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Objective This study aimed to determine the differences in characteristics and outcomes of early-onset and late-onset Preeclampsia.Methods A retrospective cross-sectional study was conducted on female patients giving birth with preeclampsia admitted into the Department of Obstetrics and Gynecology of Dr. Hasan Sadikin Hospital Bandung from January 2020 to December 2022 who met the study criteria. A total of 435 subjects met the inclusion criteria were divided into two groups: early-onset preeclampsia and late-onset preeclampsia. Differences in outcomes were analyzed using the Chi-square or Fisher test for categorical data and the T-independent or Mann–Whitney test for numerical data.Results There were differences in the incidence of HELLP syndrome (9.0 vs. 2.7%; p = 0.009), prematurity (77.7 vs. 21.4%; p = 0.000), early neonatal death (10.4 vs. 2.7%; p = 0.002), asphyxia (22.7 vs. 8.0%; p = 0.000), SGA (41.7 vs 21.9%; p = 0.000), and LBW (78.7 vs 40.2%; p = 0.000) in early-onset preeclampsia with late-onset. Length of stay was longer in early-onset preeclampsia cases (4.0 vs 3.0 days; p = 0.000). Increased ureum and liver enzymes results were significantly higher in early-onset preeclampsia.Conclusion There is a difference in the outcome of pregnant women with early-onset and late-onset preeclampsia. Women with early-onset preeclampsia tend to have more adverse maternal and neonatal outcomes. In terms of maternal outcome, they tend to have higher liver enzymes level and HELLP syndrome, while in terms of neonatal outcome they tend to have prematurity, early neonatal death, asphyxia, SGA, and LBW.

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

Disturbed 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. The 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 5 mC 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. KvDMR, PEG3 DMR, PEG10 DMR and DLK1 - GTL2 IG-DMR were differentially methylated in the spermatozoa and placental villi of preeclampsia group. Global 5 mC 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. The 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. • DLK1-GTL2 IG-DMR was hypomethylated in spermatozoa of preeclampsia (PE) group. • KvDMR, PEG3 and PEG10 were hypermethylated in spermatozoa of PE group. • PEG3 , IGF2 , PHLDA2 , CDKN1C and DLK1 transcripts were upregulated in PE placentae. • Birth weight was associated with sperm DNA methylation of imprinted genes. • Aberrant paternal epigenetic status was associated with preeclampsia. [ABSTRACT FROM AUTHOR]

Background: Early onset preeclampsia (PE) is considered a fetal disorder that is associated with placental dysfunction. While late onset preeclampsia is considered a maternal disorder that associated with a normal placenta. An imbalance of angiogenesis factors, namely soluble Fms-like tyrosine kinase 1 (sFlt-1) and placental growth factor (PlGF) is not only a strong predictor of PE but can also be a predictor of poor outcomes or adverse complications of PE. This study was conducted to analyze the difference between angiogenesis factor sFlt-1 and PlGF in maternal serum between patients with early and late onset PE. Material and Methods: This was a cross-sectional study involving pregnant women with PE who were ≥18 years old and gestational age >20 weeks had singleton pregnancies. Subjects who had a major morphological abnormality of a fetus diagnosed with USG and chromosomal abnormality of the fetus were be excluded. Systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial pressure (MAP) were measured using a digital blood pressure measuring instrument. sFlt-1 and PlGF levels were measured using enzyme linked immunosorbent assay (ELISA). Result: This study showed the level of maternal serum sFlt-1 was 7522.95 pg/mL and the level of maternal serum PlGF was 222.25 pg/mL. There was a difference between sflt-1, PlGF, and the sflt-1/PlGF ratio (p=0.00; p=0.00; p=0.00) in early and late onset of PE where at early onset PE was found higher sflt-1 and late-onset PE had lower PlGF and higher sflt-1/PlGF ratio. Conclusion: There are differences in sFlt-1, PlGF, and sFlt-1/PlGF in early and late onset PE, as higher sflt-1 is found in early onset preeclampsia, while lower PlGF and higher sflt-1/PlGF ratio are found in late onset preeclampsia. Keywords: early onset, late onset, preeclampsia, maternal angiogenesis factor, Flt-1, PlGF

