Severe Form Of Preeclampsia Research Articles

Preeclampsia: Are platelet count and indices useful for its prognostic?

IntroductionPreeclampsia (PE) is characterized by hypertension and proteinuria after the 20th week gestation. The aim of this study was to investigate whether platelet count (PC) and platelet indices (mean platelet volume (MPV), platelet distribution width (PDW), and plateletcrit (PCT)) could predict severe form of preeclampsia (sPE).MethodsThree groups were evaluated; G1-pregnant with sPE (N = 29); G2-normotensive pregnant (N = 28) and Group 3: non-pregnant women (N = 30). Platelet parameters were obtained using the same automatic blood cells count. Statistical analysis was performed by analysis of variance, t-test, and receiver operating characteristic (ROC) curve. P ≤ 0.05 was considered significant.ResultsLower PC and PCT were observed in sPE comparing to normal pregnant (P = 0.031 and 0.035, respectively) and to non-pregnant women (P < 0.001 and 0.004, respectively). PDW was higher in sPE comparing to normotensive pregnant (P = 0.028) and to non-pregnant women (P < 0.001). MPV was higher in sPE comparing to normotensive pregnant and non-pregnant women (P = 0.05 and P < 0.001, respectively). Analysis from the ROC curve and its areas for each variable showed that the parameters have regular diagnostic significance, except for PCT, considered as not good for this purpose.ConclusionPC emerges as a good candidate for sPE diagnosis, since it is a simple and habitually done method, with lower cost and greater accessibility in the clinical laboratory. Further studies evaluating sequential PC and platelet indices throughout pregnancy are necessary to clarify the role of platelet parameters in PE development and severity.

Síndrome de HELLP normotensivo: caso clínico

HELLP syndrome (hemolysis, elevated liver enzymes and low platelets) represents a severe form of preeclampsia associated with serious maternal and fetal morbidities and even death. Usually HELLP syndrome appears during the evolution of a severe preeclampsia; however HELLP syndrome can have atypical clinical manifestations. We report a 22-year-old female who consulted at 20 weeks of pregnancy for lumbar pain, dysuria and fever. A urinalysis revealed the presence of white blood cells. The patient was admitted to hospital and treated with antimicrobials. Forty eight hours after admission a proteinuria of 440 mg/24 h was detected. A severe pre eclampsia-HELLP syndrome was diagnosed. However the patient remained with normal blood pressure. An elevation of liver enzymes and creatinine were observed. Five days later fetal death was confirmed and an abortion was induced. The patient required a platelet transfusion. Four days after the abortion, the patient was discharged in good conditions.

Abstract 279: Hypertension in Hemolysis, Elevated Liver Enzyme, Low Platelet Syndrome is Associated with Increased Endothelin-1

INTRODUCTION. HELLP syndrome (hemolysis, elevated liver enzymes, and low platelets) is a severe form of preeclampsia, a hypertensive disorder that occurs during pregnancy. We have shown that HELLP syndrome in both women and in an animal model causes hypertension and elevated TNF-α, IL-6, and agonistic autoantibodies to the angiotensin II receptor, all of which have been shown to activate the endothelin-1 system (ET-1). Therefore we tested the hypothesis that hypertension in response to HELLP syndrome is associated with ET-1 activation. METHODS. Plasma was collected from women with HELLP syndrome or pregnant women without maternal/fetal complications at the time of delivery. Endothelin (ET-1) was extracted from the plasma and measured with a Quantikine ET-1 enzyme linked immunosorbent assay kit. On gestational day (GD) 12 miniosmotic pumps infusing sEndoglin (7ug/kg/day) and sFlt-1 (4.7ug/kg/day) were implanted into normal pregnant rats to induce HELLP syndrome. On GD18 carotid catheters were inserted into HELLP and normal pregnant (NP) rats and mean arterial pressure (MAP) was recorded on GD19; serum, urine and tissues were collected for molecular analysis. RESULTS. Women with HELLP syndrome (n=4) had significantly more circulating ET-1 (3.35pg/mL) compared to normal pregnant women (0.75pg/mL; n=3; p=0.006) and increased MAP (120.8±6.2 mmHg HELLP vs. 87.33±6.67mmHg NP; p=0.015). In rats MAP increased from 91±2mmHg in NP rats (n=4) to 129.8±4.5mmHg in HELLP rats (n=4; p=0.0002). Preproendothelin mRNA expression was 3 fold higher in placentas and 1.3 fold higher in livers from HELLP rats compared to NP rats (p=0.02; p=0.05). In addition we measured ET-1 secretion from endothelial cells exposed to serum from NP and HELLP rats. ET-1 in response to NP serum was 4.03±.68pg/mg/mL and increased to 9.69±3.5pg/mg/mL with HELLP serum (p=0.04) after 24hrs. CONCLUSION. These data support the hypothesis that hypertension in both women and animals with HELLP syndrome is accompanied by increased ET-1 expression.

