Early-onset Preeclampsia Research Articles

The role and research progress of gut microbiota in placenta-derived diseases

Gut microbiota plays an important role in maintaining the normal function of intestinal tract, regulating the body's immunity, metabolism and other physiological processes. In recent years, the theory that gut microbiota dysbiosis affects the disease occurrence of various organ systems through the gut-organ axis has been gradually confirmed. Placental diseases of pregnancy includes early onset preeclampsia, fetal growth restriction, etc., the pathogenesis of which is unclear, but can cause adverse pregnancy outcomes. Researches show that gut microbiota dysbiosis has a certain correlation with the occurrence of placental diseases, and its mechanism may affect the occurrence of placental diseases by regulating systemic and local placental metabolism, inflammatory response and immune response. This article reviews the research progress on the effects of maternal gut microbiota dysbiosis on the occurrence of placenta-derived diseases, and provides clues for exploring the application of gut microecology to the prevention and treatment of placenta-derived diseases.

Methylation aberrations in partner spermatozoa and impaired expression of imprinted genes in the placentae of early-onset preeclampsia

IntroductionDisturbed paternal epigenetic status of imprinted genes has been observed in infertility and recurrent spontaneous abortions. Shallow placentation has been associated with early-onset preeclampsia. Hence, the present study aimed to investigate the methylation patterns of imprinted genes involved in placental development, in the spermatozoa of partners of women experiencing preeclampsia. MethodsThe study involved recruitment of couples into preeclampsia (n = 14) and control (n = 25) groups. Methylation analysis of imprinted gene differentially methylated regions (DMRs) and LINE1 repetitive element was carried out by pyrosequencing in the spermatozoa and placental villi. Global 5mC levels in the spermatozoa were measured through ELISA. Expression of imprinted genes was quantified in the placental villi by real time qPCR. Association of birth weight with DNA methylation and gene expression was assessed. ResultsKvDMR, PEG3 DMR, PEG10 DMR and DLK1-GTL2 IG-DMR were differentially methylated in the spermatozoa and placental villi of preeclampsia group. Global 5mC content and LINE1 methylation levels did not differ between the spermatozoa of the two groups. Increased transcript levels of PEG3, IGF2, DLK1, PHLDA2 and CDKN1C were observed in the preeclamptic placental villi. Birth weight showed significant association with KvDMR, PEG10 DMR, DLK1-GTL2 IG-DMR and LINE1 methylation levels in the spermatozoa. DLK1 expression levels showed a negative association with birth weight. DiscussionThe study highlighted the paternal contribution to early-onset preeclampsia, in the form of disrupted sperm DNA methylation patterns at imprinted gene loci. These loci, after further evaluation in future studies, could serve as sperm-based preeclampsia predictive markers, for couples planning pregnancy.

Prediction of perinatal mortality in early-onset fetal growth restriction: A post hoc analysis of the Dutch STRIDER trial to predict perinatal mortality in early-onset fetal growth restriction

ObjectiveEarly-onset fetal growth restriction affects about 0.3% of pregnancies, posing high perinatal risks due to placental insufficiency. Early-onset fetal growth restriction often coincides with early-onset pre-eclampsia, associated with significant mortality and morbidity. Clinical management varies among clinicians, with emphasis on intensive monitoring and timely delivery. Our objective was to improve clinical prediction of perinatal mortality in early-onset fetal growth restriction for parental counseling. Study designThis was a secondary analysis of prospective cohort data from the Dutch STRIDER trial. The study included 215 pregnant women diagnosed with severe early-onset fetal growth restriction between 20 + 0 and 29 + 6 weeks of gestation, from tertiary and secondary antenatal care centers in The Netherlands. Maternal and fetal characteristics were collected at inclusion, including sonographic and laboratory measurements. Analysis was performed using univariable and multivariable binary logistic regression to create a prediction model for perinatal mortality. The main outcome measures were fetal demise and neonatal mortality up to discharge. Results215 Participants were included for this analysis. Perinatal mortality occurred in 84 (39 %) cases; 51 (24 %) were fetal and 33 (15 %) neonatal. Fetal abdominal circumference, gestational age at diagnosis, estimated fetal weight Multiple of Median, absent or reversed end-diastolic flow of the umbilical artery, umbilical artery pulsatility index Multiple of Median, non-Caucasian ethnicity, male sex, placental growth factor level and uterine artery pulsatility index were independent predictors of perinatal mortality. Randomization allocation (sildenafil or placebo) had no predictive value for mortality. The prediction model including gestational age at diagnosis, estimated fetal weight Multiple of Median and umbilical artery pulsatility index Multiple of Median showed an area under the receiver operating characteristic curve of 0.840 (P < 0.01). Placental growth factor was measured in a subset of patients and was an independent prognostic factor and performed significantly better within the predictive model, however it did not improve the predictive value of the model. ConclusionsPrediction of perinatal mortality in early-onset fetal growth restriction is feasible with commonly available tests and measurements and could support decision making in management of pregnancy. However, implementation in practice requires further studies.

