Maternal Syndrome Of Preeclampsia Research Articles

Differential 5'-tRNA Fragment Expression in Circulating Preeclampsia Syncytiotrophoblast Vesicles Drives Macrophage Inflammation.

The relationship between placental pathology and the maternal syndrome of preeclampsia is incompletely characterized. Mismatch between placental nutrient supply and fetal demands induces stress in the syncytiotrophoblast, the layer of placenta in direct contact with maternal blood. Such stress alters the content and increases the release of syncytiotrophoblast extracellular vesicles (STB-EVs) into the maternal circulation. We have previously shown 5'-tRNA fragments (5'-tRFs) constitute the majority of small RNA in STB-EVs in healthy pregnancy. 5'-tRFs are produced in response to stress. We hypothesized STB-EV 5'-tRF release might change in preeclampsia. We perfused placentas from 8 women with early-onset preeclampsia and 6 controls, comparing small RNA expression in STB-EVs. We used membrane-affinity columns to isolate maternal plasma vesicles and investigate placental 5'-tRFs in vivo. We quantified 5'-tRFs from circulating STB-EVs using a placental alkaline phosphatase immunoassay. 5'-tRFs and scrambled RNA controls were added to monocyte, macrophage and endothelial cells in culture to investigate transcriptional responses. 5'-tRFs constitute the majority of small RNA in STB-EVs from both preeclampsia and normal pregnancies. More than 900 small RNA fragments are differentially expressed in preeclampsia STB-EVs. Preeclampsia-dysregulated 5'-tRFs are detectable in maternal plasma, where we identified a placentally derived load. 5'-tRF-Glu-CTC, the most abundant preeclampsia-upregulated 5'-tRF in perfusion STB-EVs, is also increased in preeclampsia STB-EVs from maternal plasma. 5'-tRF-Glu-CTC induced inflammation in macrophages but not monocytes. The conditioned media from 5'-tRF-Glu-CTC-activated macrophages reduced eNOS (endothelial NO synthase) expression in endothelial cells. Increased release of syncytiotrophoblast-derived vesicle-bound 5'-tRF-Glu-CTC contributes to preeclampsia pathophysiology.

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.

Fetal growth restriction and preeclampsia differ in intensity of the maternal inflammatory response

Placental insufficiency can cause both fetal growth restriction (FGR) and preeclampsia (PE). Yet, why some patients develop FGR and others PE is unknown. The maternal syndrome of PE has been attributed to an exaggerated intravascular inflammatory response. We propose that the severity of the inflammatory response will be different in FGR and PE. To assess, we measured the concentrations of soluble suppression of tumorigenesis-2 (sST2), a member of a cytokine family that buffers proinflammatory responses.

Maternal endothelial dysfunction in HIV-associated preeclampsia comorbid with COVID-19: a review.

This review assesses markers of endothelial dysfunction (ED) associated with the maternal syndrome of preeclampsia (PE). We evaluate the role of antiretroviral therapy (ART) in human immunodeficiency virus (HIV)-infected preeclamptic women. Furthermore, we briefly discuss the potential of lopinavir/ritonavir (LPV/r), dolutegravir (DTG) and remdesivir (RDV) in drug repurposing and their safety in pregnancy complicated by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. In HIV infection, the trans-activator of transcription protein, which has homology with vascular endothelial growth factor, impairs angiogenesis, leading to endothelial injury and possible PE development despite neutralization of their opposing immune states. Markers of ED show strong evidence supporting the adverse role of ART in PE development and mortality compared to treatment-naïve pregnancies. Coronavirus disease 2019 (COVID-19), caused by SARS-CoV-2 infection, exploits angiotensin-converting enzyme 2 (ACE 2) to induce ED and hypertension, thereby mimicking angiotensin II-mediated PE in severe cases of infection. Upregulated ACE 2 in pregnancy is a possible risk factor for SARS-CoV-2 infection and subsequent PE development. The potential effectiveness of LPV/r against COVID-19 is inconclusive; however, defective decidualization, along with elevated markers of ED, was observed. Therefore, the safety of these drugs in HIV-positive pregnancies complicated by COVID-19 requires attention. Despite the observed endothelial protective properties of DTG, there is a lack of evidence of its effects on pregnancy and COVID-19 therapeutics. Understanding RDV-ART interactions and the inclusion of pregnant women in antiviral drug repurposing trials is essential. This review provides a platform for further research on PE in the HIV-COVID-19 syndemic.