Widespread DNA hypomethylation at gene enhancer and low CpG density regions in placentas associated with early-onset preeclampsia

s / Placenta 34 (2013) A1–A99 A86 P2.88. WIDESPREAD DNA HYPOMETHYLATION AT GENE ENHANCER AND LOW CPG DENSITY REGIONS IN PLACENTAS ASSOCIATEDWITH EARLY-ONSET PREECLAMPSIA John Blair , Ryan Yuen , Brendan Lim , Deborah McFadden , Peter von Dadelszen , Wendy Robinson 1 University of British Columbia, Vancouver, BC, Canada; University of Toronto, Toronto, ON, Canada Preeclampsia is a serious complication of pregnancy that can affect both maternal and fetal outcomes. Early-onset preeclampsia (EOPET) is a severe form of preeclampsia that is associated with altered physiological characteristics and gene expression in the placenta. DNA methylation is a relatively stable epigenetic modification to DNA that can reflect gene expression, and can provide insight into the mechanisms underlying such expression changes. Objectives: We sought to profile DNA methylation changes in EOPET to better characterize the pathology underlying this condition and the relationship to clinical features. Methods: DNA methylation was profiled in placentas from 20 EOPET and 20-gestational age matched control pregnancies using the Infinium HumanMethylation450 Beadchip. This analysis was followed up using the HT-12v4 Expression BeadChip microarray, bisulfite pyrosequencing and bioinformatic analysis. Results: We identified 38,840 CpG sites with significant (FDR 12.5% methylation difference compared to the gestational age-matched normotensive controls. Significant sites were enriched at the enhancers and low CpG density regions of the associated genes and the majority (74.5%) of these sites were hypomethylated in EOPET. No stratification of the EOPET DNA methylation profile was apparent based on presence/absence of intrauterine growth restriction (IUGR) or severe proteinuria. CpG sites from four genes relevant to preeclampsia (INHBA, BHLHE40, SLC2A1, and ADAM12) were followed up using bisulfite pyrosequencing in a larger cohort, and they showed different extent of changes in related pregnancy disorders (late-onset preeclampsia (LOPET) and normotensive IUGR (nIUGR)). Genome-wide expression in a subset of samples showed that some of the gene expression changes were negatively correlated with DNA methylation changes, particularly for genes that are responsible for angiogenesis (such as EPAS1 and FLT1). Conclusion: Based on DNA methylation profiling, we conclude that there are widespread DNA methylation alterations in EOPET that may be associated with changes in placental function. This property may provide a useful tool for early screening of such placentas. http://dx.doi.org/10.1016/j.placenta.2013.06.254 P2.89. MORPHOLOGY OF THE MOUSE MESOMETRIAL DECIDUA DURING EARLY PREGNANCY Alex Kors Vidsiunas , Sergio Ferreira de Oliveira 2 Nove de Julho University, Sao Paulo-SP, Brazil; University of Sao Paulo, Sao

Reversal of gene dysregulation in cultured cytotrophoblasts reveals possible causes of preeclampsia.

