{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T19:54:17Z","timestamp":1781812457490,"version":"3.54.5"},"reference-count":27,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,1,19]],"date-time":"2026-01-19T00:00:00Z","timestamp":1768780800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,19]],"date-time":"2026-01-19T00:00:00Z","timestamp":1768780800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["obgyn.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Intl J Gynecology &amp; Obste"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To develop and internally validate a mechanistic, three\u2010domain framework for early classification and prediction of pre\u2010eclampsia (PE) using first\u2010trimester angiogenic, uteroplacental, and maternal vascular biomarkers.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In a prospective cohort of 1925 singleton pregnancies screened at 11 to 13.6\u2009weeks, placental growth factor (PGF), uterine artery pulsatility index (UtA\u2010PI), and mean arterial pressure (MAP) were log\u2010transformed and standardized to gestational age\u2013adjusted multiples of the median. Prespecified percentile thresholds (PGF &lt;10th; UtA\u2010PI &gt;95th; MAP &gt;95th) defined domain abnormalities and mechanistic phenotypes. Associations with PE, fetal growth restriction (FGR), and the composite of PE or FGR were assessed using logistic regression. Discrimination (area under the [receiver operating characteristic] curve [AUC]), calibration, and clinical utility were evaluated; bootstrap internal validation was used for optimism correction; and decision\u2010curve analysis quantified net clinical benefit.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      PE occurred in 104 of 1925 pregnancies (5.4%). Phenotypes were distributed as normo (81.7%), molecular (7.6%), hemodynamic (3.2%), tensional (5.1%), dual (\u22652 domains; 2.1%), and triple (3\/3; 0.3%). The risk of PE increased stepwise from 3.9% (normo) to 80.0% (triple) (\n                      <jats:italic>P<\/jats:italic>\n                      for trend &lt;0.001). The three\u2010domain model improved discrimination to an AUC\u2009of 0.81 (95%\u2009confidence interval [CI], 0.77\u20130.86) versus the clinical model (AUC, 0.68;\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&lt;\u20090.001), achieved good discrimination for isolated FGR (AUC, 0.75 [95%\u2009CI, 0.70\u20130.81]), and provided higher net clinical benefit among 5% to 30% thresholds. In early\u2010onset PE (n\u2009=\u200914), discrimination was high (AUC, 0.99 [95%\u2009CI, 0.98\u20131.00]); estimates should be interpreted cautiously given the small number of events.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>A first\u2010trimester, mechanistic three\u2010domain framework captures the pathophysiologic continuum of placental insufficiency and supports accurate, clinically meaningful early risk stratification for PE. Findings were internally validated; external validation\u2014particularly for early\u2010onset PE\u2014is warranted.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ijgo.70804","type":"journal-article","created":{"date-parts":[[2026,1,20]],"date-time":"2026-01-20T07:06:57Z","timestamp":1768892817000},"page":"182-191","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["A first\u2010trimester mechanistic framework integrating three Physiopathologic biomarker domains for pre\u2010eclampsia classification"],"prefix":"10.1002","volume":"174","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9524-4133","authenticated-orcid":false,"given":"Johnatan","family":"Torres\u2010Torres","sequence":"first","affiliation":[{"name":"Department of Reproductive and Perinatal Health Research Instituto Nacional de Perinatologia Isidro Espinosa de los Reyes  Mexico City Mexico"},{"name":"Iberoamerican Research Network in 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