Hypertension Editors' Picks Preeclampsia.

Hypertension Editors' Picks Preeclampsia.

Superimposed Preeclampsia Exacerbates Postpartum Renal Injury Despite Lack of Long-Term Blood Pressure Difference in the Dahl Salt-Sensitive Rat.

Preeclampsia results in increased susceptibility to hypertension and chronic kidney disease postpartum; however, the mechanisms responsible for disease progression in these women remain unknown. The purpose of this study was to test the hypothesis that 2 mechanisms contribute to the link between the maternal syndrome of preeclampsia and the increased postpartum risk of cardiovascular and renal disease: (1) increased T cells in the kidney and (2) a decreased NO:ET-1 (endothelin-1) ratio. Dahl S rats (a previously characterized model of preeclampsia superimposed on chronic hypertension) who experienced 2 pregnancies and virgin littermate controls were studied at 6 months of age. Mean arterial pressure was measured via telemetry, and renal injury was assessed through both histological analysis and measurement of urinary markers including nephrin, podocalyxin, and KIM-1 (kidney injury marker 1). Contributing mechanisms were assessed through flow cytometric analysis of renal T cells, quantification of plasma TNF-α (tumor necrosis factor-α) and IL-10 (interleukin-10), and quantification of urinary concentrations of NO metabolites and ET-1. Although prior pregnancy did not exacerbate the hypertension at 6 months, this group showed greater renal injury compared with virgin littermates. Flow cytometric analyses revealed an increase in renal T cells after pregnancy, and cytokine analysis revealed a systemic proinflammatory shift. Finally, the NO:ET-1 ratio was reduced. These results demonstrate that the link between the maternal syndrome of superimposed preeclampsia and postpartum risk of chronic kidney disease could involve both immune system activation and dysregulation of the NO:ET-1 balance.

Preeclampsia and the 20th century: "Le siècle des Lumières".

The authors delineate seven quantum leap forward and, or revolutions having occurred during the 20th century in the understanding of the physiopathology of preeclampsia. First the discovery of the inflatable arm band permitting to measure blood pressure in 1896. Second, the discovery that eclamptic (convulsions), and later "pre"eclamptic (proteinuria) women presented hypertension in 1897 and confirmed in 1903, discovery of the hypertensive disorders of pregnancy. Third, the eight major textbooks published all along the 20th century by delineating risk factors of preeclampsia with the concept of "preeclampsia, disease of primigravidae". Fourth, the discovery in the 1970's that human trophoblast implantation was far deeper than in other mammalian species. Fifth, and a major step forward, description at the end of the 1980's that the maternal syndrome in preeclampsia (glomeruloendotheliosis, HELLP syndrome, eclampsia) could be unified in a global endothelial cell inflammation. Sixth, the epidemiological descriptions in the 1970-1990's that indeed preeclampsia was a disease of first pregnancies at the level of a couple ("primipaternity concept"), leading to an explosion in immunological research in the last decade, beginning in 1998. Seventh and finally, in the search for the "factor X" explaining the vascular inflammation in preeclamptic women (inositol phospho glycans P-type were described in 2000, while soluble Flt-1 and S-endoglins have been clearly predicted since 1997). The majority of the seeds or findings have been grounded or realized in the 20th century. Indeed, for preeclampsia, the 20th century has been le "Siècle des Lumières" (the Enlightments).