During human pregnancy, a subset of placental cytotrophoblasts (CTBs) differentiates into cells that aggressively invade the uterus and its vasculature, anchoring the progeny and rerouting maternal blood to the placenta. In preeclampsia (PE), CTB invasion is limited, reducing placental perfusion and/or creating intermittent flow. This syndrome, affecting 4%-8% of pregnancies, entails maternal vascular alterations (e.g., high blood pressure, proteinuria, and edema) and, in some patients, fetal growth restriction. The only cure is removal of the faulty placenta, i.e., delivery. Previously, we showed that defective CTB differentiation contributes to the placental component of PE, but the causes were unknown. Here, we cultured CTBs isolated from PE and control placentas for 48 hours, enabling differentiation and invasion. In various severe forms of PE, transcriptomics revealed common aberrations in CTB gene expression immediately after isolation, including upregulation of SEMA3B, which resolved in culture. The addition of SEMA3B to normal CTBs inhibited invasion and recreated aspects of the PE phenotype. Additionally, SEMA3B downregulated VEGF signaling through the PI3K/AKT and GSK3 pathways, effects that were observed in PE CTBs. We propose that, in severe PE, the in vivo environment dysregulates CTB gene expression; the autocrine actions of the upregulated molecules (including SEMA3B) impair CTB differentiation, invasion and signaling; and patient-specific factors determine the signs.

Widespread DNA hypomethylation at gene enhancer regions in placentas associated with early-onset pre-eclampsia.

Pre-eclampsia is a serious complication of pregnancy that can affect both maternal and fetal outcomes. Early-onset pre-eclampsia (EOPET) is a severe form of pre-eclampsia that is associated with altered physiological characteristics and gene expression in the placenta. DNA methylation is a relatively stable epigenetic modification to DNA that can reflect gene expression, and can provide insight into the mechanisms underlying such expression changes. This case–control study focused on DNA methylation and gene expression of whole chorionic villi samples from 20 EOPET placentas and 20 gestational age-matched controls from pre-term births. DNA methylation was also assessed in placentas affected by late-onset pre-eclampsia (LOPET) and normotensive intrauterine growth restriction (nIUGR). The Illumina HumanMethylation450 BeadChip was used to assess DNA methylation at >480 000 cytosine-guanine dinucleotide (CpG) sites. The Illumina HT-12v4 Expression BeadChip was used to assess gene expression of >45 000 transcripts in a subset of cases and controls. DNA methylation analysis by pyrosequencing was used to follow-up the initial findings in four genes with a larger cohort of cases and controls, including nIUGR and LOPET placentas. Bioinformatic analysis was used to identify overrepresentation of gene ontology categories and transcription factor binding motifs. We identified 38 840 CpG sites with significant (false discovery rate <0.01) DNA methylation alterations in EOPET, of which 282 had >12.5% methylation difference compared with the controls. Significant sites were enriched at the enhancers and low CpG density regions of the associated genes and the majority (74.5%) of these sites were hypomethylated in EOPET. EOPET, but not associated clinical features, such as intrauterine growth restriction (IUGR), presented a distinct DNA methylation profile. CpG sites from four genes relevant to pre-eclampsia (INHBA, BHLHE40, SLC2A1 and ADAM12) showed different extent of changes in LOPET and nIUGR. Genome-wide expression in a subset of samples showed that some of the gene expression changes were negatively correlated with DNA methylation changes, particularly for genes that are responsible for angiogenesis (such as EPAS1 and FLT1). Results could be confounded by altered cell populations in abnormal placentas. Larger sample sizes are needed to fully address the possibility of sub-profiles of methylation within the EOPET cohort. Based on DNA methylation profiling, we conclude that there are widespread DNA methylation alterations in EOPET that may be associated with changes in placental function. This property may provide a useful tool for early screening of such placentas. This study identifies DNA methylation changes at many loci previously reported to have altered gene expression in EOPET placentas, as well as in novel biologically relevant genes we confirmed to be differentially expressed. These results may be useful for DNA- methylation-based non-invasive prenatal diagnosis of at-risk pregnancies.

COHELLP: collaborative randomized controlled trial on corticosteroids in HELLP syndrome.