Induction of FAM46C expression mediated by DNMT3A downregulation is involved in early-onset preeclampsia through gene body methylation

BackgroundAberrant methylation of genomic DNA has been found in preeclamptic placentas, which is characterized by elevated DNA methylation and hypermethylation of gene body regions, but the underlying mechanism is not yet fully understood. MethodsGlobal DNA methylation was assessed through ELISA and HPLC. The methylation sites were detected using the Illumina Human Methylation 450 K Microarray. The methylation level of FAM46C promoter and gene body was detected through the bisulfite sequencing. RNA-seq was utilized to investigate the mechanism by which DNMT3A and FAM46C mediate the migration and invasion of trophoblast cells. ResultsWe discovered that DNMT3A knockdown led to elevated levels of gene body methylation and FAM46C transcription. FAM46C downregulation completely rescued the suppressive effects caused by DNMT3A knockdown on the migration and invasion of trophoblast cells. Mechanistically, DNMT3A reduction led to an increase in the enrichment of DNMT3B and DNMT1 in the gene body region of FAM46C. The results of transcriptome sequencing showed that DNMT3A and FAM46C regulate the adhesion of trophoblast cells. Elevated expression of FAM46C and increased methylation levels within its gene body region were observed in extravillous trophoblast cells of early-onset preeclamptic placentas. ConclusionsDNMT3A-mediated aberrant FAM46C gene body methylation is relevant to the development of early-onset preeclampsia.

Simulated ischaemia/reperfusion impairs trophoblast function through divergent oxidative stress- and MMP-9-dependent mechanisms.

Early-onset pre-eclampsia is believed to arise from defective placentation in the 1st trimester, leading to placental ischaemia/reperfusion (I/R) and oxidative stress. However, our current understanding of the effects of I/R and oxidative stress on trophoblast function is ambiguous in part due to studies exposing trophoblasts to hypoxia instead of I/R, and which report conflicting results. Here we present a model of simulated ischaemia/reperfusion (SI/R) to recapitulate the pathophysiological events of early-onset PE, by exposing 1st trimester cytotrophoblast HTR-8/SVneo cells to a simulated ischaemia buffer followed by reperfusion. We examined different ischaemia and reperfusion times and observed that 1h ischaemia and 24h reperfusion induced an increase in reactive oxygen species (ROS) production (p < 0.0001) and oxygen consumption rate (p < 0.01). SI/R-exposed trophoblast cells exhibited deficits in migration, proliferation and invasion (p < 0.01). While the deficits in migration and proliferation were rescued by antioxidants, suggesting a ROS-dependent mechanism, the loss of invasion was not affected by antioxidants, which suggests a divergent ROS-independent pathway. In line with this, we observed a decrease in MMP-9, the key regulatory enzyme necessary for trophoblast invasion (p < 0.01), which was similarly unaffected by antioxidants, and pharmacological inhibition of MMP-9 replicated the phenotype of deficient invasion (p < 0.01). Collectively, these data demonstrate that I/R impairs trophoblast migration and proliferation via a ROS-dependent mechanism, and invasion via a ROS-independent loss of MMP-9, disambiguating the role of oxidative stress and providing insights into the response of trophoblasts to I/R in the context of early-onset PE.