25 Low dose aspirin corrects in vitro the placental cell derived sFlt-1/PlGF imbalance characteristic of preeclampsia

Introduction Preeclampsia (PE) is a multi-system disorder typically involving pregnancy-induced maternal hypertension and proteinuria presenting in the second half of pregnancy. The placenta is the key organ responsible for the pathogenesis of PE, with altered release of placenta-derived anti- (eg sFlt-1) and pro- (eg PlGF) angiogenic proteins implicated in maternal PE pathophysiological events. Epidemiological data indicate that low-dose aspirin (LDA) commenced before 16 weeks gestation is clinically effective in preventing PE, but its mechanism of action is unclear. We hypothesized that the prophylactic efficacy of LDA treatment may be associated with a corrective effect of LDA on the altered release of placenta-derived angiogenic proteins seen in PE pregnancies. Objective To test this hypothesis, we examined the effects of pregnancy sera from normotensive and PE cases with and without LDA on the in vitro production and release of sFlt-1 and PlGF from a trophoblast-derived cell line (BeWo). Methods The effects of LDA (5 μg/mL) following treatment of BeWo cells in vitro with either PE or normotensive serum on the expression of angiogenic proteins sFlt-1 and PlGF were determined using real-time PCR. The secretion of these angiogenic proteins in the conditioned media was screened with a commercially designed protein array. Candidate protein validation was then performed using an ELISA. All experiments were performed in triplicate at least six independent occasions. A p-value Results Angiogenic profiling at the mRNA level identified significantly increased expression of Flt-1 [Normotensive: 1.04 ± 0.03 vs PE: 2.68 ± 0.07, p Conclusion Increased placental release of the anti-angiogenic protein sFlt-1 and reduced placental release of the pro-angiogenic protein PlGF into the maternal circulation are key contributors to the maternal vascular endothelial cell dysfunction that is central to the development of the maternal syndrome of PE. The ability of LDA to rebalance these key angiogenic proteins in an in vitro trophoblast cell-line model may offer an important mechanistic insight at a molecular level regarding the clinical utility of LDA in preventing PE.

61 Melatonin supplementation prevents endothelial cell activation, possible relevance to preeclampsia

Introduction Preeclampsia, a human pregnancy-specific disease, is a leading cause of maternal and perinatal mortality and morbidity. It is characterised by maternal endothelial cell dysfunction. Although the exact causes of this disease are unclear, it is thought that there is an increase in oxidative stress in the placenta and leading to the release of a toxic factor (s) from the placenta that triggers maternal endothelial cell activation. Endothelial cell activation precedes the clinical signs and symptoms of the maternal syndrome of preeclampsia. Trophoblast debris, which is shed from the placenta into the maternal blood, is hypothesised to be one such trigger. Our previous studies showed that treating placentae with antiphospholipid antibodies (aPL), which increase the risk of women developing preeclampsia 10 fold [1, 2], or preeclamptic sera, results in the production of toxic trophoblastic debris which induces endothelial cell activation [3]. Melatonin is a lipid soluble hormone originally found to be released by the pineal gland but which has been shown to have antioxidant activities and to be produced in the placenta. Given the action of melatonin in regulating oxidative stress and cell death, we investigated whether melatonin supplementation can reverse the effects of preeclamptic sera or aPL on placental oxidative damage and the production of toxic trophoblastic debris. Methods First trimester placental explants were cultured with aPL (20 μ g/ml) or preeclamptic sera (n = 6) in the presence or absence of melatonin (1 μ M, 10 μ M) for 24 h. Trophoblastic debris was collected from the explants and then exposed to monolayers of endothelial cells (HMEC-1) for 24 h and cell surface ICAM-1 expression was measured by cell-based ELISA to determine endothelial cell activation. The expression of nitrotyrosine in placental explants that were treated with aPL or preeclamptic sera was measured by immunohistochemistry or western blotting. Results 1) Trophoblastic debris from placental explants that were treated with aPL or preeclamptic sera (n = 6) significantly (p 2) In contrast, trophoblastic debris from explants that were treated with aPL or preeclamptic sera in the presence of melatonin (n = 6) did not significantly increased the expression of ICAM-1 compared to control-treated endothelial cells 3) The expression of nitrotyrosine was significantly increased in placentae that had been treated with aPL or preeclamptic sera. However, this increase in levels of nitrotyrosine was not found in placental explants where aPL or PE sera were added in the presence of melatonin. Conclusions Our results suggest that there is oxidative damage induced in placentae by either aPL or preeclamptic sera and consequently trophoblastic debris produced by these placentae is more toxic to endothelial cells. Melatonin can reverse this placental oxidative damage and reduced the toxicity of the trophoblastic debris. Since the pathogenesis of preeclampsia is thought to be partially dependent on the maternal response to placental factors such as toxic trophoblastic debris shed from placentae, our results encouraging suggest that melatonin might be a useful tool to alleviate the clinical manifestations of preeclampsia.