BackgroundHemolysis, elevated liver enzymes, and low platelets (HELLP) syndrome is one of the most severe forms of preeclampsia and aggravates both maternal and perinatal prognosis. The systematic review available in Cochrane Library compared corticosteroid (dexamethasone, betamethasone, or prednisolone) given during pregnancy, just after delivery or in the postnatal period, or both before and after birth, with placebo or no treatment. Those receiving steroids showed significantly greater improvement in platelet counts which was greater for those receiving dexamethasone than those receiving betamethasone. There was no clear evidence of any effect of corticosteroids on substantive clinical outcomes. These benefits appear to be greater in Class I HELLP syndrome.ObjectivesTo determine the effectiveness of dexamethasone for accelerating postpartum recovery in patients with Class I HELLP syndrome in a multicenter randomized controlled trial.Methods/DesignThe study is a triple blind randomized controlled trial including women with class I HELLP syndrome, and exclusion criteria were dexamethasone use in the last 15 days before diagnosis of HELLP syndrome; chronic use of corticosteroids; chronic diseases that alter laboratory parameters of HELLP Syndrome, such as chronic liver disease or purpura, patients unable to consent (coma or critical clinical condition) and without accompanying persons that may consent to study participation.Eligible patients will be invited to participate and those who agree will be included in the study and receive placebo or dexamethasone according to a random list of numbers and subjects will receive the study medication every 12 hours for two days.During the study the women will be subject to strict control of blood pressure and urine output. Laboratory tests will be performed at regular intervals during treatment and 24 hours and 48 hours after its suspension. If worsening of clinical or laboratory variables is observed, a rescue scheme of dexamethasone will be administrated. This proposal has already obtained approval of the local Institutional Review Board of the coordinating center (IMIP, Recife, Brazil), all other participating centers and of the National Council for Ethics in Research (CONEP) of the Brazilian Ministry of Health.Trial RegistrationClinical Trials Register under the number NCT00711841.

PP009. Hypoxia alters syncytiotrophoblastic microparticles (STBM)-related coagulation capacities

Endothelial dysfunction is thought to be the cause of preeclampsia (PE) symptoms. Severe forms of PE are correlated to the release of syncytiotrophoblastic microparticles (STBM), which triggers inflammatory processes on the endothelium. The thrombogenic potential of STBMs is not well characterized. We investigated the pro-coagulant activity of STBMs. STBMs were derived from placentae perfused under norm- and hypoxic conditions and quantified with our house-"ELISA". Surface phospholipid-dependent thrombin formation of microparticles was determined with a commercial ELISA. Rate and absolute platelet aggregation in platelet-rich plasma (PRP), while fibrin production in platelet free plasma, was measured in absence and presence of STBMs using a PAP-4 aggregometer. STBM concentration and STBM-induced thrombin formation is stable under normoxic and elevated under hypoxic conditions. STBMs derived from hypoxic placentae increase the rate of fibrinogenesis. Maximum platelet aggregation is stable under normoxic, while highly variable under hypoxic conditions. STBMs of hypoxic placentae cannot alter the rate of platelet aggregation, while normoxic STBMs adjust the rate according to need. Hypoxia negatively affects fibrinogenesis and the platelet aggregation-modulating effects of STBMs, which might be due to a phenotype alteration. All observed results may contribute to the impaired microcirculation seen in PE.

Long term cardiovascular outcomes for mother and child

Preeclampsia is well established as one of the leading causes of maternal and fetal mortality and morbidity. Furthermore, it is now clear that women who have had preeclampsia have an increased risk of cardiovascular events over the next 10-15 years. Indeed, preeclampsia is associated with a fourfold increased risk of hypertension and double the risk of fatal and non fatal ischaemic heart disease and stroke. More recently, it has been emerging that offspring born to preeclampsia are also more likely to have a higher blood pressure from the childhood and stroke in the later life. Furthermore, the risk to mother and offspring is greatest when preeclampsia is diagnosed at an earlier gestation, suggesting a more severe form of preeclampsia. As the long term cardiovascular risk to both mother and child is known from delivery there is increasing interest in key phenotypic variations that are identifiable in mothers and children during the years between the episode of preeclampsia and the emergence of established cardiovascular disease. These might help explain the link between the two conditions, provide a means to identify subjects at greatest risk of later cardiovascular disease and establish intermediate endpoints for future preventative interventions. A range of studies from research groups around the world are beginning to unravel the links between preeclampsia and long term variations in cardiac and vascular structure and function, as well as persistent biological differences in both the mother and children. This increased understanding allows both better characterisation of long term cardiovascular outcomes and better identification of optimal approaches to improve long term outcomes.

