{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T16:56:32Z","timestamp":1788281792107,"version":"build-2803163510"},"reference-count":44,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2019,10,4]],"date-time":"2019-10-04T00:00:00Z","timestamp":1570147200000},"content-version":"vor","delay-in-days":3,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001826","name":"ZonMw","doi-asserted-by":"publisher","award":["Project 90700412"],"award-info":[{"award-number":["Project 90700412"]}],"id":[{"id":"10.13039\/501100001826","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["obgyn.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Ultrasound in Obstet &amp; Gyne"],"published-print":{"date-parts":[[2019,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Objectives<\/jats:title><jats:p>Abnormal placentation in early pregnancy may play a role in the pathogenesis of pre\u2010eclampsia. Human chorionic gonadotropin <jats:bold>(<\/jats:bold>hCG) regulates placental development and angiogenesis and may affect the ratio of soluble fms\u2010like tyrosine kinase\u20101 (sFlt\u20101) and placental growth factor (PlGF) in the serum. The aims of this study were to investigate the association of total hCG with the risk of pre\u2010eclampsia and to examine the potential effect of pro\u2010 and anti\u2010angiogenic factors on this association.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This was a population\u2010based prospective cohort study of 7754 women with a singleton pregnancy. Total hCG was measured in the first available sample (median gestational age, 14.4\u2009weeks; 95% range, 10.1\u201326.1\u2009weeks) and sFlt\u20101 and PlGF concentrations in early (&lt;\u200918\u2009weeks; median, 13.2\u2009weeks; 95% range, 9.6\u201317.6\u2009weeks) and in mid\u2010 (18\u201325\u2009weeks; median, 20.4\u2009weeks; 95% range, 18.5\u201323.5\u2009weeks) pregnancy. We tested the association of hCG concentration and risk of pre\u2010eclampsia using regression analysis, adjusting for maternal age, ethnicity, body mass index, parity, education level, smoking status and fetal sex. Additionally, we assessed whether this association was affected by the sFlt\u20101\/PlGF ratio.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>High hCG concentration was associated with a 1.5\u20132.7\u2010fold increased risk of pre\u2010eclampsia (<jats:italic>P<\/jats:italic>\u2009=\u20090.0001), depending on the cut\u2010off used, and with increased sFlt\u20101\/PlGF ratio during early pregnancy (<jats:italic>P<\/jats:italic>\u2009&lt;\u20090.0001). The association between high hCG and pre\u2010eclampsia attenuated by roughly 40% after adjustment for early\u2010pregnancy sFlt\u20101\/PlGF ratio (\u03b2\u2010estimate change from 0.19\u2009\u00b1\u20090.10 (<jats:italic>P<\/jats:italic>\u2009=\u20090.052) to 0.12\u2009\u00b1\u20090.10 (<jats:italic>P<\/jats:italic>\u2009=\u20090.22)).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>High total hCG concentration in early pregnancy is associated with an increased risk of pre\u2010eclampsia. The effect of high hCG concentration on the balance between pro\u2010 and anti\u2010angiogenic factors during pregnancy may have a role in the pathophysiology of pre\u2010eclampsia. \u00a9 2019 The Authors. <jats:italic>Ultrasound in Obstetrics &amp; Gynecology<\/jats:italic> published by John Wiley &amp; Sons Ltd on behalf of the International Society of Ultrasound in Obstetrics and Gynecology.<\/jats:p><\/jats:sec>","DOI":"10.1002\/uog.20256","type":"journal-article","created":{"date-parts":[[2019,3,5]],"date-time":"2019-03-05T08:04:26Z","timestamp":1551773066000},"page":"477-483","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":38,"title":["Human chorionic gonadotropin and risk of pre\u2010eclampsia:  prospective population\u2010based cohort study"],"prefix":"10.1002","volume":"54","author":[{"given":"M.","family":"Barjaktarovic","sequence":"first","affiliation":[{"name":"The Generation R Study Group Erasmus Medical Center, Sophia Children's Hospital  Rotterdam The Netherlands"},{"name":"Department of Internal Medicine, Academic Center for Thyroid Diseases Erasmus Medical Center, Sophia Diseases, Sophia Children's Hospital, Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T. I. M.","family":"Korevaar","sequence":"additional","affiliation":[{"name":"The Generation R Study Group Erasmus Medical Center, Sophia Children's Hospital  Rotterdam The Netherlands"},{"name":"Department of Internal Medicine, Academic Center for Thyroid Diseases Erasmus Medical Center, Sophia Diseases, Sophia Children's Hospital, Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V. W. V.","family":"Jaddoe","sequence":"additional","affiliation":[{"name":"The Generation R Study Group Erasmus Medical Center, Sophia Children's Hospital  Rotterdam The Netherlands"},{"name":"Department of Epidemiology and Pediatrics Erasmus Medical Center, Sophia Children's Hospital  Rotterdam The\u00a0Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Y. B.","family":"de Rijke","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Academic Center for Thyroid Diseases Erasmus Medical Center, Sophia Diseases, Sophia Children's Hospital, Rotterdam, The Netherlands"},{"name":"Department of Clinical Chemistry Erasmus Medical Center, Sophia Children's Hospital  Rotterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R. P.","family":"Peeters","sequence":"additional","affiliation":[{"name":"The Generation R Study Group Erasmus Medical Center, Sophia Children's Hospital  Rotterdam The Netherlands"},{"name":"Department of Internal Medicine, Academic Center for Thyroid Diseases Erasmus Medical Center, Sophia Diseases, Sophia Children's Hospital, Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E. A. 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