Preeclampsia, biomarkers, syncytiotrophoblast stress, and placental capacity

The maternal syndrome of preeclampsia is mediated by dysfunctional syncytiotrophoblast (STB). When this is stressed by uteroplacental malperfusion, its signaling to the mother changes, as part of a highly coordinated stress response. The STB signals are both proinflammatory and dysangiogenic such that the preeclamptic mother has a stronger vascular inflammatory response than normal, with an antiangiogenic bias. Angiogenic factors have limitations as preeclampsia biomarkers, especially for prediction and diagnosis of preeclampsia at term. However, if they are recognized as markers of STB stress, their physiological changes at term demonstrate that STB stress develops in all pregnancies. The biomarkers reveal that the duration of pregnancies is restricted by placental capacity, such that there is increasing placental dysfunction, at and beyond term. This capacity includes limitations imposed by the size of the uterus, the capacity of the uteroplacental circulation and, possibly, the supply of villous progenitor trophoblast cells. Limited placental capacity explains the increasing risks of postmaturity, including preeclampsia. Early-onset preeclampsia is predictable because STB stress and changes in its biomarkers are intrinsic to poor placentation, an early pregnancy pathology. Prediction of preeclampsia at term is not good because there is no early STB pathology. Moreover, biomarkers cannot accurately diagnose term preeclampsia against a background of universal STB dysfunction, which may or may not be clinically revealed before spontaneous or induced delivery. In this sense, postterm pregnancy is, at best, a pseudonormal state. However, the markers may prove useful in screening for women with more severe problems of postmaturity.

Study of angiotensin converting enzyme and genotype among Egyptian preeclampsia patients

Preeclampsia is a frequent disorder with reported incidence in pregnancies. In Egypt, it complicates 6%-8% of pregnancies and reaches 15% in referral centers. The renin-angiotensin system activation during the early stages of Preeclampsia proved to be a direct cause. Women carrying the D allele of the ACE-I/D polymorphism have higher measures of uterine artery resistance, which is a marker for development of intrauterine growth retardation and preeclampsia. The maternal syndrome of preeclampsia (PE) during the latter half of pregnancy is believed to result from impaired placentation in early gestation and a failure to develop low resistance uteroplacental circulation. Aim: The aim of this study was to evaluate the association with angiotensin converting enzyme gene polymorphism and changes in its enzyme serum level in preeclamptic patients compared to non preeclamptic control group together with studying the changes in umbilical artery and uterine artery Doppler. Subjects: The study was conducted on 180 pregnant women allocated into two groups having the same inclusion and exclusion criteria except for hypertension and proteinuria; each group comprised of 90 pregnant women with matched age. Methods: Doppler study of umbilical and uterine arteries and the detection of Angiotensin converting gene polymorphism by PCR with Estimation of serum ACE in serum by ELISA technique. Results: The distribution of the ACE-I/D genotypes and allelic frequencies in the present study of polymorphism was 37.8% for the DD, 48.9% for the ID, 13.3% for the II in preeclampsia group while it was 33.3% for the DD, 46.7% for the ID, and 20% for the II in the control group. There was no significant difference between cases and controls regarding the cumulative D effect. Conclusions: No existence of a relation between preeclampsia and ACE gene polymorphism considering different modes of inheritance whether is dominance or recessiveness. No effect of ACE gene polymorphism is on ACE serum level. Positive correlation between ACE gene polymorphism and the uterine artery Doppler changes gives strong evidence that ACE gene may have a role in the histopathological changes taking place in these vessels, therefore affecting maternal prognosis. It is unclear to explain this mismatched ACE genetic influence on the incidence of preeclampsia, but the multifactorial pathogenesis of the development and complication in preeclampsia and also physician’s intervention may contribute to the pregnancy outcome. Recommendations: International collaborations, particularly among countries with a high incidence of preeclampsia, may help to include participants with different cultural and genetic backgrounds, which can provide further insight into the etiology of the disease both genetic and environmental.

Placental Disease and the Maternal Syndrome of Preeclampsia: Missing Links?

Preeclampsia remains a significant obstetric risk worldwide. The pathophysiology of preeclampsia is complex, with multiple stages involving maladaptations in both placental and maternal physiology. The placenta links the pre-clinical stage of impaired remodeling of the uterine vasculature, occurring in early pregnancy, to the later clinical stages characterised by the maternal syndrome of hypertension and proteinuria. This review focuses on some of the recent candidates for the missing links in this process.