Hellp syndrome and composite major maternal morbidity: importance of Mississippi classification system

Objective: We explored the prevalence of Composite Major Maternal Morbidity (CMMM) for patients with severe preeclampsia (SPRE) and each class or category of HELLP syndrome.Methods: In a retrospective cohort study from 2000 to 2010, we reviewed maternal charts of patients categorized with complete or partial HELLP syndrome. From 2005 to 2007, the maternal charts for every patient with a diagnosis of SPRE without HELLP syndrome were also evaluated for comparison. The CMMM for each patient group included cardiopulmonary; hematologic/coagulation, central nervous system/visual, hepatic or renal complications. During the study interval patients with class 1 and class 2 HELLP syndrome received Mississippi Protocol management.Results: Four hundred and ninety-five mothers had a form of HELLP syndrome in years 2000–2010; 688 mothers experienced a non-HELLP severe form of preeclampsia during 2005–2007. The prevalence of CMMM for each patient group was: class 1 = 44%; class 2 = 13%; class 3 = 24%; partial HELLP = 20% and SPRE = 18%. CMMM for class 1 HELLP syndrome is significantly higher than all other groups (p < 0.001).Conclusions: Patients who develop class 1 HELLP syndrome have significantly higher CMMM. Avoiding this most advanced stage of HELLP syndrome and minimizing the development of new MMM becomes a measure of medical management effectiveness and a tool to assess overall quality of care.

Seeking the mechanism(s) of action for corticosteroids in HELLP syndrome: SMASH study

Administration of dexamethasone to the hemolysis, elevated liver enzymes, and low platelet count (HELLP) syndrome patients (10 mg intravenously [IV] every 12 hours) shortens the disease course and reduces maternal morbidity in patients treated at the University of Mississippi Medical Center (UMMC), associated with this severe form of preeclampsia. However, the pathophysiological mechanisms involved with this intervention remain unclear. We sought to investigate the potential role of IV dexamethasone to restore the imbalance among antiangiogenic and inflammatory factors known to be significantly elevated in women with HELLP syndrome. This was a single-center prospective study of women diagnosed with HELLP syndrome who were treated for IV dexamethasone at UMMC. Blood was drawn prior to dexamethasone administration and again 12 and 24 hours after the initial dexamethasone administration. Enzyme-linked immune assays were used to measure circulating inflammatory cytokines and antiangiogenic factors. A repeated-measures analysis of variance was used to analyze the data collected before, after, and during dexamethasone administration. Seventeen women with HELLP syndrome were enrolled in this study. Dexamethasone significantly decreased evidence of hemolysis (P = .002) and liver enzymes (P = .003), and significantly increased platelets (P = .0001) within 24 hours of administration. Circulating interleukin-6 levels after 24 hours were decreased (P < .001); soluble fms-like tyrosine kinase-1 and soluble endoglin were also significantly decreased by 24 hours after dexamethasone administration (P < .002 and P < .004, respectively). There were no significant differences in circulating levels of placental growth factor (P = .886) due to dexamethasone administration. Angiotensin II receptor autoantibody levels were unchanged by dexamethasone administration. We conclude that 1 important mechanism of dexamethasone administration is to blunt the release of both antiangiogenic and inflammatory factors suggested to play role in the pathophysiology of HELLP syndrome.

Rheological parameters in the umbilical cord blood in moderate and severe forms of preeclampsia

