OBJECTIVE:This study aimed to identify which subtypes of preeclampsia and fetal growth restriction (FGR) are associated with the greatest maternal cardiovascular strain, as indicated by laboratory biomarkers of cardiac dysfunction. METHODS:Women were recruited at diagnosis and serum levels of NT-proBNP, troponin T, and copeptin were analyzed. The cohort comprised 35 women with early-onset FGR, 54 with late-onset FGR, 53 with early-onset preeclampsia, and 29 with late-onset preeclampsia. Among preeclamptic patients, 58 had and 24 lacked concomitant FGR. Biomarkers were normalized for gestational age relative to uncomplicated pregnancies using Z-scores from log-transformed values. RESULTS:All biomarkers showed a consistent pattern across pregnancy pathologies. The highest Z-scores for NT-proBNP (2.70, p < 0.001) and troponin T (3.25, p < 0.001) were found in early-onset preeclampsia, followed by preeclampsia with and without FGR, with no significant difference between these subgroups. Lower values occurred in late-onset preeclampsia and early-onset FGR, with the lowest in late-onset FGR. CONCLUSION:All forms of preeclampsia and early-onset FGR demonstrated increased cardiovascular strain, whereas late-onset FGR showed minimal involvement. In preeclampsia, earlier disease manifestation was more closely associated with higher cardiovascular burden than concomitant FGR. Although cardiomarkers were elevated in pathological pregnancies, their utility for routine monitoring or postpartum follow-up appears limited.
Objective This study aimed to examine the associations between hypertensive disorders during pregnancy and intelligence quotient (IQ) in children at the ages of 8 and 16 years.Methods Our study sample comprised participants in the Avon Longitudinal Study of Parents and Children (ALSPAC) cohort, an ongoing population-based longitudinal birth cohort in Bristol, Avon, United Kingdom. Offspring IQ was assessed using a shortened version of the Wechsler Intelligence Scale for Children (WISC-III) at age 8 and the Wechsler Abbreviated Scale of Intelligence (WASI) at approximately age 16. This study included over 4900 and 3300 mother‒child pairs at ages 8 and 16, respectively. Binary and multinomial logistic regression models were used to estimate odds ratios and 95% confidence intervals for the associations.Results Hypertensive disorders of pregnancy were not associated with lower offspring IQ at ages 8 or 16. Although gestational hypertension, but not pre-eclampsia, was associated with higher odds of above-average IQ compared with average IQ at age 16 in the multinomial logistic regression model, this association was not observed at age 8 or replicated in the sensitivity analysis using age-specific IQ tertiles.Conclusion We found no evidence that hypertensive disorders of pregnancy were associated with lower offspring IQ at ages 8 or 16. Further studies are warranted to confirm these findings.
OBJECTIVE:Early diagnosis of preeclampsia (PE) remains challenging. We previously linked the long non-coding (lnc) RNA MIR210HG to pathological placental development. Here, we investigated its differential expression, pathophysiological phenotypic specificity, and non-invasive diagnostic potential for PE in the peripheral blood and placental tissue. METHODS:We enrolled 88 PE patients (case group) and 81 normal pregnant women (control group) from the Affiliated Hospital of Qingdao University during January 2020-December 2021. MIR210HG expression was detected via RT-PCR and western blotting, and was modulated using siRNA/overexpression plasmid transfection in human trophoblasts and vascular endothelial cells. RESULTS:MIR210HG expression was specifically upregulated in the peripheral blood of patients with early-onset PE, with superior diagnostic efficacy for the PE-fetal growth restriction subtype. Additionally, CDHR5 was upregulated in PE-associated placental tissues (P = 0.004). Cellular assays confirmed that MIR210HG knockdown reduced CDHR5 expression in trophoblasts and endothelial cells (Bewo: P = 0.019; JEG3: P = 0.006), and CDHR5 knockdown also downregulated MIR210HG expression (Bewo: P = 0.023). CONCLUSION:Therefore, MIR210HG may contribute to placental pathological injury by regulating CDHR5, though the pathogenic mechanism remains unclear. In contrast to the invasive and lagging placental-derived lncRNA biomarkers reported in previous studies, peripheral blood MIR210HG allows for non-invasive monitoring during pregnancy, making it more clinically applicable for early screening and phenotypic stratification of PE.