Gasotransmitters

Preeclampsia complicates 2% to 8% of all pregnancies and is a major contributor to maternal mortality worldwide. The only therapy is delivery, often before term.1 Nitric oxide, carbon monoxide, and hydrogen sulfide are gasotransmitters that regulate vascular development, vascular tone, and affect antioxidant status.2 Abnormalities in gasotransmitter signaling and production are linked to hypertension, atherosclerosis, and inflammation.2 Drugs that enhance gasotransmitter signaling have proven therapeutic potential in the clinical and experimental setting. Gasotransmitters are involved in the vascular adaptations of normal pregnancy,3–7 and experimental studies have shown that abnormal production is associated with preeclampsia.8–12 The aim of this review is to give an overview of the role of gasotransmitters in the physiology of pregnancy and relate their aberrant production to preeclampsia. Specific emphasis will be put on and overview their therapeutic potential for preeclampsia. Preeclampsia is defined by hypertension and proteinuria during the second half of gestation. Although the exact cause of preeclampsia is unknown, the placenta and the maternal inflammatory response play a key role in its pathogenesis.1,13 Preeclampsia is often described as a 2-stage disease. During placentation in normal pregnancy, trophoblasts invade into the endometrium and spiral arteries resulting in spiral artery dilation.1 In preeclampsia, trophoblast invasion is incomplete resulting in inadequate spiral artery remodeling and placental hypoperfusion; this is stage 1 of the disease.1 Subsequently, the oxygen-deprived placenta produces factors that enter the maternal circulation, causing maternal endothelial dysfunction and maternal immune response activation, leading to the signs of preeclampsia; this is stage 2 of the disease.1 Some of the factors produced by the placenta are antiangiogenic factors, such as soluble fms-like tyrosine kinase receptor 1 (sFlt1).14 They are (partly) responsible for the maternal syndrome in preeclampsia because increased sFlt1 is …

Stress responses and pre-eclampsia

Biological stress may affect individual cells, tissues or whole organisms, arising from disturbed homoeostasis of any cause. Stress is rarely localised. Because biological systems are closely integrated, it spreads to involve other systems. Stress responses are highly integrated and work to restore homoeostasis. Different response pathways overlap and interlink. If the responses fail or decompensate, distress ensues, of which the end-stage is death. Pre-eclampsia results from a series of biological stresses, possibly from conception, which become established by abnormal placentation and affect the mother, her foetus and her placenta. The stresses involve dialogue between mother and placenta. Even a normal placenta imposes substantial stress on maternal systems. When placental growth and perfusion is abnormal (poor placentation) then the placenta, particularly its outer trophoblast layer, becomes stressed - loosely denoted hypoxic damage or oxidative stress. Signals from the placenta spread the stress to the mother, who develops signs of pre-eclampsia. Cellular stress sensors initiate stress responses. Different stresses may trigger similar responses in specific cell types. The first cell response is reduced protein synthesis. However some synthetic pathways are spared or activated to produce stress signals. In relation to pre-eclampsia and the placenta, an excessive release of sFlt-1 a soluble decoy receptor for vascular endothelial growth factor (VEGF) is a trophoblast related stress signal. SFlt1 perturbs the angiogenic balance in the maternal circulation and is considered to cause many of the specific features of the maternal syndrome in pre-eclampsia. Three key points will be emphasised. First, multiple stressors, not simply hypoxia, stimulate the release of sFlt-1 from trophoblast. Second, sFlt-1 is only one of the group of stress signals delivered by trophoblast to the mother. Third, sFlt-1 is not the only trophoblast derived factor to perturb the maternal circulation in pre-eclampsia.