Senescent Syncytiotrophoblast Secretion During Early Onset Preeclampsia.

Preeclampsia is a severe hypertensive disorder in pregnancy that causes preterm delivery, maternal and fetal morbidity, mortality, and life-long sequelae. Understanding the pathogenesis of preeclampsia is a critical first step toward protecting mother and child from this syndrome and increased risk of cardiovascular disease later in life. However, effective early predictive tests and therapies for preeclampsia are scarce. To identify novel markers and signaling pathways for early onset preeclampsia, we profiled human maternal-fetal interface units (fetal villi and maternal decidua) from early onset preeclampsia and healthy controls using single-nucleus RNA sequencing combined with spatial transcriptomics. The placental syncytiotrophoblast is in direct contact with maternal blood and forms the barrier between fetal and maternal circulation. We identified different transcriptomic states of the endocrine syncytiotrophoblast nuclei with patterns of dysregulation associated with a senescence-associated secretory phenotype and a spatial dysregulation of senescence in the placental trophoblast layer. Elevated senescence markers were validated in placental tissues of clinical multicenter cohorts. Importantly, several secreted senescence-associated secretory phenotype factors were elevated in maternal blood already in the first trimester. We verified the secreted senescence markers, PAI-1 (plasminogen activator inhibitor 1) and activin A, as identified in our single-nucleus RNA sequencing model as predictive markers before clinical preeclampsia diagnosis. This indicates that increased syncytiotrophoblast senescence appears weeks before clinical manifestation of early onset preeclampsia, suggesting that the dysregulated preeclamptic placenta starts with higher cell maturation resulting in premature and increased senescence-associated secretory phenotype release. These senescence-associated secretory phenotype markers may serve as an additional early diagnostic tool for this syndrome.

Analysis of risk factors for postpartum depression after cesarean section in women with early-onset preeclampsia.

Early-onset preeclampsia significantly increases maternal and fetal morbidity and mortality. Many pregnant women with early onset preeclampsia choose cesarean section as their delivery method. Although extensive research has explored the association between postpartum depression (PPD) and cesarean section, few studies have investigated the risk factors after cesarean section in women with early-onset preeclampsia. To examine these risk factors through a retrospective, observational analysis of 287 women who underwent a cesarean section for early preeclampsia between June 2014 and March 2024. Participants were assessed in person during the 32nd week of pregnancy, 2 days post-cesarean, and 6 weeks postpartum. According to the Edinburgh Postnatal Depression Scale (EPDS), participants who underwent cesarean section were divided into PPD (n = 60) and non-PPD groups (n = 227). Furthermore, PPD was diagnosed at 6 weeks postpartum according to depressive symptoms (EPDS score ≥ 11). The demographic and clinical features of PPD were screened. Multivariate logistic regression analysis was used to identify PPD risk factors. The prevalence of PPD was 20.9% (60/287) among the 287 women who underwent cesarean section for early-onset preeclampsia. Multivariate logistic regression analyses revealed that advanced age (age > 40 years) [odds ratio (OR) = 1.93, 95%CI: 1.31-2.82], previous preeclampsia (OR = 7.15, 95%CI: 5.81-8.85), pre-pregnancy obesity (OR = 2.42, 95%CI: 1.62-3.63), gestational diabetes mellitus (OR = 3.52, 95%CI: 2.51-4.92), preexisting hypertension (OR = 1.35, 95%CI: 1.03-1.89), PPD symptoms (EPDS ≥ 11) at 2 days postpartum (OR = 6.15, 95%CI: 1.32-28.35), high prenatal self-rating anxiety scale score (OR = 1.13, 95%CI: 1.06-1.18), and pain at 6 weeks postpartum (OR = 2.16, 95%CI: 1.28-3.66) were independently associated with PPD. Risk factors for PPD after cesarean section in women with early-onset preeclampsia include advanced age (age > 40 years), pre-pregnancy obesity, previous preeclampsia, gestational diabetes mellitus, preexisting hypertension, PPD symptoms (EPDS ≥ 11) at 2 days postpartum, prenatal anxiety, and pain at 6 weeks postpartum. The early identification of these factors and interventions can mitigate the risk of PPD.

