Onset Severe Preeclampsia Research Articles

Clinical significance of S100B protein in pregnant woman with early- onset severe preeclampsia.

Preeclampsia is one of the most feared complications of pregnancy, which can progress rapidly to serious complications such as death of both mother and fetus. To present, the leading cause of preeclampsia is still debated. The purpose of this article was to explore the clinical significance of S100B protein, a kind of Ca2+ -sensor protein, in the early-onset severe preeclampsia. Nine pregnant women with early-onset severe preeclampsia (the study group) and 13 healthy pregnant women (the control group) were included in this study. The level of S100B in the amniotic fluid, maternal blood, and umbilical cord blood were detected by enzyme-linked immunosorbent assay (ELISA) and surface plasmon resonance imaging (SPRi) methods. Diagnostic values of S100B for early-onset severe preeclampsia were assessed by Receiver Operating Characteristic (ROC) curve analysis. The levels of S100B in maternal blood and amniotic fluid in the study group were higher than those in the control group (p < 0.05). ROC curve analysis showed that S100B detected by SPRi method (SPRi-S100B) showed a cut-off level of 181 ng/mL with sensitivity of 100%, a specificity of 84.6%, and a Youden index of 0.846 in the maternal blood, which had better clinical significance and diagnostic value (at than that detected by ELISA (ELISA-S100B). The levels of S100B detected by SPRi in maternal blood can indicate early-onset severe preeclampsia and perinatal brain injury.

Maternal and perinatal outcome of women with early-onset severe pre-eclampsia before 28 weeks: Is expectant management beneficial in a low-resource country? A prospective observational study.

To study the maternal and perinatal outcomes in women with severe pre-eclampsia before 28 weeks of pregnancy. A descriptive study from a tertiary care center. All consecutive women with severe pre-eclampsia withonset before 28 weeks of pregnancy were included. The details were collected in a predesigned structured proforma prospectively. The study cohort included 145 women with a mean maternal age of 26.97 ± 5.36 years (range 19-47 years). The mean duration of prolongation of pregnancy was 13.04 ± 10.57 days (range 1-51 days). A total of 29.7% (n = 43) of women had at least one major adverse maternal outcome, and the most common was HELLP (hemolysis, elevated liver enzymes, low platelet count) syndrome (n = 24,16.6%), followed by eclampsia (n = 12,8.3%). The stillbirth rate was high (n = 103,68.7%), and most occurred in the antepartum period. Of 47 (31.3%) neonates born alive, only eight (17.02%;8/47) survived up to 28 days of life. Fetal growth restriction with Doppler abnormalities and neonatal sepsis were the most common reasons for perinatal mortality. Expectant management should not be considered routinely when the onset of severe pre-eclampsia is before 25+6 weeks of pregnancy. Between 26 and 27+6 weeks it can be offered under close monitoring and the perinatal survival depends on the neonatal services available in their facility.

Impact of different referral timing on the pregnancy outcomes of severe pre-eclampsia in the referral system

Impact of different referral timing on the pregnancy outcomes of severe pre-eclampsia in the referral system

Clinical characteristics of severe pre-eclampsia in a single tertiary referral center