Preeclampsia (PE) is a pregnancy complication marked by high blood pressure, posing risk to maternal and fetal health. "Genomic imprinting", an epigenetic phenomenon regulated by DNA methylation at Differently Methylated Regions (DMR's), influences placental development. Research on circulating extracellular vesicles (EVs) in PE suggests them as potential source for early biomarkers, but methylation status of EV-DNA in Preeclampsia is not reported yet. This study examines the methylation and expression profile of imprinted genes - PEG10 , PEG3 , MEST , and DLK1 in circulating EVs of 1st and 3rd trimester control and early onset preeclampsia (EOPE) pregnant women (n = 15) using pyrosequencing and qRT-PCR respectively. In 1st trimester, PEG3 was significantly hypermethylated, whereas no significant methylation changes were noted in PEG10 and MEST in EOPE. In 3rd trimester, significant hypomethylation in PEG10 , PEG3 and IGDMR was observed whereas significant hypermethyaltion noted in MEST. mRNA expression of PEG10 , PEG3 and DLK1 was not affected in circulating EVs of 1st trimester EOPE. However, in 3rd trimester significant increased expression in PEG10 , PEG3 and DLK1 noted. MEST expression was reduced in 3rd trimester EOPE. No correlation was observed between average DNA methylation and gene expression in PEG10 and PEG3 in 1st trimester. However, in 3rd trimester, significant negative correlation was noted in PEG10 (r = −0.426, p = 0.04), PEG3 (r = −0.496, p = 0.01), MEST (r = −0.398, p = 0.03) and DLK1 (r = −0.403, p = 0.03). The results of our study strengthen the potential of circulating EVs from maternal serum as non-invasive indicators of placental pathophysiology, including preeclampsia. • DNA methylation of imprinted genes is altered in circulating EVs in EOPE group. • Expression of imprinted genes changes from 1st to 3rd trimester in EOPE group. • DNA methylation of imprinted genes negatively correlated with the expression in EVs. • Circulating EVs may serve as non-invasive markers for placental pathophysiology. [ABSTRACT FROM AUTHOR]

Objective: To investigate the association between polymorphisms of TNF- α (rs1799724, rs1800629), VEGF (rs3025039) and VEGFR1 (rs 722503) and early onset preeclampsia (EOPE) in Chinese. Methods: A total of 132 EOPE patients from January 2016 to December 2018 at the Second Hospital of Tianjin Medical University were selected as the EOPE group, and 156 normal pregnant patients as the Control group. In both groups, 5 ml of peripheral venous blood was obtained after admission. The characteristics of genotype and allele distribution at the four SNPs in the study subjects were examined by matrix-assisted laser desorption ionization time-of-flight mass spectrometric genotyping. Results: The genotype frequency distribution and allele frequency distribution of rs1799724 were significantly different between the EOPE group and the Control group (P = 0.002，P = 0.003). The T allele was statistically associated with the development of EOPE under a dominant genetic model (P = 0.001). The genotype and allele frequency distributions of rs1800629, rs3025039, and rs 722503 did not differ significantly between the EOPE group and the Control group (P > 0.05). There was no linkage disequilibrium among rs1799724, rs1800629 and rs3025039 loci, the corresponding haploid cannot be formed. Conclusions: The rs1799724 of TNF- α gene is a genetic susceptibility locus for EOPE and may be a potential predictors of preeclampsia.