OBJECTIVE:Preeclampsia is a serious pregnancy complication associated with substantial maternal and infant morbidity worldwide. The adverse outcomes related to preeclampsia increase healthcare costs, highlighting the importance of quantifying its economic burden to inform healthcare policy and resource allocation. This systematic review aimed to synthesize evidence on the economic burden of preeclampsia and identify key cost drivers. METHODS:MEDLINE, PubMed, Web of Science, and the Cochrane Library were searched for English-language studies published between 2014 and 2024. Studies reporting healthcare resource utilization or costs associated with preeclampsia were included. The review followed PRISMA 2020 guidelines and was registered in PROSPERO (CRD42025650091). RESULTS:Of 3,107 records identified, 12 studies were included; most were conducted in high-income countries. All cost estimates were converted to 2024 US dollars for comparability. Direct medical costs ranged from US$109.84 to US$87,339.71, with a mean cost of US$33,585.48 per patient. National healthcare system costs were estimated at €6.5-€9.1 million in Ireland and US$2.18 billion in the United States. CONCLUSION:Preterm birth was identified as a major driver of economic burden, with earlier gestational age significantly increasing maternal and infant costs. Indirect costs and regional disparities remain underexplored, highlighting important gaps for future research.
OBJECTIVE:Hypertensive disorders of pregnancy (HDP) are a major cause of illness and death and it can be prevented. METHODS:We analysed Global Burden of Disease (GBD) 2023 estimates for maternal hypertensive disorders (ICD-10 O10-O16) in six locations (China, Japan, Democratic People's Republic of Korea [DPRK], Republic of Korea, Mongolia, and Taiwan [Province of China]) from 1990-2023 among women aged 20-54 years, reporting counts and age-standardised rates (per 100 000 population) for incidence, deaths and disability-adjusted life years (DALYs), and the maternal mortality ratio (MMR; per 100 000 live births), with 95% uncertainty intervals (UIs). RESULTS:In 2023, incident HDP cases were highest in China (654 396; 95% UI 446 312-949 988), while the age-standardised incidence rate peaked in Mongolia (419.03; 388.67-450.37). Mortality and disability burden were greatest in DPRK (age-standardised death rate 0.393; 0.184-0.749; DALY rate 25.73; 12.92-48.12; MMR 31.61; 13.23-60.86), followed by Mongolia, and lowest in Japan and the Republic of Korea. Across 1990-2023, rates declined markedly in all locations; for example, China's age-standardised death rate fell from 1.15 (0.82-1.57) to 0.03 (0.02-0.05) and its DALY rate from 80.08 (58.66-106.68) to 4.73 (3.04-6.87). CONCLUSION:With the increasing proportion of advanced maternal age, we must optimize antenatal risk stratification, adopt context-appropriate prevention and treatment, strengthen emergency obstetric care, and establish systematic postpartum cardiovascular follow-up to reduce HDP incidence.
BACKGROUND:The risk factors for perinatal complications in pregnant women with pulmonary arterial hypertension (PAH) remain controversial. This study aimed to explore the risk factors and constructed a prediction model for perinatal complications in pregnant women with PAH. METHOD:A total of 116 pregnant women with PAH were retrospectively recruited from the Union Hospital affiliated with the Fujian Medical University between January 2016 and December 2016. The risk factors for perinatal complications were identified by using logistic regression model, while the predictive value of identified factors was assessed using the area under a receiver operating characteristic (ROC) curve. RESULTS:Multivariate results indicated moderate PAH (OR: 15.38; 95% CI: 1.54-166.67; P = 0.020), and congenital heart disease (OR: 2.60; 95% CI: 1.25-5.41; p = 0.010) were associated with an increased risk of perinatal complications. A predictive model based on the aforementioned factors for perinatal complications in pregnant women with PAH was constructed, and the area under a ROC curve was 0.73 (95% CI: 0.60-0.86). CONCLUSION:Perinatal complications in pregnant women with PAH could be affected by the severity of PAH and congenital heart disease and that the predictive value of the constructed model was moderate.