Objective: To explore the feasibility and key point of improvement in preventing and postponing the onset of severe pre-eclampsia (SPE) and its severe complications in the tertiary referral system by analyzing the clinical characteristics of SPE in a single tertiary referral center. Methods: The clinical data of 217 patients with SPE who were hospitalized and terminated pregnancy in Peking University Third Hospital from January 2020 to December 2020 were retrospectively analyzed. The risk factors, clinical characteristics and severe complications of SPE between the patients referred from primary hospitals (referral group) and the patients received regular prenatal care in the tertiary referral center (central group) were compared, as well as the influence of the referral timing on the characteristics and perinatal outcome. Results: (1) Clinical characteristics: among the 217 cases of SPE, 84 cases were in the referral group and 133 cases were in the central group. The gestational ages at SPE clinical diagnosis [31.5 weeks (28.1-34.6 weeks) vs 35.6 weeks (33.3-37.2 weeks); Z=-6.547, P<0.01], termination of pregnancy [32.3 weeks (29.5- 35.1 weeks) vs 36.3 weeks (34.4-37.5 weeks); Z=-6.554, P<0.01] and onset of SPE severe complications [30.6 weeks (26.4-32.7 weeks) vs 34.9 weeks (32.7-36.5 weeks); Z=-4.040, P<0.01] in the referral group were significantly earlier than those in the central group, the rates of ICU [10.7% (9/84) vs 3.8% (5/133); χ²=4.126, P=0.042] and neonatal ICU hospitalization [72.9% (51/70) vs 54.7% (70/128); χ²=6.286, P=0.012] were higher than those in the central group, while the live birth rate [83.3% (70/84) vs 96.2% (128/133); χ²=10.736, P=0.001] was lower than that of the central group. (2) Analysis of risk factors: for the patient whose risk factors were obesity, advanced age or pre-eclampsia history, the gestational ages at SPE clinical diagnosis and termination of pregnancy in the referral group were significantly earlier than those in the central group (P<0.05). For those with chronic hypertension, the gestational ages at severe complications onset in the referral group were significantly later than those in the central group (P<0.05). For those without obvious risk factors, the gestational ages at SPE clinical diagnosis, termination of pregnancy and onset of SPE severe complications in the referral group were earlier than those in the central group (P<0.05). (3) Analysis of severe complications: the top three severe complications in the referral group and the central group were hypertensive encephalopathy/cerebrovascular accident [20.2% (17/84) vs 7.5% (10/133)], HELLP syndrome [7.1% (6/84) vs 8.3% (11/133)] and placental abruption [8.3% (7/84) vs 7.5% (10/133)]. The rate of hypertensive encephalopathy/cerebrovascular accident in the referral group was significantly higher than that in the central group (χ²=7.645,P=0.006). (4) Analysis of referral timings: the timings included referral after onset of SPE severe complications (8.3%, 7/84), referral after onset of SPE (67.9%, 57/84), referral after detection of SPE early warning signs (14.3%, 12/84) and referral after detection of SPE risk factors in the 2nd and 3rd trimester (9.5%, 8/84). The earlier the referral, the longer the interval from clinical diagnosis to onset of severe complications, from referral to termination of pregnancy, and from referral to severe complications onset (P<0.05). The earlier the referral, the lower the NICU hospitalization rates, the higher the live birth rates. The ICU hospitalization rate of referrals after severe complications onset was significantly higher than those of the other three referral timing groups (P<0.05). Conclusions: SPE occurs in hospitals of different levels. Although tertiary referral center may postpone the onset of SPE and its severe complications, reduce the severity of SPE and prolong the gestational age, its awareness of prevention and control still needs to be further improved. Early identification of the risk of SPE and timely referral are important parts of improving SPE adverse outcomes in primary medical institutions. The significance and value of referral system need to be brought into full play.

THE RELATIONSHIP BETWEEN THE ONSET OF SEVERE PREECLAMPSIA AND PERINATAL COMPLICATIONS AT RUMKITAL Dr. RAMELAN IN SURABAYA

Abstract Background: Preeclampsia is one of the biggest causes of maternal-fetal morbidity and mortality. Based on the prognosis, the classification of Preeclampsia is early onset (&lt;34 weeks) and late onset (&gt; 34 weeks). Purpose: to investigate the relationship between the onset of severe Preeclampsia and perinatal complications. Method: This research is a quantitative study with a retrospective observational analytic study type and collected medical record data. The study population was severe Preeclampsia patients who gave birth at RUMKITAL Dr. Ramelan Surabaya for the period January 2018 - June 2020 and has no previous history of chronic hypertension. The research sample was 79 subjects with 44 subjects early onset, and 35 subjects late onset. Perinatal complications examined are preterm delivery, asphyxia, LBW, IUGR, stillbirth. The chi-square test or Fisher’s Exact Test was used to analyze relationships. Result: From the results of the study, the comparison of the percentage from early onset and late onset that experienced complications was 93.2% vs 48.6%, p-value = 0.000, OR = 14.5, CI = 3,764–55,635. At preterm delivery, it was found that 75% vs 28.6%, p-value = 0.000, OR = 7.5, CI = 2,754-20,422. . In asphyxia, it was found 41.7% vs 31.4%, p-value = 0.46. At LBW, it was found 72.7% vs 17.1%, p-value = 0,000, OR = 12.9, CI = 4,285-38,771. In IUGR, it was found that 15.9% vs 2.9%, p-value = 0.000. In stillbirth, it was found 18.2% vs 0% and p-value = 0.008. Conclusion: the onset of severe Preeclampsia is related with perinatal complications. Complications associated with the onset severe Preeclampsia are preterm, LBW, stillbirth. Meanwhile, complications that are not related with the onset severe Preeclampsia are asphyxia and IUGR

HIF‑1α affects trophoblastic apoptosis involved in the onset of preeclampsia by regulating FOXO3a under hypoxic conditions.

