Biomarker For Preeclampsia Research Articles

Lysosome-related biomarkers in preeclampsia and cancers: Machine learning and bioinformatics analysis

BackgroundLysosomes serve as regulatory hubs, and play a pivotal role in human diseases. However, the precise functions and mechanisms of action of lysosome-related genes remain unclear in preeclampsia and cancers. This study aimed to identify lysosome-related biomarkers in preeclampsia, and further explore the biomarkers shared between preeclampsia and cancers. Materials and methodsWe obtained GSE60438 and GSE75010 datasets from the Gene Expression Omnibus database, pre-procesed them and merged them into a training cohort. The limma package in R was used to identify the differentially expressed mRNAs between the preeclampsia and normal control groups. Differentially expressed lysosome-related genes were identified by intersecting the differentially expressed mRNAs and lysosome-related genes obtained from Gene Ontology and GSEA databases. Gene Ontology annotations and Kyoto Encyclopedia of Genes and Genomes enrichment analysis were performed using the DAVID database. The CIBERSORT method was used to analyze immune cell infiltration. Weighted gene co-expression analyses and three machine learning algorithm were used to identify lysosome-related diagnostic biomarkers. Lysosome-related diagnostic biomarkers were further validated in the testing cohort GSE25906. Nomogram diagnostic models for preeclampsia were constructed. In addition, pan-cancer analysis of lysosome-related diagnostic biomarkers were identified by was performed using the TIMER, Sangebox and TISIDB databases. Finally, the Drug-Gene Interaction, TheMarker and DSigDB Databases were used for drug-gene interactions analysis. ResultsA total of 11 differentially expressed lysosome-related genes were identified between the preeclampsia and control groups. Three molecular clusters connected to lysosome were identified, and enrichment analysis demonstrated their strong relevance to the development and progression of preeclampsia. Immune infiltration analysis revealed significant immunity heterogeneity among different clusters. GBA, OCRL, TLR7 and HEXB were identified as lysosome-related diagnostic biomarkers with high AUC values, and validated in the testing cohort GSE25906. Nomogram, calibration curve, and decision curve analysis confirmed the accuracy of predicting the occurrence of preeclampsia based on OCRL and HEXB. Pan-cancer analysis showed that GBA, OCRL, TLR7 and HEXB were associated with the prognosis of patients with various tumors and tumor immune cell infiltration. Twelve drugs were identified as potential drugs for the treatment of preeclampsia and cancers. ConclusionThis study identified GBA, OCRL, TLR7 and HEXB as potential lysosome-related diagnostic biomarkers shared between preeclampsia and cancers.

Statins Prevent the Deleterious Consequences of Placental Chemerin Upregulation in Preeclampsia.

Chemerin, an inflammatory adipokine, is upregulated in preeclampsia, and its placental overexpression results in preeclampsia-like symptoms in mice. Statins may lower chemerin. Chemerin was determined in a prospective cohort study in women suspected of preeclampsia and evaluated as a predictor versus the sFlt-1 (soluble fms-like tyrosine kinase-1)/PlGF (placental growth factor) ratio. Chemerin release was studied in perfused placentas and placental explants with or without the statins pravastatin and fluvastatin. We also addressed statin placental passage and the effects of chemerin in chorionic plate arteries. Serum chemerin was elevated in women with preeclampsia, and its addition to a predictive model yielded significant effects on top of the sFlt-1/PlGF ratio to predict preeclampsia and its fetal complications. Perfused placentas and explants of preeclamptic women released more chemerin and sFlt-1 and less PlGF than those of healthy pregnant women. Statins reversed this. Both statins entered the fetal compartment, and the fetal/maternal concentration ratio of pravastatin was twice that of fluvastatin. Chemerin constricted plate arteries, and this was blocked by a chemerin receptor antagonist and pravastatin. Chemerin did not potentiate endothelin-1 in chorionic plate arteries. In explants, statins upregulated low-density lipoprotein receptor expression, which relies on the same transcription factor as chemerin, and NO release. Chemerin is a biomarker for preeclampsia, and statins both prevent its placental upregulation and effects, in an NO and low-density lipoprotein receptor-dependent manner. Combined with their capacity to improve the sFlt-1/PlGF ratio, this offers an attractive mechanism by which statins may prevent or treat preeclampsia.

Chimeric RNA landscape in the placenta: A transcriptomic analysis revealing novel diagnostic biomarkers forpreeclampsia

Chimeric RNA landscape in the placenta: A transcriptomic analysis revealing novel diagnostic biomarkers forpreeclampsia

Preeclampsia Management and Maternal Ophthalmic Artery Doppler Measurements between 19 and 23 Weeks of Gestation.

