Preeclamptic Pregnancies Research Articles

Sexually dimorphic pubertal development and adipose tissue kisspeptin dysregulation in the obese and preeclamptic-like BPH/5 mouse model offspring.

Preeclampsia (PE) is a devastating hypertensive disorder of pregnancy closely linked to obesity. Long-term adverse outcomes may occur in offspring from preeclamptic pregnancies. Accordingly, sex-specific changes in pubertal development have been described in children from preeclamptic women, but the underlying mechanisms remain vastly unexplored. Features of PE are spontaneously recapitulated by the blood pressure high subline 5 (BPH/5) mouse model, including obesity and dyslipidemia in females before and throughout pregnancy, superimposed hypertension from late gestation to parturition and fetal growth restriction. A sexually dimorphic cardiometabolic phenotype has been described in BPH/5 offspring: while females are hyperphagic, hyperleptinemic, and overweight, with increased reproductive white adipose tissue (rWAT), males have similar food intake, serum leptin concentration, body weight and rWAT mass as controls. Herein, pubertal development and adiposity were further investigated in BPH/5 progeny. Precocious onset of puberty occurs in BPH/5 females, but not in male offspring. When reaching adulthood, the obese BPH/5 females display hypoestrogenism and hyperandrogenism. Kisspeptins, a family of peptides closely linked to reproduction and metabolism, have been previously shown to induce lipolysis and inhibit adipogenesis. Interestingly, expression of kisspeptins (Kiss1) and their cognate receptor (Kiss1r) in the adipose tissue seem to be modulated by the sex steroid hormone milieu. To further understand the metabolic-reproductive crosstalk in the BPH/5 offspring, Kiss1/Kiss1r expression in male and female rWAT were investigated. Downregulation of Kiss1/Kiss1r occurs in BPH/5 females when compared to males. Interestingly, dietary weight loss attenuated circulating testosterone concentration and rWAT Kiss1 downregulation in BPH/5 females. Altogether, the studies demonstrate reproductive abnormalities in offspring gestated in a PE-like uterus, which appear to be closely associated to the sexually dimorphic metabolic phenotype of the BPH/5 mouse model.

Overexpression of facilitative glucose transporter-3 and membrane procoagulation in maternal platelets of preeclamptic pregnancy

BackgroundPreeclampsia (PE) is a hypertensive disorder during pregnancy that results in significant adverse maternal and neonatal outcomes. Platelet activation is present in PE and contributes to the thrombo-hemorrhagic states of the disorder. However, the mechanisms that initiate and/or sustain platelet activation in PE are ill-defined. ObjectivesWe aimed to characterise this mechanism and the procoagulant potentials of platelets in PE. MethodsIn this quantitative observational study, we analyzed platelet procoagulant membrane dynamics in patients with PE (n = 21) compared with age-matched normotensive pregnancies (n = 20), gestational hypertension (n = 10), and non-pregnant female controls (n = 19). We analyzed fluorescently labeled indicators of platelet activation, bioenergetics, and procoagulation (phosphatidylserine exposure and thrombin generation), coupled with high-resolution imaging and thrombelastography. We then validated our findings using flow cytometry, immunoassays, classical pharmacology, and convolutional neural network analysis. ResultsPE platelets showed significant ultra-structural remodeling, are more extensively preactivated than in healthy pregnancies and can circulate as microaggregates. Preactivated platelets of PE externalized phosphatidylserine and thrombin formed on the platelet membranes. Platelets’ expression of facilitative glucose transporter-1 increased in all pregnant groups. However, PE platelets additionally overexpress glucose transporter-3 to enhance glucose uptake and sustain activation and secretion events. Although preeclampsia platelets exposed to subendothelial collagen showed incremental activation, the absolute hemostatic response to collagen was diminished, and likely contributed to greater blood loss perioperatively. ConclusionsWe revealed 2 bioenergetic mediators in the mechanism of sustained platelet procoagulation in preeclampsia. Although glucose transporter-1 and glucose transporter-3 remain elusive antiprocoagulant targets, they may be sensitive monitors of PE onset and progression.