The landscape of N1-methyladenosine (m1A) modification in mRNA of the decidua in severe preeclampsia.

Recent discoveries in mRNA modification have highlighted N1-methyladenosine (m1A), but its role in preeclampsia (PE) pathogenesis remains unclear. In this study, we utilized methylated RNA immunoprecipitation sequencing (MeRIP-seq) and RNA sequencing (RNA-seq) to identify m1A peaks and the expression profile of mRNA in the decidua of humans with early-onset PE (EPE), late-onset PE (LPE), and normal pregnancy (NP). We assessed the m1A modification patterns in preeclamptic decidua using 10 m1A modulators. Our bioinformatic analysis focused on differentially methylated mRNAs (DMGs) and differentially expressed mRNAs (DEGs) in pairwise comparisons of EPE vs. NP, LPE vs. NP, and EPE vs. LPE, as well as m1A-related DEGs. The comparisons of EPE vs. NP, LPE vs. NP, and EPE vs. LPE identified 3110, 2801, and 2818 DMGs, respectively. We discerned three different m1A modification patterns from this data. Further analysis revealed that key PE-related DMGs and m1A-related DEGs predominantly influence signaling pathways critical for decidualization, including cAMP, MAPK, PI3K-Akt, Notch, and TGF-β pathways. Additionally, these modifications impact pathways related to vascular smooth muscle contraction, estrogen signaling, and relaxin signaling, contributing to vascular dysfunction. Our findings demonstrate that preeclamptic decidua exhibits unique mRNA m1A modification patterns and gene expression profiles that significantly alter signaling pathways essential for both decidualization and vascular dysfunction. These differences in m1A modification patterns provide valuable insights into the molecular mechanisms influencing the decidualization process and vascular function in the pathogenesis of PE. These m1A modification regulators could potentially serve as potent biomarkers or therapeutic targets for PE, warranting further investigation.

Alteration in sB7-H4 Serum Levels and Placental Biomarker Expression after Therapeutic Plasma Exchange in Early-Onset Preeclampsia Patients.

Therapeutic plasma exchange (TPE) is a widely used treatment for numerous diseases including pregnancy-related conditions. Our prior study on 20 early-onset preeclampsia patients undergoing TPE revealed a significant extension in pregnancy duration and reduced serum levels of sFlt-1, sFlt-1/PlGF, and sEndoglin. Here, we investigated the impact of TPE on serum sB7-H4, an immunological checkpoint molecule, and placental proteins (Flt-1, Eng, B7-H4, iNOS, TNF-α) in TPE-treated early-onset preeclampsia patients (N = 12, 23 + 2-28 + 5 weeks), conventionally treated counterparts (N = 12, 23 + 5-30 weeks), and gestational age-matched controls (N = 8, 22 + 4-31 + 6 weeks). Immunoblotting, ELISA, and co-immunohistochemistry were used for biomarker analysis, including placental inflammation factors (iNOS, TNF-α). The results showed that TPE extended pregnancy by a median of 6.5 days in this cohort of early-onset preeclampsia. Serum sB7-H4, sFlt-1, and sEndoglin levels decreased, along with reduced expression of their membrane-bound proteins in placental tissue upon TPE treatment. Moreover, TPE-treated patients displayed reduced placental inflammation compared to preeclampsia patients receiving standard-of-care treatment. In conclusion, TPE may improve pregnancy outcomes in early-onset preeclampsia by lowering circulating levels of sB7-H4, sFlt-1, and sEndoglin, as well as reducing placental inflammation. This translational approach holds promise for enhancing placental function and extending gestation in high-risk pregnancies including very preterm PE or HELLP cases.