Background: The ophthalmic Doppler is a reliable and impartial way to assess the severity of preeclampsia (PE). The study aimed to assess the potential utility of Doppler measurements of the maternal ophthalmic arteries during the weeks 19-23 of gestation, both independently and in combination with established biomarkers for PE. Methods: A prospective cohort study was conducted involving women who were recruited from a variety of standard appointments, including booking, scanning, and regular prenatal visits. A total of 200 women that were divided into high-risk and low-risk groups for developing PE were involved during the period between April 2023 and November 2023. Results: The ophthalmic ratio had significantly higher values in high-risk patients than in low-risk women (p = 0.000). There was a significant relationship between PSV2/PSV1 and gestational age at birth in women with PE compared to the ones who did not develop PE. Conclusions: An ophthalmic artery Doppler can play a crucial role in the early detection of PE, allowing for timely intervention and management. Incorporating the ophthalmic artery Doppler as a screening tool for PE in Bulgaria has the potential to improve early detection, risk stratification, and overall maternal and fetal health outcomes.

Is salivary uric acid, a putative biomarker of pre-eclampsia, of maternal, placental, or fetal origin?

ObjectivesIncreased salivary uric acid (sUA) represents a potential biomarker predictive of pre-eclampsia (PE), but its origin is unclear. The study explores whether sUA levels reflect maternal or feto-placental physiological stress and whether sUA levels in these cases correlate with amniotic fluid (fetal origin), maternal blood (maternal origin), or cord blood (fetal vs placental origin). Study designPregnant women (n = 39) undergoing amniotomy or caesarean section after 34 gestational weeks were designated into three groups of either maternal, feto-placental, or no signs of physiological stress: women (n = 15) in the established first phase of active labour and without any signs of fetal growth restriction (FGR) or PE were assigned to the maternal stress group, women (n = 6) with an ultrasound-based diagnosis of FGR, with or without PE, were assigned to the feto-placental stress group, and women (n = 18) not yet in active labour and without any signs of FGR or PE, were assigned to the control group. Uric acid levels in corresponding samples of amniotic fluid, saliva, maternal blood, and cord blood were compared between groups and between body compartments within each group. ResultsThe feto-placental stress group showed increased UA levels in saliva (median, interquartile range [IQR]: 0.47 [0.38] mmol/L, P = 0.023) and maternal blood (0.42 [0.13] mmol/L, P = 0.032), but no differences in amniotic fluid or cord blood compared with the other groups. Within the control and maternal stress group, sUA levels were lower compared with maternal blood (0.20 [0.08] vs 0.25 [0.08] mmol/L, Pcontrol = 0.018; 0.20 [0.06] vs 0.26 [0.08] mmol/L, Pmaternal = 0.001) and highest in amniotic fluid (control group (0.49 [0.18] mmol/L): Pmaternal,blood = 0.001, Pumbilical,artery = <0.001, Pumbilical,vein = <0.001, Psaliva = <0.001) (maternal stress group (0.56 [0.23] mmol/L): Pmaternal,blood = 0.021, Pumbilical,artery = 0.006, Pumbilical,vein = 0.004, Psaliva = 0.003). Levels did not differ between compartments in the feto-placental stress group. ConclusionsSalivary and maternal blood UA levels were increased in the feto-placental stress group with salivary levels increasing more than blood levels compared with the maternal stress and control groups, whilst UA in amniotic fluid were not different between the groups, suggesting a placental origin and potential use of sUA as a biomarker of placental dysfunction, including FGR and severe PE.

Biomarkers of Pre-eclampsia in Pregnant Women With Gestational Diabetes and Pre-existing Type 2 Diabetes: A Systematic Review.

