Search Results (120)

Preeclampsia (PE) is not merely a pregnancy complication but a clinical manifestation of underlying vascular dysfunction with long-term health implications. It is diagnosed after 20 weeks of gestation as new-onset hypertension with proteinuria or organ involvement. The condition arises from impaired placental development, particularly defective spiral artery remodeling, which leads to placental ischemia and the release of antiangiogenic factors such as soluble fms-like tyrosine kinase-1 (sFlt-1) and soluble endoglin (sEng). These circulating factors contribute to systemic endothelial dysfunction, resulting in hypertension, inflammation, and multiorgan stress. Histopathological findings, including acute atherosis and abnormal vascular remodeling, further reflect the cardiovascular damage underlying PE. This review synthesizes emerging evidence on the vascular and histological mechanisms of PE, highlighting novel biomarkers such as microRNAs and neprilysin, and the potential of advanced diagnostic tools, including machine learning. Importantly, PE is now recognized not only as an obstetric disorder but also as an early marker of future cardiovascular disease. This paradigm shift emphasizes the need for personalized prevention strategies, close surveillance of high-risk women, and long-term cardiovascular follow-up. Pregnancy thus represents a critical window for early detection and intervention in women’s cardiovascular health. Full article

Objective: To describe first-trimester maternal, biochemical, biophysical, and ultrasound characteristics in women with recurrent pregnancy loss (RPL) compared to women without RPL. Methods: This was a retrospective cohort study analyzing data from 4440 pregnant women, including 142 women with previous RPL. Maternal and pregnancy characteristics, first-trimester biochemical markers, biophysical assessments, early-onset preeclampsia (EOPE) risk, and perinatal outcomes were compared. Results: Women with RPL were older (37.8 vs. 34.0 years, p < 0.001) and had higher rates of antiphospholipid syndrome (4.9% vs. 0.9%, p < 0.001), other thrombophilias (5.6% vs. 0.8%, p < 0.001), and thyroid disorders (14% vs. 7.5%, p = 0.010) than women without RPL. First-trimester uterine artery pulsatility index (UtA-PI) values, pregnancy-associated plasma protein-A (PAPP-A) levels, mean arterial pressure, and final risk for EOPE were comparable between groups. However, the RPL group had higher rates of very high risk for PE (10.6 vs. 5.1, p = 0.011). Likewise, second-trimester UtA-PI was higher in this group (1.10 vs. 1.01, p = 0.045). Aspirin and low molecular weight heparin prophylaxis were more frequent in women with RPL (23.8% vs. 9.6%, p < 0.001; 14.7% vs. 0.1%, p < 0.001). Regarding perinatal outcomes, we found a higher incidence of second-trimester intrauterine demise in the RPL group (6.4% vs. 1.4%, p = 0.011), with no other differences observed in the remaining outcomes. Conclusions: Women with RPL exhibit distinct maternal characteristics and worse pregnancy outcomes, although first-trimester markers do not seem to significantly differ from findings in women without RPL. These findings underscore the importance of tailored screening and intervention protocols to improve perinatal outcomes in this high-risk population. Full article

Preeclampsia (PE), a major cause of perinatal morbidity and mortality, is frequently under-recognized as an early indicator of future cardiovascular (CV) disease. This study examines early-onset preeclampsia (eoPE) across three phases—pre-pregnancy, diagnosis, and follow-up—to dynamically reclassify risk of eoPE in the second-trimester and assess long-term CV implications. A case-control study involving 50 women with eoPE (diagnosed before 34 weeks) and 50 matched controls with uncomplicated pregnancies employed supervised machine learning to develop two predictive models: one for reevaluating first-trimester eoPE risk, with test sensitivity/specificity of 95.0% (92.2–97.8%)/99.0% (97.6–100.0%) and another for predicting post-pregnancy hypertension (HT), with test sensitivity/specificity of 74.1% (67.2–80.9%)/89.1% (85.5–92.8%). Metaheuristic methods identified key features for risk reevaluation and prediction, achieving high predictive performance using routine early pregnancy data and diagnostic information. These findings should be interpreted with caution due to the sample size limitations. Additionally, unsupervised machine learning on follow-up data (median 7.5 years postpartum) was used to explore how pregnancy conditions shape long-term health in eoPE patients. Full article

