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      Predictive values of various serum biomarkers in women with suspected preeclampsia: A prospective study

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          Abstract

          Background

          Preeclampsia (PE) prediction has been shown to improve the maternal and fetal outcomes in pregnancy. We aimed to evaluate the PE prediction values of a series of serum biomarkers.

          Methods

          The singleton pregnant women (20–36 gestational weeks) with PE‐related clinical and/or laboratory presentations were recruited and had the blood drawn at their first visits. The following markers were tested with the collected serum samples: soluble fms‐like tyrosine kinase 1 (sFlt‐1), placental growth factor (PlGF), thrombomodulin (TM), tissue plasminogen activator inhibitor complex (tPAI‐C), complement factors C1q, B, H, glycosylated fibronectin (GlyFn), pregnancy‐associated plasma protein‐A2 (PAPP‐A2), blood urea nitrogen (BUN), creatinine (Cre), uric acid (UA), and cystatin C (Cysc).

          Results

          Of the 196 recruited subjects, 25% ( n = 49) developed preeclampsia before delivery, and 75% remained preeclampsia negative ( n = 147). The serum levels of sFlt‐1, BUN, Cre, UA, Cysc, and PAPP‐A2 were significantly elevated, and the PlGF level was significantly decreased in the preeclampsia‐positive patients. In the receiver operating characteristics (ROC) analyses, the area under the curves were listed in the order of decreasing values: 0.73 (UA), 0.67 (sFlt‐1/PlGF), 0.66 (Cysc), 0.65 (GlyFn/PlGF), 0.64 (PAPP‐A2/PlGF), 0.63 (BUN), 0.63 (Cre), and 0.60 (PAPP‐A2). The positive predictive values of these serum markers were between 33.1% and 58.5%, and the negative predictive values were between 80.9% and 89.5%.

          Conclusions

          The serum markers investigated in current study showed better performance in ruling out than ruling in PE. Absence of pre‐defined latency period between blood draw and the onset of PE limits the clinical utility of these markers.

          Abstract

          In present study, we evaluated the predictive values of the following serum biomarkers in a prospective study with the women suspected to develop preeclampsia (PE): soluble fms‐like tyrosine kinase 1 (sFlt‐1), placental growth factor (PlGF), pregnancy‐associated plasma protein‐A2 (PAPP‐A2), glycosylated fibronectin (GlyFn), thrombomodulin (TM), tissue plasminogen activator inhibitor complex (tPAI‐C), uric acid (UA), blood urea nitrogen (BUN), creatinine (Cre), and cystatin C (Cysc). The graphical image showed the ROC analyses of the serum markers for PE prediction in the prospective cohort with PE‐related clinical or laboratory presentations. A. ROC analyses for sFlt‐1 and sFlt‐1/PlGF; B. BUN, Cre, UA, and Cysc; C. PAPP‐A2, GlyFn/PlGF and PAPP‐A2/PlGF; D. PlGF.

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          Most cited references28

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          Comparing the areas under two or more correlated receiver operating characteristic curves: a nonparametric approach.

          Methods of evaluating and comparing the performance of diagnostic tests are of increasing importance as new tests are developed and marketed. When a test is based on an observed variable that lies on a continuous or graded scale, an assessment of the overall value of the test can be made through the use of a receiver operating characteristic (ROC) curve. The curve is constructed by varying the cutpoint used to determine which values of the observed variable will be considered abnormal and then plotting the resulting sensitivities against the corresponding false positive rates. When two or more empirical curves are constructed based on tests performed on the same individuals, statistical analysis on differences between curves must take into account the correlated nature of the data. This paper presents a nonparametric approach to the analysis of areas under correlated ROC curves, by using the theory on generalized U-statistics to generate an estimated covariance matrix.
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            Global and regional estimates of preeclampsia and eclampsia: a systematic review.

