Clinical Manifestations Of Preeclampsia Research Articles

Early age at menarche is associated with an increased risk of preeclampsia and adverse neonatal outcomes: a 6‑year retrospective study.

Preeclampsia affects between 2 to 8% of pregnancies worldwide and is associated with significant adverse outcomes for both mothers and their offspring. The present study aims to investigate whether there is a correlation between early age at menarche and an increased risk of developing preeclampsia and experiencing adverse neonatal outcomes. The study involved a review of medical records of 4227 pregnant women who gave birth at The First Affiliated Hospital of Chengdu Medical College between January 2017 and December 2022. The collected data included demographic characteristics, clinical manifestations of preeclampsia, laboratory indicators, gestational complications, and neonatal outcomes. Pregnant women were categorized into four groups based on their age at menarche (≤ 12, 13, 14, and ≥ 15years). Logistic regression analysis was conducted to calculate the odds ratios (ORs) and 95% confidence intervals (CIs) for the association between different menarche age groups and the risk of preeclampsia and adverse neonatal outcomes. Pregnant women who had an age at menarche of ≤ 12years had a higher risk of preeclampsia than women who had their menarche at 13, 14, and ≥ 15years of age, with adjusted ORs (95% CIs) for preeclampsia of 1.00 (reference), 0.78 (0.45-0.91), 0.76 (0.59-0.88), and 0.73 (0.56-0.94), respectively. The predictive efficacy of age at menarche for preeclampsia was assessed with a sensitivity and specificity of 85.2% and 76.4%, respectively, and an AUC of 0.82. Moreover, infants born to women with an age at menarche of ≤ 12years had a higher risk of adverse neonatal outcomes, including small for gestational age, preterm birth, low birth weight, neonatal respiratory distress syndrome, and neonatal intensive care unit admission. Our findings suggest that an early age at menarche is associated with an increased risk of preeclampsia and adverse neonatal outcomes. This information could be useful for obstetricians to identify women at risk for preeclampsia early on and implement timely interventions to reduce the incidence of preeclampsia and associated adverse neonatal outcomes.

Association of pro-fibrinolytic receptor AnnexinA2 with tissue plasminogen activator/Inhibitor-1 in pre-eclampsia.

The clinical manifestations of pre-eclampsia are related to placental anti-angiogenic factor alteration. These variations are mainly due to the alteration of plasminolytic components. The study aims to compare the expression of plasminolytic components in the placenta of women with and without pre-eclampsia. The study included pregnant women with pre-eclampsia as PE group (n = 30) and without pre-eclampsia as a control group (n = 30). Placental bed biopsy tissues were collected. AnxA2, tPA, PAI-1 expression in the placental villous tissue was quantitatively evaluated using immunohistochemistry, western blot, and real time-PCR analysis. The results of the study showed a significant decrease in the expression of ANXA2 and increased expression of tPA and PAI-1 in PE group compared to control group (p<0.005). AnxA2 expression showed positive correlation with tPA (r=+0.895, p=0.002) and negative correlation with PAI-1(r=-0.905, p=0.020) in control group whereas in the PE group AnxA2 expression was negatively correlated with tPA ((r=-0.801, p=0.016) and PAI-1 (R=-0.831, P=0.010). Decreased AnxA2 with increased expression of PAI-1 and tPA may be responsible for the altered fibrinolytic activity and play a significant role in pre-eclampsia pathogenesis.

Molecular Development of Placenta and Its Relationship with Preeclampsia and Fetal Growth Restriction

Preeclampsia (PE) is the leading causes of maternal death worldwide as well as a significant cause of fetal morbidity and mortality, including fetal growth restriction (FGR). The concept that PE and FGR shared a common etiology is widely accepted, i.e., the maladaptive response to the impaired placentation. Normal placentation is the result of dynamic integration of cell proliferation, differentiation, and migration, in which trophoblast cells play a crucial role. Impaired trophoblast invasion into the maternal decidua leads to a decrease in uteroplacental blood flow and changes in intervillous hemodynamic. The dynamic interaction of these process with maladaptive decidual immune response, impaired cytokines and angiogenic factors regulation, and oxidative stress will lead into the clinical manifestation of PE and/or FGR.