Preeclampsia (PE) is a pregnancy-specific syndrome that has severe implications on perinatal mortality and morbidity. Excessive apoptosis of trophoblasts induced by hypoxia may be associated with the development of PE, but the exact pathogenesis is unknown. Forkhead box O transcription factor 3a (FOXO3a) is activated under hypoxic conditions. Furthermore, hypoxia-inducible factor-1α (HIF-1α) is sensitive to variations in partial oxygen pressure. Thus, the aims of the present study were to investigate the expression levels of HIF-1α and FOXO3a in placental samples of early onset severe PE, and their effect on trophoblastic apoptosis under hypoxic conditions. Cobalt chloride was used to establish the hypoxic model. The present study examined the expression levels of HIF-1α and FOXO3a in the placental tissues and HTR8/SVneo cells under hypoxic conditions. It was found that HIF-1α and FOXO3a were highly expressed in placental tissues of patients with PE and in HTR8/SVneo cells under hypoxic conditions. Furthermore, knockdown of FOXO3a using a specific small interfering RNA (siRNA) decreased apoptosis in HTR8/SVneo cells. Moreover, it was found that after knockdown of HIF-1α using siRNA, FOXO3a expression and the apoptotic rate were reduced in HTR8/SVneo cells. Therefore, the present results indicated that the elevated expression of HIF-1α increased trophoblastic apoptosis by regulating FOXO3a, which may be involved in the pathogenesis of PE.

Potential correlation between EDN1 gene polymorphisms with preeclampsia.

To explore the potential correlation between endothelin 1 (EDN1) gene polymorphisms with preeclampsia (PE). The single nucleotide polymorphisms (SNPs) of 248 PE patients and 232 healthy controls were genotyped by Polymerase Chain Reaction (PCR). The possible association between EDN1 polymorphisms and PE was revealed through the t-test and the Chi-square test. PE risk was significantly correlated with the C allele of polymorphism rs5370 in EDN1. The polymorphism rs5370 in EDN1 was remarkably associated with the onset of severe PE, rather than mild PE. The markedly increased risk of early-onset PE was related to the C allele of polymorphism rs5370 in EDN1, while no significant difference in the allele frequency of polymorphism rs1800541 was detected between the PE group and the control group. In the co-dominant model, the CC genotype of polymorphism rs5370 in EDN1 was associated with the increased PE risk. PE risk in the population carrying TC genotype was 1.59 times higher than those with TT/CC genotype, while polymorphism rs1800541 had no apparent association with PE risk. In the severe PE group, there was an evident difference in the genotype frequency between the dominant and over-dominant models of polymorphism rs5370. In the recessive model, the raised risk of early-onset PE was notably correlated with the TT/CC genotype compared with that of TT genotype. However, no evident association with the genotype frequency of polymorphism rs1800541 was observed between PE patients and controls. EDN1 gene polymorphism rs5370 is correlated with the increased risk of PE.

Analysis of clinical early warning informations of severe preeclampsia before onset

Objective: To explore the early warning informations of severepre-eclampsia before onset. Methods: The study was an observational case-control study. The study group consisted of 77 single-pregnancy preeclampsia pregnant women and the control group took 154 normal cases who were delivered to Tianjin Fifth Central Hospital (Peking University binhai Hospital) from January 2014 to December 2017 in the perinatal care referral system in Tianjin. To analyze changes in clinical indicators before the onset of severe pre-eclampsia with statistical methods. Results: Prehypertension, weight gain>0.85 kg/week, fetal growth restriction, edema and decline of plasma albumin, thrombocytopenia, poor compliance, perinatal examinations and examinations in tertiary hospitals were associated with severe pre-eclampsia (P<0.001). Multivariate regression analysis showed that the risk factors of severe preeclampsia were pre-hypertension, weight gain>0.85 kg/week, edema, thrombocytopeniaand poor compliance. The increase in the number of prenatal examinations in tertiary hospitals was a protective factor for severe preeclampsia. Conclusion: Prehypertension, weight gain during pregnancy (>0.85 kg/week), edema, thrombocytopenia, and poor compliance were warning informations of severe pre-eclampsia, and the increased number of prenatal examinations in tertiary hospitals was a protective factor for severe pre-eclampsia.