Previous studies have dealt with maternal blood rheology in preeclampsia (PE), but only a few focused on the fetal rheological parameters in this maternal state. PE is one of the most common severe complications of pregnancy world-wide associated with high maternal morbidity and mortality and intrauterine fetal growth restriction. Our objective was to explore the rheological parameters in the umbilical cord blood at term in the presence of moderate and severe forms of PE. A subgroup analysis was performed in a community based retrospective study of 4,951 consecutively recorded singleton pregnant women of whom 423 had PE. In the latter, umbilical cord blood was collected during delivery for testing of hematological and blood rheological parameters of their fetus. Fetal results from uneventful pregnancy were compared with those associated with preeclampsia. Furthermore, results were also evaluated in the presence of moderate and severe forms of PE. Plasma viscosity (pv) was examined using KSPV 1 Fresenius and Red Blood Cell (RBC) aggregation (stasis: E0 and low shear: E1) using MA1-Aggregometer; Myrenne. According to the definition of the German Society of Gynecology and Obstetrics (DGGG) 314 women had moderate (74.2%), while 109 had severe forms of PE due to the presence of a blood pressure > 170/110 mmHg (n = 41; 9.7%), and/or IUGR < 5th percentile (n = 28; 6.6%), and/or HELLP-Syndrome (n = 10; 2.4%), and/or proteinuria ≥ 5 g/24 h (n = 30; 7.1%). When comparing the fetal results from pregnancies with and without preeclampsia mean hemoglobin values (p < 0.001) and hematocrit (p < 0.001) were markedly higher, while plasma viscosity (p = 0.006) and erythrocyte aggreagtion (stase: p = 0.35; low shear: p = 0.08) were lower in association with preeclampsia. Gestational age, fetal birth-weight and umbilical arterial cord blood pH in women with severe PE was statistically significant lower as compared to those with moderate disease (p < 0.001). Mean hemoglobin level and hematocrit were higher in fetus from women with severe compared to moderate PE, while plasma viscosity (1.03 ± 0.07 mPas vs. 1.05 ± 0.07; p = 0.05) and erythrocyte aggregation in stase (2.3 ± 2.47 vs. 2.41 ± 2.46; p = 0.11) as well as under low shear (7.86 ± 4.63 vs. 8.06 ± 4.60; p = 0.15) were lower. HELLP-Syndrome was associated with the lowest plasma viscosity (1.00 ± 0.07 mPas; p = 0.019) and erythrocyte aggregation (low shear: 5.1 ± 5.0; p = 0.04) in fetus. The results of this study including a notable number of patients with PE and their newborns revealed an in part statistically significant association between variables of blood rheology and the presence, severity and type of preeclampsia with a trend towards hyperviscosity in severe forms of preeclampsia. The behaviour of blood rheological components in the neonate is remarkable since the number of red blood cells is raised while RBC aggregability and plasma viscosity is low.

Assessment of hemostatic function in pregnant women undergoing surgery using a Platelet Function Analyzer-100

Assessment of hemostatic function in pregnant women undergoing surgery using a Platelet Function Analyzer-100

Synergistic effects of angiotensinogen −217 G→A and T704C (M235T) variants on the risk of severe preeclampsia

The rate-limiting step of the renin-angiotensin system is the enzymatic cleavage of angiotensinogen (AGT) by renin. The aims of the present study were to investigate the association between AGT T704C (M235T) and -217 G→A polymorphisms with the risk of preeclampsia and synergistic effects of both polymorphisms on the susceptibility to preeclampsia. We studied AGT variants in 170 women with preeclampsia, including 84 women with mild and 86 women with severe forms of preeclampsia, and 100 age and parity matched controls. There was a trend towards increased risk of severe preeclampsia in the presence of -217 AA (odds ratio (OR)=1.5, 95% confidence interval (CI)= 0.38-5.84, p=0.57) and TC+CC genotypes (OR=1.32, 95% CI= 0.67-2.58, p=0.42). However, the interaction of both alleles of -217A and 704C highly increased the risk of severe preeclampsia, by 2.23-fold, although this did not reach statistical significance. The frequency of the CC genotype of the T704C polymorphism in early-onset preeclampsia tended to be higher (35%) compared with that in patients with late-onset preeclampsia (21.7%). The present study demonstrates that both variants of AGT -217 G→A and T704C might work in synergism to influence the risk of severe preeclampsia, which needs to be confirmed in studies with larger sample size.

MTHFR C677T and eNOS G894T variants in preeclamptic women: Contribution to lipid peroxidation and oxidative stress

ObjectivesWe aimed to investigate the association between methylenetetrahydrofolate reductase (MTHFR) C677T and endothelial nitric oxide synthase (eNOS) G894T polymorphisms with lipid peroxidation, total antioxidant capacity (TAC) and the risk of preeclampsia in preeclamptic women. Design and MethodsWe screened a sample of 198 unrelated women with mild and severe forms of preeclampsia and 101 unrelated women with normal pregnancy with the eNOS and MTHFR variants using PCR-RFLP method. Also, the serum malondialdehyde (MDA) and TAC levels were determined using HPLC and commercial kits, respectively. ResultsThe frequency of combined genotypes of MTHFR CT and TT (CT+TT) and T allele tended to be higher in severe preeclamptic women compared to controls. There was no significant difference for eNOS G894T genotype and allele frequencies between patients and controls. A significantly higher level of triglycerides was observed in the presence of combined genotypes of MTHFR CT and TT and also eNOS GT and TT (GT+TT) in preeclamptic women compared to controls with the same genotype. Also, the presence of MTHFR TT genotype in severe preeclamptic women was significantly associated with the increased serum MDA level compared to CC genotype. In severe preeclamptic women the presence of CT and combined genotypes of CT and TT was significantly associated with the decreased TAC level compared to CC genotype. Also, a higher MDA level was observed in mild preeclamptic women with eNOS TT genotype compared to those with GG genotype but the difference was not significant. ConclusionThe present study indicates that MTHFR C677T polymorphism through affecting on TG level, lipid peroxidation and oxidative stress might be involved in the pathogenesis of severe preeclampsia.