Pre-eclampsia (PE) is one of the leading causes of maternal and perinatal health morbidity, producing more than 4.6% of complications in pregnancy worldwide. This systematic review was conducted to determine the significance of specific biomarkers in predicting PE in gestational diabetes mellitus (GDM) and type 2 diabetes mellitus (DM). The review measured and explained the significant abnormalities in lipids, blood glucose, cytokines, inflammatory markers, placental proteins, urinary proteins, and other serum biomarkers that contribute to the development of PE in GDM and type 2 DM populations. We searched CINAHL, EMBASE, Medline, Maternity and Infant care, Scopus, and Web of Science.Studies were included if they had a measurable component in the blood serum or urine of women who developed PE and suffered from GDM or pre-existing type 2 DM.A narrative synthesis was conducted instead of a meta-analysis due to the high heterogeneity of data from the studies. A total of 2,593 studies were screened, producing eight relevant studies. Twenty-seven different biomarkers were investigated from the study group of 40 to 1,344 participants. No single biomarker was identified; however, there is a need for further research on specific biomarkers of PE, especially in CRP, FABP4, and microalbuminuria in the GDM-PE group and calprotectin in the type 2 DM population.Many biomarkers were identified as practical in predicting PE when combined with other biomarkers and more data are required to verify the predictability of the diagnostic markers in pregnant women.

Potential urinary biomarkers in preeclampsia: a narrative review.

Preeclampsia (PE) is a highly relevant pregnancy-related disorder. An early and accurate diagnosis is crucial to prevent major maternal and neonatal complications and mortality. Due to the association of kidney dysfunction with the pathophysiology of the disease, urine samples have the potential to provide biomarkers for PE prediction, being minimally invasive and easy to perform. Therefore, searching for novel biomarkers may improve outcomes. This narrative review aimed to summarize the scientific literature about the traditional and potential urinary biomarkers in PE and to investigate their applicability to screen and diagnose the disorder. A non-systematic search was performed in PubMed/MEDLINE, Scopus, and SciELO databases. There is significant divergence in the literature regarding traditionally used serum markers creatinine, cystatin C, and albuminuria, accuracy in PE prediction. As for the potential renal biomarkers investigated, including vascular epithelial growth factor (VEGF), placental growth factor (PlGF), and soluble fms-like tyrosine kinase (sFlt-1), urinary levels of PlGF and sFtl-1/PlGF ratio in urine seem to be the most promising as screening tests. The assessment of the global load of misfolded proteins through urinary congophilia, podocyturia, and nephrinuria has also shown potential for screening and diagnosis. Studies regarding the use of proteomics and metabolomics have shown good accuracy, sensitivity, and specificity for predicting the development and severity of PE. However, there are still many divergences in the literature, which requires future and more conclusive research to confirm the predictive role of urinary biomarkers in pregnant women with PE.

Novel Associations Between Mid-Pregnancy Cardiovascular Biomarkers and Preeclampsia: An Explorative Nested Case-Control Study.

Prediction of women at high risk of preeclampsia is important for prevention and increased surveillance of the disease. Current prediction models need improvement, particularly with regard to late-onset preeclampsia. Preeclampsia shares pathophysiological entities with cardiovascular disease; thus, cardiovascular biomarkers may contribute to improving prediction models. In this nested case-control study, we explored the predictive importance of mid-pregnancy cardiovascular biomarkers for subsequent preeclampsia. We included healthy women with singleton pregnancies who had donated blood in mid-pregnancy (~ 18weeks' gestation). Cases were women with subsequent preeclampsia (n = 296, 10% of whom had early-onset preeclampsia [< 34weeks]). Controls were women who had healthy pregnancies (n = 333). We collected data on maternal, pregnancy, and infant characteristics from medical records. We used the Olink cardiovascular II panel immunoassay to measure 92 biomarkers in the mid-pregnancy plasma samples. The Boruta algorithm was used to determine the predictive importance of the investigated biomarkers and first-trimester pregnancy characteristics for the development of preeclampsia. The following biomarkers had confirmed associations with early-onset preeclampsia (in descending order of importance): placental growth factor (PlGF), matrix metalloproteinase (MMP-12), lectin-like oxidized LDL receptor 1, carcinoembryonic antigen-related cell adhesion molecule 8, serine protease 27, pro-interleukin-16, and poly (ADP-ribose) polymerase 1. The biomarkers that were associated with late-onset preeclampsia were BNP, MMP-12, alpha-L-iduronidase (IDUA), PlGF, low-affinity immunoglobulin gamma Fc region receptor II-b, and T cell surface glycoprotein. Our results suggest that MMP-12 is a promising novel preeclampsia biomarker. Moreover, BNP and IDUA may be of value in enhancing prediction of late-onset preeclampsia.