Aim: to assess the blood level of biological endothelial damage markers in women with previous early-onset preeclampsia (еPE) during both the preconception (PC) stage and the first trimester of pregnancy.Materials and Methods. A prospective single-center cohort study was conducted. The control group comprised 40 women with uncomplicated pregnancies. The observation group consisted of 97 patients with a history of ePE, stratified based on pregnancy outcome into the comparison group (n = 59) characterized by a favorable gestational course, and the main group (n = 38) with relapsed еPE (30 patients were excluded from the study). Markers of systemic endotheliosis were determined in women at the PC stage and at 11–13 weeks of gestation: endothelin-1 (ET-1) and endothelial extracellular vesicles (EVs; CD-144).Results. At the PC stage, women in the control group and patients from the comparison group had comparable median (Me) ET-1 levels – 0.39 and 0.40 pmol/ml (p = 0.5935), respectively; at the same time, patients with relapsed еPE vs. control group had it significantly elevated (Me = 0.55 pmol/ml; p = 0.0382). At gestational age of 11–13 weeks, ET-1 level was significantly higher in the group with relapsed еPE (Me = 0.93 pmol/ml) than in control group (Me = 0.29 pmol/ml; p < 0.0001) and comparison group (Me = 0.42 pmol/ml; p = 0.0003). No significant changes in E-EVs (CD-144) level at various PС stages were observed, whereas in the study groups such parameters remained differed.Conclusion. Biological markers evidencing about systemic endothelial dysfunction/destruction – ET-1 and E-EVs (CD-144) in patients with previous ePE can be considered as predictive tests of disease relapse with an accuracy of 63.5 % and 83.0 % at the PС stage and 85.7 % and 94.2 % at gestational age of 11–13 weeks, respectively.

Preeclampsia (PE) is a severe pregnancy disorder posing significant health risks to both the mother and the fetus without available preventive measures or treatments. More specifically, the main pathological feature of early-onset PE (EO-PE) is the incomplete transformation of the spiral artery. Meanwhile, aspirin has proven effective for the treatment and prevention of PE. Previous studies indicated a relationship between the phytochemical compound of kopyor coconut water (KCW) and nutritional treatment for PE. Therefore, the objective of this study was to determine the efficacy of KCW as a potential preventive treatment for PE. An experimental laboratory method was used with pre-test and post-test control group designs. The samples comprised 35 pregnant Wistar rats, divided into five groups with seven members each. Rats were then randomized into control and groups exposed to L-NAME, L-NAME and aspirin, L-NAME and KCW 2 ml/200 gBW, as well as L-Name and KCW 2 ml/200 gBW for GD4 to 19. The results showed that after administering L-NAME to induce EO-PE, mean arterial pressure (MAP), proteinuria, placental hypoxia, oxidative stress, and endothelial dysfunction decreased due to KCW nutritional treatment. Specifically, KCW nutrition prevented the uterine spiral artery from expanding and reduced the number of neutrophils. The decreased survival rate caused by L-NAME-induced PE was reversed by providing KCW nutrition. Moreover, results indicated that KCW was a potential alternative for the prevention and treatment of EO-PE even at doses of 2 or 3 ml/200 gBW, offering insights for the community and clinical practitioners in treating PE as a therapeutic option.