Маркери ангіоґенезу та їх роль у прогнозуванні прееклампсії при багатоплідній вагітності

Purpose - to identify changes in biochemical markers of endothelial dysfunction, preclinical manifestations of preeclampsia in pregnant women with multiple pregnancies after the use of assisted reproductive technologies. Materials and methods. A prospective study of pregnant women with dichorionic diamniotic twins after assisted reproductive technologies was conducted: 35 pregnant women with twins who were offered a developed monitoring algorithm (main (І) group) and 27 pregnant women who were monitored according to generally accepted methods of managing multiple pregnancies (control (ІІ) group). Statistical processing of the research results was carried out using standard programs “Microsoft Excel 5.0” and “Statistica 6.0”. Results. During the analysis of the main and control observation groups, an increase in the pro-angiogenic biomarker PlGF was noted up to 28 weeks (I group 604.9 (83.4-814.5) pg/ml vs. 568.6 (68.1-765.3) pg/ml in the II group). Іn the term of 26-28 weeks, in the main group, we noted a decrease in the level of PlGF below 100 pg/ml in 4 (11.4%) women, and in the II group in 6 (22.2%), however, clinical manifestations of preeclampsia, in patients, it was not noted. In the period of 32-34 weeks, the results of PlGF below the level of 100 pg/ml were obtained in 6 (17.1%) women of the I group against 7 (25.9%) of the women of the II group. In the group I we found 2 cases of moderate preeclampsia at 32 and 33 weeks of pregnancy. In the II group 4 cases of preeclampsia were identified. Two cases of moderate preeclampsia, which clinically manifested at 30 weeks. Conclusions. The anti-angiogenic factor, sFlt-1 and the pro-angiogenic factor PIGF, and their relationship are promising markers in the prediction and early diagnosis of preeclampsia in the multiple pregnancies after assisted reproductive technologies. Based on monitoring the growth dynamics of the sFlt-1/PIGF ratio, it is possible to predict the early development of preeclampsia even without clinical symptoms, and to make a decision about the possibility of extending the pregnancy or the need for urgent delivery. The research was carried out in accordance with the principles of the Helsinki Declaration. The study protocol was approved by the Local Ethics Committee of the participating institution. The informed consent of the patient was obtained for conducting the studies. No conflict of interests was declared by the authors.

Pathogenetic Approach to Early Preeclampsia and the Feasibility of Pregnancy Prolongation

Aim. To evaluate the efficacy of cascade plasma filtration (CPF) for the correction of lipid profile and biochemical markers (sFlt-1, PIGF, sFlt-1/PIGF) in pregnant women with early preeclampsia. Materials and Methods. A prospective controlled study of 23 CPF procedures was conducted in 11 pregnant women with early preeclampsia at gestational ages 22 to 31 weeks. The evolution of clinical manifestations of preeclampsia (BP, urine output, and proteinuria), laboratory biochemical parameters (protein/creatinine ratio, lipid profile), blood coagulation tests, and thromboelastometry (ROTEM) were assessed. In addition, the effect of CPF on the level of preeclampsia markers (sFlt-1, PIGF, sFlt-1/PIGF-ratio) as predictors of endothelial aggression was analyzed. The efficacy of extracorporeal therapy was evaluated based on the duration of pregnancy prolongation. Results. The use of CPF as an adjunct for the treatment of early preeclampsia had a positive effect on the lipid profile by reducing cholesterol and LDL, which helped to decrease atherogenic aggression on the vascular endothelium. In addition, the extracorporeal therapy promoted reduction of the anti-angiogenic effect of sFlt-1, which was confirmed by a significant decrease in the sFlt-1/PIGF ratio from 515 [347; 750] to 378 [285; 557] (P = 0.013). The period of prolongation of pregnancy was longer in the main group (with CPF) and was 19 [5; 26] days, whereas in the comparison group (without CPF) it was 3 [1; 4] days (P &lt; 0.001). All newborns were discharged from the hospital in a stable condition. The paper is supplemented with a clinical observation of the effective use of CPF in early preeclampsia. Conclusion. The use of cascade plasma filtration in the treatment of early preeclampsia to prolong pregnancy could be a promising approach.