Background/Objectives: Preeclampsia (PE) is a major cause of maternal and perinatal morbidity and mortality, particularly in low- and middle-income countries. Early-onset PE (EOP) and late-onset PE (LOP) are distinct clinical entities with differing pathophysiological mechanisms and prognoses. However, few studies have explored differential risk factors for EOP and LOP in Latin American populations. This study aimed to identify and assess clinical risk factors for predicting EOP and LOP in a cohort of pregnant women from Bogotá, Colombia, using traditional statistics and machine learning (ML). Methods: A cross-sectional observational study was conducted on 190 pregnant women diagnosed with PE (EOP = 80, LOP = 110) at a tertiary hospital in Bogotá between 2017 and 2018. Risk factors and perinatal outcomes were collected via structured interviews and clinical records. Traditional statistical analyses were performed to compare the study groups and identify associations between risk factors and outcomes. Eleven ML techniques were used to train and externally validate predictive models for PE subtype and secondary outcomes, incorporating permutation-based feature importance to enhance interpretability. Results: EOP was significantly associated with higher maternal education and history of hypertension, while LOP was linked to a higher prevalence of allergic history. The best-performing ML model for predicting PE subtype was linear discriminant analysis (recall = 0.71), with top predictors including education level, family history of perinatal death, number of sexual partners, primipaternity, and family history of hypertension. Conclusions: EOP and LOP exhibit distinct clinical profiles in this cohort. The combination of traditional statistics with ML may improve early risk stratification and support context-specific prenatal care strategies in similar settings. Full article

Preeclampsia (PE) is a multifactorial hypertensive disorder unique to pregnancy and a leading cause of maternal and fetal morbidity and mortality worldwide. Its pathogenesis involves placental dysfunction and an exaggerated maternal inflammatory response. Uric acid (UA), traditionally regarded as a marker of renal impairment, is increasingly recognized as an active contributor to the development of PE. Elevated UA levels are associated with oxidative stress, endothelial dysfunction, immune activation, and reduced renal clearance. Clinically, UA is measured in the second and third trimesters to assess disease severity and guide obstetric management, with higher levels correlating with early-onset PE and adverse perinatal outcomes. Its predictive accuracy improves when combined with other clinical and biochemical markers, particularly in low-resource settings. Mechanistically, UA and its monosodium urate crystals can activate the NLRP3 inflammasome, a cytosolic multiprotein complex of the innate immune system. This activation promotes the release of IL-1β and IL-18, exacerbating placental, vascular, and renal inflammation. NLRP3 inflammasome activation has been documented in placental tissues, immune cells, and kidneys of women with PE and is associated with hypertension, proteinuria, and endothelial injury. Experimental studies indicate that targeting UA metabolism or inhibiting NLRP3 activation, using agents such as allopurinol, metformin, or MCC950, can mitigate the clinical and histopathological features of PE. These findings support the dual role of UA as both a biomarker and a potential therapeutic target in the management of the disease. Full article

Pre-eclampsia (PE) is a hypertensive pregnancy complication. Oxidative stress is hypothesized to contribute to the pathophysiology of PE. Both the hydrogen sulfide (H₂S) and oxytocin (OT) systems might play a role in the pathophysiology of PE, like their antioxidant and hypotensive effects. Thus, the role of the interaction of the OT and H₂S systems in the context of PE was further elucidated in the present clinical case–control study “NU-HOPE” (Nürnberg-Ulm: The role of H₂S and Oxytocin Receptor in Pre-Eclampsia; ethical approval by the Landesärztekammer Bayern, file number 19033, 29 August 2019), comparing uncomplicated pregnancies, early onset PE (ePE, onset < 34 weeks gestational age) and late onset PE (lPE, onset > 34 weeks gestational age). Routine clinical data, serum H₂S and homocysteine levels, and tissue protein expression, as well as nitrotyrosine formation, were determined. The main findings were (i) unchanged plasma sulfide levels, (ii) significantly elevated homocysteine levels in ePE, but not lPE, (iii) significantly elevated expression of H₂S enzymes and OT receptor in the placenta in lPE, and (iv) significantly elevated nitrotyrosine formation in the lPE myometrium. Taken together, these findings suggest a role for the interaction of the endogenous H₂S- and OT/OTR systems in the pathophysiology of pre-eclampsia, possibly linked to impaired antioxidant protection. Full article