UNLOCKING THE FUTURE OF MATERNAL HEALTH: PLATELET INDICES AS PREDICTORS OF PREECLAMPSIA

Objective: Preeclampsia is a dangerous pregnancy condition that puts the health of the mother and fetus at great risk. Early diagnosis and treatment of this illness depend on predictive signs. Because of their correlation with coagulation problems, platelet indices, such as platelet count (PC), platelet distribution width (PDW), mean platelet volume (MPV), and platelet crit (PCT), may be useful as biomarkers for preeclampsia. The purpose of this study is to find out how well platelet indices can predict preeclampsia.&#x0D; Methods: From Mar 1, 2021, to Feb 28, 2022, the study was carried out at the Kamla Nehru State Hospital for Mother and Child in Shimla, Himachal Pradesh. Pregnant women without pre-existing illnesses were removed, and those with normotension who had singleton pregnancies after 20 w of gestation were included. Patients were classified according to the degree and course of preeclampsia, and platelet indices were monitored during pregnancy. To ascertain the significance of fluctuations in the platelet index, statistical tests were conducted and data were analyzed using SPSS-PC-25.&#x0D; Results: According to the study, patients with preeclampsia (PE) and normotensive individuals had significantly different platelet indices. Compared to people with normotension, PE patients showed higher platelet distribution width (PDW), a lower platelet count, and an elevated mean platelet volume (MPV). Interestingly, MPV increased noticeably in PE before blood pressure rose. In severe PE patients, the platelet count drastically reduced. The potential of MPV and platelet count as predictors of PE was shown by Receiver Operating Characteristic (ROC) curve analysis. These results demonstrate the importance of platelet indices in the diagnosis of PE and the potential use of these indices as early indicators of this hypertensive condition in pregnancy.&#x0D; Conclusion: Platelet indices show potential as early indicators for identifying and tracking preeclampsia, especially platelet count, MPV, and PDW. Monitoring platelet indices in addition to blood pressure may help determine the extent and course of the illness, which might lead to better results for both the mother and the fetus. To improve clinical usefulness and improve prediction models, more research in this area is necessary.

Ophthalmic artery Doppler at 36 weeks' gestation in prediction of pre-eclampsia: validation and update of previous model.

To validate and extend a model incorporating maternal ophthalmic artery Doppler at 35-37 weeks' gestation in the prediction of subsequent development of pre-eclampsia (PE). This was a prospective validation study of screening for PE (defined according to the 2019 American College of Obstetricians and Gynecologists criteria) by maternal ophthalmic artery peak systolic velocity (PSV) ratio in 6746 singleton pregnancies undergoing routine care at 35 + 0 to 36 + 6 weeks' gestation (validation dataset). Additionally, the data from the validation dataset were combined with those of 2287 pregnancies that were previously used for development of the model (training dataset), and the combined data were used to update the original model parameters. The competing-risks model was used to estimate the individual patient-specific risk of delivery with PE at any time and within 3 weeks from assessment by a combination of maternal demographic characteristics and medical history with PSV ratio alone and in combination with the established PE biomarkers of mean arterial pressure (MAP), uterine artery pulsatility index (UtA-PI), serum placental growth factor (PlGF) and serum soluble fms-like tyrosine kinase-1 (sFlt-1). We evaluated the predictive performance of the model by examining, first, the ability to discriminate between the PE and non-PE groups using the area under the receiver-operating-characteristics curve and the detection rate (DR) at fixed screen-positive (SPR) and false-positive rates of 10% and, second, calibration by measuring the calibration slope and calibration-in-the-large. McNemar's test was used to compare the performance of screening by a biophysical test (maternal factors, MAP, UtA-PI and PSV ratio) vs a biochemical test (maternal factors, PlGF and sFlt-1), low PlGF concentration (< 10th percentile) or high sFlt-1/PlGF concentration ratio (> 90th percentile). In the validation dataset, the performance of screening by maternal factors and PSV ratio for delivery with PE within 3 weeks and at any time after assessment was consistent with that in the training dataset, and there was good agreement between the predicted and observed incidence of PE. In the combined data from the training and validation datasets, good prediction for PE was achieved in screening by a combination of maternal factors, MAP, UtA-PI, PlGF, sFlt-1 and PSV ratio, with a DR, at a 10% SPR, of 85.0% (95% CI, 76.5-91.4%) for delivery with PE within 3 weeks and 65.7% (95% CI, 59.2-71.7%) for delivery with PE at any time after assessment. The performance of a biophysical test was superior to that of screening by low PlGF concentration or high sFlt-1/PlGF concentration ratio but not significantly different from the performance of a biochemical test combining maternal factors with PlGF and sFlt-1 for both PE within 3 weeks and PE at any time after assessment. Maternal ophthalmic artery PSV ratio at 35-37 weeks' gestation in combination with other biomarkers provides effective prediction of subsequent development of PE. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.