Health profile of the patients with pre-eclampsia in a referral hospital in the Amazon region.

To describe the epidemiological and clinical profile of the patients with preeclampsia in a hospital in the Amazon region. Observational descriptive cross-sectional study, performed at Fundação Santa Casa de Misericórdia do Pará, a maternity hospital in Pará, Brazil. The pregnant patients admitted between July 1st and December 31st 2018 due to pre-eclampsia had their medical records researched to describe their epidemiological profile, medical history, obstetric profile and clinical manifestations of pre-eclampsia. Patients with incomplete data were not included in the missing variable's rate. 3450 pregnant patients were admitted, and 381 of them due to pre-eclampsia, revealing a 11.04% prevalence. Both arithmetic mean and median of maternal age were approximately 27 years. 94.25% of the participants were parda. Regarding medical history, 50.27% had chronic hypertension, and 37.23% had urinary tract infection during pregnancy. The obstetric profile revealed that 42.26% were primigravid, and 30% of the multigravid participants had already manifested pregnancy hypertension. 78.1% of the participants attended less than 6 prenatal consultations, and 10.03% used chemical substances during pregnancy. Twin pregnancy had a 3.14% prevalence. Beyond hypertension and proteinuria, scotoma was the most frequent (28.57%) clinical manifestation. 2.36% of the patients developed seizures, mostly (55.55%) before 37 weeks of pregnancy. The profile of the participants was mean age 27 years, parda race, with chronic hypertension, single fetus, multigravid without previous pregnancy hypertension, with less than 6 prenatal consultations, no use of chemical substances and without any manifestations of pre-eclampsia beyond hypertension and proteinuria.

Efek Skopoletin dari Ekstrak Buah Mengkudu (Morinda Citrifolia) sebagai Modalitas Herbal dalam Penanganan Preeklamsia

ABSTRACT&#x0D; Introduction: Preeclampsia is a disorder which usually occurs in normotensive women and characterized by hypertension. Preeclampsia often causes morbidity and mortality in both mother and fetus. Lots of deaths have been caused by preeclampsia every year. Thus, good and proper treatment need to be done. The aim of this writing is to find out and make a literature review about preeclampsia’s herbal-based treatment which is safe for pregnant women.&#x0D; Discussion: Many factors take part in the pathogenesis of preeclampsia, including increased oxidative stress and decreased nitric oxide (NO). Increased oxidative stress can cause placental dysfunction which will cause clinical manifestations of preeclampsia. Decreased NO can also cause clinical manifestations of preeclampsia. Scopoletin antioxidant from Morinda citrifolia fruit extract is able to prevent cell damage caused by oxidative stress and prevent inactivation of NO due to free radicals. Scopoletin was proven to significantly decrease blood pressure in rats with oxidative stress-related hypertension (PNL) and to significantly increase NO in the PNL group and the general hypertension group (PN).&#x0D; Conclusion: Treatment of preeclampsia can be done by scopoletin antioxidant, resulting in the effect on systolic and diastolic blood pressure and mean arterial pressure. Scopoletin also increases NO, resulting in a vasodilation effect. This writing is expected to be a help in advancing the treatment of preeclampsia in the future.&#x0D; Keywords: Morinda citrifolia, preeclampsia, scopoletin