AbstractBackground In the current study, we sought to characterise the methylation haplotypes and nucleosome positioning patterns of placental DNA and plasma cell-free DNA of pregnant women with early-onset preeclampsia using whole genome bisulphite sequencing (WGBS) and methylation capture bisulphite sequencing (MCBS) and further develop and examine the diagnostic performance of a generalised linear model (GLM) by incorporating the epigenetic features for early-onset preeclampsia.Methods This case-control study recruited pregnant women aged at least 18 years who delivered their babies at our Hospital. In addition, non-pregnant women with no previous history of diseases were included. Placental samples of the villous parenchyma were taken at the time of delivery and venous blood was drawn from pregnant women during non-invasive prenatal testing at 12–15 weeks of pregnancy and nonpregnant women during the physical check-up. WGBS and MCBS were carried out of extracted genomic DNA. Then, we established the GLM by incorporating preeclampsia-specific methylation haplotypes and nucleosome positioning patterns and examined the diagnostic performance of the model by receiver operating characteristic (ROC) curve analysis.Results The study included 135 pregnant women and 50 non-pregnant women. Our high-depth MCBS revealed notably different DNA methylation and nucleosome positioning patterns between women with and without preeclampsia. Preeclampsia-specific hypermethylated sites were found predominantly in the promoter regions and particularly enriched in CTCF on the X chromosome. Totally, 2379 preeclampsia-specific methylation haplotypes were found across the entire genome. ROC analysis showed that the area under the ROC curve (AUC) was 0.938 (95%CI 0.877, 1.000). At a GLM cut-off of 0.341, the AUC was the maximum, with a sensitivity of 95.6% and a specificity of 89.7%.Conclusion Pregnant women with early-onset preeclampsia exhibit DNA methylation and nucleosome positioning patterns in placental and plasma DNA.

Objective To estimate incidence, risk of early and late-onset preeclampsia (PE) and understand their relationship with severity of COVID-19. Methods Pregnant women with COVID-19 (n = 1929) were enrolled from 1 April 2020 to 24 February 2022. Primary outcome measure was incidence and risk of early onset PE in women with COVID-19. Results The incidence of early and late-onset PE was 11.4% and 5.6%. Moderate to severe COVID-19 was associated with eight times higher risk of early onset PE [aOR = 8.13 (1.56–42.46), p = 0.0129] compared to asymptomatic group. Conclusions Risk of early onset PE was higher in pregnant women with symptomatic COVID-19 as compared to asymptomatic women.

Background Preeclampsia (PE) is a serious pregnancy complication, resulting in potentially life-threatening conditions for both mother and foetus. It is worth noting that early-onset PE has become a great challenge for clinicians due to its complex manifestation, rapid progression and serious complications. This study aims to investigate differential serum proteome profiles in patients with early-onset PE. Methods Each serum sample was separated using a nanoliter flow rate Easy-nLC chromatography system. Then the samples were analysed by mass spectrometry. Bioinformatics analyses were conducted to analyse the functional categories or signal transduction pathways for differentially abundant proteins. Key proteins identified by mass spectrometry were verified by ELISA. Results We found 30 and 34 proteins were upregulated and downregulated in early-onset PE patients (n = 3) vs controls (n = 3), respectively. Functional enrichment analysis revealed differentially expressed proteins related to the immune response and regulation of peptidase activity. ELISA confirmed that there were lower CSH1 levels and higher LPA concentrations in the serum samples of early-onset PE patients (n = 22) than in healthy controls (n = 19) (p

Objective To identify the factors affecting expectant management of early-onset preeclampsia, and evaluate the correlation between expectant treatment and foetal growth restriction.Materials and Methods The retrospective study included 72 women who were admitted for early-onset preeclampsia between February 2018 to April 2021. Data included maternal clinical parameters, demographic and maternal and neonatal outcomes, which were analysed for correlation.Results Multiple logistic regression analysis demonstrated that the time interval from the onset of 24-h proteinuria to termination of pregnancy showed a strong correlation with the expectant treatment; Univariate logistic analysis confirmed that there was no correlation between expectant treatment and foetal growth restriction.Conclusion There was a negative correlation between the duration of 24-h proteinuria and the expectant treatment of patients with early-onset preeclampsia; Expectant treatment could not improve the development of foetal growth restriction in patients with early-onset preeclampsia.KEY MESSAGESThe duration of 24-h proteinuria affects the effectiveness of expectant management of early-onset preeclampsia.Expectant management can reduce adverse neonatal outcomes due to iatrogenic preterm delivery, but it cannot improve the occurrence of foetal growth restriction.