Point-of-care diagnosis of pre-eclampsia based on microfiber Bragg grating biosensor

Pre-eclampsia is a serious multi-organ complication that severely threatens the safety of pregnant women and infants. To accurate and timely diagnose pre-eclampsia, point-of-care (POC) biosensing of the specific biomarkers is urgently required. However, one of the key biomarkers of pre-eclampsia, placental growth factor (PlGF), has a reduced level of expression in patients, which challenges the quantification capability and Limit-of-detection (LOD) of biosensors. Herein, we reported a microfiber Bragg grating biosensor for the quantification of PlGF in clinical serum samples. The Bragg grating was inscribed in a unilateral tapered fiber to generate the segmented Fabry-Perot spectrum for improving the capability of detection. Furthermore, a temperature-calibrated Bragg grating was added to enable dual parametric detection of PlGF and temperature simultaneously for removing the crosstalk. Finally, the biosensor was envisaged to be perfectly compatible with microfluidic chips, and thus dramatically reducing the sample consumption to as small as 10 μL. The proposed biosensor can respond to PlGF with concentrations ranging from 5 to 120 pg mL−1, attaining a LOD of 5 pg mL−1 of clinical relevance. More importantly, the biosensor achieved micro volume detection of clinical serum samples from patients, and the ROC curve with an AUC of 0.977 confirmed the viability of the device. Our study paves the way to a new idea for cost-effective and high-precision screening of patients with pre-eclampsia, and hence envisages a promising prospect for point-of-care (POC) diagnosis of patients with pre-eclampsia.

Autophagy-related biomarkers in preeclampsia: the underlying mechanism, correlation to the immune microenvironment and drug screening

BackgroundPreeclampsia is a life-threatening disease of pregnancy that lacks effective pharmaceuticals which can target its pathogenesis. Since preeclampsia involves complex pathological processes, including autophagy, this study aims to explore autophagy-related mechanisms of preeclampsia and to screen potential drugs.MethodsFirstly, the datasets GSE75010, GSE24129, GSE66273, and autophagic genes lists were downloaded from public databases. Then, a weighted gene co-expression network analysis (WGCNA) was applied to filter autophagic-related hub genes of preeclampsia. The differential expression levels of the hub genes were validated with datasets GSE24129 and GSE66273. Next, the GO and KEGG enrichment, protein-protein interacting (PPI) network, as well as the downstream pathways was analyzed via the starBase, STRING and Cytoscape to determine the functions and regulatory network of the hub genes. Additionally, the immune microenvironment of preeclampsia was investigated by the CIBERSORTX database. Finally, three herb ingredients, berberine, baicalein, and luteolin were screened by molecular docking in comparison to pravastatin, metformin, and aspirin, to predict potential drugs for treating preeclampsia.ResultsA total of 54 autophagy-related genes were filtered by WGCNA. After filtering with |GS| > 0.5 and |MM| > 0.8, three hub genes, namely PKM, LEP, and HK2, were identified and validated. Among these genes, PKM and LEP were overexpressed in women older than 35 years old ( p<0.05; p<0.05); the expression of PKM, LEP, and HK2 differed remarkably in women with different BMI (all p<0.05); PKM overexpressed in women with hypertension (p<0.05). The regulatory network of hub genes demonstrated that they were mainly enriched in metabolic pathways, including the AMPK signaling pathway, glucagon signaling pathway, adipocytokine signaling pathway, and central carbon metabolism. Then, immune microenvironment analysis turned out that M2 macrophages were reduced in preeclampsia women (p<0.0001) and were negatively correlated with the expression of PKM (r=-0.2, p<0.05), LEP (r=-0.4, p<0.0001), and HK2 (r=-0.3, p<0.001). Lastly, molecular docking showed baicalein and luteolin could bind intimately to hub genes.ConclusionPKM, LEP, and HK2 could be promising biomarkers for preeclampsia, which might regulate the pathogenesis of preeclampsia via metabolism pathways and immune microenvironment. Baicalein and luteolin could be potential therapeutics for preeclampsia.