OBJECTIVE:Gestational diabetes mellitus (GDM) refers to glucose intolerance, insulin sensitivity, and beta islet cell dysfunction during pregnancy. GDM pathogenesis is associated with hypertension, impaired placental and renal function, oxidative stress, and increased circulating CD4+ T cells. There are limited animal models to explore GDM pathology and treatment. This study sought to determine a role for GDM placental CD4+ T cells to parallel manifestations of the GDM phenotype in pregnant athymic nude rats. METHODS:GDM placental CD4+ T cells (GDM T cells) were isolated upon delivery and injected into pregnant nude rats on gestational day (GD) 12. Mean arterial pressure and markers of renal injury, proteinuria, kidney injury molecule-1, and neutrophil gelatinase-associated lipocalin, were assessed on GD19. Glucose, insulin tolerance, and glucose tolerance tests were also performed. Renal and pancreatic tissues were stained using Periodic acid Schiff and hematoxylin and eosin, respectively. A one-way ANOVA was used for statistical analysis. RESULTS:Adoptive transfer of GDMT cells increased blood pressure (120.8 ± 2.2 mmHg, p < 0.05) compared to controls (105.4 ± 2.8 mmHg) and normotensive Tcell recipients (96.3 ± 3.9 mmHg). Metformin or MitoTEMPO attenuated this response. GDM T cell recipients had elevated blood glucose (p < 0.05) and impaired glucose tolerance and insulin sensitivity, which improved with metformin or MitoTEMPO treatment. Renal injury was more severe in GDM T cell recipients, but attenuated with metformin or MitoTEMPO. Pancreatic morphology showed reduced beta islet numbers in GDM T cell recipients. CONCLUSION:GDM CD4+ T cells contribute to hypertension, glucose intolerance, and renal dysfunction, improved byMitoTEMPO. These findings supports optional therapeutics that support mitochondrial function during pregnancy.
OBJECTIVE:To quantify extracellular fluid expansion in preeclampsia using bioelectrical impedance analysis (BIA) and to evaluate whether BIA-derived extracellular water (ECW) indices are associated with perinatal outcomes. METHODS:In this prospective cohort study, 16 hospitalized women with high-risk pregnancies (7 with preeclampsia and 9 normotensive controls) underwent segmental BIA at a mean gestational age of 32 weeks. Total body water (TBW), intracellular water (ICW), ECW, and ECW/TBW were compared between groups. Fluid indices were additionally expressed as weight-adjusted and height-indexed measures. Associations between ECW/TBW and perinatal outcomes were reviewed and analyzed. RESULTS:Compared with normotensive controls, women with preeclampsia had higher TBW, ICW, ECW, and ECW/TBW (all p < 0.05), with consistent segmental elevations most prominent in the lower extremities. Weight adjustment eliminated between-group differences in absolute fluid volumes, whereas height-indexing preserved significant elevations across compartments (all p ≤ 0.002). In the overall high-risk cohort, higher ECW/TBW was associated with earlier gestational age at delivery and lower 1-minute Apgar scores (both p < 0.05). CONCLUSION:Preeclampsia is characterized by measurable extracellular fluid expansion on bedside BIA. Elevated ECW/TBW is associated with adverse perinatal outcomes among hospitalized high-risk pregnancies, supporting the potential clinical utility of non-invasive fluid assessment for risk stratification in hypertensive disorders of pregnancy.