Association between polymorphism in Cyclophilin A gene and its serum and placental expression in Han Chinese women with severe preeclampsia.

Cyclophilin A (CypA) plays important roles in inflammation and oxidative stress and is significantly increased in serum of preeclampsia (PE) patients. We aimed to investigate CypA genetic polymorphism and its serum and placenta expressions in severe PE of Han Chinese women. A case-control study of 82 severe PE patients and 179 healthy pregnancies was conducted. Single-nucleotide polymorphism (SNP) sites of rs3735481, rs9638978 and rs11984372 were analyzed by TaqMan assay. CypA serum levels were determined by enzyme-linked immunosorbent assay (ELISA). CypA mRNA levels and protein expressions in placentas were assessed by quantitative real-time polymerase chain reaction (PCR), western blot, and immunofluorescence assay, respectively. There were significantly lower frequency of rs3735481 allele C (odds ratio (OR): 0.60, 95% confidence interval (CI): 0.36-0.98; p = .04), and significantly higher frequency of rs9638978 allele A in severe PE especially in early onset PE patients (OR: 2.23, 95% CI: 1.35-3.71, p = .002). Frequency of rs9638978 AA genotype was significantly higher in early onset PE (p < .001). CypA serum levels were significantly higher in severe PE especially in early onset PE (p < .001). Meanwhile, CypA serum levels were significantly lower in carriers with the AC genotype of rs3735481 (p = .019) and significantly higher in carriers with the AA genotype of rs9638978 (p = .017). CypA mRNA levels and protein expressions were found to be significantly increased in PE placentas (both p < .01). The CypA genetic polymorphisms of rs3735481 and rs9638978 may be associated with severe PE, and rs9638978 AA genotype may be associated with an increasing risk of early onset severe PE in Han Chinese women. High CypA levels in serum and placenta may contribute to the pathogenesis of severe PE. Our results may provide a new clue for the etiology of severe PE.

96 Inflammatory stress and deposition markers in the serum and on adipose tissue in normal and hypertensive pregnancy

Introduction Not only in hypertensive pregnancy but also in normal course, homeostatic inflammation on adipocyte and adipose tissue has been confirmed by basic pilot study. We previously showed inflammatory and anti-inflammatory genetic action of the adipose tissue under the new culture method in preeclamptic serum compared with normal pregnancy (Naruse K, et al. Mediators Inflamm, 2015). Objectives In this study, we measured Interleukins, proteases and cell death markers on the inflammatory pathway, in the culture supernatants of visceral adipose tissue with normal and preeclamptic serum. Additionally, other markers for lipid oxidative stress and adipose storage were measured in the serum from normal pregnancy and preeclampsia. Methods All samples were taken under informed consent of the patients. Subcutaneous fat tissue from repeated cesarean section and omentum (visceral fat) from probe laparotomy for ovarian cancer were dissected, vessels were removed and captured in Peptide Hydrogel (BD Biosciences, Inc.). After 24 h starvation, tissues were cultured additional 24 h with medium containing 10% of maternal serum from severe preeclampsia (n = 5) and gestational age-matched healthy pregnant maternal serum (n = 5). Ratio of M30 (Apoptosis marker)/M65 (all cell death marker including necrosis) protein were measured with ELISA after correction with original serum concentrations of the molecules. Concentration of LDH (cytotoxicity marker) was measured with specific assay. Interleukin (IL)-6 and Matrix Metalloproteinase (MMP)-2 were measured with SearchLightR Multiplex Immunoassay. On the serum samples taken from 1st, 2nd and 3rd trimester of normal pregnancy and at onset of severe preeclampsia (n = 10 each), Malondialdehyde (MDA: a lipid marker for oxidative stress) were measured with Thiobarbituric Acid Reactive Substances (TBARS) Assay and cell death-inducing DFFA-like effector c (CIDEC/FSP27: lipid storage and adipocyte apoptosis marker) were measured with ELISA. Results In adipose tissue culture, M30/M65 ratio showed trend to increase in preeclampsia than normal pregnancy (p = 0.053). However, LDH was significantly increased in normal pregnancy than preeclampsia (p Conclusions In the adipose tissue, increase of apoptosis was shown after addition of preeclamptic serum. On the other hand, total tissue injury seemed to be stronger in normal pregnancy than preeclampsia, suggesting that adipose tissue act as not only an inflammatory focus but as a systemic buffer for acute inflammation in severe preeclampsia. Inflammatory stress on adipose tissue in normal pregnant subjects and preeclampsia were shown firstly by MDA concentrations. Taken together, adipose tissue is proposed as a key organ of variated pathophysiology of preeclampsia.

