechanism of preeclampsia is strongly related to inflammation and oxidative stress, which influence placentation and provoke endothelial dysfunction in the mother. However, as of yet, no "key players" regulating all these processes have been discovered. This might be why current therapeutic strategies intended for prevention or treatment are not fully effective, and the only effective method to stop the disease is the premature induction of delivery, mostly by caesarean section. Therefore, there is a need for further research into new pharmacological strategies for the treatment and prevention of preeclampsia. This review presents new preventive methods and therapies for PE not yet recommended by obstetrical and gynaecological societies. As many of these therapies are in preclinical studies or under evaluation in clinical trials, this paper reports the molecular targets of the tested agents or methods.
Topics: Pregnancy; Female; Humans; Pre-Eclampsia; Cesarean Section; Placentation; Oxidative Stress; Vascular Endothelial Growth Factor Receptor-1
PubMed: 37569476
DOI: 10.3390/ijms241512100 -
European Heart Journal Nov 2023Observational studies show that hypertensive disorders of pregnancy (HDPs) are related to unfavourable maternal cardiovascular disease (CVD) risk profiles later in life....
OBJECTIVE
Observational studies show that hypertensive disorders of pregnancy (HDPs) are related to unfavourable maternal cardiovascular disease (CVD) risk profiles later in life. We investigated whether genetic liability to pre-eclampsia/eclampsia and gestational hypertension is associated with CVD risk factors and occurrence of CVD events.
METHODS
We obtained genetic associations with HDPs from a genome-wide association study and used individual-participant-data from the UK Biobank to obtain genetic associations with CVD risk factors and CVD events (defined as myocardial infarction or stroke). In our primary analysis, we applied Mendelian Randomisation using inverse-variance weighted regression analysis in ever pregnant women. In sensitivity analyses, we studied men and nulligravidae to investigate genetic liability to HDPs and CVD risk without the ability to experience the underlying phenotype.
RESULTS
Our primary analysis included 221,155 ever pregnant women (mean age 56.8 [SD 7.9]) with available genetic data. Odds ratios for CVD were 1.20 (1.02-1.41) and 1.24 (1.12-1.38) per unit increase in the log odds of genetic liability to pre-eclampsia/eclampsia and gestational hypertension, respectively. Furthermore, genetic liability to HDPs was associated with higher levels of systolic and diastolic blood pressure and younger age at hypertension diagnosis. Sensitivity analyses revealed no statistically significant differences when comparing the findings to those of nulligravidae and men.
CONCLUSIONS
Genetic liability to HDPs is associated with higher CVD risk, lower blood pressure levels, and earlier hypertension diagnosis. Our study suggests similar findings in ever pregnant women, nulligravidae and men, implying biological mechanisms relating to HDPs are causally related to CVD risk.
Topics: Female; Humans; Middle Aged; Pregnancy; Cardiovascular Diseases; Eclampsia; Genome-Wide Association Study; Hypertension, Pregnancy-Induced; Pre-Eclampsia; Risk Factors; Mendelian Randomization Analysis
PubMed: 38304335
DOI: 10.1093/eurheartj/ehad655.2726 -
Best Practice & Research. Clinical... Mar 2024Preeclampsia is a relatively common pregnancy complication and constitutes a major cause of morbidity and mortality for mothers and children worldwide. It... (Review)
Review
Preeclampsia is a relatively common pregnancy complication and constitutes a major cause of morbidity and mortality for mothers and children worldwide. It disproportionally affects low-resource countries. Appropriate identification of individuals at increased risk and prevention of the disease and its complications remain healthcare and research priorities, and the investigation of potential interventions to prevent preeclampsia has driven much of the obstetric research in recent decades. In this article, we review the scientific literature on the topic, highlighting established benefits and remaining questions regarding different non-pharmacological and pharmacological strategies, including exercise, the timing of birth, aspirin and calcium use, among others, as well as potential novel therapies under investigation.
Topics: Pregnancy; Female; Child; Humans; Pre-Eclampsia; Aspirin; Pregnancy Complications
PubMed: 38373378
DOI: 10.1016/j.bpobgyn.2024.102481 -
JAMA Network Open Jan 2024Lower educational attainment is associated with increased risk of adverse pregnancy outcomes, but it is unclear which pathways mediate this association.
IMPORTANCE
Lower educational attainment is associated with increased risk of adverse pregnancy outcomes, but it is unclear which pathways mediate this association.
OBJECTIVE
To investigate the association between educational attainment and pregnancy outcomes and the proportion of this association that is mediated through modifiable cardiometabolic risk factors.
DESIGN, SETTING, AND PARTICIPANTS
In this 2-sample mendelian randomization (MR) cohort study, uncorrelated (R2 < 0.01) single-nucleotide variants (formerly single-nucleotide polymorphisms) associated with the exposure (P < 5 × 10-8) and mediators and genetic associations with the pregnancy outcomes from genome-wide association studies were extracted. All participants were of European ancestry and were largely from Finland, Iceland, the United Kingdom, or the US. The inverse variance-weighted method was used in the main analysis, and the weighted median, weighted mode, and MR Egger regression were used in sensitivity analyses. In mediation analyses, the direct effect of educational attainment estimated in multivariable MR was compared with the total effect estimated in the main univariable MR analysis. Data were extracted between December 1, 2022, and April 30, 2023.
EXPOSURE
Genetically estimated educational attainment. The mediators considered were genetically estimated type 2 diabetes, body mass index, smoking, high-density lipoprotein cholesterol level, and systolic blood pressure.
MAIN OUTCOMES AND MEASURES
Ectopic pregnancy, hyperemesis gravidarum, gestational diabetes, preeclampsia, preterm birth, and offspring birth weight.
RESULTS
The analyses included 3 037 499 individuals with data on educational attainment, and those included in studies on pregnancy outcomes ranged from 141 014 for ectopic pregnancy to 270 002 with data on offspring birth weight. Each SD increase in genetically estimated educational attainment (ie, 3.4 years) was associated with an increased birth weight of 42 (95% CI, 28-56) g and an odds ratio ranging from 0.53 (95% CI, 0.46-0.60) for ectopic pregnancy to 0.81 (95% CI, 0.71-0.93) for preeclampsia. The combined proportion of the association that was mediated by the 5 cardiometabolic risk factors ranged from -17% (95% CI, -46% to 26%) for hyperemesis gravidarum to 78% (95% CI, 10%-208%) for preeclampsia. Sensitivity analyses accounting for pleiotropy were consistent with the main analyses.
CONCLUSIONS AND RELEVANCE
In this MR cohort study, intervening for type 2 diabetes, body mass index, smoking, high-density lipoprotein cholesterol level, and systolic blood pressure may lead to reductions in several adverse pregnancy outcomes associated with lower levels of education. Such public health interventions would serve to reduce health disparities attributable to social inequalities.
Topics: Female; Humans; Infant, Newborn; Pregnancy; Birth Weight; Cholesterol; Cohort Studies; Diabetes Mellitus, Type 2; Educational Status; Genome-Wide Association Study; Hyperemesis Gravidarum; Lipoproteins, HDL; Mediation Analysis; Mendelian Randomization Analysis; Pre-Eclampsia; Pregnancy, Ectopic; Premature Birth; Pregnancy Outcome
PubMed: 38206626
DOI: 10.1001/jamanetworkopen.2023.51166 -
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