The relationship between early-onset preeclampsia and the prognostic nutritional index and inflammatory markers

Background Preeclampsia is still a disease whose cause and treatment have not been fully characterised. Early-onset preeclampsia occurs before the 34th week of pregnancy, and late-onset preeclampsia occurs at 34 weeks or older. In our study, we investigated whether the prognostic nutritional index (PNI) and pan immune inflammation value (PIV), which are used in the prognosis and prediction of diseases in new studies in the literature, are useful for predicting early-onset preeclampsia. Methods The first group consisted of healthy pregnant women who had a single foetus without any additional disease between 24 and 34 gestational weeks, and the second group consisted of pregnant women who were diagnosed with early-onset preeclampsia and did not have any additional disease or foetal anomalies during the same gestational week. Neutrophil, lymphocyte, monocyte, thrombocyte, ALB, pan immune inflammation value (PIV) and prognostic nutritional index (PNI) scores were recorded. Results In our case control study, 70 patients with early-onset preeclampsia and 140 pregnant women composed the normotensive (control) group. There was a significant difference between the groups according to PIV (p = 0.04). The prognostic nutritional index (PNI) was significantly lower in the early-onset preeclampsia group than in the normotensive group (p < 0,001). A PNI lower than 36, 30 could only predict early-onset preeclampsia with a low sensitivity of 31.1% and specificity of 45%; the area under the curve was 0,24 (95% confidence interval 0.18–0.31), p < 0,001. Conclusion Patients with PNI scores lower than 36,30 may have early-onset preeclampsia.

Development of non-invasive biomarkers for pre-eclampsia through data-driven cardiovascular network models

Computational models can be at the basis of new powerful technologies for studying and classifying disorders like pre-eclampsia, where it is difficult to distinguish pre-eclamptic patients from non-pre-eclamptic based on pressure when patients have a track record of hypertension. Computational models now enable a detailed analysis of how pregnancy affects the cardiovascular system. Therefore, new non-invasive biomarkers were developed that can aid the classification of pre-eclampsia through the integration of six different measured non-invasive cardiovascular signals. Datasets of 21 pregnant women (no early onset pre-eclampsia, n = 12; early onset pre-eclampsia, n = 9) were used to create personalised cardiovascular models through computational modelling resulting in predictions of blood pressure and flow waveforms in all major and minor vessels of the utero-ovarian system. The analysis performed revealed that the new predictors PPI (pressure pulsatility index) and RI (resistance index) calculated in arcuate and radial/spiral arteries are able to differentiate between the 2 groups of women (t-test scores of p < .001) better than PI (pulsatility index) and RI (Doppler calculated in the uterine artery) for both supervised and unsupervised classification. In conclusion, two novel high-performing biomarkers for the classification of pre-eclampsia have been identified based on blood velocity and pressure predictions in the smaller placental vasculatures where non-invasive measurements are not feasible.

Association of genetic ancestry with pre-eclampsia in multi-ethnic cohorts of pregnant women

ObjectivesMaternal self-reported ethnicity is recognised as a risk factor for pre-eclampsia in clinical screening tools and models. This study investigated whether ethnicity is acting as a proxy for genetic variants in this context. Study designA total of 436 women from multi-ethnic backgrounds recruited to two UK observational pregnancy hypertension cohort studies were genotyped. Genetically-computed individual ancestry estimates were calculated for each individual through comparison to the multi-ethnic 1000 Genomes reference panel genotypes. Regression models for pre-eclampsia using clinical risk factors including self-reported ethnicity with and without ancestry estimates were built and compared using Likelihood Ratio Tests (LRT). Main outcome measuresPre-eclampsia (early- and late-onset). ResultsIn these multi-ethnic cohorts (mean age 34.9 years; 41.3 % White, 34.2 % Black, 13.1 % Asian ethnic backgrounds; 82.6 % chronic hypertension), discrepancies between self-reported ethnicity and genetically-computed individual ancestry estimates were present in all ethnic groups, particularly minority groups. Genetically-computed pan-African ancestry percentage was associated with early-onset (< 34 weeks) pre-eclampsia in adjusted models (aOR 100 % vs 0 % African ancestry: 3.81, 95 % CI 1.04–14.14, p-value 0.044) independently of self-reported ethnicity and established clinical risk factors. Addition of genetically-computed African ancestry to a clinical risk factor model including self-reported ethnicity, improved model fit (Likelihood ratio test p-value 0.023). ConclusionsSelf-reported maternal ethnicity is an imperfect proxy for genetically-computed individual ancestry estimates, particularly in ethnic minority groups. Genetically-computed African ancestry percentage was associated with early-onset pre-eclampsia independently of self-reported maternal ethnicity. Well-powered studies in multi-ethnic cohorts are required to delineate the genetic contribution to pre-eclampsia.

