Serum screening with Down's syndrome markers to predict pre-eclampsia and small for gestational age: Systematic review and meta-analysis

<p>Abstract</p> <p>Background</p> <p>Reliable antenatal identification of pre-eclampsia and small for gestational age is crucial to judicious allocation of monitoring resources and use of preventative treatment with the prospect of improving maternal/perinatal outcome. The purpose of this systematic review was to determine the accuracy of five serum analytes used in Down's serum screening for prediction of pre-eclampsia and/or small for gestational age.</p> <p>Methods</p> <p>The data sources included Medline, Embase, Cochrane library, Medion (inception to February 2007), hand searching of relevant journals, reference list checking of included articles, contact with experts. Two reviewers independently selected the articles in which the accuracy of an analyte used in Downs's serum screening before the 25^thgestational week was associated with the occurrence of pre-eclampsia and/or small for gestational age without language restrictions. Two authors independently extracted data on study characteristics, quality and results.</p> <p>Results</p> <p>Five serum screening markers were evaluated. 44 studies, testing 169,637 pregnant women (4376 pre-eclampsia cases) and 86 studies, testing 382,005 women (20,339 fetal growth restriction cases) met the selection criteria. The results showed low predictive accuracy overall. For pre-eclampsia the best predictor was inhibin A>2.79MoM positive likelihood ratio 19.52 (8.33,45.79) and negative likelihood ratio 0.30 (0.13,0.68) (single study). For small for gestational age it was AFP>2.0MoM to predict birth weight < 10^thcentile with birth < 37 weeks positive likelihood ratio 27.96 (8.02,97.48) and negative likelihood ratio 0.78 (0.55,1.11) (single study). A potential clinical application using aspirin as a treatment is given as an example.</p> <p>There were methodological and reporting limitations in the included studies thus studies were heterogeneous giving pooled results with wide confidence intervals.</p> <p>Conclusion</p> <p>Down's serum screening analytes have low predictive accuracy for pre-eclampsia and small for gestational age. They may be a useful means of risk assessment or of use in prediction when combined with other tests.</p

Resistance to activated protein C and impaired TFPI activity in women with previous hormone-induced venous thromboembolism

Introduction: Hormonal contraception is a well-known risk factor for venous thromboembolism (VTE). APC resistance and impaired functions of protein S and TFPI are thought to play an important role in the pathogenesis of hormone-related VTE. It is unknown, whether women, who develop VTE during hormonal contraception possess a vulnerability in these pathways, making them susceptible to thrombosis. Materials and methods: Plasma samples were obtained from 57 premenopausal women in average 15.3 years after hormone-associated VTE and from 31 healthy controls. Thrombin generation at high tissue factor (TF) in the absence and in the presence of activated protein C (APC) and at low TF without and with inhibiting anti-protein S- and anti-TFPI-antibodies was measured via calibrated automated thrombography. Results: Women with previous hormone-related thrombosis had higher thrombin generation at low TF, higher APC resistance, protein S- and TFPI ratios, differences: 219.9 nM IIa.min (95%CI:90.4 to 349.3); 1.88 (95% CI:0.71 to 3.05); 0.13 (95%CI:0.01 to 0.26) and 0.19 (95%CI:0.08 to 0.30), respectively. Thrombin generation at high TF without APC did not differ between the groups. Smoking decreased thrombin generation at low TF by -222.6 nM IIa.min (95%CI: -381.1 to -64.1), the APC sensitivity ratio by -2.20 (95%CI: -3.63 to -0.77) and the TFPI ratio by -0.16 (95%CI: -0.29 to -0.03), but did not influence thrombin generation at high TF. Discussion: We demonstrated impairment of the protein S/TFPI system and increased APC resistance in women with previous hormone-induced VTE. Smoking decreased thrombin generation at assay conditions, dependent on the function of the TFPI system

Increased thrombin generation in women with a history of preeclampsia

Introduction: Women with a history of preeclampsia have an increased risk for cardiovascular disease in later Life. We evaluated thrombogenic characteristics of women with a previous history of preeclampsia, expressed in levels of thrombin generation, number of micropartictes and related to menstrual cycle and endothelial function, measured as flow-mediated dilatation. Materials and methods: We included 18 primipara women with a history of preeclampsia and 17 healthy primipara controls, 15 (+/- 3) months after the index pregnancy. Thrombin generation was measured by tissue factor triggered assay, microparticle levels were measured by flow cytometry and the endothelial function was previously examined by measuring flow-mediated dilatation by high-resotution ultrasound, during follicular and luteal phases of the menstrual cycle. Results: Women with previous preeclampsia produced more total amount of thrombin as calculated from thrombin max, thrombin potential and max slope levels p<0.05, 0.01 and 0.01 respectively. Platelet derived microparticle levels were higher in women with a history of preeclampsia, p=0.07. Flow-mediated dilatation was significantly decreased in comparison to healthy controls (p<0.0001). There were no variation in levels of thrombin, microparticies and flow-mediated dilatation during the menstrual phases. Conclusion: Women with a history of preectampsia show signs of hypercoagutability as indicated by higher thrombin generation and higher platelet derived microparticle levels. Since these women were investigated more than one year after delivery, these results may be indicative of an increased risk of cardiovascular events later in life. (c) 2008 Elsevier Ltd. Alt rights reserved

The APC-PCI concentration as an early marker of activation of blood coagulation A study of women on combined oral contraceptives

Background: The risk of venous tromboembolism (VTE) in women taking combined oral contraceptives (COCs) is attributed to changes in coagulation and fibrinolysis. The impact of the COCs may be greater in women with preexisting thrombophilic defects. Nevertheless most women who suffer from venous thrombosis do not have any of the well known hereditary or acquired risk factors. A simple and sensitive marker of "thrombogenicity" has not been identified. Objectives: To investigate the effects of two different monophasic combined oral contraceptives (COCs) on the plasma concentrations of activated protein C-inhibitor of protein C (APC-PCI) and on comparable hemostatic factors in fertile women. Method: Forty four healthy nulliparous women with regular menstrual periods were included and randomly assigned to start with a monophasic preparation containing 30 mu g ethinylestradiol and 150 mu g levonogestrel (LNG/EE) or a preparation containing 30 mu g ethinylestradiol and 150 mu g desogestrel (DG/EE). After a wash out period of two months, treatment with the alternate preparation was initiated and continued for two more cycles. Results: The plasma concentration of the APC-PCI complex and thrombin-antithrombin complex (TAT) increased during treatment with the two COCs. During DG/EE treatment the APC-PCI complex increased significantly more than during LNG/EE (p < 0,01). The plasma concentration of D-dimer did not increase during OC treatment. Conclusion: The APC-PCI complex concentration, which serves as a marker for thrombin generation and indicates hypercoagulability, was increased during COC treatment compared to baseline. The method is a sufficiently sensitive marker to detect even small differences in the activation of coagulation. c (c) 2011 Elsevier Ltd. All rights reserved

Cadmium exposure in pregnancy and lactation in relation to iron status

Objectives. The purpose of this study was to determine the impact of iron status on cadmium dose among pregnant women. Methods. Iron status and cadmium concentration in blood, urine, and placenta were determined among women followed for 2 years from early pregnancy. Results. Blood cadmium and urinary cadmium were correlated with iron status throughout the study period. Urinary cadmium increased longitudinally among women with exhausted iron stores during their pregnancy. The increase in urinary cadmium with age was more pronounced in multiparous than in nulliparous women. Conclusions. Iron deficiency during pregnancy leads to increased cadmium absorption and body burden. Multiparous women exhibit additional increases with increasing age