Abstract 176: Hypertension in a Rat Model of HELLP Syndrome is Associated with T Helper 1 Type Immune Activation

HELLP syndrome (hemolysis, elevated liver enzymes, low platelets) is a severe form of preeclampsia, which is a hypertensive disorder that occurs during pregnancy. While the symptoms and consequences of HELLP syndrome are often severe, the physiological mechanisms involved are still unknown. Previous studies demonstrate that simultaneously elevated sFlt-1 and sEndoglin, causes symptoms similar to HELLP syndrome in pregnant rats. In this study we utilized this HELLP syndrome rodent model to determine if an immunological cascade occurs similarly to that seen in HELLP patients. On gestational day (GD) 14 miniosmotic pumps infusing sEndoglin (7ug/kg/day) and sFlt-1 (3.7ug/kg/day) were implanted into normal pregnant (NP) rats. On GD18 carotid catheters were inserted and mean arterial pressure (MAP) was recorded on GD19. Plasma and tissue was also collected to determine adverse pathology and markers of inflammation. MAP increased from NP (n=7) 104+3 to 122+3mmHg in HELLP rats (n=14) (P=0.002). Alanine aminotransferase liver enzymes were also increased from 37.78+4.5 IU/L in NP to 62.85+6.1 IU/L in HELLP rats (P=0.007) and platelets were decreased in HELLP rats (6286+1209uL) compared to NP rats (28375+4547uL, P = 0.0007). TNF alpha and IL-6 were increased in HELLP rats (54.74+12.67pg/mL vs. 25.65+3.5pg/mL n=8; P = 0.04) and (103.6+26.5pg/mL vs. 40.18+ 8.2pg/mL/ P = 0.04) compared to NP rats. Furthermore, HELLP rats had increased CD4+ T lymphocytes compared to NP rats, circulating 14.37% vs. 9% gated; placental 8.67% vs. 5.99% gated; spleen 12.4% vs. 7.84% gated; liver 8.27% vs. 1.7% gated. In this study we demonstrate that hypertension in a newly adapted rat model of HELLP syndrome, is associated with a T helper 1 immune activation similar to that seen in HELLP patients.

Utilisation de l’urapidil injectable dans l’hypertension gravidique et la prééclampsie

To evaluate the efficacy and tolerance of injectable urapidil (Eupressyl(®)) for the treatment of severe pregnancy-associated arterial hypertension. We carried out a prospective study of 100cases encompassing the various types of severe pregnancy-associated arterial hypertension, with clinical and biological monitoring of the mother and the collection of neonatal data. Treatment was initiated if the blood pressure was higher than 160/110mmHg and efficacy was defined as a lowering of blood pressure to 150/100mmHg or below. Treatment with urapidil alone was effective in 80cases (80%). In 20% of cases, essentially the most severe forms of preeclampsia, efficacy was achieved only if urapidil was associated with labetalol or if urapidil was replaced with nicardipine. We observed no material complications other than two cases of hypotension due to excessively rapid administration of a bolus of nicardipine to replace urapidil treatment. Injectable urapidil seems to be an antihypertensive agent that is easy to use and effective in 80% of cases and that has very few secondary effects on the mother or the foetus. Further comparative studies are required to determine the potential of this drug for use in the management of pregnancy-associated hypertension.