Morphometric Analysis of Placental Terminal Villi, Capillaries, and Intervillous Space in Normal and Pre-Eclamptic Pregnancies

Background: The placenta reflects the prenatal problems that are linked to high perinatal morbidity and mortality both macroscopically and microscopically. A pregnancy syndrome called pre-eclampsia has terrible consequences for both the mother and the unborn child. It may result in more frequent inductions of labor, fetal growth limitation, respiratory issues in newborns, increased admission rates to neonatal critical care units, and an elevated risk of perinatal or fetal death. To understand the relation of preeclampsia and fetal growth identification of its effects on various components of the placenta is mandatory hence the current study was designed to evaluate the Placental Terminal Villi, Capillaries, and Intervillous Space in Normal and Pre-eclamptic Pregnancies. Methodology: It was a cross sectional study, carried out on 50 samples of placentas, out of which 25 were preeclamptic and 25 were normal. The placentas were recruited after cesarean session, processed as per guidelines and were analyzed for histopathological examination. The set inclusion criteria were Registered cases of Pre-eclampsia, Blood Pressure ≥ 140/90 mmHg, Parity 0 – 4, Age of mother (25 – 35) Years., Gestational Age (36 – 42) Weeks, Mode of delivery Cesarean Sections. The set exclusion criteria were known hypertensive patients, and patient diagnosed with other chronic illnesses. Results: Number of terminal villi, Transverse diameter of terminal villi (μm), Intervillous space (μm), and Transverse diameter of terminal villous capillaries decreased significantly (p=0.001) in preeclamptic group however, Number of terminal villous Capillaries were found to be increased in preeclamptic group (p=0.001). Conclusion: Preeclampsia leads to more significant alterations in placental structure compared to normal pregnancies, emphasizing the importance of early detection and management of this condition to improve maternal and fetal outcomes. Keywords: Pregnancy, preeclampsia, terminal villi, Intervillous space, terminal villous Capillaries

Expression of HMGB1-TLR4 in Placentas from Preeclamptic Pregnancies and Its Effect on Proliferation and Invasion of HTR-8/SVneo Cells

Objectives: Placental inflammation possibly underlies preeclampsia (PE) pathogenesis. This study aimed to investigate the expression of the high mobility box group 1 (HMGB1)-toll-like receptor 4 (TLR4) signalling pathway in preeclamptic placentas and determine whether HMGB1 regulates the biological behaviour of trophoblasts in vitro. Design: Placental biopsies were taken from 30 preeclamptic patients and 30 normotensive controls. In vitro experiments were carried out in HTR-8/SVneo human trophoblast cells. Participants/Materials, Setting, Methods: HMGB1, TLR4, and nuclear factor kappa B (NF-κB) mRNA and protein were quantified to compare their expression in human placentas from preeclamptic and normotensive pregnancies. HTR-8/SVneo cells were stimulated with HMGB1 (50–400 μg/L) for 6–48 h, and proliferation and invasion of HTR-8/SVneo cells were measured via Cell Counting Kit-8 and transwell assays. HTR-8/SVneo cells were also transfected with HMGB1 and TLR4 small interfering RNA (siRNA) to investigate the effect of knocking down these proteins. The mRNA and protein expression of TLR4, NF-κB, and matrix metalloproteinase 9 (MMP-9) were determined using quantitative real-time PCR and Western blotting, respectively. Data were analysed with either a t-test or one-way analysis of variance. Results: The mRNA and protein levels of HMGB1, TLR4, and NF-κB were significantly higher in the placentas from preeclamptic pregnancies than from normal pregnancies (p < 0.05). HMGB1 stimulation (at concentrations up to 200 μg/L) of HTR-8/SVneo cells significantly increased invasion and proliferation over time. However, at an HMGB1 stimulation concentration of 400 μg/L, the invasion and proliferation ability of HTR-8/SVneo cells decreased. Compared to controls, mRNA and protein expression levels of TLR4, NF-κB, and MMP-9 increased (mRNA level fold change: 1.460, 1.921, 1.667; protein level fold change: 1.600, 1.750, 2.047) when stimulated with HMGB1 (p < 0.05) but decreased when HMGB1 was knocked down (p < 0.05). TLR4 siRNA transfection combined with HMGB1 stimulation reduced the mRNA (fold change: 0.451) and protein (fold change: 0.289) expression of TLR4 (p < 0.05), while NF-κB and MMP-9 were unaffected (p > 0.05). Limitations: Only one trophoblast cell line was used in this study, and the findings were not confirmed in animal studies. Conclusions: This study explored the pathogenesis of PE from two aspects: inflammation and trophoblast invasion. The overexpression of HMGB1 in placentas from preeclamptic pregnancies suggests this protein may be involved in PE pathogenesis. In vitro, HMGB1 was found to regulate the proliferation and invasion of HTR-8/SVneo cells by activating the TLR4-NF-κB-MMP-9 pathway. These findings have implications for targeting HMGB1 could be a therapeutic strategy for treating PE. In the future, we will further verify this in vivo and in other trophoblast cell lines, further exploring the molecular interactions of the pathway.