ANTERIOR PLACENTA POSITION AS A CAUSING FACTOR OF PRE-ECLAMPSIA

The aim of the study – to determine the frequency of preeclampsia in pregnant females with anterior location of the placenta and to determine the prognostic significance when combined with a marker of acute renal damage – cystatin C level.&#x0D; Materials and Methods. In 2018–2020, a prospective cohort study that enrolled 91 pregnant women at their second trimester of gestation was conducted at Maternity Clinic and Obstetric Hospital of Maternity Hospital No. 2, Odesa. The group with the anterior location of the placenta consisted of 47 (51.65 %) pregnant women and 44 (48.35 %) had the posterior location of the placenta. Assessment of serum cystatin C was performed in women without clinical manifestations of PE at the second or third trimester of gestation (18–36 weeks), the average term was (32.22±0.41) weeks of pregnancy (p=0.011).&#x0D; Results and Discussion. 28.57 % of pregnant women were subsequently diagnosed with preeclampsia (PE), of whom 19 (20.88 %) had anterior and 7 (7.69 %) posterior placenta location. Body mass index (BMI) before pregnancy, age, and height: no statistically significant difference observed between groups (p&gt; 0.05). Analysis of maternal factors of PE in relation to the anterior location of the placenta: odds ratio (OR) higher than 1.0 was noted for combination with obesity (OR 2.38 (95 % CI 0.75–7.53)), the age over 35 years (OR 1.01 (95 % CI 0.41–2.49)) and history of PE during previous pregnancy (OR 1.38 (95 % CI 0.21–9.01)), but no statistical significance was observed (р˃0.05). When analyzing cystatin C values over 1.0 mmol/l relative to the anterior location of the placenta, the OR was 3.92 (95 % CI 1.45–10.57), sensitivity 84.09 %, specificity 42.55 %, accuracy 62.64 % were reported, p=0.011. When analyzing the frequency of preeclampsia in the anterior location of the placenta, the OR was 3.59 (95 % CI 1.32 - 9.71), sensitivity 84.09 %, specificity 40.43 %, accuracy 61.54 % were reported with statistical significance p=0.019.&#x0D; Conclusions. The risk of preeclampsia in patients with the anterior location of the placenta increases by 3.59 times with a prognostic accuracy of 61.54 %. To increase the prognostic significance for the detection of preeclampsia in women with anterior location of the placenta, it is recommended to assess the serum level of cystatin C.

Abstract 14401: Elevated Levels of Angiotensin II Type 1 Receptor Autoantibodies Are Associated With Abnormal Echocardiogram Parameters in Women With Preeclampsia

Introduction: Preeclampsia (PEC) increases the long-term risk for heart failure with preserved ejection fraction (HFpEF). While the underlying pathogenesis is unknown, angiotensin II type 1 receptor autoantibodies (AT1-AA) have been implicated. AT1-AA bind agonistically to the AT1 receptor and may result in clinical manifestations of preeclampsia. We aimed to determine whether women with PEC have elevated AT1-AA levels compared to normotensive women (controls) during pregnancy and at 4 years postpartum, and whether AT1-AA levels correlate with abnormal echocardiographic parameters. Methods: We performed a prospective longitudinal cohort study comparing women with PEC (n=21) to controls (n=20). AT1-AA and echocardiographic measurements were obtained during pregnancy and 4 years postpartum. Linear regression analyses were performed to evaluate the association between AT1-AA levels and important echocardiographic parameters. Results: Mean AT1-AA level during pregnancy differed significantly between women with PEC versus healthy pregnant controls (10.21±3.20 vs 6.33±3.40 μg/ml, p&lt;0.001). Women with PEC were more likely to be black and deliver at an earlier gestational age. Higher AT1-AA was associated with increased systolic/diastolic blood pressure, echocardiographic markers of biventricular systolic function (tricuspid annular systolic plane excursion and left ventricular (LV) ejection fraction), concentric LV hypertrophy and worsened diastolic function. AT1-AA remained persistently elevated at 4 years in women with PEC at baseline compared to controls (12.76±5.13 vs 4.47±1.49 μg/ml, p&lt;0.001) (Figure 1). Conclusions: Women with PEC have elevated AT1-AA compared to controls, both during pregnancy and 4 years postpartum. Higher AT1-AA is associated with abnormal diastolic parameters, LV remodeling, and hyperdynamic biventricular function. These findings suggest that AT1-AA plays an important role in the risk of HFpEF in PEC.

