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      Prognostic Value of Angiogenic Markers in Pregnant Women With Chronic Hypertension

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          Abstract

          Background

          Women with chronic hypertension face a 5‐ to 6‐fold increased risk of developing preeclampsia compared with normotensive women. Angiogenic markers, especially soluble fms‐like kinase 1 (sFlt‐1) and placental growth factor (PlGF), were identified as clinically useful markers predicting the development of preeclampsia, but data on the prediction of superimposed preeclampsia are scarce. Therefore, we aimed to evaluate the predictive value of the sFlt‐1/PlGF ratio for delivery because of superimposed preeclampsia in women with chronic hypertension.

          Methods and Results

          This retrospective study included 142 women with chronic hypertension and suspected superimposed preeclampsia. Twenty‐seven women (19.0%) delivered because of maternal indications only, 17 women (12.0%) because of fetal indications primarily, and 98 women (69.0%) for other reasons. Women who both delivered because of maternal indications and for fetal indications had a significantly higher sFlt‐1/PlGF ratio (median 99.9 and 120.2 versus 7.3, respectively, P<0.001 for both) and lower PlGF levels (median 73.6 and 53.3 versus 320.0 pg/mL, respectively, P<0.001 for both) compared with women who delivered for other reasons. SFlt‐1/PlGF ratio and PlGF were strong predictors for delivery because of superimposed preeclampsia, whether for maternal or fetal indications ( P<0.05). Half of women with angiogenic imbalance (sFlt‐1/PlGF ratio ≥85 or PlGF levels <100 pg/mL) delivered because of maternal or fetal indications within 1.6 weeks (95% CI, 1.0–2.4 weeks).

          Conclusions

          Angiogenic marker imbalance in women with suspected superimposed preeclampsia can predict delivery because of maternal and fetal indications related to superimposed preeclampsia and is associated with a significantly shorter time to delivery interval.

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          Most cited references27

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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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            The classification, diagnosis and management of the hypertensive disorders of pregnancy: A revised statement from the ISSHP.

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              Chronic hypertension and pregnancy outcomes: systematic review and meta-analysis

              Objective To provide an accurate assessment of complications of pregnancy in women with chronic hypertension, including comparison with population pregnancy data (US) to inform pre-pregnancy and antenatal management strategies. Design Systematic review and meta-analysis. Data sources Embase, Medline, and Web of Science were searched without language restrictions, from first publication until June 2013; the bibliographies of relevant articles and reviews were hand searched for additional reports. Study selection Studies involving pregnant women with chronic hypertension, including retrospective and prospective cohorts, population studies, and appropriate arms of randomised controlled trials, were included. Data extraction Pooled incidence for each pregnancy outcome was reported and, for US studies, compared with US general population incidence from the National Vital Statistics Report (2006). Results 55 eligible studies were identified, encompassing 795 221 pregnancies. Women with chronic hypertension had high pooled incidences of superimposed pre-eclampsia (25.9%, 95% confidence interval 21.0% to 31.5 %), caesarean section (41.4%, 35.5% to 47.7%), preterm delivery <37 weeks’ gestation (28.1% (22.6 to 34.4%), birth weight <2500 g (16.9%, 13.1% to 21.5%), neonatal unit admission (20.5%, 15.7% to 26.4%), and perinatal death (4.0%, 2.9% to 5.4%). However, considerable heterogeneity existed in the reported incidence of all outcomes (τ2=0.286-0.766), with a substantial range of incidences in individual studies around these averages; additional meta-regression did not identify any influential demographic factors. The incidences (the meta-analysis average from US studies) of adverse outcomes in women with chronic hypertension were compared with women from the US national population dataset and showed higher risks in those with chronic hypertension: relative risks were 7.7 (95% confidence interval 5.7 to 10.1) for superimposed pre-eclampsia compared with pre-eclampsia, 1.3 (1.1 to 1.5) for caesarean section, 2.7 (1.9 to 3.6) for preterm delivery <37 weeks’ gestation, 2.7 (1.9 to 3.8) for birth weight <2500 g, 3.2 (2.2 to 4.4) for neonatal unit admission, and 4.2 (2.7 to 6.5) for perinatal death. Conclusions This systematic review, reporting meta-analysed data from studies of pregnant women with chronic hypertension, shows that adverse outcomes of pregnancy are common and emphasises a need for heightened antenatal surveillance. A consistent strategy to study women with chronic hypertension is needed, as previous study designs have been diverse. These findings should inform counselling and contribute to optimisation of maternal health, drug treatment, and pre-pregnancy management in women affected by chronic hypertension.
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                Author and article information

                Contributors
                julia.binder@medunwien.ac.at
                Journal
                J Am Heart Assoc
                J Am Heart Assoc
                10.1002/(ISSN)2047-9980
                JAH3
                ahaoa
                Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease
                John Wiley and Sons Inc. (Hoboken )
                2047-9980
                28 August 2021
                07 September 2021
                : 10
                : 17 ( doiID: 10.1002/jah3.v10.17 )
                : e020631
                Affiliations
                [ 1 ] Department of Obstetrics and Feto‐Maternal Medicine Medical University of Vienna Austria
                [ 2 ] Department of Statistics Faculty of Arts and Sciences Middle East Technical University Ankara Turkey
                [ 3 ] Department of Obstetrics and Gynecology Faculty of Medicine Koc University Istanbul Turkey
                [ 4 ] Department of Biostatistics Faculty of Medicine Hacettepe University Ankara Turkey
                [ 5 ] Fetal Medicine Unit St George's Hospital St George's University of London London United Kingdom
                [ 6 ] Vascular Biology Research Centre Molecular and Clinical Sciences Research Institute St George's University of London London United Kingdom
                Author notes
                [*] [* ] Correspondence to: Julia Binder, MD, PhD, Department of Obstetrics and Feto‐Maternal Medicine, Medical University of Vienna, Währinger Gürtel 18‐20, 1090 Vienna, Austria. E‐mail: julia.binder@ 123456medunwien.ac.at

                Author information
                https://orcid.org/0000-0002-5725-9270
                https://orcid.org/0000-0003-2449-2575
                https://orcid.org/0000-0001-9206-6856
                https://orcid.org/0000-0003-2802-7670
                Article
                JAH36382
                10.1161/JAHA.120.020631
                8649241
                34459247
                f8785bd7-7578-456d-b133-6f5e00fce3cd
                © 2021 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

                This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

                History
                : 29 December 2020
                : 03 May 2021
                Page count
                Figures: 3, Tables: 3, Pages: 11, Words: 13928
                Categories
                Original Research
                Original Research
                Hypertension
                Custom metadata
                2.0
                September 7, 2021
                Converter:WILEY_ML3GV2_TO_JATSPMC version:6.0.7 mode:remove_FC converted:07.09.2021

                Cardiovascular Medicine
                angiogenic markers,chronic hypertension,preeclampsia,superimposed preeclampsia,high blood pressure,biomarkers,pregnancy

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