130 Maternal and perinatal outcomes according to gestational age of diagnosis of preeclampsia: A retrospective cohort study

Introduction Preeclampsia represents a multisystemic disorder characterized by hypertension and proteinuria, or dysfunction of target organs, with onset after twenty weeks of pregnancy. It is a frequent condition and its complications are important causes of maternal morbidity and mortality Objective To evaluate the clinical outcomes of women affected by severe pre-eclampsia and perinatal complications, determining its association with gestational age at the moment of diagnosis Methods An analytical and observational study was developed from the secondary analysis of a pre-existing database of 565 patients with severe maternal morbidity, which included 376 pregnant women with severe preeclampsia conducted in a school maternity in Northeast of Brazil. Statistical analysis was performed using Epi Info version 7.1. With the objective to compare the maternal, fetal and neonatal complications in women with early (less than 34 weeks of pregnancy) and late preeclampsia (34 weeks of pregnancy or more) we used the chi-square test of association and Fisher’s exact test, whenever appropriate, calculating the prevalence ratio (PR) and its 95% confidence interval Results Women with early onset of severe preeclampsia had significantly higher risk for developing acute renal failure (PR: 17.60; 95% CI 2.19 to 141.40), abruption placenta (PR: 3.6; 95% CI: 1.40 to 9.19) and prolonged hospitalization (PR: 3.44; 95% CI: 2.42 to 4.90). Comparing the perinatal outcomes among women with early and late preeclampsia, the first had significantly higher prevalence ratio of having children with low birth weight (PR: 2.85; 95% CI: 2, −3.39), stillbirths (PR: 5.75; 95% CI: 2.43 to 13.60) and early neonatal deaths (PR: 6.28; 95% CI: 1.24 to 31.91). In addition, newborns of women with early-onset severe preeclampsia more often required neonatal intensive care (PR: 8.17; 95% CI: 5.48 to 12.20) Conclusion This study confirms the heterogeneity of preeclampsia, showing that the precocity of onset is an important indicator of the severity and possibly of the disease’s the etiology. There is a clear need to increase medical adherence to guidelines of preeclampsia for early diagnosis and prevention of its complications

The role of glutathione peroxidase maternal serum level in late onset of severe preeclampsia

ABSTRACTObjective: This study was done to investigate the association between maternal serum glutathione peroxidase (GP) and late onset of severe preeclampsia. Methods: Cross-sectional study was undertaken comparing normal pregnancy and severe preeclampsia at 37–42 weeks of gestational age. Maternal venous blood was taken to assess the level of GP. Result: Twenty normal pregnancy and 20 severe preeclampsia patients were investigated. The median (max–min) of GP level for preeclampsia was 4.31 (0.03–327.41) mU/mL significantly lower than in normal pregnancy 318.90 (6.46–694.11) mU/mL (p < 0.001). A receiver operating characteristics (ROC) analysis showed that the cutoff point for GP to differentiate between normal pregnancy and severe preeclampsia was 41.74 mU/mL. Multivariate analysis was done to investigate the impact of BMI and parity showed that a low level of GP will increase the risk of severe preeclampsia. Conclusion: Low level of GP was associated with the diagnosis of severe preeclampsia.