To assess the association between known (PlGF, sFlt-1, betaHCG, PAPPA) and novel (cell-free DNA, cfDNA, and total endothelial and platelet microvesicles, MVs) maternal blood biomarkers measured at the first trimester with the later development of preeclampsia (PE) and PE-related severe adverse events (SAE), we conducted a retrospective case–control study including women with an established diagnosis of preeclampsia (cases) and healthy pregnant women (controls). Biomarkers were measured from first-trimester blood samples stored in a hospital biobank. A total of 89 women, 54 women with PE and 35 controls were included. PlGF showed good performance for diagnosing overall preeclampsia (AUC: 0.71; 95% CI 0.59–0.82), early-onset preeclampsia (AUC 0.80; 95% CI 0.68–0.9) and fetal-neonatal SAEs (AUC: 0.73; 95% CI 0.63–0.84). Multivariate models including clinical variables, PlGF and other biomarkers showed good to very good discrimination for the development of PE, early-onset PE and fetal-neonatal SAEs (AUCs of 0.87, 0.89 and 0.79, respectively). Platelet-derived MVs were the best isolated biomarker for late-onset PE and, combined with systolic blood pressure, showed good discrimination (AUC: 0.81; 95% CI 0.71–0.92). For maternal SAEs, a model incorporating cfDNA and sFlt-1 provided excellent discrimination (AUC 0.92; 95% CI 0.82–1.00). Our findings suggest that multivariate models incorporating both clinical variables and first-trimester biomarkers may improve risk stratification for PE, especially for late-onset PE and for identifying women at risk of severe maternal or fetal complications. Notably, the inclusion of novel biomarkers such as cfDNA and MVs added value in clinical scenarios where the predictive performance of existing tools remains suboptimal. Full article

The aim of this study was to evaluate and synthesize the existing evidence on N-terminal pro-brain natriuretic peptide (NT-proBNP) and brain natriuretic peptide (BNP) as biomarkers for preeclampsia as compared with a healthy pregnant group, but also comparing them in early-onset preeclampsia (EOP) versus late-onset preeclampsia (LOP). Five electronic databases, PubMed, EMBASE, Web of Science, Scopus, and LILACS, were searched for studies on pregnant women comparing NT-proBNP and BNP levels in preeclampsia vs. healthy pregnancies and EOP vs. LOP. From the 752 identified records, 31 studies were included in the review, referring to 3915 participants. When comparing PE to healthy pregnancies and EOP to LOP, there was a considerable increase in NT-proBNP levels in the PE group, respectively, in EOP: 206.19 pg/mL (95% CI 139.68–272.69) (p ≤ 0.001) in the PE group, and 182.42 pg/mL (95% CI 99.65–265.19) (p ≤ 0.001) in the EOP group. Regarding BNP, the levels were higher in the PE group (30.13 (95% CI 17.22–43.04), p ≤ 0.001), respectively in the EOP group (33.35 pg/mL (95% CI 20.26–46.43), p ≤ 0.001). NT-proBNP and BNP levels are consistently elevated in preeclampsia compared to healthy pregnancies and in EOP compared to LOP. Full article

Preeclampsia, one of the leading causes of maternal and fetal morbidity and mortality, affects approximately 3–5% of pregnancies worldwide. However, its etiology remains poorly understood. The aim of this study was to identify molecular markers of preeclampsia. Protein concentrations in blood and urine were determined using the Bio-Plex Kidney Toxicity 1 assay Bio-Rad, Hercules, CA, USA followed by magnetic separation and flow cytometry. This study included 51 patients with preeclampsia and 25 healthy pregnant women. The results revealed that five out of the six serum biomarkers of kidney injury were elevated in the preeclampsia group compared to the control group (calbindin 1, clusterin, glutathione transferase pi (GSTP1), monocyte chemotactic protein 1 (MCP-1), and kidney injury molecule type 1 (KIM-1)). Additionally, the serum concentrations of calbindin 1, clusterin, GSTP1, and KIM-1 were significantly higher in both early-onset and late-onset preeclampsia compared to the control group. The analysis of urinary proteins showed that only the KIM-1 concentration was elevated in late-onset preeclampsia compared to the control group. These findings suggest that the calbindin 1, clusterin, GSTP1, KIM-1, and MCP-1 concentrations in maternal plasma could serve as potential biomarkers for monitoring kidney injury in preeclamptic women. This study provides a foundation for future research to explore novel biomarkers of preeclampsia and renal injury in pregnant women. Full article