BACKGROUND:Preeclampsia (PE), a serious obstetric complication impacting maternal and fetal health, still lacks reliable biomarkers owing to limited sensitivity, specificity, and disease heterogeneity. METHODS:Differentially expressed genes (DEGs) were identified from placental samples in GSE114691 (20 PE, 21 controls), and module genes were determined via weighted gene co-expression network analysis (WGCNA). These genes were intersected with ERS genes. Feature genes were selected using LASSO, RF, and SVM-RFE, and a diagnostic model was constructed. Single-gene gene set enrichment analysis (GSEA), interaction network analysis (including PPI, miRNA/TF-target gene, chemical-gene interaction), immune infiltration, and molecular docking were performed. RESULTS:Using analyses performed in R, along with WGCNA and ML algorithms, four ERS-related feature genes (HTRA1, GBA1, KL, PC) were identified, which showed high discriminatory power (AUC = 0.846). GSEA linked these genes to metabolic reprogramming, involving central energy metabolism, amino acid metabolism, short-chain fatty acid metabolism, and redox homeostasis. Immune infiltration analysis showed KL and PC negatively correlated with M1 but positively with M2 macrophages, opposite to HTRA1 and GBA1. Molecular docking showed stable binding between aspirin and the signature gene-encoded proteins. CONCLUSIONS:HTRA1, GBA1, KL, and PC may serve as diagnostic biomarkers for PE, potentially influencing M1 polarization of placental macrophages via metabolic reprogramming.
OBJECTIVE:Advanced maternal age (AMA, ≥35 years), particularly prevalent in Japan, is associated with adverse perinatal outcomes, including hypertensive disorders of pregnancy (HDP), which vary in severity based on the timing of onset (early-onset and late-onset). This study aimed to investigate the association between maternal age and early-onset and late-onset HDP. METHODS:A total of 80,872 pregnant women were included in this prospective birth cohort study. Associations between maternal age and early-onset, preterm late-onset, and term late-onset HDP were evaluated using a multinomial logistic regression model adjusted for potential confounding factors. Maternal age was categorized into five: <25, 25‒29.9, 30‒34.9, 35‒39.9, and ≥40 years, with the reference category set as 30‒34.9 years. RESULTS:Higher maternal age was significantly associated with increased odds of developing early-onset, preterm late-onset, and term late-onset HDP. The adjusted odds ratios (aORs) for early-onset HDP in women aged 35‒39.9 and ≥40 years were 2.724 (95% confidence interval [CI]: 2.095-3.542) and 3.493 (95% CI: 2.349-5.196), respectively. Regarding preterm late-onset HDP, the aORs were 1.346 (95% CI: 1.057-1.714) and 3.011 (95% CI: 2.171-4.176) for these age groups, respectively. Similarly, the aORs for term late-onset HDP were 1.417 (95% CI: 1.206-1.664) and 1.762 (95% CI: 1.341-2.316), respectively. CONCLUSION:Higher maternal age was associated with an increased HDP risk, irrespective of diagnosis timing. Associations between maternal age and early-onset and preterm late-onset HDP were stronger than that with t erm late-onset HDP.
Objective To evaluate and compare the effects of continuous analgesia versus standard pain management on pain intensity, psychological status (anxiety and depression), and maternal-infant outcomes in pregnant women with hypertensive disorders.Methods This retrospective cohort study analyzed 124 pregnant women with hypertensive disorders admitted between December 2021 and December 2023. Participants were categorized into two groups based on the labor analgesia received: a non-continuous analgesia group (n = 51) and a continuous analgesia group (n = 73). Outcome measures included pain scores at different stages of dilation (4 cm and 8 cm) and anxiety/depression levels assessed pre-delivery, post-delivery, and 24 hours postpartum.Results The continuous analgesia group demonstrated significantly lower pain scores at both 4 cm dilation (t = 8.888, P < 0.001) and 8 cm dilation (t = 9.604, P < 0.001) compared to the non-continuous group. Regarding psychological outcomes, the continuous analgesia group showed significantly lower anxiety levels pre-delivery (t = 2.606, P = 0.011), post-delivery (t = 2.343, P = 0.022), and 24 hours postpartum (t = 5.084, P < 0.001). Similarly, depression scores were significantly lower in the continuous analgesia group at all three time points: pre-delivery (t = 2.019, P = 0.046), post-delivery (t = 2.66, P = 0.009), and 24 hours postpartum (t = 4.103, P < 0.001). Correlation analysis revealed significant negative associations between continuous analgesia and maternal pain, anxiety, and depression (P < 0.05).Conclusion Continuous analgesia during labor is associated with superior pain relief and a significant reduction in anxiety and depression levels for pregnant women with hypertensive disorders compared to standard pain management. These findings suggest that continuous analgesia may be a beneficial intervention for improving the maternal psychological experience in this high-risk population.
