{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,6]],"date-time":"2026-05-06T20:18:24Z","timestamp":1778098704777,"version":"3.51.4"},"reference-count":32,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2023,4,3]],"date-time":"2023-04-03T00:00:00Z","timestamp":1680480000000},"content-version":"vor","delay-in-days":2,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["obgyn.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Ultrasound in Obstet &amp; Gyne"],"published-print":{"date-parts":[[2023,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Objectives<\/jats:title><jats:p>To assess levels of total placental growth factor (PlGF), soluble fms\u2010like tyrosine kinase\u20101 (sFlt\u20101) and free PlGF  in women with pre\u2010eclampsia (PE) with or without a small\u2010for\u2010gestational\u2010age (SGA) neonate in order to establish whether low free PlGF levels associated with PE and SGA are due to enhanced sFlt\u20101 binding or decreased PlGF production.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This was a secondary analysis of a prospective multicenter cohort study involving 407 pregnancies with suspected or confirmed PE, in which total PlGF levels were calculated from measured sFlt\u20101 and free PlGF levels. The control group included women who were suspected to have PE at a certain point in pregnancy but did not develop PE. The analysis was stratified according to whether PE was early\u2010 or late\u2010onset (gestational age &lt;\u200934\u2009weeks <jats:italic>vs<\/jats:italic> \u2265\u200934\u2009weeks) and according to the presence of SGA at birth, which was used as a proxy of fetal growth restriction in the absence of Doppler ultrasound and biometric data.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In early\u2010onset PE, both women with and those without SGA had lower free (19 and 45\u2009pg\/mL) and total  (44 and 100\u2009pg\/mL) PlGF levels compared with women without PE (free and total PlGF, 300 and 381\u2009pg\/mL, respectively). SGA alone did not affect free and total PlGF in this condition (free and total PlGF, 264 and 352\u2009pg\/mL, respectively). Observations in women with late\u2010onset PE were similar, although the changes were more modest. Both SGA (gestational age &lt;\u200934\u2009weeks) and PE were individually associated with increased sFlt\u20101 and, in women with both PE and SGA, the upregulation of sFlt\u20101 occurred in a synergistic manner, thus resulting in the highest sFlt\u20101\/free PlGF ratio in this group. This occurred in both early\u2010 and late\u2010onset PE.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Particularly in pregnancies with early\u2010onset PE and SGA, diminished PlGF production is an important cause of low free PlGF levels. Under such conditions, sFlt\u20101 lowering is unlikely to restore the angiogenic balance. \u00a9 2022 The Authors. <jats:italic>Ultrasound in Obstetrics &amp; Gynecology<\/jats:italic> published by John Wiley &amp; Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.<\/jats:p><\/jats:sec>","DOI":"10.1002\/uog.26088","type":"journal-article","created":{"date-parts":[[2022,10,3]],"date-time":"2022-10-03T18:39:27Z","timestamp":1664822367000},"page":"466-473","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Angiogenic imbalance in pre\u2010eclampsia and fetal growth restriction: enhanced soluble fms\u2010like tyrosine kinase\u20101 binding or diminished production of placental growth factor?"],"prefix":"10.1002","volume":"61","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4115-372X","authenticated-orcid":false,"given":"A. C. M.","family":"Kluivers","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, Division of Pharmacology and Vascular Medicine Erasmus MC University Hospital  Rotterdam The\u00a0Netherlands"},{"name":"Department of Gynecology and Obstetrics Erasmus MC University Hospital  Rotterdam The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A.","family":"Biesbroek","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Pharmacology and Vascular Medicine Erasmus MC University Hospital  Rotterdam The\u00a0Netherlands"},{"name":"Department of Gynecology and Obstetrics Erasmus MC University Hospital  Rotterdam The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"W.","family":"Visser","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Pharmacology and Vascular Medicine Erasmus MC University Hospital  Rotterdam The\u00a0Netherlands"},{"name":"Department of Gynecology and Obstetrics Erasmus MC University Hospital  Rotterdam The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6219-3109","authenticated-orcid":false,"given":"L.","family":"Saleh","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Pharmacology and Vascular Medicine Erasmus MC University Hospital  Rotterdam The\u00a0Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"H.","family":"Russcher","sequence":"additional","affiliation":[{"name":"Department of Clinical Chemistry Erasmus MC University Hospital  Rotterdam The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A. H. J.","family":"Danser","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Pharmacology and Vascular Medicine Erasmus MC University Hospital  Rotterdam The\u00a0Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2471-9461","authenticated-orcid":false,"given":"R. I.","family":"Neuman","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Pharmacology and Vascular Medicine Erasmus MC University Hospital  Rotterdam The\u00a0Netherlands"},{"name":"Department of Gynecology and Obstetrics Erasmus MC University Hospital  Rotterdam The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2023,4,3]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.semperi.2009.02.010"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(05)17987-2"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.5830\/CVJA-2016-009"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.117.09913"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI17189"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.placenta.2009.08.003"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.120.15338"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.121.17258"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1097\/OGX.0b013e3182331028"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/uog.23142"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.3109\/10641950109152635"},{"key":"e_1_2_8_13_1","first-page":"1","article-title":"Physical status: the use and interpretation of anthropometry. 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