Effects of maternal hypertension on cord blood Arginine vasopressin receptor expression.

Arginine vasopressin (AVP) signaling is altered in preeclampsia and physiologic stress. AVP is implicated in fluid homeostasis and cardiovascular (CV) function, which is disrupted in some progeny from preeclamptic pregnancies. However, whether altered fetal AVP signaling occurs in preeclampsia is unknown. Here, we measured CV-related transcripts (e.g., AVP receptors) in cord blood via quantitative PCR. Chronic hypertension decreased AVPR1b, AVPR2, OXTR, LNPEP, and CUL5. AVPR1a, AVPR1b, and AVPR2 were decreased while OXTR was increased in preeclamptic cord blood. In sum, we found prenatal exposure to hypertension in pregnancy alters fetal AVP signaling and may thereby prime offspring CV disease risk.

The evaluation of serum bisphenol A in patients with preeclampsia.

High bisphenol A (BPA) concentration may compromise normal placental development. The aim of this study was to determine maternal serum BPA concentrations in pregnant women with complicated preeclampsia (PE) and normal pregnant women, to compare BPA concentrations, and to examine pregnancy outcomes. This prospective case-control study was conducted between March 2021 and October 2021. Serum BPA levels of preeclamptic pregnancy and normal pregnancy were statistically evaluated. In addition, the PE group was divided into three subgroups according to the course of pregnancy. Group 1: patients with non-severe PE who delivered at 37 weeks or later, Group 2: patients with severe PE who delivered at less than 34 weeks, Group 3: patients with severe PE who delivered between 34 and 37 weeks. The association between BPA levels and pregnancy outcome was investigated. Forty-six cases in the PE group were compared with 46 cases of normal pregnancies. The median BPA level was 19.46 ng/mL in the PE group and 16.36 ng/mL in the control group. The median BPA levels in the PE group were significantly higher than those in the control group (p=0.007). Serum BPA levels were significantly lower in women who delivered at 37 weeks or later than in women who delivered at less than 34 weeks due to severe PE (p ≤ 0.018). Our study highlights the association between elevated maternal serum levels of BPA and PE. Moreover, knowledge of BPA levels in women with PE may provide information about the prognosis of pregnancy.

Pre-eclampsia.

Pre-eclampsia is a life-threatening disease of pregnancy unique to humans and a leading cause of maternal and neonatal morbidity and mortality. Women who survive pre-eclampsia have reduced life expectancy, with increased risks of stroke, cardiovascular disease and diabetes, while babies from a pre-eclamptic pregnancy have increased risks of preterm birth, perinatal death and neurodevelopmental disabilityand cardiovascular and metabolic disease later in life. Pre-eclampsia is a complex multisystem disease, diagnosed by sudden-onset hypertension (>20 weeks of gestation) and at least one other associated complication, including proteinuria, maternal organ dysfunction or uteroplacental dysfunction. Pre-eclampsia is found only when a placenta is or was recently present and is classified as preterm (delivery <37 weeks of gestation), term (delivery ≥37 weeks of gestation) and postpartum pre-eclampsia. The maternal syndrome of pre-eclampsia is driven by a dysfunctional placenta, which releases factors into maternal blood causing systemic inflammation and widespread maternal endothelial dysfunction. Available treatments target maternal hypertension and seizures, but the only 'cure' for pre-eclampsia is delivery of the dysfunctional placenta and baby, often prematurely. Despite decades of research, the aetiology of pre-eclampsia, particularly of term and postpartum pre-eclampsia, remains poorly defined. Significant advances have been made in the prediction and prevention of preterm pre-eclampsia, which is predicted in early pregnancy through combined screening and is prevented with daily low-dose aspirin, starting before 16 weeks of gestation. By contrast, the prediction of term and postpartum pre-eclampsia is limited and there are no preventive treatments. Future research must investigate the pathogenesis of pre-eclampsia, in particular of term and postpartum pre-eclampsia, and evaluate new prognostic tests and treatments in adequately powered clinical trials.