P103. Relationship between severe preeclampsia onset with IUGR incidence at Dr. Soetomo General Hospital in 2013

Introduction Intrauterine growth restriction can be a serious problem in neonates because it is associated with increased morbidity and mortality and long-term sequel in the future. One of the main maternal risk factors of intrauterine growth restriction is severe preeclampsia in pregnancy. As we know preeclampsia has two types, first is early onset of severe preeclampsia that caused by failed of trophoblast invasion to the spiral artery and the second is late onset of severe preeclampsia that caused by such as chronic hypertension, diabetes mellitus, obese, tuberculosis, SLE ( systemic lupus erythematosus) and other autoimmune disease. Objectives We are curious about relationship onset of severe preeclampsia with intrauterine growth restriction. This study analyzed the relationship between the onset of severe preeclampsia and the incidence of intrauterine growth restriction in Dr. Soetomo General Hospital Surabaya. The aim of this study was to prove whether early onset severe preeclampsia is a risk factor for intrauterine growth restriction compared with late-onset severe preeclampsia. Methods This was an analytic observational cross-sectional study. Sampling technique we used in this study was random sampling. The data in this study were taken from the medical records at the Department of Obstetrics and Gynecology Dr. Soetomo General Hospital Surabaya in January 2013 until December 2013, which include in these data are gestational age, preeclampsia onset, sex, birth weight, and intrauterine growth restriction incidence. The onset of severe preeclampsia was divided into two categories: first, early onset (⩽34 weeks) and second, late onset (>34 weeks). Data analysis was performed in two stages, the univariate and bivariate analysis. Data analysis used was cross tabulation and chi-square test with level of significance of 95% ( p Results Results showed that prevalence rate of IUGR in early-onset severe preeclampsia was 1.32 times higher compared with late-onset severe preeclampsia. However, there was no statistically significant association between early-onset preeclampsia and the incidence of IUGR. ( p = 0.53; PR=0.71; 95% CI = 0.25–2.07). Late-onset severe preeclampsia also had no effect on the incidence of intrauterine growth restriction ( p = 0.53; PR = 1.40; 95% CI = 0.48–4.08). Conclusion It can be concluded that the onset of severe preeclampsia had no effect on the incidence of intrauterine growth restriction.

96-POS

Objectives VEGF is key component in the differentiation, invasion, regulation of vascular remodeling and the survival of cytotrophoblasts. In preeclampsia expression of cytotrophoblasts is disregulated. Evidence supports the hypothesis that VEGF plays an important role in the pathogenesis of preeclampsia. In this study, we aimed to determine whether VEGF genetic polymorphisms are associated with risk of early onset of severe preeclampsia. Methods A cross-sectional study with observational analytic was conducted in 32 pregnant women with early onset severe preeclampsia and 32 normal pregnant women. After peripheral blood was obtained from all women and genomic DNA was isolated, we genotyped +405G>C polymorphisms in the 5′- untranslated region and +936C>T polymorphisms in 3′-untranslated region of the VEGF gene genotype using Allelic Specific Oligonucleotide–Polymerase Chain Reaction (ASO–PCR) methods. Results The distribution of G allele of VEGF +405 more dominant (60.9%) than C allele (39.1%) in early onset severe preeclampsia. Conversely in normal pregnant women, the frequency of C allele of +405 (53.1%) little bit higher than G allele (46.9%). The distribution of the T allele of +936 approximately was the same between early onset severe preeclampsia (35.9%) and normal pregnant women (31.3%). Overall, the genotype and allele frequency distribution of the two polymorphisms (+405 and +936) were not significantly different between women with and without the disease ( p > 0.05). Conclusions There was no evidence of an association between VEGF allele or genotype frequencies and early onset preeclampsia in our study. VEGF gene polymorphisms studied are unlikely to be major predisposing for early onset severe preeclampsia in the Indonesian population. Disclosures M. Susanna: None. E.G. Dachlan: None.

