PE Women Research Articles

Complement component C4A and apolipoprotein A-I in plasmas as biomarkers of the severe, early-onset preeclampsia

Preeclampsia is a common pregnancy complication that is associated with maternal perinatal morbidity and mortality. Because of its early onset (before 34 weeks) and the potential for serious outcomes, severe, early-onset preeclampsia (sePE) should be regarded as a different form of preeclampsia. It is an important cause of preterm birth and fetal growth restriction and adverse maternal and neonatal outcomes. As there is no diagnostic test yet available for this disease, we used a proteomic approach to identify novel plasma biomarkers for developing severe, early-onset preeclampsia. We conducted case-control studies comparing nulliparous women with severe preeclampsia requiring delivery prior to 34 weeks of gestation with healthy nulliparous women matched by gestational age at sampling. Plasma was depleted of albumin and IgG and analyzed by two-dimensional gel electrophoresis (2DE). Seven specific plasma proteins for early-onset preeclampsia were detected by mass spectrometry had statistically significant expression differences when compared to controls. The expression of complement component C4A and apolipoprotein A-I were validated by immunoblotting. The complement component C4A in the plasmas of sePE women is lower than the severe, late-onset PE (slPE) women [mean ± SD; 3.05 ± 0.14 times reference level (normal/sePE) in sePE women vs. 2.73 ± 0.10 times reference level (normal/slPE) in slPE women, P < 0.05]. Apolipoprotein A-I is higher in sePE women than slPE women [mean ± SD; 1.58 ± 0.14 times reference level (sePE/normal) in sePE women vs. 1.04 ± 0.16 times reference level (slPE/normal) in slPE women, P < 0.05]. Furthermore, C4A can accurately distinguish severe PE (sePE and slPE) from mild PE (mePE and mlPE) and was proved by the results of ELISA. Further studies have been done to determine the relation between PE and hypoxia. JAR cells were cultured under hypoxia for 72 h. Total cellular proteins were gathered and lysed. Lower C4A and higher apolipoprotein A-I had been observed in JAR of hypoxia conditions than normoxia conditions through western blotting. The result proved that PE is correlated with hypoxia. In summary, C4A and apolipoprotein A-I are able to function as markers to distinguish ePE women from lPE women, and severe PE from mild PE, or perhaps even as disease predictors that might become relevant for diagnostics.

Hemodynamic and neurohumoral profile in patients with different types of hypertension in pregnancy

Hypertension in pregnancy is a frequent disorder that includes a spectrum of conditions. We aimed at comparatively evaluating the hemodynamic, echocardiographic and biohumoral profile of a sample of pregnant Caucasian women with different form of pregnancy-related hypertension. We enrolled 39 non-hypertensive pregnant women (NP), 26 with Chronic HBP in pregnancy (CH), 24 with gestational hypertension (G-PIH), and 33 with pre-eclampsia. We recorded and compared blood pressure (BP), echocardiographic parameters, resting plasma renin activity (PRA) and plasma aldosterone (PA), Plasma levels of atrial (ANP) and brain natriuretic peptide (BNP). PE patients had a significantly higher BP than either G-PIH or NP patients. PE patients had also significantly lower cardiac output than NP, G-PIH and CH. In comparison to NP patients, the total peripheral vascular resistance was 61% higher in PE women and 38% higher in CH patients. All echographic parameters were significantly more altered in PE patients when compared with NP, in respect to any other form of hypertension. Either ANP (+35%) and BNP (+40%) were significantly higher in PE patients than in controls. The PRA was reduced in PE and CH patients when compared either with NP (-38 and -35%, respectively) or G-PIH (-47 and -43%, respectively). On the basis of our data, we can conclude that PE is the gestation associated hypertension with the largest anatomical, functional and biohumoral involvement, and so it has to be involved in a more intensive monitoring and evaluation.