            Reduction of maternal mortality is a target within the Millennium Development Goals. Data on the incidence of preeclampsia and eclampsia, one of the main causes of maternal deaths, are required at both national and regional levels to inform policies. We conducted a systematic review of the incidence of hypertensive disorders of pregnancy (HDP) with the objective of evaluating its magnitude globally and in different regions and settings. We selected studies using pre-specified criteria, recorded database characteristics and assessed methodological quality of the eligible studies reporting incidence of any HDP during the period 2002-2010. A logistic model was then developed to estimate the global and regional incidence of HDP using pre-specified predictor variables where empiric data were not available. We found 129 studies meeting the inclusion criteria, from which 74 reports with 78 datasets reporting HDP were analysed. This represents nearly 39 million women from 40 countries. When the model was applied, the overall estimates are 4.6% (95% uncertainty range 2.7-8.2), and 1.4% (95% uncertainty range 1.0-2.0) of all deliveries for preeclampsia and eclampsia respectively, with a wide variation across regions. The figures we obtained give a general idea of the magnitude of the problem and suggest that some regional variations might exist. The absence of data in many countries is of concern, however, and efforts should be made to implement data collection and reporting for substantial statistics. The implementation of large scale surveys conducted during a short period of time could provide more reliable and up-to-date estimations to inform policy. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.
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              Predictive Value of the sFlt-1:PlGF Ratio in Women with Suspected Preeclampsia

              The ratio of soluble fms-like tyrosine kinase 1 (sFlt-1) to placental growth factor (PlGF) is elevated in pregnant women before the clinical onset of preeclampsia, but its predictive value in women with suspected preeclampsia is unclear.
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                Author and article information

                Contributors
                bjfcyyzj@126.com
                zhengcao2011@ccmu.edu.cn
                Journal
                J Clin Lab Anal
                J Clin Lab Anal
                10.1002/(ISSN)1098-2825
                JCLA
                Journal of Clinical Laboratory Analysis
                John Wiley and Sons Inc. (Hoboken )
                0887-8013
                1098-2825
                22 February 2021
                May 2021
                : 35
                : 5 ( doiID: 10.1002/jcla.v35.5 )
                : e23740
                Affiliations
                [ 1 ] Department of Laboratory Medicine Beijing Obstetrics and Gynecology Hospital Capital Medical University Beijing China
                [ 2 ] Guangzhou Kangrun Biotech Co. Ltd Guangdong China
                [ 3 ] Department of Obstetrics Beijing Obstetrics and Gynecology Hospital Capital Medical University Beijing China
                [ 4 ] Department of Information and Statistics Beijing Obstetrics and Gynecology Hospital Capital Medical University Beijing China
                [ 5 ] Scientific & Application Division Sysmex Shanghai Ltd Beijing China
                [ 6 ] Department of Pathology and Laboratory Medicine Weill Cornell Medicine New York NY USA
                [ 7 ] Hospital Administration Office Beijing Obstetrics and Gynecology Hospital Capital Medical University Beijing China
                Author notes
                [*] [* ] Correspondence

                Zheng Cao and Juan Zhao, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, 251 Yaojiayuan Road, Beijing 100026, China.

                Email: zhengcao2011@ 123456ccmu.edu.cn ; bjfcyyzj@ 123456126.com

                Author information
                https://orcid.org/0000-0002-0968-1864
                Article
                JCLA23740
                10.1002/jcla.23740
                8128315
                33616216
                5960c90b-0941-4f67-ae17-d820097224d8
                © 2021 The Authors. Journal of Clinical Laboratory Analysis published by Wiley Periodicals LLC

                This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                History
                : 05 February 2021
                : 04 January 2021
                : 09 February 2021
                Page count
                Figures: 3, Tables: 4, Pages: 8, Words: 5658
                Funding
                Funded by: Beijing Municipal Administration of Hospitals Incubating Program
                Award ID: PX2020060
                Funded by: National Natural Science Foundation of China , open-funder-registry 10.13039/501100001809;
                Award ID: 81702057
                Categories
                Research Article
                Research Articles
                Custom metadata
                2.0
                May 2021
                Converter:WILEY_ML3GV2_TO_JATSPMC version:6.0.2 mode:remove_FC converted:17.05.2021

                Clinical chemistry
                cohort,prediction,preeclampsia,prospective,serum biomarker
                Clinical chemistry
                cohort, prediction, preeclampsia, prospective, serum biomarker

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