161-POS

Objectives Failure of blood pressure management often leads to early termination of preeclamptic pregnancies. Preeclampsia is – besides hypertension and proteinuria – characterized by renal sodium retention and suppressed renin–angiotensin system. There is a prominent and aberrant glomerular filtration of the plasma zymogen plasminogen to urine with subsequent activation to plasmin. Urine with plasmin from preeclamptic patients activates the epithelial sodium channel (ENaC) in vitro and there is a positive correlation between urinary total plamin(ogen) and blood pressure in preeclamptic women. It was hypothesized that urine total plasmin/plasminogen activity are biomarkers in preeclampsia that can predict severe preeclampsia. A study was conducted to test if u-plasmin(ogen) could be used as a predictive marker for the development of severe preeclampsia Methods Longitudinal observational study with consecutive inclusion of 91 women with preeclampsia. Patients were stratified into severe (SPE) and non-severe preeclampsia (non-SPE) (Severe: systolic ⩾160 mmHg and/or diastolic ⩾110 mmHg and ⩾ +1 for albuminuria on urine dipstick or HELLP syndrome). Blood pressure, plasma, urine and clinical data were collected at debut of preeclampsia and again at follow up and at delivery. Results Of the listed covariates only a difference in gestational age were observed. There was a significant lower gestational age at SPE debut (inclusion samples) p -value 0.00022 and also at delivery p -value 0.004. A clear indication of a weak correlation was found between u-albumin and u-plasmin(ogen) Conclusions In this small cohort u-total plasmin(ogen)/creatinine ratio did not predict the onset of severe preeclampsia. Significant difference in gestational age at debut and delivery in the severe and non-severe preeclampsia groups could support the theory of different phenotypes. Disclosures B. Frederiksen-Moller: None. B.L. Jensen: None. M.H. Falk: None. J.V. Hjelmborg: None. J.S. Jorgensen: None.

2-Methoxyestradiol deficiency is strongly related to hypertension in early onset severe pre-eclampsia

2-Methoxyestradiol (2ME) deficiency leading to placental insufficiency has been related to pre-eclampsia (PE). Here we investigate whether 2ME is related to clinical profiles and vasoactive factors in early onset severe PE patients. 28 severe PE patients and 20 uncomplicated normal pregnant women, with gestational weeks between 24 and 32weeks, were recruited. All cases and controls had singleton pregnancies and were matched for maternal age, parity, body mass index, and gestational weeks. Plasma levels of 2ME, estradiol (E2), soluble Fms-like tyrosine kinase-1 (sFLT-1), endothelin-1 (ET-1), nitric oxide (NO) were determined. PE patients had significant lower 2ME [906(422-1768) vs. 2032(1400-2910)pg/mL, P=0.002], higher sFLT-1 [5.55(3.24-11.22) vs. 3.13(2.17-5.36)ng/mL, P=0.015] and higher NO [122.40(72.92-168.23) vs. 45.83(25.52-61.46)μmol/L, P=0.0008] levels in their plasma than the controls. In the PE group, plasma 2ME level correlated negatively with systolic pressure (r=-0.48, P=0.012), diastolic pressure (r=-0.52, P=0.007) and mean arterial pressure (r=-0.54, P=0.005) even after controlling for maternal age; 2ME level did not correlate with proteinuria, plasma levels of E2, sFLT-1, ET-1 or NO. In the control group, plasma 2ME level did not correlate with any of the above clinical profiles or laboratory measurements. 2ME levels were markedly lower in early onset severe PE and they correlated inversely with blood pressure only in women with PE. Although we cannot tell whether lower 2ME level is the causation or the result of PE, our study provides clinical evidences that 2ME deficiency is strongly related to hypertension in early onset severe PE patients.

Alterations of IL-6, IL-6R and gp130 in early and late onset severe preeclampsia

Objective: Interleukin-6 (IL-6) and its receptor complex participate in a number of critical biological activities through several signaling pathways. Placental dysfunction and increased inflammation are believed to underlie the pathogenesis of severe preeclampsia (PE), which may involve IL-6-induced signaling. We investigate whether the changes in the expression of IL-6 and its cognate receptors, IL-6 receptor (IL-6R) and glycoprotein (gp)130, occur between early and late onset severe PE. Methods: A total of 18 healthy gravidas and 41 severe preeclamptic women were recruited, including 20 pregnancies with early onset and 21 pregnancies with late onset. The IL-6, soluble IL-6R (sIL-6R) and soluble gp130 (sgp130) levels in maternal and umbilical cord sera were tested by enzyme-linked immunosorbent assay; the immunoactivities of IL-6, IL-6R and gp130 in the placentas were determined by immunohistochemistry and immunoblotting. Results: We found that (1) maternal serum IL-6 and sIL-6R levels were increased, whereas sgp130 was decreased in women with early onset severe PE compared with those with late onset severe PE and normal controls. In contrast to normal controls, IL-6 and sIL-6R expression was up-regulated in late onset severe PE, and similar alterations of IL-6 and its soluble receptors were detected in early and late onset severe PE umbilical sera and (2) compared with late onset severe PE, reduced IL-6 and IL-6R but not gp130 expression was observed in early onset severe PE placentas. Conclusion: These results suggest a probable contributing role of alterations in IL-6 and its corresponding receptors to the pathophysiology of early and late onset severe PE.