The phenotype of human placental extravillous trophoblast (EVT) at the end of pregnancy reflects both differentiation from villous cytotrophoblast (CTB) and later gestational changes, including loss of proliferative and invasive capacity. Invasion abnormalities are central to major obstetric pathologies, including placenta accreta spectrum, early onset preeclampsia, and fetal growth restriction. Characterization of the normal differentiation processes is, thus, essential for the analysis of these pathologies. Our gene expression analysis, employing purified human CTB and EVT cells, demonstrates a mechanism similar to the epithelial–mesenchymal transition (EMT), which underlies CTB–EVT differentiation. In parallel, DNA methylation profiling shows that CTB cells, already hypomethylated relative to non-trophoblast cell lineages, show further genome-wide hypomethylation in the transition to EVT. A small subgroup of genes undergoes gains of methylation (GOM), associated with differential gene expression (DE). Prominent in this GOM-DE group are genes involved in epithelial–mesenchymal plasticity (EMP). An exemplar is the transcription factor RUNX1, for which we demonstrate a functional role in regulating the migratory and invasive capacities of trophoblast cells. This analysis highlights epigenetically regulated genes acting to underpin the epithelial–mesenchymal plasticity characteristic of human trophoblast differentiation. Identification of these elements provides important information for the obstetric disorders in which these processes are dysregulated. Full article

Purpose: Preeclampsia is a serious pregnancy complication without curative treatment. The central nervous system (CNS) is affected in severe cases of preeclampsia. Until now, no biomarker or other predictive method has been established for predicting severe CNS injury, including the development of eclampsia and/or long-term complications. In this systematic review, we aimed to investigate the association between maternal blood (serum or plasma) S100B levels and preeclampsia, focusing on its predictive value and correlation with the severity of the disease, with a particular focus on neurological symptoms. Methods: A search of online databases, including Medline via PubMed, Scopus databases, and Web of Science, was performed based on the PRISMA guidelines for systematic reviews. Results: Ten case–control studies that met the inclusion criteria were identified and further evaluated according to the Newcastle–Ottawa Scale (NOS). All of the studies revealed that S100B blood levels were higher in preeclampsia compared to uncomplicated pregnancies before onset, after its diagnosis, and one year postpartum. Its predictive value seems to be adequate long before the onset of preeclampsia, especially in the early third trimester. Furthermore, its levels seem to correlate with severe complications during pregnancy, such as eclampsia and HELLP syndrome, as well as neurological dysfunction postpartum. Conclusions: S100B is a promising biomarker for the prediction of acute and long-term CNS injury in preeclampsia. Still, additional studies should be conducted in order to establish a standard method of measurement and solidify its clinical use in preeclampsia management, providing individualized care in order to improve perinatal outcomes and provide personalized follow-up postpartum. Full article

Background: Mitochondria are essential for placental function as they regulate energy metabolism, oxidative balance, and apoptotic signaling. Increasing evidence suggests that placental mitochondrial dysfunction may play a role in the development of many poor perinatal outcomes, including preeclampsia, intrauterine growth restriction (IUGR), premature birth, and stillbirth. Nonetheless, no systematic review has thoroughly investigated this connection across human research. This study aims to consolidate evidence from human research concerning the link between placental mitochondrial dysfunction and negative birth outcomes. Methods: A systematic search of PubMed, Scopus, and Web of Science identified human research examining placental mitochondrial features (e.g., mtDNA copy number, ATP production, oxidative stress indicators) in connection with adverse pregnancy outcomes. Methodological variety resulted in narrative data extraction and synthesis. Results: Twenty-nine studies met the inclusion criteria. Mitochondrial dysfunction was consistently associated with PE, IUGR, FGR, and PTB. The most often observed outcomes included diminished mtDNA copy number, decreased ATP production, elevated reactive oxygen species (ROS), and disrupted mitochondrial dynamics, characterized by increased DRP1 and decreased MFN2. Early-onset preeclampsia and symmetric fetal growth restriction exhibited particularly severe mitochondrial abnormalities, indicating a primary placental origin of the condition. Conclusions: A significant factor contributing to adverse pregnancy outcomes is the dysfunction of placental mitochondria. The analogous molecular signatures across many disorders suggest promising avenues for developing targeted therapies aimed at improving maternal–fetal health and predictive biomarkers. Full article