Preeclampsia: Recent Advances in Predicting, Preventing, and Managing the Maternal and Fetal Life-Threatening Condition.

Preeclampsia accounts for one of the most common documented gestational complications, with a prevalence of approximately 2 to 15% of all pregnancies. Defined as gestational hypertension after 20 weeks of pregnancy and coexisting proteinuria or generalized edema, and certain forms of organ damage, it is life-threatening for both the mother and the fetus, in terms of increasing the rate of mortality and morbidity. Preeclamptic pregnancies are strongly associated with significantly higher medical costs. The maternal costs are related to the extra utility of the healthcare system, more resources used during hospitalization, and likely more surgical spending due to an elevated rate of cesarean deliveries. The infant costs also contribute to a large percentage of the expenses as the babies are prone to preterm deliveries and relevant or causative adverse events. Preeclampsia imposes a considerable financial burden on our societies. It is important for healthcare providers and policy-makers to recognize this phenomenon and allocate enough economic budgets and medical and social resources accordingly. The true cellular and molecular mechanisms underlying preeclampsia remain largely unexplained, which is assumed to be a two-stage process of impaired uteroplacental perfusion with or without prior defective trophoblast invasion (stage 1), followed by general endothelial dysfunction and vascular inflammation that lead to systemic organ damages (stage 2). Risk factors for preeclampsia including race, advanced maternal age, obesity, nulliparity, multi-fetal pregnancy, and co-existing medical disorders, can serve as warnings or markers that call for enhanced surveillance of maternal and fetal well-being. Doppler ultrasonography and biomarkers including the mean arterial pressure (MAP), uterine artery pulsatility index (UtA-PI), and serum pregnancy-associated plasma protein A (PAPP-A) can be used for the prediction of preeclampsia. For women perceived as high-risk individuals for developing preeclampsia, the administration of low-dose aspirin on a daily basis since early pregnancy has proven to be the most effective way to prevent preeclampsia. For preeclamptic females, relevant information, counseling, and suggestions should be provided to facilitate timely intervention or specialty referral. In pregnancies complicated with preeclampsia, closer monitoring and antepartum surveillance including the Doppler ultrasound blood flow study, biophysical profile, non-stress test, and oxytocin challenge test can be arranged. If the results are unfavorable, early intervention and aggressive therapy should be considered. Affected females should have access to higher levels of obstetric units and neonatal institutes. Before, during, and after delivery, monitoring and preparation should be intensified for affected gravidas to avoid serious complications of preeclampsia. In severe cases, delivery of the fetus and the placenta is the ultimate solution to treat preeclampsia. The current review is a summary of recent advances regarding the knowledge of preeclampsia. However, the detailed etiology, pathophysiology, and effect of preeclampsia seem complicated, and further research to address the primary etiology and pathophysiology underlying the clinical manifestations and outcomes is warranted.

A longitudinal epigenome-wide association study of preeclamptic and normotensive pregnancy