OBJECTIVE:To compare epidemiological trends and burden of maternal hypertensive disorders (MHD) between China and the globe from 1990 to 2023 and project future trends through 2035. METHODS:Based on Global Burden of Disease (GBD) 2023 data, temporal trends and age-period-cohort effects were analyzed using Joinpoint regression, Age-Period-Cohort (APC) models, and Nordpred forecasting. RESULTS:From 1990 to 2023, China's MHD incident cases and disability-adjusted life years (DALYs) decreased by 79.73% and 95.33%, respectively. China's age-standardized incidence rate (ASIR) and age-standardized DALY rate (ASDR) remained consistently lower than global averages with a greater magnitude of decline. Joinpoint analysis showed China's ASIR fluctuated, while ASDR declined steadily. APC models revealed an incidence increase among Chinese females aged 35-54, particularly in the 45-49 group (local drift: 3.28%/year), while global incidence declined across all ages. In China, incidence risk was lowest in 2009-2013, with birth cohort risk peaking in 1972-1976. Overall MHD burden is projected to continue declining by 2035. CONCLUSION:Despite overall progress, the rising risk among older pregnant women in China remains a key challenge, necessitating enhanced age-based screening and specialized perinatal care.
Posterior reversible encephalopathy syndrome (PRES) is a neurological complication linked to preeclampsia and eclampsia. This study compared the clinical and radiological features of PRES in patients with these conditions. This retrospective single-center cohort study from 2010 to 2024 included patients diagnosed with preeclampsia and eclampsia who underwent MRI due to neurological symptoms. Two radiologists, blinded to the clinical data, re-evaluated the MRIs twice. PRES cases were assessed based on the sites and patterns of involvement. Maternal and perinatal outcomes, along with laboratory characteristics, were reviewed through medical records. The study included 157 patients with preeclampsia and eclampsia who underwent MRI for neurological symptoms. PRES was diagnosed in 55 patients (35.0%), with a higher incidence of eclampsia (64.71%) compared to preeclampsia (20.75%). Patients with PRES were younger, had lower gravidity and parity, and were at an earlier gestational age than those with normal MRI findings. The parietal and occipital regions were the most affected in both preeclampsia and eclampsia patients with PRES. Parietal lobe and bilateral involvement were more common in the eclampsia group. Atypical involvement, including brainstem and cerebellar lesions, was observed in both groups. These findings suggest that eclampsia may represent a neurological manifestation of PRES.
OBJECTIVE:Preeclampsia is a significant pregnancy complication associated with abnormal placental formation. Cadherin-11, a cell adhesion molecule, plays a role in trophoblast differentiation and placental development. The aim of this study was to evaluate the relationship between cadherin-11 levels in maternal serum in early second trimester and subsequent development of preeclampsia. METHODS:In this retrospective nested case-control study, 160 pregnant women (80 preeclampsia, 80 control) who were evaluated and followed up between 15-20 weeks of gestation between 1 March and 1 June 2024 were included. Serum cadherin-11 levels were measured by enzyme-linked immunosorbent assay method. Clinical, biochemical and obstetric data were compared. Diagnostic values were determined by receiver operating characteristic curve and logistic regression analyses. RESULTS:Cadherin-11 levels were significantly higher in the preeclampsia group compared to the control group (p < 0.001). This increase was more pronounced in early-onset preeclampsia. According to receiver operating characteristic analysis, area under the curve was 0.880 in the diagnosis of preeclampsia and 0.903 in early-onset preeclampsia. In addition, the mean age of pregnant women in the early-onset preeclampsia group was significantly higher than both the control and late-onset preeclampsia groups. CONCLUSION:Maternal serum cadherin-11 levels may be a significant biomarker for predicting preeclampsia, especially early-onset forms. This finding may provide a new insight for early intervention and prophylactic strategies.