Pre-eclampsia predictive ability of maternal miR-125b: a clinical and experimental study

Pre-eclampsia (PE) is a systemic maternal syndrome affecting 2-8% of pregnancies worldwide and involving poor placental perfusion and impaired blood supply to the foetus. It manifests after the 20th week of pregnancy as new-onset hypertension and substantial proteinuria and is responsible for severe maternal and newborn morbidity and mortality. Identifying biomarkers that predict PE onset prior to its establishment would critically help treatment and attenuate outcome severity. MicroRNAs are ubiquitous gene expression modulators found in blood and tissues. Trophoblast cell surface antigen (Trop)-2 promotes cell growth and is involved in several cancers. We assessed the PE predictive ability of maternal miR-125b in the first trimester of pregnancy by measuring its plasma levels in women with normal pregnancies and with pregnancies complicated by PE on the 12th week of gestation. To gain insight into PE pathogenesis we investigated whether Trop-2 is targeted by miR-125b in placental tissue. Data analysis demonstrated a significant association between plasma miR-125b levels and PE, which together with maternal body mass index before pregnancy provided a predictive model with an area under the curve of 0.85 (95% confidence interval, 0.70-1.00). We also found that Trop-2 is a target of miR-125b in placental cells; its localization in the basal part of the syncytiotrophoblast plasma membrane suggests a role for it in the early onset of PE. Altogether, maternal miR-125b proved a promising early biomarker of PE, suggesting that it may be involved in placental development through its action on Trop-2 well before the clinical manifestations of PE.

Опыт применения каскадной плазмофильтрации при ранней преэклампсии

Objective. To assess the efficacy of cascade filtration plasmapheresis (CFP) for the correction of lipid profile in pregnant women with early preeclampsia. Patients and methods. We analyzed the effect of 5 CFP procedures in 4 pregnant women with preeclampsia detected at gestational age of 23(+0)–30(+4) weeks. We evaluated the dynamics of clinical manifestations of preeclampsia (blood pressure, daily diuresis, and severity of proteinuria), laboratory parameters (Р/С-ratio, lipid profile), and thromboelastometry parameters (ROTEM). We also analyzed the effect of CFP on the sFlt-1 level as it is believed to be a predictor of endothelial aggression in early preeclampsia. Treatment efficacy was assessed by prolongation of pregnancy and neonatal outcomes. Results. The inclusion of CFP in the comprehensive therapy for early preeclampsia had a positive effect on the lipid profile, in particular, it ensured a 30% decrease in the level of cholesterol, triglycerides, LDL, and VLDL, which reduced atherogenic aggression on the vascular endothelium. Moreover, CFP improved blood rheological properties by decreasing the level of fibrinogen, Willebrand factor, and structural coagulation parameters (MCF FIBTEM) according to the results of rotational thromboelastometry (ROTEM). However, we observed no significant changes in sFlt-1 levels in response to lipoprotein apheresis. All women delivered by caesarean section due to clinical and laboratory deterioration of preeclampsia. The time of pregnancy prolongation varied between 4 and 26 days. All newborns were discharged from the hospital in a satisfactory condition. Conclusion. Our experience with CFP demonstrated high effectiveness of extracorporeal therapy in correcting the lipid profile (cholesterol, triglycerides, LDL, and VLDL) and reducing atherogenic aggression on the vascular endothelium. At the same time CFP did not decrease the anti-angiogenic effect of sFlt-1. Further studies are needed to confirm our findings. Key words: cascade filtration plasmapheresis, preeclampsia, sFlt-1, therapeutic aspects