BackgroundWhile preeclampsia (PE) is a leading cause of pregnancy-related morbidity/mortality, its underlying mechanisms are not fully understood. DNA methylation (DNAm) is a dynamic regulator of gene expression that may offer insight into PE pathophysiology and/or serve as a biomarker (e.g., risk, subtype, a therapeutic response). This study’s purpose was to evaluate for differences in blood-based DNAm across all trimesters between individuals eventually diagnosed with PE (cases) and individuals who remained normotensive throughout pregnancy, did not develop proteinuria, and birthed a normally grown infant (controls).ResultsIn the discovery phase, longitudinal, genome-wide DNAm data were generated across three trimesters of pregnancy in 56 participants (n=28 cases, n=28 controls) individually matched on self-identified race, pre-pregnancy body mass index, smoking, and gestational age at sample collection. An epigenome-wide association study (EWAS) was conducted, using surrogate variable analysis to account for unwanted sources of variation. No CpGs met the genome-wide significance p value threshold of 9×10-8, but 16 CpGs (trimester 1: 5; trimester 2: 1; trimester 3: 10) met the suggestive significance threshold of 1×10-5. DNAm data were also evaluated for differentially methylated regions (DMRs) by PE status. Three DMRs in each trimester were significant after Bonferonni-adjustment. Since only third-trimester samples were available from an independent replication sample (n=64 cases, n=50 controls), the top suggestive hits from trimester 3 (cg16155413 and cg21882990 associated with TRAF3IP2-AS1/TRAF3IP2 genes, which also made up the top DMR) were carried forward for replication. During replication, DNAm data were also generated for validation purposes from discovery phase third trimester samples. While significant associations between DNAm and PE status were observed at both sites in the validation sample, no associations between DNAm and PE status were observed in the independent replication sample.ConclusionsThe discovery phase findings for cg16155413/cg21882990 (TRAF3IP2-AS1/TRAF3IP2) were validated with a new platform but were not replicated in an independent sample. Given the differences in participant characteristics between the discovery and replication samples, we cannot rule out important signals for these CpGs. Additional research is warranted for cg16155413/cg21882990, as well as top hits in trimesters 1–2 and significant DMRs that were not examined in the replication phase.

Maternal Steroids on Fetal Doppler Indices, in Growth-Restricted Fetuses with Abnormal Umbilical Flow from Pregnancies Complicated with Early-Onset Severe Preeclampsia.

Corticoids are largely used for fetal interest in expected preterm deliveries. This study went further, evaluating the effect of maternal administration of dexamethasone (Dex) on the umbilical artery (UA), middle cerebral artery (MCA), and ductus venous (DV) spectrum, in growth-restricted fetuses, with the absent end-diastolic flow (AEDF) in UA, from singleton early-onset severe preeclamptic pregnancies. Supplementary, the impact on both uterine arteries (UTAs) flow was also evaluated. In 68.7% of cases, the EDF was transiently restored (trAEDF group), in the rest of 31.2% remained persistent absent (prAEDF group). UA-PI significantly decreased in the first day after Dex (day 1/0; p < 0.05), reaching its minimum during day 2 (day 2/1; p > 0.05), revealing a significant recovery to day 4 (day 4/2; p < 0.05), in both groups. The MCA-PI decreased from day 1 until day 3 in both groups, but significantly only in the trAEDF group (p = 0.030 vs. p = 0.227. The DV-PI's decrease (during day 1) and the CPR's increase (between days 0 and 2) were not significant in both groups. UTAs-PIs did not vary. The prAEDF group had a significantly increased rate of antenatal worsening Doppler and a poorer perinatal outcome compared with the trAEDF group. In conclusion, Dex transiently restored the AEDF in UA in the majority of cases, a "positive" effect being a useful marker for better perinatal prognosis. UA-PI significantly decreased in all cases. The improvement in umbilical circulation probably was responsible for the short but not significant DV-PI reduction. MCA-PI decreased only in sensitive cases, probably due to an already cerebral "full" vasodilation in the prAEDF group. Furthermore, the CPR's nonsignificant improvement was the result of a stronger effect of Dex on UA-PI than on MCA-PI. Finally, despite the same etiology, it was only a weak correlation between the severity of the umbilical and uterine abnormal spectrum.