Novel insights into the complex interplay of immune dysregulation and inflammatory biomarkers in preeclampsia and fetal growth restriction: A two-step Mendelian randomization analysis

BackgroundThe relationship between genetic immune dysregulation and the occurrence of preeclampsia (PE) or PE with fetal growth restriction (PE with FGR) has yielded inconsistent findings, and the underlying mediators of this association remain elusive. We aimed to explore the causal impact of genetic immune dysregulation on the risk of PE or PE with FGR and to elucidate the role of specific transcriptomes in mediating this relationship. MethodsA two-step Mendelian randomization (MR) analysis was performed to explore the link between immune dysregulation and PE or PE with FGR, as well as to identify potential inflammatory biomarkers that act as mediators. GWAS summary data for outcomes were obtained from the FinnGen dataset. The analyses encompassed five systemic immune-associated diseases, four chronic genital inflammatory diseases, and thirty-one inflammatory biomarkers. Summary-data-based MR (SMR) and HEIDI analysis were conducted to test whether the effect size of single nucleotide polymorphisms (SNPs) on outcomes was mediated by the expression of immune-associated genes. ResultsThe primary univariable analysis revealed a significant positive correlation between systemic lupus erythematosus (SLE), type 1 diabetes (T1D), type 2 diabetes (T2D), and rheumatoid arthritis (RA) with the risk of PE or PE with FGR. Surprisingly, a counterintuitive finding showed a significant negative association between endometriosis of pelvic peritoneum (EMoP) and the risk of PE with FGR. None of the inflammatory factors had a causal relationship with PE or PE with FGR. However, there was a significant association between lymphocyte count and the risk of PE with FGR. Within the lymphocyte subset, both the proportion of Natural Killer (NK) cells and absolute counts of naïve CD4+ T cells demonstrated significant effects on the risk of PE with FGR. Two-step MR analysis underscored the genetically predicted lymphocyte count as a significant mediator between T1D and PE with FGR. Additionally, SMR analysis indicated the potential involvement of SH2B3 in the occurrence of PE with FGR. ConclusionsOur findings provided substantial evidence of the underlying causal relationship between immune dysregulation and PE or PE with FGR and some of these diseases proved to accelerate immune cells disorders and then contribute to the risk of incident PE or PE with FGR.

MTHFR A1298C Polymorphism and Risk of Preeclampsia: A Meta-Analysis

Background: Published research findings regarding the relationship between the methylenetetrahydrofolate reductase (MTHFR) A1298C polymorphism and the risk of preeclampsia (PE) have generated conflicting results. A meta-analysis was conducted to investigate whether the MTHFR A1298C polymorphism is associated with preeclampsia. Methods: We conducted a systematic search across several databases, including PubMed, Embase, Web of science, China National Knowledge Infrastructure, and Chinese Biomedicine Databases, to identify relevant studies. We then calculated pooled odds ratios (ORs) and their corresponding 95% confidence intervals (CIs) to assess the association between the MTHFR A1298C polymorphism and preeclampsia (PE) risk. Results: A total of 11 studies were enrolled in this meta-analysis. The pooled analyses revealed that MTHFR A1298C polymorphism significantly decreased the risk of PE (allele contrast (A (alanine) vs. C (glutamate) ): OR, 0.81; 95% CI, 0.71–0.93, p = 0.207; homozygote (AA vs. CC): OR, 0.57; 95% CI, 0.40–0.79, p = 0.056; heterozygote (AC vs. CC): OR, 0.62; 95% CI, 0.45–0.87, p = 0.010; dominant model (AA + AC vs. CC): OR, 0.59; 95% CI, 0.43–0.81, p = 0.031; recessive model (AA vs. AC + CC): OR, 0.83; 95% CI, 0.70–0.98), p = 0.817. Conclusion: Present meta-analysis reveals that MTHFR A1298C variant may serve as genetic biomarkers of PE. The study was registered on PROSPERO (https://www.crd.york.ac.uk/prospero/), registration number: CRD42023459681.

Prognostic Biomarkers of Pre-Eclampsia in Pregnant Women

Summary. According to various authors, the incidence of preeclampsia (PE) in pregnant women in our country ranges from 8 to 20% and does not tend to decrease. It has been shown that the pathogenesis of preeclampsia fits into the systemic inflammatory response syndrome with disturbances in the immune system and an imbalance in cytokine regulation. The aim of the study was to study pro-inflammatory (IL-1β, IL-6, IL-8) and anti-inflammatory (IL-4, IL-10) cytokines in women with preeclampsia of varying severity. Material and methods. We examined 76 pregnant women with PE aged from 24 to 36 years at a gestation period of 28–38 weeks. Of these, 42 developed PE (main group), and 34 women had no symptoms of PE (comparison group). 28 women with a physiological pregnancy formed the control group. The levels of pro- and anti-inflammatory cytokines (IL-1β, IL-6, IL-8, IL-4 and IL-10) in blood serum were studied by ELISA. Results. In pregnant women with PE upon admission to the hospital, the blood serum levels of IL-1β increased by 1.3 times (p &lt; 0.05), IL-8 by 7 times (p &lt; 0.001) and a decrease in the level of IL-4 by 2 times (p &lt; 0.001). And in pregnant women without signs of PE, these changes in cytokine synthesis were less pronounced (p &lt; 0.01). Conclusion. Maintaining a dynamic balance in the cytokine system plays an important role for the normal development of pregnancy. Th2-type cytokines promote normal trophoblast differentiation and its full invasion and, therefore, mediate the prolongation of physiological pregnancy. Switching to the synthesis of Th1-type cytokines and their enhanced production leads to disruption of trophoblast differentiation and invasion with the development of pregnancy pathology.