PP077. New prognostic marker for the risk to develop early-onset preeclampsia

ESM-1 plays a role in the regulation of angiogenesis and is released by activated endothelial cells. To test the hypothesized that ESM-1 is increased in preeclampsia (PE). Plasma samples from high risk pregnancies divided in 23 healthy (CON), 11 severe early-onset PE (SE) and 7 severe late-onset PE (SL) pregnancies were collected at regular intervals between week 12 and birth. ESM-1 was measured by ELISA. (see figure) Between GA week 24 and birth, ESM-1 concentrations were significantly increased in both early and late preeclampsia compared to controls (Mann Whitney, p<0.05). Surprisingly, the concentration of ESM-1 also differed between the three groups at weeks 12 and 16. The ESM-1 concentration of healthy pregnancies (mean±SEM:1857±861pg/ml) and those that developed severe late-onset PE (1298±371pg/ml) are comparable, but in those pregnancies that develop severe early-onset PE, the concentration (410±355pg/ml) is significantly lower as compared with healthy pregnancies. ESM-1 concentrations are increased during early and late severe preeclampsia, which may be due to endothelial cell activation in these conditions. Interestingly, since ESM-1 is decreased at 12-16 weeks in patients that later on develop early onset severe PE, it might be a prognostic marker which can determine the risk of women to develop severe early-onset PE already as early as 12 to 16 weeks of gestation.

Analysis on application and gestational outcomes of expectant management in treatment of early onset severe preeclampsia

Objective To explore the curative effect and influence of expectant management on early-onset severe preeclampsia.Methods According to gestational age,126 cases of early-onset severe preeclampsia from 2009 to 2011 were divided into group A (＜28 weeks),group B (28～31 weeks) and group C (32～34 weeks).Each group was given an expectant management then analyzed the outcomes of the patients as well as the maternal and perinatal complications.Results Expectant number of treatment days and termination of pregnancy in group A were lower than those of group B and C while the incidence of maternal and perinatal infants complications was higher (P＜0.05).Conclusion The early onset of severe preeclampsia on maternal and child health leads to serious harm,the shorter the gestational age is,the worse the prognosis becomes.Giving expectant treatment can extend the gestational age to a degree,thus improve the prognosis. Key words: Early-onset severe preeclampsia; Expectant management; Gestational outcomes

Association of 14 bp insertion/deletion polymorphism of the HLA‐G gene in father with severe preeclampsia in Chinese

Preeclampsia (PE), especially severe PE including early (before 34 weeks' gestation) and late (after 34 weeks' gestation) onset PE, is one of the leading causes of maternal and fetal mortality and morbidity. It is well known that abnormal human leukocyte antigen subtype G (HLA-G) expression may contribute to PE. In this study, we investigated allelic and genotypic frequencies of the 14 bp deletion/insert polymorphism in the 3(')-untranslated region (3(')-UTR) of the HLA-G gene in cases (120 pairs of mother-offspring, 82 couples, and 67 pairs of father-offspring with severe PE) and controls (158 pairs of mother-offspring, 87 couples, and 75 pairs of father-offspring with normal pregnancy). We found that the frequencies of the +14 bp/+14 bp HLA-G genotype of the offspring were significantly higher in the severe and early onset severe PE cases compared with controls, and the frequencies of the -14 bp/-14 bp HLA-G genotype of the offspring were significantly lower in the early onset severe PE cases compared with controls. The frequency of combined -14 bp/+14 bp mother/+14 bp/+14 bp offspring genotypes was significantly higher in the severe and early onset severe PE cases compared with controls, and the frequency of combined -14 bp/+14 bp mother/-14 bp/-14 bp offspring genotypes was significantly lower in the early onset severe PE cases compared with late onset severe PE cases. The frequency of combined -14 bp/-14 bp father/-14 bp/-14 bp offspring genotypes was significantly lower in the early onset severe PE cases compared with late onset severe PE cases and controls. In overview, the HLA-G 14 bp deletion/insert polymorphism is associated with severe PE in father-offspring, and its distribution is different between the early and late onset severe PE.