Assessing erythroferrone and iron homeostasis in preeclamptic and normotensive pregnancies: A retrospective study

IntroductionPreeclampsia (PE) is a pregnancy-related disorder associated with maternal hypertension and placental dysfunction. A significant micronutrient during pregnancy is iron, which is important in cellular functions. While iron absorption increases in pregnancy, little is known about the exact mechanisms regulating maternal iron levels and transfer through the placenta in normal and complicated pregnancies. MethodsIn this retrospective study, we investigated the regulation of maternal and placental iron availability and storage, in normotensive and pregnancies complicated by early- or late-onset PE. Methods used were analysis of clinical records, ELISA analysis on plasma samples, immunofluorescent and Prussian Blue analysis on placenta biopsies. ResultsFocusing on erythroferrone (ERFE) as a new marker and hormonal regulator of iron, our results demonstrated altered maternal ERFE levels in PE. We are the first to report the expression of ERFE in trophoblasts and indicate its lower levels in early-onset PE placentas. These changes were associated with lower placental transferrin receptor 1 (TfR1) in syncytiotrophoblasts in both early- and late-onset PE. In addition, maternal plasma ERFE levels were elevated in both early- and late-onset PE and hepcidin levels reduced in early-onset PE. Unaltered maternal plasma IL-6 levels suggest mechanism other than inflammation being involved in altered iron regulation in PE pregnancy. DiscussionOur data supports a deregulation in maternal iron bioavailability in early- and late-onset PE vs normotensive pregnancies. The exact role of placental ERFE in regulating maternal-placental-fetal iron transport axis requires further investigation.

Metabolic profiling of pregnancies complicated by preeclampsia: A longitudinal study.

Preeclampsia is associated with maternal metabolic disturbances, but longitudinal studies with comprehensive metabolic profiling are lacking. We aimed to determine metabolic profiles across gestation in women who developed preeclampsia compared with women with healthy pregnancies. We also explored the respective effects of body mass index (BMI) and preeclampsia on various metabolic measures. We measured 91 metabolites by high-throughput nuclear magnetic resonance spectroscopy at four time points (visits) during pregnancy (weeks 14-16, 22-24, 30-32 and 36-38). Samples were taken from a Norwegian pregnancy cohort. We fitted a linear regression model for each metabolic measure to compare women who developed preeclampsia (n=38) and healthy controls (n=70). Among women who developed preeclampsia, 92% gave birth after 34 weeks of gestation. Compared to women with healthy pregnancies, women who developed preeclampsia had higher levels of several lipid-related metabolites at visit 1, whereas fewer differences were observed at visit 2. At visit 3, the pattern from visit 1 reappeared. At visit 4 the differences were larger in most subgroups of very-low-density lipoprotein particles, the smallest high-density lipoprotein, total lipids and triglycerides. Total fatty acids were also increased, of which monounsaturated fatty acids and saturated fatty acids showed more pronounced differences. Concentration of glycine tended to be lower in pregnancies with preeclampsia until visit 3, although this was not significant after correction for multiple testing. After adjustment for age, BMI, parity and gestational weight gain, all significant differences were attenuated at visits 1 and 2. The estimates were less affected by adjustment at visits 3 and 4. In early pregnancy, the metabolic differences between preeclamptic and healthy pregnancies were primarily driven by maternal BMI, probably representing the women's pre-pregnancy metabolic status. In early third trimester, several weeks before clinical manifestation, the differences were less influenced by BMI, indicating preeclampsia-specific changes. Near term, women with preeclampsia developed an atherogenic metabolic profile, including elevated total lipids, very-low-density lipoprotein, triglycerides, and total fatty acids.

Vital NETosis vs. suicidal NETosis during normal pregnancy and preeclampsia.

Background: NETosis occurs in the context of infection or inflammation and results in the expulsion of decondensed DNA filaments called NETs (Neutrophil Extracellular Traps) into the extracellular environment. NETosis activates coagulation and contributes to the thrombotic risk of inflammatory diseases. To date, two mechanisms of NETosis have been identified: suicidal NETosis, in which neutrophils die after expelling the filaments; and vital NETosis, in which expulsion appears without altering the membrane. Human pregnancy is associated with a mild pro-inflammatory state, which is increased in the event of complications such as preeclampsia (PE). NETosis has been observed in these situations, but the mechanism of its production has not yet been studied. The aim of our study was to evaluate the balance of vital vs. suicidal NETosis in normal pregnancy and in PE. Patients/Methods: Neutrophils from healthy volunteers were stimulated with plasma from normal pregnancies (n = 13) and from women developing preeclampsia (n = 13). Immunofluorescent labelling was performed to determine the percentages and origin of NETs in both groups. Inhibition with suicidal or vital NETosis inhibitors was also performed to validate our results. Results: We found a significant increase in NETs in women with PE compared to women with normal pregnancies. We showed that vital and non-vital NETosis are present in normal and preeclamptic pregnancies. We demonstrated that the higher proportion of NETs observed in PE was due to non-vital NETosis whose main component is represented by suicidal NETosis. Discussion: These results suggest the important part of non-vital NETosis in the pathophysiology of PE.