Profiling of MicroRNAs for the Identification of Unique and Common MicroRNAs in Preeclamptic Patients of South India Using Next-Generation Sequencing.

Preeclampsia (PE) is a serious pregnancy complication with an unclear cause. Recent studies suggest that microRNAs (miRNAs), particularly miR-1, may play a role in controlling the genes associated with this condition. This study aimed to compare the expression of miRNAs in the blood and placental tissues of women with PE to those with normal pregnancies. We conducted small RNA sequencing on blood and placental samples from three groups: (a) early-onset preeclampsia (EOPE), (b) late-onset preeclampsia (LOPE), and (c) normal pregnancies. Bioinformatics tools were used to compare the miRNA profiles across these groups. A total of 744 miRNAs were detected in placental samples, while 913 miRNAs were found in blood samples. We further analyzed the target genes using protein-protein interaction (PPI) maps to understand how these miRNAs may influence gene functions. Our analysis revealed significant differences in miRNA expression between the EOPE, LOPE, and control groups. Eight miRNAs were consistently detected in both blood and placental samples across all groups, while other miRNAs were either specific to PE or certain tissue types. The 492 target genes identified formed dense interaction networks, with several key genes occupying central roles. These findings suggest that altered miRNA expression and the resulting disruption of gene networks may contribute to the development of PE. The distinct differences between EOPE and LOPE indicate that these two subtypes may be driven by different underlying mechanisms. This paves the way for future research to explore new treatments targeting these miRNAs and their associated genes.

Effect of low-molecular-weight heparin calcium combined with magnesium sulfate and labetalol on coagulation, vascular endothelial function and pregnancy outcome in early-onset severe preeclampsia.

This paper was aimed at unveiling the effect of low-molecular-weight heparin calcium (LMWH) combined with magnesium sulfate and labetalol on coagulation, vascular endothelial function, and pregnancy outcome in early-onset severe preeclampsia (EOSP). Pregnant women with EOSP were divided into the control group and the study group, each with 62 cases. Patients in the control group were treated with labetalol and magnesium sulfate, and those in the study group were treated with LMWH in combination with the control grou Blood pressure (systolic blood pressure [SBP] and diastolic blood pressure [DBP]), 24-h urine protein, coagulation indices [D-dimer (D-D), plasma fibrinogen (Fg), prothrombin time (PT), activated partial thromboplastin time (APTT), and prothrombin time (TT)], endothelial function [endothelin (ET-1) and nitric oxide (NO)], oxidative stress indices [oxidized low-density lipoproteins (ox-LDL), lipid peroxidation (LPO), superoxide dismutase (SOD), and malondialdehyde (MDA)], pregnancy outcome, and adverse effects occurred in the two groups were compared. After treatment, lower SBP, DBP, and 24-h urine protein levels; lower Fg and D-D levels; higher PT, APPT, and TT levels; higher NO levels; lower ET-1 levels; lower ox-LDL, MDA, and LPO levels; higher SOD levels; and lower incidence of adverse pregnancy and adverse reactions were noted in the study group in contrast to the control group. EOSP patients given with LMWH combined with magnesium sulfate and labetalol can effectively reduce the patient's blood pressure and urinary protein level; improve coagulation function, oxidative stress, and vascular endothelial function indices; reduce the adverse pregnancy outcomes; and improve the safety of treatment.

Clinical significance of S100B protein in pregnant woman with early- onset severe preeclampsia.