P60 Role of EGF-like Domain 7 (Egfl7) in placental development and implantation

Preeclampsia is a state of antiangiogenesis, with high levels of maternal circulating sVEGFR-1 (soluble vascular endothelial growth factor receptor 1, also named sFlt1) and low levels of PlGF (placenta growth factor). Various autoantibodies have been detected in preeclamptic patients. We hypothesize that circulating autoantibodies against VEGF-A (AA-VEGF-A), VEGFR-1 (AA-VEGFR-1) and PlGF (AA-PlGF) are present in preeclamptic women, with different levels from pregnant women with normotensive pregnancies. Secondly, we wanted to analyze if autoantibody levels are associated to sFlt1 or PLGF levels.Retrospective cross sectional study of 88 women with singleton pregnancies who delivered at Oslo University Hospital of whom 46 had preeclampsia and 42 had uncomplicated normotensive pregnancies. Novel immunoassays for IgG-autoantibodies against VEGFA, VEGFR-1 and PlGF were developed and serum samples were assayed.AA-VEGF-A, AA-VEGF-R1 and AA-PlGF were significantly lower in preeclamptic pregnancies (n = 42) compared to normotensive pregnancies (n = 46) (p < 0.05). On unadjusted analysis, only AA-VEGFA and AA-VEGFR-1 were predictors of PE, but none were independent predictors after adjusting for BMI (body mass index) and parity. In the subgroup of normotensive and PE women with overlapping sVEGFR-1/PlGF-ratios, AA-VEGF was a significant predictor of PE with AUC: 0.735.IgG autoantibodies against VEGF-A VEGFR-1 and PlGF can be found in pregnant women. They are dysregulated in preeclampsia. The roles of these autoantibodies are unknown, but this study suggests they play a protective role in pregnancy. The levels of AA against VEGF-A, VEGFR-1 and PlGF might be important factors contributing to anti-angiogenesis regulation.

Cardiovascular risk factor assessment after pre-eclampsia in primary care

BackgroundPre-eclampsia is associated with an increased risk of development of cardiovascular disease later in life. It is not known how general practitioners in the Netherlands care for these women after delivery with respect to cardiovascular risk factor management.MethodsReview of medical records of 1196 women in four primary health care centres, who were registered from January 2000 until July 2007 with an International Classification of Primary Care (ICPC) code indicating pregnancy. Records were searched for indicators of pre-eclampsia. Of those who experienced pre-eclampsia and of a random sample of 150 women who did not, the following information on cardiovascular risk factor management after pregnancy was extracted from the records: frequency and timing of blood pressure, cholesterol and glucose measurements - and vascular diagnoses. Additionally the sensitivity and specificity of ICPC coding for pre-eclampsia were determined.Results35 women experienced pre-eclampsia. Blood pressure was more often checked after pregnancy in these women than in controls (57.1% vs. 12.0%, p < 0.001). In 50% of the cases blood pressure was measured within 3 months after delivery with no further follow-up visit. A check for glucose and cholesterol levels was rare, and equally frequent in PE and control women. 20% of the previously normotensive women in the PE group had hypertension at one or more occasions after three months post partum versus none in the control group. The ICPC coding for pre-eclampsia showed a sensitivity of 51.4% and a specificity of 100.0%.ConclusionDespite the evidence of increased risk of future cardiovascular disease in women with a history of pre-eclampsia, follow-up of these women is insufficient and undeveloped in primary care in the Netherlands.

Activated T Lymphocytes in Pre‐Eclampsia

The aim of our study was to investigate the activation markets of T CD3(+), T helper CD4(+) and T cytotoxic CD8(+) cells, as well as, the populations of T naïve CD4(+) CD45RA(+), T memory CD4(+) CD45RO(+) and T regulatory lymphocytes in PE and healthy pregnant women. Twenty-five patients with PE and thirty healthy third trimester pregnant women were included in the study. Peripheral blood mononuclear cells were isolated from peripheral blood, stained with monoclonal antibodies and estimated using the flow cytometric method. The percentages of CD4(+)CD25(+), CD4(+)CD25(dim), CD3(+)HLA-DR(+), CD4(+)HLA-DR(+) and CD8(+)HLA-DR(+) cells did not differ between study groups. The population of T regulatory CD4(+)CD25(bright) lymphocytes was significantly lower in the group of patients with PE when compared with the controls (P < 0.01). The percentages of CD3(+)CD25(+) (P < 0.05), CD8(+)CD25(+) (P < 0.05), CD4(+)45RO(+) (P < 0.01) lymphocytes were significantly higher, while CD4(+)CD45RA(+) (P < 0.01) cells--significantly lower in peripheral blood of patients with PE when compared with the control group. The increased levels of T CD4(+)45RO(+) and T CD8(+) CD25(+) cells can suggest the activation of CD4(+) and CD8(+) T lymphocytes in pre-eclampsia. It seems possible that the activation of T lymphocytes is associated with the deficiency of T regulatory cells in PE.