Increased levels of nectin-4 as a serological marker for pre-eclampsia

Nectin-4 is a cell adhesion molecule with vital functions at adherens and tight junctions. Cumulative evidence now indicates that the NECTIN4 gene is overexpressed in a variety of cancers, and that the nectin-4 protein is both a disease marker and therapeutic target in a subset of these cancers. We previously demonstrated that NECTIN4 is overexpressed in placenta during pre-eclamptic pregnancy, which is one of the most serious obstetric disorders. Nectin-4 protein levels were measured in maternal sera from pregnant women with pre-eclampsia and its related disorder, unexplained fetal growth retardation. Maternal serum concentrations of nectin-4 were significantly elevated in pre-eclamptic women compared with those with an uncomplicated normotensive pregnancy. However, no increase was observed in pregnancies with unexplained fetal growth retardation. Serum nectin-4 levels were higher in cases with early-onset pre-eclampsia that generally showed more severe clinical symptoms, but levels were not correlated to other clinical indicators of disease severity. Nectin-4 is a potential new diagnostic and predictive biomarker for severe pre-eclampsia.

Study of Use of Shear Wave Elastography in Placental Dysfunction by Comparison of Elasticity Values in Normal and Pre-eclamptic Pregnancies

Study of Use of Shear Wave Elastography in Placental Dysfunction by Comparison of Elasticity Values in Normal and Pre-eclamptic Pregnancies

Nifuroxazide Has Better Efficacy Than Probiotic Treatment in Adult Patients with Acute Diarrheal Syndrome.

Zonulin is a physiological protein that regulates the tight connections and permeability of the intestine, serving as a biomarker for impaired intestinal permeability. The aim of this study was to examine zonulin levels in preeclampsia, to investigate its associations with the cellular immune response marker soluble interleukin-2 receptor (sIL-2R) and exogenous antigen load marker lipopolysaccharide binding protein (LBP) and to evaluate the implications of these findings in the etiopathogenesis of preeclampsia. We designed a cross-sectional case-control study and enrolled 22 pregnant women with preeclampsia and 22 healthy pregnant controls. Plasma zonulin levels were determined by ELISA. Serum sIL-2R and LBP levels were assessed by chemiluminescent immunometric methods. Women with preeclampsia had lower levels of plasma zonulin and serum LBP than normotensive healthy controls (p<0,05). The difference in serum sIL-2R levels was not significant (p: 0,751). There was a negative correlation between plasma zonulin and serum urea (r: -0.319, p: 0.035) and a positive correlation between serum sIL-2R and ALT (r: 0,335, p: 0,026) and AST (r: 0,319, p: 0,035). We found that zonulin and LBP, but not sIL-2R, levels were significantly lower in pregnant women with preeclampsia as compared with healthy pregnant controls. Reduced intestinal permeability in preeclampsia might be associated with impaired immune system functions or a lower fat mass and malnutrition. Further studies are needed to elucidate the exact pathogenetic role of intestinal permeability in preeclampsia.

Placental Expression of Stanniocalcin 2 (STC2) in Healthy and Preeclamptic Pregnancies

Placental Expression of Stanniocalcin 2 (STC2) in Healthy and Preeclamptic Pregnancies

Inflammatory Marker Levels in Preeclampsia versus Normal Pregnancies and Prediction of Preeclampsia Occurrence: A Prospective Mixed Methods Study

