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      First Trimester Aneuploidy Screening Program for Preeclampsia Prediction in a Portuguese Obstetric Population

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          Abstract

          Objective. To evaluate the performance of a first trimester aneuploidy screening program for preeclampsia (PE) prediction in a Portuguese obstetric population, when performed under routine clinical conditions. Materials and Methods. Retrospective cohort study of 5672 pregnant women who underwent routine first trimester aneuploidy screening in a Portuguese university hospital from January 2009 to June 2013. Logistic regression-based predictive models were developed for prediction of PE based on maternal characteristics, crown-rump length (CRL), nuchal translucency thickness (NT), and maternal serum levels of pregnancy-associated plasma protein-A (PAPP-A) and free beta-subunit of human chorionic gonadotropin (free β -hCG). Results. At a false-positive rate of 5/10%, the detection rate for early-onset (EO-PE) and late-onset (LO-PE) PE was 31.4/45.7% and 29.5/35.2%, respectively. Although both forms of PE were associated with decreased PAPP-A, logistic regression analysis revealed significant contributions from maternal factors, free β -hCG, CRL, and NT, but not PAPP-A, for prediction of PE. Conclusion. Our findings support that both clinical forms of EO-PE and LO-PE can be predicted using a combination of maternal history and biomarkers assessed at first trimester aneuploidy screening. However, detection rates were modest, suggesting that models need to be improved with additional markers not included in the current aneuploidy screening programs.

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          Pre-eclampsia.

          Pre-eclampsia remains a leading cause of maternal and perinatal mortality and morbidity. It is a pregnancy-specific disease characterised by de-novo development of concurrent hypertension and proteinuria, sometimes progressing into a multiorgan cluster of varying clinical features. Poor early placentation is especially associated with early onset disease. Predisposing cardiovascular or metabolic risks for endothelial dysfunction, as part of an exaggerated systemic inflammatory response, might dominate in the origins of late onset pre-eclampsia. Because the multifactorial pathogenesis of different pre-eclampsia phenotypes has not been fully elucidated, prevention and prediction are still not possible, and symptomatic clinical management should be mainly directed to prevent maternal morbidity (eg, eclampsia) and mortality. Expectant management of women with early onset disease to improve perinatal outcome should not preclude timely delivery-the only definitive cure. Pre-eclampsia foretells raised rates of cardiovascular and metabolic disease in later life, which could be reason for subsequent lifestyle education and intervention. Copyright 2010 Elsevier Ltd. All rights reserved.
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            Epidemiology of pre-eclampsia and the other hypertensive disorders of pregnancy.

            Hypertensive disorders of pregnancy include chronic hypertension, gestational hypertension, pre-eclampsia and chronic hypertension with superimposed pre-eclampsia. Pre-eclampsia complicates about 3% of pregnancies, and all hypertensive disorders affect about five to 10% of pregnancies. Secular increases in chronic hypertension, gestational hypertension and pre-eclampsia have occurred as a result of changes in maternal characteristics (such as maternal age and pre-pregnancy weight), whereas declines in eclampsia have followed widespread antenatal care and use of prophylactic treatments (such as magnesium sulphate). Determinants of pre-eclampsia rates include a bewildering array of risk and protective factors, including familial factors, sperm exposure, maternal smoking, pre-existing medical conditions (such as hypertension, diabetes mellitus and anti-phospholipid syndrome), and miscellaneous ones such as plurality, older maternal age and obesity. Hypertensive disorders are associated with higher rates of maternal, fetal and infant mortality, and severe morbidity, especially in cases of severe pre-eclampsia, eclampsia and haemolysis, elevated liver enzymes and low platelets syndrome. Copyright © 2011 Elsevier Ltd. All rights reserved.
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              Competing risks model in early screening for preeclampsia by biophysical and biochemical markers.

              To develop models for prediction of preeclampsia (PE) based on maternal characteristics, biophysical and biochemical markers at 11-13 weeks' gestation in which the gestation at the time of delivery for PE is treated as a continuous variable. This was a screening study of singleton pregnancies at 11-13 weeks including 1,426 (2.4%) that subsequently developed PE and 57,458 that were unaffected by PE. We developed a survival time model for the time of delivery for PE in which Bayes' theorem was used to combine the prior information from maternal characteristics with uterine artery pulsatility index (PI), mean arterial pressure (MAP), serum pregnancy-associated plasma protein-A (PAPP-A) and placental growth factor (PLGF) multiple of the median (MoM) values. In pregnancies with PE, there was a linear correlation between MoM values of uterine artery PI, MAP, PAPP-A and PLGF with gestational age at delivery and therefore the deviation from normal was greater for early than late PE for all four biomarkers. Screening by maternal characteristics, biophysical and biochemical markers detected 96% of cases of PE requiring delivery before 34 weeks and 54% of all cases of PE at a fixed false-positive rate of 10%. A new model has been developed for effective first-trimester screening for PE. Copyright © 2012 S. Karger AG, Basel.
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                Author and article information

                Journal
                Obstet Gynecol Int
                Obstet Gynecol Int
                OGI
                Obstetrics and Gynecology International
                Hindawi Publishing Corporation
                1687-9589
                1687-9597
                2014
                28 May 2014
                : 2014
                : 435037
                Affiliations
                1Department of Pathology, Porto Hospital Center, 4099-001 Porto, Portugal
                2Department of Health Information and Decision Sciences (CIDES), Faculty of Medicine, University of Porto, 4200-450 Porto, Portugal
                3Institute for Molecular and Cell Biology (IBMC), University of Porto, 4150-180 Porto, Portugal
                4Department of Women, Porto Hospital Center, 4099-001 Porto, Portugal
                5Center for Research in Health Technologies and Information Systems (CINTESIS), Faculty of Medicine, University of Porto, 4200-450 Porto, Portugal
                6Department of Biochemistry, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal
                Author notes

                Academic Editor: João Bernardes

                Article
                10.1155/2014/435037
                4058475
                24991215
                9fe4fcbf-1b51-4f12-b279-bce4651a006f
                Copyright © 2014 Cláudia Teixeira et al.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 28 March 2014
                : 30 April 2014
                Categories
                Research Article

                Obstetrics & Gynecology
                Obstetrics & Gynecology

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