Microvesicles and pre-eclampsia

The maternal syndrome of pre-eclampsia is characterised by an excessive inflammatory response associated with endothelial dysfunction, brought about by the release of multiple factors from the placenta into the maternal circulation. While some of these factors are released as soluble molecules it is now apparent that many of them are associated with syncytiotrophoblast microvesicles and exosomes (collectively termed STBM), which are present in increased amounts in the circulation of women with pre-eclampsia. We have shown that STBM have proinflammatory, anti-endothelial and procoagulant activities in vitro, all of which are features of the maternal syndrome. We propose that the different effects of STBM result from different types of vesicles within the circulation the smaller exosomes being immunoregulatory and the larger microvesicles being proinflammatory, with a shift to the latter in pre-eclampsia. In support of this, we have demonstrated using a novel technique, Nanoparticle Tracking Analysis, that pre-eclampsia STBM are indeed larger than those from normal placentas. Furthermore, the range and types of factors they carry (and hence their functions) may differ in pre-eclampsia, where the syncytiotrophoblast is subjected to oxidative and inflammatory stress. We have carried out proteomic analysis on vesicles prepared from normal and pre-eclampsia placentas by perfusion and have identified differences in the repertoire of molecules they carry. Candidates include immunoregulatory molecules (B7-H1, CD200 and Galectin 1), complement and complement regulatory molecules (C1q, C3, CD55, CD59 and vitronectin), proinflammatory molecules (HSP70, HMGB1, Galectin 3 and Synctin 1), anti-angiogenic molecules (CD49e, CD51, CD26, Flt-1 and endoglin) and procoagulant molecules (tissue factor and phosphatidylserine). Characterising the molecular cargos of the STBM may lead to the discovery of new biomarkers for pre-eclampsia and inform future treatments.

Doppler Flowmetry in the Maternal Syndrome of Preeclampsia: Preliminary Report

Doppler Flowmetry in the Maternal Syndrome of Preeclampsia: Preliminary Report

Chlamydia pneumoniae Infection in Preeclampsia

Objective. The maternal syndrome of preeclampsia results from systemic endothelial activation by a number of factors that primarily derive from the intervillous space, so-called intervillous soup. Co-precipitants, such as innate immune activators, may lower the threshold to develop the maternal syndrome in preeclampsia. We examined whether, like atherosclerosis, preeclampsia is associated with infection with Chlamydia pneumoniae (C. pneumoniae). Study Design. A case-control study was performed on 50 women with preeclampsia, 57 women with normal pregnancies at term, and 25 non-pregnant controls. Anti-C. pneumoniae antibodies were examined by enzyme-linked immunosorbent assay and C. pneumoniae genomic DNA (gDNA) loads were measured by real-time PCR. We also performed a data synthesis of the relationship between anti-C. pneumoniae seroprevalence and preeclampsia risk. Results. Neither the number of women with measurable copy numbers of C. pneumoniae gDNA, the anti-C. pneumoniae seroprevalence, nor antibody indices of IgG, IgM, or IgA to C. pneumonia varied between groups. However, when measurable, gDNA copy numbers of C. pneumoniae were increased in women with preeclampsia compared with the normal pregnant (p < 0.05) and non-pregnant controls (p < 0.05). For women with measurable C. pneumoniae gDNA, their copy numbers were correlated with anti-C. pneumoniae IgG concentrations (r2 = 0.49; p < 0.0001). Data synthesis reveals that anti-C. pneumoniae IgG seroprevalence is associated with preeclampsia risk. Conclusion. Our data suggest an association between C. pneumoniae infection and preeclampsia. While not a uniform and singular precipitant of the maternal syndrome of preeclampsia, C. pneumoniae infection may be a co-precipitant with other components of the intervillous soup. Further investigations appear warranted.

Relationship Between Maternal Obesity And Increased Risk Of Preeclampsia

Introduction: The incidence of obesity has risen over the past several decades and in spite of advancement in modern medicine, it remains a risk factor for maternal morbidity and mortality. Objective: To determine the association between obesity (increased body mass index) and increased risk of preeclampsia. The possible role of serum leptin was also evaluated. Methods: 250 pregnant women were included in this study. They were selected according to their BMI at 20 weeks of gestation and allocated into 5 study groups (each n= 50). At 20 weeks of gestation, BMI, mean arterial blood pressure was calculated. Proteinuria, serum uric acid and leptin were measured. At 28 weeks of gestation reevaluation of BMI, mean arterial blood pressure and serum uric acid were done. While serum leptin estimation was only reevaluated on the 37 weeks. Cases of preeclampsia were diagnosed and classified either mild or severe. Results: It was found that preeclampsia was diagnosed in 20 cases. Among them 12 cases were diagnosed as mild preeclampsia in group A , 2 cases ( 4% of normal BMI) , 2 cases in group C ( 4% of obese class 1 ) , 6 cases in group D ( 12 % of obese class 11 ) and 2 cases in group E ( 4 % of obese class 111). Severe preeclampsia was diagnosed in 4 cases of group C ( 8 % of obese class 1 ) , 2 cases of group D ( 4% of obese class 11 ) and 2 cases of group E ( 4 % of obese class 111 ) . The relative risk of preeclampsia in cases of increased BMI was 2.25. The cases that developed preeclampsia had statistically significant elevated serum uric acid when compared to the normotensive cases at 28 and 37 weeks of gestation. Serum leptin level increased significantly with the increase in BMI and preeclamptic cases had statistically significant higher mean serum leptin at 28 and 37 weeks than normotensive cases. Conclusion: Maternal obesity is associated with a higher risk of adverse maternal and perinatal outcomes including preeclampsia.The dyslipidemia and the exaggerated inflammatory response associated with maternal obesity are thought to contribute to widespread endothelial dysfunction and the subsequent maternal syndrome in preeclampsia. Obesity is associated with higher mean serum leptin level. The levels of serum leptin are significantly higher in pre-eclampsia when compared to normotensive pregnant women and may contribute to endothelial dysfunction involved in the pathogenesis of preeclampsia. Keywords: preeclampsia –maternal obesity