Initial-onset symptoms of preeclampsia and their relation to pregnancy outcomes

Preeclampsia (PE) is a serious gestational idiopathic hypertensive disease, threatening both maternal and foetal safety. As a systemic disease, the initial-onset symptoms (IOSs) and clinical manifestations of PE can vary widely from patient to patient. However, a lack of evidence-based data on IOS and their relationship to their corresponding clinical features and pregnancy outcomes persists. We hypothesised that there would be a significant difference between the morbidity time, subsequent organ dysfunction and the status of mother and foetus in PE patients with different IOS. Moreover, early identification of the characteristics of the PE patients with different IOS could improve pregnancy outcomes through individualised prevention or intervention. This study aimed to analyse maternal and foetal condition and pregnancy outcomes of PE patients with different IOS, and to explore the disease progression and characteristics of maternal and foetal outcomes for different IOS, so as to provide the basis for future maternal and foetal monitoring of PE patients. Impact statement What is already known on this subject? In 2013, the American College of Obstetricians and Gynecologists revised their definition of PE, sparking a heated debate. Subsequently in 2015, China updated its guidelines to define PE as hypertensive pregnancy accompanied by involvement of any other organ or organ system, to include the heart, lungs, liver and kidneys, among others. However, IOS can be varied in PE, so the maternal management and foetal monitoring should be classified through different IOS. No evidence-based data on IOS in PE patients exist. What the results of this study add? Significant differences in mean morbidity times and mean delivery times were demonstrated among patients with different IOS; medians of the interval from morbidity to delivery were between 4 and 6 weeks. Significant differences in laboratory values were found in patients with different IOS. In patients that did not present with proteinuria as an IOS, 89.1% experienced proteinuria following diagnosis. Patients with the most severe complications presented with hypertension as an IOS. Follow-up visits demonstrated different foetal weight medians. What the implications are of these findings for clinical practice and/or further research ? IOS could be an indicator to help evaluate the potential for different maternal and foetal complications and PE outcomes. Moreover, the duration of treatment for PE maybe 4–6 weeks.

Pro- to Anti-angiogenic Ratio in Preeclampsia

Background: During fetal development, human placenta undergoes both angiogenesis and vasculogenesis. An imbalance in proangiogenic [placental growth factor (PlGF) and vascular endothelial growth factor] and antiangiogenic factors [soluble fms like tyrosine kinase-1 (sFlt-1), soluble endoglin (sEng)] seems to play an important role in the pathophysiology of preeclampsia. Heme oxygenase-1 HO-1 is induced by ROS (reactive oxygen species) and NO (nitric oxide) and was recently discovered to be involved in angiogenesis. Methods: Hence, the present study was designed to analyze the proangiogenic and antiangiogenic role of heme oxygenase-1 and endoglin in maternal and cord blood of normotensive and preeclamptic women. Fifty pregnant women were selected and grouped as group 1 (control, n=25) comprising of normotensive women immediately after delivery; group 2 (study group) comprising of age -and sex-matched preeclamptic women. Study samples were drawn (maternal venous blood and umbilical cord blood) and heme oxygenase-1 and endoglin levels were analyzed by competitive enzymelinked immunosorbent assay. Results: Maternal and cord blood heme oxygenase-1 levels were significantly elevated in preeclamptic mothers as compared to normotensive pregnant women (p&lt;0.001). Serum and cord blood endoglin levels were significantly lower in preeclamptic women as compared to normotensive pregnant women (p&lt;0.001). HO-1/Eng ratio was drastically doubled in preeclamptics as compared to normotensive pregnant women. In normotensive [HO]/ [Eng+ IGF] were lower in normotensive pregnant and drastically increased in preeclamptics. Conclusion: The findings of a present study indicating a shift towards antiangiogenic profile in women with preeclampsia confirm their possible role to induce characteristic clinical manifestations of preeclampsia such as proteinuria and hypertension.

Preeclampsia: the role of persistent endothelial cells in uteroplacental arteries

We explore the potential role of the endothelial lining of uteroplacental arteries in the pathogenesis of preeclampsia, a severe pregnancy disorder characterized by incomplete invasion of the uterine vasculature by extravillous trophoblast and angiogenic imbalance. In normal pregnancy, the endothelium disappears progressively from the uteroplacental arteries and is replaced by trophoblast and deposition of fibrofibrinoid structure, underpinning the so-called physiological transformation of uterine spiral arteries. We hypothesize that partial persistence of the endothelium, albeit injured, initiates a chain of events leading to the emergence of preeclampsia in 3 sequential stages. The first stage results in retention of the endothelium in uteroplacental arteries secondary to incomplete physiological transformation of the vessels. Consequently, the uteroplacental vessels are reactive to pathological cues, which drives local arteriopathy. The second stage starts with progressive reduction in uteroplacental blood flow, generating oxidative stress in the whole placenta, and heightened maternal inflammation in response to circulating trophoblastic debris. In the third stage, generalized endotheliosis causes systemic angiogenic imbalance, hypertension, and other clinical manifestation of preeclampsia.