Aim: to determine a role of specific parameters of coagulation hemostasis for development of severe early-onset preeclampsia (еPE) in low-risk patients.Materials and Methods. A single-center prospective study included 40 patients with a physiological course of pregnancy and term delivery (control group) as well as 41 pregnant women with developed severe еPE (study group). Patients at the gestational age of 19–21 and 27–28 weeks in the comparison groups were examined for serum tissue factor (TF) activity; tissue factor pathway inhibitor (TFPI) and potential to generate thrombin in calibrated thrombography test.Results. Patients with developed ePE vs. control group were found to have significantly increased TF activity at both time points: 49.1 pmol/ml vs. 5.3 pmol/ml (p < 0.0001) and 56.7 pmol/ml vs. 6.6 pmol/ml (p < 0.0001); respectively. At gestational age of 19–21 weeks; patients in the study vs. control group had serum TFPI level significantly lower (1.1 U/ml vs. 1.6 U/ml; p < 0.0001) that was significant elevated up to 2.1 U/ml by 82 % at 27–28 weeks of pregnancy. At both time points; a significantly increased thrombin generation was detected in women with developed ePE.Conclusion. The development of ePE is characterized by increased potential to generate thrombin. TF has been identified as a more sensitive marker of activated coagulation hemostasis; and its significantly increased activity was recorded at gestational age of 19–21 weeks that allows us to consider TF as a prognostic biomarker.

Despite the numerous studies on the clinical aspects of early-onset preeclampsia, our understanding of the immunological consequences of inadequate placenta development remains incomplete. The Th1-predominance characteristic of early-onset preeclampsia significantly impacts maternal immunotolerance, and the role of immune checkpoint molecules in these mechanisms is yet to be fully elucidated. Our study aims to fill these crucial knowledge gaps. A total of 34 pregnant women diagnosed with early-onset preeclampsia and 34 healthy pregnant women were enrolled in this study. A mononuclear cell fragment from the venous blood was separated and frozen. The CD8+ and CD8− NK cell subpopulations were identified and compared to their immune checkpoint molecule expressions using multicolor flow cytometry. The serum CD226 levels were measured by ELISA. Based on our measures, the frequency of the CD8− subpopulation was significantly higher than that of the CD8+ counterpart in both the NKdim and NKbright subsets. Significantly lower CD226 surface expressions were detected in the preeclamptic group compared to healthy women in all the investigated subpopulations. However, while no difference was observed in the level of the soluble CD226 molecule between the two groups, the CD112 and CD155 surface expressions were significantly different. Our study's findings underscore the significant role of the CD8+ and CD8− NK subpopulations in the Th1-dominated immune environment. This deepens our understanding of early-onset preeclampsia and suggests that each subpopulation could contribute to the compensation mechanisms and the restoration of the immunological balance in this condition, a crucial step toward developing effective interventions. [ABSTRACT FROM AUTHOR]

Problem: Early‐onset preeclampsia (EOPE) is a severe gestational hypertensive disorder with significant feto‐maternal morbidity and mortality due to uteroplacental insufficiency. Circulating extracellular vesicles of placental origin (EV‐P) are known to be involved in the pathophysiology of EOPE and might serve as an ideal reservoir for its specific biomarkers. Therefore, we aimed to characterize and perform comparative proteomics of circulating EV‐P from healthy pregnant and EOPE women before delivery. Method of Study: The EV‐P from both groups were isolated using immunoaffinity and were characterized using transmission electron microscopy, dynamic light scattering, nanoparticle tracking analysis, and immunoblotting. Following IgG albumin depletion, the pooled proteins that were isolated from EV‐P of both groups were subjected to quantitative TMT proteomics. Results: Circulating term EV‐P isolated from both groups revealed ∼150 nm spherical vesicles containing CD9 and CD63 along with placental PLAP and HLA‐G proteins. Additionally, the concentration of EOPE‐derived EV‐P was significantly increased. A total of 208 proteins were identified, with 26 among them being differentially abundant in EV‐P of EOPE women. This study linked the pathophysiology of EOPE to 19 known and seven novel proteins associated with innate immune responses such as complement and TLR signaling along with hemostasis and oxygen homeostasis. Conclusion: The theory suggesting circulating EVs of placental origin could mimic molecular information from the parent organ—"the placenta"—is strengthened by this study. The findings pave the way for possible discovery of novel prognostic and predictive biomarkers as well as provide insight into the mechanisms driving the pathogenesis of EOPE. [ABSTRACT FROM AUTHOR]