Preeclampsia is one of the most feared complications of pregnancy, which can progress rapidly to serious complications such as death of both mother and fetus. To present, the leading cause of preeclampsia is still debated. The purpose of this article was to explore the clinical significance of S100B protein, a kind of Ca2+ -sensor protein, in the early-onset severe preeclampsia. Nine pregnant women with early-onset severe preeclampsia (the study group) and 13 healthy pregnant women (the control group) were included in this study. The level of S100B in the amniotic fluid, maternal blood, and umbilical cord blood were detected by enzyme-linked immunosorbent assay (ELISA) and surface plasmon resonance imaging (SPRi) methods. Diagnostic values of S100B for early-onset severe preeclampsia were assessed by Receiver Operating Characteristic (ROC) curve analysis. The levels of S100B in maternal blood and amniotic fluid in the study group were higher than those in the control group (p < 0.05). ROC curve analysis showed that S100B detected by SPRi method (SPRi-S100B) showed a cut-off level of 181 ng/mL with sensitivity of 100%, a specificity of 84.6%, and a Youden index of 0.846 in the maternal blood, which had better clinical significance and diagnostic value (at than that detected by ELISA (ELISA-S100B). The levels of S100B detected by SPRi in maternal blood can indicate early-onset severe preeclampsia and perinatal brain injury.

A 5-year review of preeclampsia screening in a tertiary private hospital in the Philippines: A retrospective cohort study

Preeclampsia remains a significant cause of maternal and perinatal morbidity and mortality worldwide, contributing to about 76,000 maternal deaths and 150,000 perinatal deaths annually. Despite numerous studies on predictive factors and screening tests for preeclampsia, local consensus on the optimal strategy remains elusive. This study aimed to assess the predictive accuracy and detection rate of preeclampsia screening in a tertiary private hospital. A retrospective descriptive cohort study was conducted on pregnant patients who underwent preeclampsia screening from 2018 to 2022. Data analysis involved quantitative methods, assessing predictive accuracy and detection rates for preeclampsia onset at &lt; 34, &lt; 37, and &lt; 40 weeks of gestation. Of the 156 subjects, 8.3% developed preeclampsia, with most cases exhibiting severe features (3.8%). Based on the onset, 3.8% were late-onset, 3.2% early-onset, and 1.2% postpartum. Chronic hypertension emerged as a significant risk factor. Predictive accuracy was highest for early-onset preeclampsia (&lt;34 weeks), reaching 94.23%, while overall predictive accuracy across all gestational ages was 83.12%. Detection rate was also highest for early-onset preeclampsia (100%) but was noted to decrease in later onset specifically 75% and 25% for &lt;37 weeks and &lt;40 weeks, respectively. Aspirin prophylaxis was administered to screen-positive patients, resulting in a 75% reduction in preeclampsia development. This local study underscores the importance of preeclampsia screening, showcasing its strengths in detecting early-onset cases but also its limitations, particularly in identifying term preeclampsia. Compared to traditional tests relying on maternal factors, it demonstrated superior accuracy and higher detection rates, maximizing the benefits of aspirin prophylaxis.

Evaluation of outcomes and risk factors for recurrent preeclampsia in a subsequent pregnancy.

The aim was to evaluate the pregnancy outcomes and identify risk factors for recurrent preeclampsia (PE). Retrospective analysis of patients discharged with PE between January 1, 2010, and January 1, 2023, from two tertiary referral hospitals. They were classified into recurrent and non-recurrent groups based on the presence of PE in subsequent pregnancies. Among 519 women who had a subsequent pregnancy after a history of PE, 153 developed recurrent PE while 366 did not. The recurrent cases included 81 preterm PE, of which 41 were early-onset PE (EOPE). Recurrent PE correlated significantly with prior EOPE, HELLP syndrome, placental abruption, and stillbirth, as well as with current chronic hypertension (CH) and type 2 diabetes. The recurrent group showed a 5.8-fold higher risk of preterm birth (PTB) compared to the non-recurrent group (50.7% vs. 8.7%). Notably, 58.1% of the PTBs in the non-recurrent group were spontaneous. Logistic regression identified previous EOPE (aOR: 4.22 [95% CI: 2.50-7.13]) and current CH (aOR: 1.86 [95% CI: 1.09-3.18]) as independent contributors for recurrent PE. Furthermore, recurrent preterm PE shared the same risk factors: previous EOPE (aOR: 5.27 [95% CI: 2.82-9.85]) and current CH (aOR: 2.99 [95% CI: 1.57-5.71]). The morbidity of CH in subsequent pregnancy peaked at 31.9% when women with a history of EOPE delivered within three years. Previous EOPE and current CH were sequentially crucial risk factors for the development of PE and preterm PE during the next pregnancy. This may clarify risk stratification in prenatal management for women with a history of PE.