Increased circulating levels of Epidermal Growth Factor-like Domain 7 in pregnant women affected by preeclampsia

Proper placental development is crucial to establish a successful pregnancy. Defective placentation is the major cause of several pregnancy complications, including preeclampsia (PE). We have previously demonstrated that the secreted factor Epidermal Growth Factor-like Domain 7 (EGFL7) is expressed in trophoblast cells of the human placenta and that it regulates trophoblast migration and invasion, suggesting a role in placental development. In the present study, we demonstrate that circulating levels of EGFL7 are undetectable in nonpregnant women, increase during pregnancy and decline toward term. Close to term, circulating levels of EGFL7 are significantly higher in patients affected by PE when compared to normal pregnancies. Consistent with these results, villus explant cultures obtained from placentas affected by PE display increased release of EGFL7 in the culture medium when compared to those from normal placentas. Our results suggest that increased release of placenta-derived EGFL7 and increased circulating levels of EGFL7 are associated with the clinical manifestation of PE.

Obesity and Preeclampsia: Common Pathophysiological Mechanisms.

Preeclampsia is a disorder specific of the human being that appears after 20 weeks of pregnancy, characterized by new onset of hypertension and proteinuria. Abnormal placentation and reduced placental perfusion associated to impaired trophoblast invasion and alteration in the compliance of uterine spiral arteries are the early pathological findings that are present before the clinical manifestations of preeclampsia. Later on, the endothelial and vascular dysfunction responsible of the characteristic vasoconstriction of preeclampsia appear. Different nutritional risk factors such as a maternal deficit in the intake of calcium, protein, vitamins and essential fatty acids, have been shown to play a role in the genesis of preeclampsia, but also an excess of weight gain during pregnancy or a pre-pregnancy state of obesity and overweight, which are associated to hyperinsulinism, insulin resistance and maternal systemic inflammation, are proposed as one of the mechanism that conduce to endothelial dysfunction, hypertension, proteinuria, thrombotic responses, multi-organ damage, and high maternal mortality and morbidity. Moreover, it has been demonstrated that pregnant women that suffer preeclampsia will have an increased risk of future cardiovascular disease and related mortality in their later life. In this article we will discuss the results of studies performed in different populations that have shown an interrelationship between obesity and overweight with the presence of preeclampsia. Moreover, we will review some of the common mechanisms that explain this interrelationship, particularly the alterations in the L-arginine/nitric oxide pathway as a crucial mechanism that is common to obesity, preeclampsia and cardiovascular diseases.

Different Effects of Pravastatin on Preeclampsia-like Symptoms in Different Mouse Models.