Background: 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., Aim: 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., Methods: Participants were assessed in person during the 32 nd 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., Results: 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., Conclusion: 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., Competing Interests: Conflict-of-interest statement: The authors declare no conflicts of interest for this article., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Cases of hydatidiform moles with a coexisting fetus are sparse and patients are at high risk for severe complications. Patients and physicians often face the dilemma of the wish to continue pregnancy until viability of the fetus while the risk for maternal complications increases. We present an educational case of a twin pregnancy presenting with a hydatidiform mole and coexisting normal fetus with a placenta praevia. The patient developed severe, early onset preeclampsia with beginning HELLP-syndrome and was tested Covid-19 positive in the further course. Termination of pregnancy was conducted via caesarean section at 18 + 6 weeks of pregnancy. Histopathology and genetic analysis confirmed a complete hydatidiform mole next to a normal placenta. Close follow-up examinations were conducted and showed normal findings including ß HCG levels normalizing within 5 months. This case combines several rare, difficult and severe medical conditions and demonstrates how an individualized therapy by an interdisciplinary team covering a highly sensitive topic was developed in a situation where no guidelines exist.

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. [ABSTRACT FROM AUTHOR]

Objective: To visually analyze the prediction model of early-onset preeclampsia based on the knowledge map drawn by CiteSpace software. Methods: CNKI, Wanfang, VIP, PubMed and Web of Science (WoS) databases from January 1st, 2004 to December 31st, 2023, were searched on the relevant research on the prediction model of early -onset preeclampsia. CiteSpace software was used to visually analyze the authors, institutions and keywords of the literature. Logarithmic likelihood rate (LLR) clustering is used to perform cluster analysis on Chinese and English data keywords. Results: A total of 693 articles were included, including 327 articles in Chinese and 366 in English. The number of published studies on the prediction of early -onset preeclampsia at home and abroad was generally on the rise. The cooperation between authors and institutions of the English literature database was relatively close, while the cooperation between authors and institutions of the Chinese literature database was relatively scattered. Two clusters were obtained from Chinese literatures, which were early onset and prediction. Seven clusters were obtained from English literatures. which were DNA methylation, early pregnancy screening, early onset preeclampsia, oxidative stress, multiple immunoassay, fetal body mass estimation and HELLP syndrome. The outburst word analysis showed that the Chinese literature database mainly focused on the analysis of clinical characteristics and treatment strategies of early -onset preeclampsia in 2019 and before, and focused on the construction of prediction models using traditional markers of eclampsia in 2020 and after. The English literature database mainly focused on the independent risk factors of early-onset preeclampsia, not only including maternal factors (history of onset preeclampsia, gestational hypertension, fetal growth restriction, etc.), traditional markers (uterine artery Doppler ultrasound, biochemical markers, vascular growth factor, placental growth factor, etc.) and other clinically reliable and practical specific indicators, but also using some specific indicators of immunity, DNA methylation, oxidative stress that could be widely used in future clinical practice. In this paper, a model was built for predicting the occurrence of early-onset preeclampsia, based on the traditional statistical methods and innovative integration of machine learning algorithms. Conclusions: At present, the construction of predictive models for the onset of early-onset preeclampsia is still a research hotspot at home and abroad. To discover the specific indicators will further enhance the reliability of the predictive models constructed under the background of fusion machine learning algorithms. [ABSTRACT FROM AUTHOR]

Background: 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., Methods: 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., Results: 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., Conclusions: 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.