Gestational diabetes mellitus (GDM) poses a significant threat to perinatal health. Diagnosis based solely on glycemic parameters shows limited accuracy. The Systemic Immune-Inflammation Index (SII), a quantitative marker of inflammation, may improve diagnostic precision. This study analyzed clinical data stratified by GDM and obesity status to evaluate the diagnostic utility of SII and its underlying mechanisms involving placental NF-κB and 5-hydroxytryptamine (5-HT) signaling. We observed elevated SII levels in GDM patients, which correlated positively with glucose levels and inflammatory indicators (white blood cell count, fasting blood glucose, postprandial blood glucose). Logistic regression and receiver operating characteristic analyses confirmed the diagnostic value of SII, which was further enhanced when combined with clinical covariates. Placental expression of tryptophan hydroxylase 1 (TPH1) and NF-κB was significantly increased in GDM and closely linked to SII levels. Dysregulation of placental 5-HT signaling, characterized by increased TPH1 and monoamine oxidase A (MAO-A) expression alongside reduced serotonin transporter (SERT), was associated with maternal overweight. Moreover, SII, BMI, TPH1, and NF-κB all correlated with insulin resistance (IR). These results support SII as a non-invasive diagnostic indicator for GDM and highlight the role of placental 5-HT/NF-κB signaling in its pathogenesis, providing insights for early diagnosis and targeted therapy.
Background Preeclampsia (PE) is a serious and progressive multisystem disease that often results in negative outcomes for neonates. This study aimed to create a nomogram to identify high-risk women with PE in their first trimester.Methods This study involved a nested case-control cohort including 47 PE patients and 122 controls from The Second Affiliated Hospital of Zhengzhou University from January 1, 2023, to May 31, 2024. We identified independent risk factors for PE via multivariate logistic regression and developed a nomogram model. Calibration curves were used to assess accuracy, and decision curve analysis (DCA) was used to evaluate clinical applicability.Results Multivariate logistic regression revealed that pre-pregnancy body mass index (BMI), mean arterial pressure (MAP), and uric acid (UA) levels were positively correlated with PE, whereas placental growth factor (PLGF) was negatively correlated. The area under the curve (AUC) for the combined diagnostic value was 0.97 (95% CI: 0.96-0.99), suggesting satisfactory discrimination. DCA demonstrated that the predictive model provided high net benefits and significant clinical utility.Conclusions The nomogram developed in this study, which includes pre-pregnancy BMI, PLGF, MAP, and UA for the prediction of PE risk, can assist clinicians in identifying high-risk individuals during the first trimester.
Background and objective Trophoblast pyroptosis contributes to the pathogenesis of preeclampsia (PE). Succinylation is a posttranslational modification that is involved in the progression of various diseases. This study aimed to explore the role of the succinyltransferase KAT2A in PE by evaluating its impact on pyroptosis.Methods Rats were injected with N-nitro-L-arginine methyl ester to generate a PE model, and blood pressure was detected. HTR-8/SVneo cells were treated with hypoxia and reoxygenation, and pyroptosis was evaluated by flow cytometry and western blotting. The mechanism was assessed using immunoprecipitation, cycloheximide chase experiment, and western blotting.Results KAT2A was highly expressed in the placentas of PE rats. Knockdown of KAT2A inhibited pyroptosis of the HTR-8/SVneo cell model in vitro and ameliorated blood pressure and pyroptosis in the placenta in vivo. Additionally, KAT2A promoted the succinylation of NLRP3 at the lysine (K)21 site, and mutation of NLRP3 at this site reduced its stability. Moreover, overexpression of NLRP3 counteracted the inhibition of pyroptosis caused by KAT2A knockdown.Conclusion Silencing of KAT2A inhibits trophoblast pyroptosis by downregulating NLRP3 expression, thereby alleviating PE. Mechanistically, KAT2A stabilizes NLRP3 by facilitating its succinylation at K21 site. These findings suggest that KAT2A may be a promising target for the treatment of PE.