P423 Genetic and polysomnographic characteristics of Korean patients with narcolepsy or obstructive sleep apnea syndrome

mal pregnant women (control), underwent overnight pulse oximetry and nasal pressure measurements (Embletta,Medcare) at mean gestation of 31 weeks.We applied The American College of Obstetricians and Gynecologists definitions for pre-eclampsia. Fasting blood samples were drawn for Tumor Necrosing Factor alpha (TNFa), Interleukin 6 (IL-6) and sensitive C Reactive Protein (CRP). Data from clinical evaluation of edema by analog scale (0 = no, 12 = severe edema), pregnancy outcomes, Epworth sleepiness scales (ESS) and Tiredness questionnaire (0 = no, 3 = severe) were collected. Results:No significant differences in age, body mass index (BMI) at sleep study, gestational age, bloodoxygen saturation (SpO2) or ESS were found between PE and controls. The nasal flow was significantly limited in PE women (Table 1), theywere significantly (p < 0.01)more tired than controls, mean (SD) 1.4 (0.5) vs. 0.1 (0.5), and had worse pregnancy outcomes (p < 0.05): 1-min Appgar score 7.9 (1.8) vs. 8.8 (0.4), relative birth weight (z-score) 1.9 (0.8) vs. +0.4 (1.2). The table shows the main findings: Conclusions: Pregnant women with pre-eclampsia showed significantly more nasal flow limitation during the night, higher fasting IL-6 and TNFa plasma levels, more edema and worse pregnancy outcomes than healthy pregnant women.

Increased plasma levels of adipokines in preeclampsia: relationship to placenta and adipose tissue gene expression

Adipokines are predominantly secretory protein hormones from adipose tissue but may also originate in placenta and other organs. Cross-sectionally, we monitored maternal plasma concentration of adiponectin, resistin, and leptin and their mRNA expression in abdominal subcutaneous adipose tissue and placenta from preeclamptic (PE; n = 15) and healthy pregnant (HP; n = 23) women undergoing caesarean section. The study groups were similar in age and BMI, whereas HOMA-IR tended to be higher in the PE group. In fasting plasma samples, the PE group had higher concentrations of adiponectin (18.3 +/- 2.2 vs. 12.2 +/- 1.1 microg/ml, P = 0.011), resistin (5.68 +/- 0.41 vs. 4.65 +/- 0.32 ng/ml, P = 0.028), and leptin (34.4 +/- 3.2 vs. 22.7 +/- 2.1 ng/ml, P = 0.003) compared with the HP group. Adiponectin and leptin concentrations were still different between PE and HP after controlling for BMI and HOMA-IR, whereas resistin concentrations differed only after controlling for BMI but not HOMA-IR. We found similar mean mRNA levels of adiponectin, resistin, and leptin in abdominal subcutaneous adipose tissue in PE and HP women. When data were pooled from PE and HP women, resistin mRNA levels in adipose tissue also correlated with HOMA-IR (r = 0.470, P = 0.012) after controlling for BMI and pregnancy duration. Resistin mRNA levels in placenta were not significantly different between PE and HP, whereas leptin mRNA levels were higher in PE placenta compared with HP. Thus increased plasma concentrations of adiponectin and resistin in preeclampsia may not relate to altered expression levels in adipose tissue and placenta, whereas both plasma and placenta mRNA levels of leptin are increased in preeclampsia.