Proteomics has emerged as a transformative tool in biomedical research, enabling comprehensive characterization of protein profiles in complex biological systems. In preeclampsia (PE) research, quantitative proteomic analyses of plasma and serum have revealed critical insights into disease mechanisms and potential biomarkers. Through a systematic review of 17 studies (2009–2024), we identified 561 differentially expressed plasma/serum proteins (p < 0.05) in PE patients versus healthy controls, with 122 proteins consistently replicated across ≥2 independent studies. Stratified analysis by clinical subtype (early-vs. late-onset PE) demonstrated both concordant and divergent protein expression patterns, reflecting heterogeneity in PE pathophysiology, methodological variations (e.g., sample processing, proteomic platforms), and differences between discovery-phase and targeted validation studies. The trimester-specific biomarker panels proposed here offer a framework for future large-scale, multicenter validation. By integrating advanced proteomic technologies with standardized preanalytical and analytical protocols, these findings advance opportunities for early prediction (first-trimester biomarker signatures); mechanistic insight (complement system involvement); and personalized management (subtype-specific therapeutic targets). This work underscores the potential of proteomics to reshape PE research, from molecular discovery to clinical translation, ultimately improving outcomes for this leading cause of maternal and perinatal morbidity. Full article

Preeclampsia (PE), a pregnancy complication characterized by high blood pressure and organ damage, has been suggested to be associated with mitochondrial dysfunction, although evidence remains limited. This study aimed to investigate the activity of oxidative phosphorylation (OXPHOS) enzymes and the expression of related proteins in placental tissues from women diagnosed with early-onset preeclampsia (eoPE, <34 weeks of gestation), late-onset preeclampsia (loPE, ≥34 weeks of gestation), and normotensive controls. Placental samples were analyzed using immunohistochemistry, western blotting, and enzymatic activity assays to assess the activity and expression of OXPHOS complexes. Complex I activity was increased by 80% in eoPE and 56% in loPE, with positive correlations between normalized complex I expression, gestational age at delivery (r = 0.85, p = 0.01), and birth weight (r = 0.88, p = 0.004) in loPE. Relative complex II expression in loPE showed positive correlations with pregnancy duration (r = 0.76, p = 0.03) and birth weight (r = 0.77, p = 0.03), while in controls, complex II expression correlated with pregnancy duration (r = 0.64, p = 0.03). Additionally, complex IV enzyme activity in eoPE was negatively correlated with maternal age at birth (r = −0.69, p = 0.03). The observed correlations highlight mitochondrial metabolism as a promising biomarker for predicting disease progression and guiding therapeutic interventions in preeclampsia. Unraveling its precise role in PE pathogenesis is critical to advancing diagnostic precision and improving maternal-fetal outcomes. Full article

Oxidative stress is a critical factor in the onset of gestational diabetes and its associated complication, pre-eclampsia. This study aimed to evaluate (1) reactive oxygen species, reactive nitrogen species, and superoxide radical levels as indicators of oxidative stress, (2) lipid and protein oxidation, (3) antioxidant enzyme activity, and (4) cytokine production in pregnant women with gestational diabetes, as well as those with both gestational diabetes and pre-eclampsia, comparing these with biomarkers of gestational diabetes mellitus. The study categorized pregnant patients with gestational diabetes mellitus into two groups based on the presence of new-onset hypertension, measured twice every four hours, and a 24 h urine protein test showing 300 mg/day or ≥1+ proteinuria detected via a visual dipstick at ≥20 weeks of gestation. These groups were compared with normotensive pregnant patients. The findings revealed that patients with both gestational diabetes and pre-eclampsia exhibited significantly elevated levels of reactive oxygen species, cytokine production, and lipid and protein oxidation end products compared to normotensive pregnant women. Additionally, these patients showed reduced nitric oxide (•NO) levels, impaired NO synthase systems (eNOS and iNOS), and decreased antioxidant enzyme activities (p < 0.05). These results indicate that patients with gestational diabetes and pre-eclampsia are unable to counteract oxidative stress effectively. The study underscores the compromised oxidative status as a contributing factor to these complications. The findings provide insights into the pathogenesis of gestational diabetes and the subsequent pre-eclampsia, the role of oxidative stress, and the resulting complications. Measuring oxidative stress levels and inflammatory biomarkers could help in the early detection and prediction of gestational-diabetes-related complications in pregnant women. Full article