Proteomic Analysis Reveals Differential Protein Expression in Placental Tissues of Early-Onset Preeclampsia Patients.

Preeclampsia, a significant cause of maternal and perinatal morbidity and mortality, remains poorly understood, in terms of its pathogenesis. This study aims to uncover novel and effective biomarkers for preeclampsia by conducting a comparative analysis of differential proteins in placentas from early onset preeclampsia (EOPE) and normal pregnancies. Utilizing tandem mass tag (TMT)-based quantitative proteomics, we identified differentially expressed proteins in placental tissues from 15 EOPE patients and 15 normal pregnant women. These proteins were subsequently validated by using parallel reaction monitoring (PRM). Our analysis revealed a total of 59 differentially expressed proteins, with 25 up-regulated and 34 down-regulated proteins in EOPE placental tissues compared to those from normal pregnancies. Validation through PRM confirmed the differential expression of 6 proteins. Our findings suggest these 6 proteins could play crucial roles in the pathogenesis of EOPE, highlighting the potential involvement of the estrogen signaling pathway and dilated cardiomyopathy (DCM) pathway in the development of preeclampsia. The data were deposited with the ProteomeXchange Consortium via the iProX partner repository with the identifier PXD055025.

Adjusting methylation levels with nucleus proportions highlights functional significance of differentially methylated cytosines associated with pre-eclampsia.

Studies on DNA methylation alterations associated with pre-eclampsia (PE) have improved our understanding of the mechanisms underlying this disorder. However, differentially methylated cytosines (DMCs) have not been adjusted for cell-type heterogeneity, hampering the identification of alterations that drive disease risk. Using a reference-based, cell-type deconvolution approach, we estimated the nuclear proportions of 335 placental samples based on DNA methylation data. We found that the nuclei of total trophoblast lineages accounted for more than 80% of the placental samples, with a significant increase in PE placentas. The nuclear proportions of stromal and Hofbauer cells decreased in PE placentas. Our nuclear proportion estimation reflected previous histological knowledge on the changes in cell type proportions in PE placentas. We corrected 2125 DMCs associated with early-onset PE for cell-type heterogeneity by adjusting for the nuclear proportions and observed a notable reduction in the association signals, with 145 probes not reaching epigenome-wide significance. After correction, the top 200 significant DMCs were strongly enriched in active enhancers in trophoblast lineages, whereas 145 non-significant probes were enriched in regions with a quiescent state of chromatin. Our results suggest that future epigenetic studies of PE should focus on functional regulatory sequences.

Evaluation of placental bed uterine in L-NAME-induced early-onset preeclampsia (EO-PE) like the rat model.

Preeclampsia (PE) is the leading cause of maternal death worldwide and is associated with long-term morbidity in both mothers and newborns. Animal modeling is considered a functional source for understanding PE pathogenesis, diagnostic standards, and therapeutic approaches. This study aimed to demonstrate and evaluate the use of N-nitro-L-arginine methyl ester (L-NAME) in a Wistar rat model under conditions similar to PE. A total of 12 rats were divided into 4 groups, each consisting of 3 members, including the pregnant control group and treatment groups administered low-dose (PE 25 mg/kg L-NAME/day), medium-dose (PE 50 mg/kg L-NAME/day), and high-dose L-NAME (PE 75 mg/kg L-NAME/day) L-NAME from gestational day 4 to 19. Measurements included blood pressure, creatinine, and proteinuria levels, placental histological changes, and placental tissue hypoxia-inducible factor 1-alpha, and plasma endothelial nitric oxide synthase levels. The results showed that intervention with L-NAME at 75 mg/kg body weight/day (PE3) induced PE earlier than that with 50 mg/kg body weight/day L-NAME. The model conditions also support further research into PE pathogenesis.