OBJECTIVE:The systemic inflammatory response index (SIRI), a novel and integrated hematological index calculated as (neutrophil count × monocyte count)/lymphocyte count, has been recognized as a reliable marker of systemic inflammation. This article undertakes an analysis of clinical data from preeclampsia (PE) patients, aiming to comprehensively assess the relationship between SIRI, PE, and the severity of PE. METHODS:A total of 783 pregnant women in their third trimester were divided into severe preeclampsia (SP) (n = 275), non-SP (n = 273), and control (n = 235) groups. Pearson correlation analysis was performed to investigate the relationship between SIRI and blood pressure. Receiver operating characteristic (ROC) curves were employed to evaluate the predictive ability of SIRI. Multivariate logistic regression analysis was used to assess the association between SIRI and the severity of PE. RESULTS:There was a significant relationship between SIRI and systolic blood pressure (r = 0.488, p < 0.001) as well as diastolic blood pressure (r = 0.462, p < 0.001). ROC curve revealed that pregnant women with SIRI ≥ 1.84 × 109/L were more likely to experience non-SP (AUC: 0.662; 95% CI: 0.615-0.710; p < 0.001), and those with SIRI ≥ 2.45 × 109/L were prone to SP (AUC: 0.879; 95% CI: 0.850-0.910; p < 0.001). Multivariate logistic regression analysis demonstrated that SIRI served as an independent risk factor for both non-SP and SP (p < 0.001). CONCLUSION:There is a strong correlation between SIRI and the severity of PE, and SIRI shows potential in predicting the severity of PE.
OBJECTIVE:To investigate the dynamic changes of soluble fms-like tyrosine kinase-1 (sFlt-1), placental growth factor (PlGF) and their ratio in maternal plasma, from preeclampsia diagnosis to postpartum, evaluating its clinical utility. METHODS:Single-center prospective longitudinal cohort study with repeated sample collection in women with established preeclampsia (PE). Seventy-five (n = 75) women with PE were included, from which 19, 21 and 35 developed early-onset (EPE), late-onset (LPE) and severe-LPE (SLPE) preeclampsia, respectively. Thirty-five (n = 35) women with normotensive pregnancy (NP) served as the reference group. RESULTS:In all subgroups of PE, PlGF decreased from diagnosis to peripartum. In contrast, sFlt-1 and the ratio rose in LPE and SLPE subgroups, whereas they remained continuously higher and stable in the EPE subgroup. In all subgroups, postpartum concentrations decreased compared to pregnancy levels. Post-term NP had higher sFlt-1 and ratio, and lower PlGF in comparison to term and late-term NP. Preeclamptic pregnancies complicated with fetal growth restriction (FGR) had continuously higher and stable sFlt-1 concentrations and ratio, and lower PlGF concentrations compared to PE without FGR. Different patterns of the three biomarker trajectories were observed in a case-by-case analysis. CONCLUSION:Further research is warranted to refine pattern analysis and to integrate trajectories of these biomarkers into clinical practice towards personalized care in preeclampsia management.
BACKGROUND:Preeclampsia (PE) is a severe pregnancy-related disorder characterized by hypertension and end-organ manifestation, and remains a leading cause of perinatal maternal and fetal mortality and morbidity in developing countries. The pathogenesis of PE involves reduced uteroplacental blood flow and impaired trophoblast invasion; however, the role of exosomes in these processes is not fully understood. METHODS:This study employed Transwell assay, wound healing assay, and CCK-8 assays to evaluate the effects of umbilical cord exosomes derived from women with PE (PE-exosomes) on trophoblast function. Additionally, miRNA sequencing, in vitro transfection, western blotting, RT-PCR amd FISH assays were used to investigate the involvement of the microRNA-548 (miR-548)/Ras homolog family member A (RhoA) axis. Statistical analysis was performed using t-tests, with a significance threshold of P < 0.01. RESULTS:Expression levels of miR-548 were significantly elevated in PE-exosomes. Both treatment with PE-exosomes and the overexpression of miR-548 inhibited trophoblast invasion and proliferation. These effects were reversed by RhoA overexpression. Together, these findings suggest that PE-exosomes suppress trophoblast invasion via the miR-548/RhoA axis. In pregnant women with PE, high miR-548 expression levels were observed, and were positively correlated with blood pressure and proteinuria. CONCLUSIONS:Elevated miR-548 levels may contribute to the development of PE, suggesting that miR-548 could serve as a novel diagnostic or therapeutic target for this condition.