Significance of maternal serum pentraxin-3 level in assessment of severity of pre-eclampsia and its effect on neonatal outcome

Abstract Background: Preeclampsia is a multisystem, highly variable disorder specific to pregnancy. Pentraxin-3 (PTX3), a recently identified multimeric inflammatory mediator, it can be considered as a promising biomarker of preeclampsia and its severity. Objective: To determine the association between maternal serum PTX3 level and preeclampsia, its severity and its effect on the neonatal outcome. Materials and Methods: This case control study was carried-out at the Department of Obstetrics and Gynecology, Azadi Teaching Hospital, Kirkuk City, Iraq from 1st of February, till 30th of November 2021. The study included 92 pregnant women at term who were divided into three groups (mild preeclampsia, severe preeclampsia, and pregnant without preeclampsia and regarded as control group). The neonatal outcomes were documented. PTX3 was measured in the serum using human PTX3 ELISA KIT. Results: PTX3 cutoff value of ≥120.8 pg/mL was associated with sensitivity of 100% and specificity of 96%. The correlation between PTX3 and urea, body mass index, birth weight, APGAR (A for neonatal appearance, P for heart rate, G for grimace, A for activity, R for respiration) score in 1 and 5 minutes showed that, there was significant positive weak correlation between PTX3 and urea, in which an increase in urea was associated with an increase in PTX3. Also, there was significant negative weak correlation between PTX3 with birth weight and APGAR 1, in which an increase in PTX3 was associated with a decrease in birth weight and APGAR in 1 min. Conclusion: PTX3 is one of the biochemical markers in diagnosing preeclampsia and distinguishing its severity and can be used as a marker for early neonatal outcome in preeclampsia.

A cross-sectional analysis of syncytiotrophoblast membrane extracellular vesicles-derived transcriptomic biomarkers in early-onset preeclampsia.

Preeclampsia (PE) is a pregnancy-specific hypertensive disorder affecting 2%-8% of pregnancies worldwide. Biomarker(s) for the disorder exists, but while these have excellent negative predictive value, their positive predictive value is poor. Extracellular vesicles released by the placenta into the maternal circulation, syncytiotrophoblast membrane extracellular vesicles (STB-EVs), have been identified as being involved in PE with the potential to act as liquid biopsies. The objective of this study was to identify the difference in the transcriptome of placenta and STB-EVs between preeclampsia and normal pregnancy (NP) and mechanistic pathways. We performed RNA-sequencing on placental tissue, medium/large and small STB-EVs from PE (n = 6) and NP (n = 6), followed by bioinformatic analysis to identify targets that could be used in the future for EV-based diagnostic tests for preeclampsia. Some of the identified biomarkers were validated with real-time polymerase chain reactions. Our analysis identified a difference in the transcriptomic STB-EV cargo between PE and NP. We then identified and verified the differential expression of FLNB, COL17A1, SLC45A4, LEP, HTRA4, PAPP-A2, EBI3, HSD17B1, FSTL3, INHBA, SIGLEC6, and CGB3. Our analysis also identified interesting mechanistic processes via an in silico prediction of STB-EV-based mechanistic pathways. In this study, using comprehensive profiling of differentially expressed/carried genes of three linked sample subtypes in PE, we identified potential biomarkers and mechanistic gene pathways that may be important in the pathophysiology of PE and could be further explored in future studies.

Urinary Nephrin Levels Among Pregnant Women With Preeclampsia in Lagos, Southwest Nigeria: An Analytical Cross-Sectional Study.