PP086. The modern search for possible predictors of preeclampsia in the first trimester of pregnancy (preliminary study)

Preeclampsia is a major complication affecting at least 3-4% of all pregnancies and is globally responsible for approximately 50,000 maternal deaths annually. Currently the main cause of preeclampsia is a shallow placentation, with abnormal invasion of cytotrophoblasts and incomplete remodeling of placenta-supplying maternal uterine spiral arteries. However, up to 20weeks, these processes are asymptomatic, although they are accompanied by the release of various macromolecules in the bloodstream of the mother, which are potential biomarkers of disease, needed to detect. Much progress has been made in recent years towards first-trimester models using combined factors that will be of realistic use in clinical practice.The ability to predict the most severe forms of preeclampsia would allow closer surveillance and earlier intervention to improve pregnancy outcomes. To determine the significance of measuring the concentration of PlGF and sFlt-1 and their ratio in 11-13 weeks of pregnancy as early markers of preeclampsia. The study included 85 pregnant women in 11-13 weeks with subsequent uncomplicated pregnancy and 11 patients which developed various hypertensive disorders, four of them have developed severe (n=2) and mild (n=2) preeclampsia later. Concentrations of markers were determined on automated analyzers Cobas E411 (Hoffmann La Roche) using test kits Elecsys PlGF and Elecsys sFlt-1. In the first trimester the concentration of sFlt-1 in healthy pregnant women was 1618,0±18,2pg/ml, PlGF - 47,5±3,5pg/ml, the sFlt-1/PLGF ratio - 35,9±3,2. In the second trimester parameters were as follows: sFlt-1 - 1898,0±29,8pg/ml, PlGF - 208,0±11,0pg/ml, the sFlt-1/PLGF ratio-11,2±2,6. Two patients with severe preeclampsia had sFlt-1 concentration at 11-12 weeks of 2185 and 14923pg/ml, PlGF - 12,8 and 61.3pg/ml, the ratio sFlt-1/PLGF - 170,7 and 243.4. In two patients with mild preeclampsia, these figures were in 1700 and 2312pg/ml, 38.2 and 37,6pg/ml, 44,4 and 61,4, respectively. The optimal prediction biomarker does probably not exist. Our preliminary results confirm the feasibility of determining concentrations of sFlt-1 and PlGF, and their ratio in the 1st trimester of pregnancy to assess the risk of preeclampsia in order to reduce the frequency of obstetric complications and perinatal loss. Effective prediction of PE can be achieved at 11-13weeks' gestation. Further studies on the development and implementation a modified integrated screening program for early diagnosis of PE at 11-14weeks of gestation should be based on the assessment of maternal factors, biophysical, biochemical, and molecular genetic markers are needed. Better individualised patient prediction will allow us to target existing prevention, as it is, and to also develop new treatments in future.

Pré-eclâmpsia precoce e tardia: uma classificação mais adequada para o prognóstico materno e perinatal?

to evaluate the differences between the maternal and perinatal outcomes of pregnancies complicated by preeclampsia, according to the classification as the severe/mild form, and the early/late onset form. a retrospective study with 211 pregnancies complicated by preeclampsia, assessed at a university reference center from 2000 to 2010. The diagnosis and disease severity were based on the values of blood pressure, proteinuria, and clinical and laboratory findings. The pregnant's age, skin color, parity, blood pressure, urine protein semiquantitative values, presence of bilateral notch in the uterine artery dopplervelocimetry and birth conditions were compared between patients with mild and severe disease, as well as between those of early/late onset. The disease was considered to be of early onset when diagnosed at less than 34 weeks of gestational age. most patients had the severe form of preeclampsia (82.8%), and the onset of the condition was early in 50.7%. Blood pressure values (133.6 ± 14.8 versus 115.4 mmHg, p=0.0004 and 132.2 ± 16.5 versus 125.7 mmHg, p=0.0004) and semiquantitative proteinuria (p=0.0003 and p=0.0005) were higher in the early and severe forms compared to mild and late forms. Infant birth weight (1,435.4 ± 521.6 versus 2,710 ± 605.0 g, 1,923.7 ± 807.9 versus 2,415.0 ± 925.0 g, p<0.0001 for both) and Apgar score (p=0.01 for both) were smaller for severe and early preeclampsia compared to mild and late preeclampsia. On the other hand, the presence of a bilateral notch in the uterine arteries was linked to the forms of early onset (69.2 versus 47.9%, p=0.02), whereas fetal growth restriction was more frequent in the severe forms of preeclampsia (30 versus 4.4%, p=0.008). the preeclampsia classification based on maternal clinical parameters better reflected the conditions of fetal nutrition, while the early onset of the condition was associated with placental vasculopathy detected by dopplervelocimetry.

Knowledge Assessment and Preparation for the Certified Emergency Nurses Examination

Knowledge Assessment and Preparation for the Certified Emergency Nurses Examination