Low catechol-O-methyltransferase and 2-methoxyestradiol in preeclampsia: more than a unifying hypothesis

Preeclampsia is a systemic disorder of pregnancy characterized by widespread maternal endothelial dysfunction. Clinical manifestations of preeclampsia include placental hypoxia, hypertension, proteinuria and fluid retention. The condition is common and affects over 5% of all pregnancies, thus remaining a leading cause of maternal and fetal morbidity and mortality worldwide [1]. Pregnancies complicated by preeclampsia are associated with greater risk and earlier onset of cardiovascular disease in both mother and infant [2,3]. Preeclampsia originates in the placenta, as it may occur only in the presence of placenta or a hydatiform mole and resolves dramatically postpartum after the delivery of the placenta. Generalized endothelial dysfunction resulting in vasoconstriction and end-organ ischaemia is attributed in all of the clinical aspects of the maternal syndrome in preeclampsia. Search for a unique circulating factor [4] resulted in an identification of multiple factors of endothelial dysfunction, activation and oxidative stress. A major breakthrough was achieved during the past five years by a series of experimental and clinical studies from Karumanchi and associates implicating that changes in circulating angiogenic factors play a decisive role in the pathogenesis of preeclampsia (reviewed in [5]). Increased expression of soluble fms-like tyrosine kinase 1 (sFlt1), a variantofthemembrane-boundvascularendothelialgrowth factor (VEGF)-receptor 1 that consists of the extracellular ligand-binding domain, was associated with decreased placental growth factor (PIGF) and VEGF signalling and consecutive defective angiogenesis [6]. Soluble Flt1 acts as a natural antagonist of the circulating VEGF and increases from mid-gestation onwards, to reach the peak 5–8 weeks before the onset of the maternal syndrome [7]. Soluble

Preeclampsia More Than 1 Disease

In this issue of Hypertension , Rasmussen and Irgens provide strong support for the relationship of preeclampsia and intrauterine growth restriction (IUGR). They also provide data that support but also some that argue against the concept that the pregnancy complication, preeclampsia, may be more than one disease.1 In previous studies these authors demonstrated that women who have had a growth-restricted infant without preeclampsia are more likely to have preeclampsia in a subsequent pregnancy.2 Those data and similar findings in the current study support pathological findings indicating the similarity of IUGR and preeclampsia.3 In preeclampsia, IUGR and interestingly also in about one third of cases of preterm birth,4 the maternal myometrial and decidual vessels perfusing the placental site do not undergo the normal remodeling of pregnancy. In normal pregnancy trophoblastic invasion is associated with a greatly increased diameter and removal of vascular smooth muscle from the wall of these vessels. This results in large diameter, flaccid, unresponsive tubes that greatly increase placental perfusion. These changes are not present in pregnancies complicated by IUGR, preeclampsia, and some with preterm births. Implicit in the current study is the concept that preterm birth as well as IUGR is related to subsequent preeclampsia. Although preterm birth is not assessed directly, the effect of low birth weight (IUGR and preterm birth) was greater than the effect of IUGR alone. In a far smaller study our group was able to more directly support the relationship of preterm birth and preeclampsia, as women with early onset preeclampsia were more likely to have preterm birth in a subsequent nonpreeclamptic pregnancy.5 The current study extends the prior observation of the relationship of IUGR and preeclampsia but also raises other interesting points. In this larger study the authors were …