Introduction: Preeclampsia is an important cause of adverse maternal and perinatal outcomes. However, this condition remains poorly understood, and since the only cure is delivery, prediction and prevention are crucial to prevent preterm birth or maternal compromise. Aim: To determine the levels of acute phase reactants, namely high-sensitivity C-reactive Protein (hsCRP) and fibrinogen, between preeclamptic and non preeclamptic pregnancies. Additionally, the study aims to determine the predictive value of these acute phase reactants for preeclampsia. Materials and Methods: A prospective mixed methods study was conducted in two tertiary hospitals and two specialist hospitals in the Ijebu/Remo axis of Ogun state, Nigeria. Preeclamptic participants were recruited during pregnancy and postpartum and matched with non preeclamptic controls (case-control arm, n=179, comprised of 87 preeclamptics and 92 controls). Additionally, a cohort of non preeclamptic women (n=71) was recruited and biomarker-assayed before 20 weeks gestation, followed-up for the development of preeclampsia. The biomarker assay was performed using the ELISA technique. The Student's t-test was used to compare the mean levels of markers between the studied groups. Categorical data were compared using the Chi-square test. A p-value &lt;0.05 was considered to be statistically significant. Results: The levels of hsCRP were significantly higher in pregnant preeclamptic women (12.71±1.99 mg/L) compared to non preeclamptic women (4.39±3.41 mg/L) (p-value=0.001). Similarly, fibrinogen levels were elevated in preeclamptic women (9.45±1.28 g/L) compared to non preeclamptic women (7.19±1.86 g/L) (p-value =0.001). This trend was also observed among postpartum women, with hsCRP levels of 10.39±2.43 mg/L in preeclamptics compared to 2.53±2.06 mg/L in non preeclamptics (p-value=0.001). The mean fibrinogen level was 8.63±1.91 g/L in preeclamptics compared to 4.09±1.66 g/L in non preeclamptics. Fibrinogen demonstrated a higher specificity (88.9%) and Negative Predictive Value (NPV) of 100% compared to hsCRP (specificity=47.1% and NPV=76.1%). The biomarker levels also correlated significantly with the severity of preeclampsia. For hsCRP, there was a correlation with Systolic Blood Pressure (SBP) (r-value=0.385, p-value=0.001), Diastolic Blood Pressure (DBP) (r-value=0.364, p-value=0.001), and proteinuria (r-value=0.314, p-value=0.001). For fibrinogen, there was a correlation with SBP (r-value=0.252, p-value=0.014), DBP (r-value=0.378, p-value=0.001), and proteinuria (r-value=0.356, p-value=0.001). Conclusion: Although hsCRP and fibrinogen levels were significantly higher and correlated well with the severity of preeclampsia, their use for prediction may be limited. However, fibrinogen appears to have better prospects.

Investigation of Matrix Metalloproteinase-2, Matrix Metalloproteinase-9, Tissue Matrix Metalloproteinase Inhibitor-1, and Tissue Matrix Metalloproteinase Inhibitor-2 levels in preeclamptic and eclamptic pregnancy

Investigation of Matrix Metalloproteinase-2, Matrix Metalloproteinase-9, Tissue Matrix Metalloproteinase Inhibitor-1, and Tissue Matrix Metalloproteinase Inhibitor-2 levels in preeclamptic and eclamptic pregnancy

STUDY OF MATERNAL LIPID PROFILE IN PREECLAMPSIA

Introduction: This study evaluates relationship between serum lipid profile and preeclampsia1 . Objective:The study is to compare the mean lipid levels in pre-eclamptic and normal pregnancy. Design:This is a descriptive study. Participants: Among patients attending Out Patient Department in Chalmeda Anand Rao institute of medical sciences, 25 singleton pregnancies diagnosed as having preeclampsia and 25 pregnancies without such diagnosis were included in study. Outcome measures: Risk of preeclampsia, pregnancy induced hypertension, preterm birth, small/large for gestational age and child loss. Results:In pre-eclamptic mean triglycerides levels were (254 mg/dl ± 0.45 versus 116.59 ± 4.9) significantly higher than normal controls (p&lt;0.05). Mean HDL-Cholesterol levels were (36.92 mg/dl ± 7.70 versus 51 ± 5.46) statistically significantly higher than normal controls (p&lt;0.05). Mean LDL-Cholesterollevels were(132.95mg/dl ± 32.26 versus 99.36 ± 17.75) statistically significantly higher in pre-eclamptic as compared to normal controls (p&lt;0.05). Conclusion: Pre-eclamptic women had deranged lipid profile as compared to normal pregnant women.