Hypertensive disorders in pregnancy are one of the leading causes of maternal and perinatal morbidity and mortality worldwide. The clinical utility of urinary nephrin as a diagnostic biomarker of preeclampsia is currently of research interest. However, this is yet to gain significant traction within clinical settings. We evaluated the association between maternal urinary nephrin levels and the occurrence and severity of preeclampsia among pregnant women in Lagos, Nigeria. We conducted an analytical cross-sectional study involving pregnant women diagnosed with preeclampsia as well as their age- and gestational-age-matched normotensive counterparts. We tested the association between high maternal urinary nephrin levels and the occurrence of preeclampsia without and with severe features. P < 0.05 was reported as statistically significant. The study showed that for every unit increase in urinary nephrin levels, the odds of preeclampsia increased by about ninefold (adjusted Odds ratio = 8.9, 95% confidence interval: 2.8-29.2, P < 0.001). The levels of urinary nephrin increased steadily with increasing severity of the disease: 1.9 ± 0.8 ng/mL in preeclampsia without severe features, 2.7 ± 0.7 ng/mL in preeclampsia with at least one severe feature, and 3.3 ±1.1 ng/mL in eclampsia. There was an association between elevated levels of urinary nephrin and preeclampsia and its severe variant. However, there is a need for more robust studies with a longitudinal characterization of urinary nephrin levels to establish causal relationships with preeclampsia, explore other potential risk factors of preeclampsia, and define the clinical usefulness of urinary nephrin as a potentially reliable and accurate predictive marker of preeclampsia among women in low- and middle-income countries (LMIC) settings.

Abstract 11949: Novel First-Trimester Serum Biomarkers for Early Prediction of Preeclampsia

Background: Preeclampsia (PE) is a leading cause of maternal and perinatal mortality and morbidity worldwide, but effective early prediction remains a challenge due to the lack of reliable biomarkers. Research questions: Could potential imbalances in cytokines and autoimmune antibodies be detectable in the first trimester of pregnancy in women who later develop PE? Goals: Our study aims to discover novel biomarkers within the first trimester and construct an efficient predictive model to enhance early PE screening strategies. Methods: Based on the extensive human biobank of our large-scale assisted reproductive cohort platform, we measured the first-trimester serum levels of 48 cytokines, total immunoglobulins (Igs), anti-phosphatidylserine (aPS) antibodies, and several previously identified PE biomarkers—including placental growth factor (PlGF), soluble fms-like tyrosine kinase-1 (sFlt-1), and activin A—in 34 women diagnosed with PE and 34 matched normotensive controls. Results: Our analysis revealed that the PE group exhibited significantly elevated first-trimester serum levels of hepatocyte growth factor (HGF), interleukin (IL)-2Rα, IL-9, RANTES, tumor necrosis factor-β (TNF-β), total IgM, and total IgG, and aPS IgG optical density (OD) value, in addition to decreased first-trimester serum levels of PlGF and total IgA and aPS-IgG immune complexes (IC) OD value compared to the control group. The combination of the top five first-trimester serum biomarkers (total IgM, total IgG, PlGF, aPS IgG, and total IgA) achieved superior predictive value [area under the curve (AUC) and 95% confidence interval (CI): 0.983 (0.952-1.000)] for PE development compared to PlGF and PlGF/sFlt-1 independently [AUC and 95% CI: 0.825 (0.726-0.924) and 0.670 (0.539-0.800), respectively]. Conclusion: We identified novel first-trimester serum biomarkers and developed an effective prediction model integrating immune-related factors and PlGF for early PE detection, which could facilitate the development of early diagnostic strategies and provide immunological insight into the further mechanistic exploration of PE.

Progress in Research on Biomarkers of Gestational Diabetes Mellitus and Preeclampsia.

Gestational diabetes mellitus (GDM) and preeclampsia (PE) are common complications in pregnancy, with incidence rates of 1-5% and 9.4%, respectively, in China. Both these phenomena can cause adverse pregnancy outcomes and are extremely harmful to the mother and fetus. In this study, we observed that several predictive factors have important value in GDM and PE. Among the GDM group, abnormal levels of adiponectin (APN), C-reactive protein (CRP), and Leptin were observed. The coexistence of PE and GDM in the pregnant population is not uncommon. Ultimately, we discovered abnormal levels of factors such as Visfatin, Advanced oxidative protein product (AOPP), Fibroblast growth factor 21 (FGF21), and resistin in both GDM and PE groups. Particularly, the FGF21 factor holds significant importance in our research. Therefore, we need to complete the analysis and discussion of relevant predictive factors to enable early prediction and disease monitoring of GDM, PE, and other pregnancy-related disorders, ultimately contributing to the long-term health of pregnant women.