Background:Pravastatin (Pra) exerts protective effects on preeclampsia. Preeclampsia is a multifactorial and pathogenic pathway syndrome. The present study compared the effects of Pra on clinical manifestations of preeclampsia in different pathogenic pathways.Methods:Two different preeclampsia-like mouse models used in this study were generated with Nω-nitro-L-arginine methyl ester (L-NAME) and used lipopolysaccharide (LPS) from day 7 of gestation, respectively. Pra treatment was administered on day 2 after the models were established in each group (L-NAME + Pra, LPS + Pra, and Control + Pra, n = 8) or normal saline (NS) for the control group (L-NAME + NS, LPS + NS, and Control + NS, n = 8). Maternal weight, serum lipids, the histopathological changes, and lipid deposition in the liver and placenta were observed. The pregnancy outcomes were compared. The blood pressure analysis was carried out on repeated measurements of variance. Student's t-test was used for comparing the two groups. The enumeration data were compared by Chi-square test.Results:The mean arterial pressure (MAP) and 24-h urinary protein in the L-NAME + NS and LPS + NS groups were significantly higher than the Control + NS group (F = 211.05 and 309.92 for MAP, t = 6.63 and 8.63 for 24-h urinary protein; all P < 0.05) and reduced in the L-NAME + Pra group as compared to the L-NAME + NS group (F = 208.60 for MAP, t = 6.77 for urinary protein; both P < 0.05). Urinary protein was decreased in the LPS + Pra group as compared to the LPS + NS group (t = 5.33; P < 0.05), whereas MAP had no statistical significance (F = 3.37; P > 0.05). Compared to the Control + NS group, the placental efficiency in the L-NAME + NS and LPS + NS groups decreased significantly (t = 3.09 and 2.89, respectively; both P < 0.05); however, no significant difference was observed in L-NAME + Pra and LPS + Pra groups (t = 1.37 and 0.58, respectively; both P > 0.05). Free fatty acid was elevated in the L-NAME + NS group as compared to the Control + NS group (t = 3.99; P < 0.05) at day 18 of pregnancy and decreased in the L-NAME + Pra group as compared to the L-NAME + NS group (t = 3.28; P < 0.05); however, no significant change was observed in the LPS model (F = 0.32; P > 0.05).Conclusion:This study suggested that Pra affected the clinical manifestations differently in preeclampsia-like mouse models generated in various pathogenic pathways.

The emerging role of endothelin-1 in the pathogenesis of pre-eclampsia.

Pre-eclampsia (PE) is the most frequently encountered medical complication during pregnancy. It is characterized by a rise in systemic vascular resistance with a relatively low cardiac output and hypovolemia, combined with severe proteinuria. Despite the hypovolemia, renin-angiotensin system (RAS) activity is suppressed and aldosterone levels are decreased to the same degree as renin. This suggests that the RAS is not the cause of the hypertension in PE, but rather that its suppression is the consequence of the rise in blood pressure. Abnormal placentation early in pregnancy is widely assumed to be an important initial event in the onset of PE. Eventually, this results in the release of anti-angiogenic factors [in particular, soluble Fms-like tyrosine kinase-1 (sFlt-1)] and cytokines, leading to generalized vascular dysfunction. Elevated sFlt-1 levels bind and inactivate vascular endothelial growth factor (VEGF). Of interest, VEGF inhibition with drugs like sunitinib, applied in cancer patients, results in a PE-like syndrome, characterized by hypertension, proteinuria and renal toxicity. Both in cancer patients treated with sunitinib and in pregnant women with PE, significant rises in endothelin-1 occur. Multiple regression analysis revealed that endothelin-1 is an independent determinant of the hypertension and proteinuria in PE, and additionally a renin suppressor. Moreover, studies in animal models representative of PE, have shown that endothelin receptor blockers prevent the development of this disease. Similarly, endothelin receptor blockers are protective during sunitinib treatment. Taken together, activation of the endothelin system emerges as an important pathway causing the clinical manifestations of PE. This paper critically addresses this concept, taking into consideration both clinical and preclinical data, and simultaneously discusses the therapeutic consequences of this observation.

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.

Selective termination in discordant twin pregnancy with early onset preeclampsia: case report

Objective: To study the effectiveness of selective termination for discordant twins in treating early onset preeclampsia. Materials and Methods: After literature review, ethical review, and discussion with the couple, one patient with early onset preeclampsia complicated with a lethal condition in one twin, was performed selective termination by intracardiac injection of potassium chloride at 27 weeks’ and four days’ gestation in an effort to reverse preeclampsia and prolong the pregnancy. Results: The clinical manifestation of preeclampsia was alleviated in this patient. At 29 weeks, the stillborn fetus was delivered because of spontaneous preterm labor. A live birth was achieved five days later. All procedures allowed continuation of the pregnancy for an additional two weeks and one day of the remaining fetus. Conclusion: Selective termination may be an option for treating early onset preeclampsia in discordant twins, instead of termination of whole pregnancy.