{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T23:16:44Z","timestamp":1790810204878,"version":"4.1.0"},"reference-count":70,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,1,30]],"date-time":"2026-01-30T00:00:00Z","timestamp":1769731200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006769","name":"Russian Science Foundation","doi-asserted-by":"publisher","award":["24-14-00140"],"award-info":[{"award-number":["24-14-00140"]}],"id":[{"id":"10.13039\/501100006769","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Imperfect first-trimester screening for hypertensive disorders of pregnancy (HDP) means many high-risk women miss the window for preventive aspirin, and the biological heterogeneity of HDPs is overlooked. This study aimed to leverage first-trimester serum proteomics to create a more precise tool for predicting preeclampsia (PE) and differentiating it from other HDPs. A prospective nested case\u2013control study (n = 172) was conducted using targeted liquid chromatography-multiple reaction monitoring-mass spectrometry (LC-MRM-MS) proteomic profiling of 115 proteins. Machine learning (ML) methods were used to develop classifiers from the proteomic data. The signature predictive of PE was characterized by dysregulation of the complement and coagulation cascades (F10, C8A, C1QA, SERPING1, VTN). The profile differentiating gestational hypertension (GAH) from chronic hypertension (CAH) was linked to lipid metabolism (HRG, APOA4, APOC2). An 18-protein support vector machine (SVM) model for predicting PE demonstrated exceptional performance, with 94% sensitivity and 100% specificity, significantly outperforming the standard Fetal Medicine Foundation (FMF) screening algorithm. Pathway analysis confirmed that PE is associated with early activation of innate immunity and coagulation pathways, while GAH is linked to a pregnancy-induced metabolic response. A targeted serum proteomic combined with ML approach represents a new perspective diagnostic tool with strong potential to personalize monitoring for women at the highest risk for specific hypertensive pregnancy complications.<\/jats:p>","DOI":"10.3390\/ijms27031402","type":"journal-article","created":{"date-parts":[[2026,1,30]],"date-time":"2026-01-30T14:35:46Z","timestamp":1769783746000},"page":"1402","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Machine Learning and Blood-Targeted Proteomics Enable Early Prediction and Etiological Discrimination of Hypertensive Pregnancy Disorders"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6650-5915","authenticated-orcid":false,"given":"Natalia","family":"Starodubtseva","sequence":"first","affiliation":[{"name":"V.I. 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Kulakov National Medical Research Center for Obstetrics Gynecology and Perinatology, Ministry of Healthcare of Russian Federation, 117997 Moscow, Russia"},{"name":"Project Center of Omics Technologies and Advanced Mass Spectrometry, 121205 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1515-9447","authenticated-orcid":false,"given":"Anna","family":"Bugrova","sequence":"additional","affiliation":[{"name":"V.I. Kulakov National Medical Research Center for Obstetrics Gynecology and Perinatology, Ministry of Healthcare of Russian Federation, 117997 Moscow, Russia"},{"name":"Emanuel Institute of Biochemical Physics, Russian Academy of Sciences, 119334 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8177-7449","authenticated-orcid":false,"given":"Maria","family":"Indeykina","sequence":"additional","affiliation":[{"name":"Project Center of Omics Technologies and Advanced Mass Spectrometry, 121205 Moscow, Russia"},{"name":"Emanuel Institute of Biochemical Physics, Russian Academy of Sciences, 119334 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8397-3574","authenticated-orcid":false,"given":"Evgenii","family":"Kukaev","sequence":"additional","affiliation":[{"name":"V.I. Kulakov National Medical Research Center for Obstetrics Gynecology and Perinatology, Ministry of Healthcare of Russian Federation, 117997 Moscow, Russia"},{"name":"V.L. Talrose Institute for Energy Problems of Chemical Physics, N.N. Semenov Federal Research Center for Chemical Physics, Russian Academy of Sciences, 119334 Moscow, Russia"},{"name":"Moscow Center for Advanced Studies, 123592 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alina","family":"Poluektova","sequence":"additional","affiliation":[{"name":"V.I. Kulakov National Medical Research Center for Obstetrics Gynecology and Perinatology, Ministry of Healthcare of Russian Federation, 117997 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Brzhozovskiy","sequence":"additional","affiliation":[{"name":"V.I. Kulakov National Medical Research Center for Obstetrics Gynecology and Perinatology, Ministry of Healthcare of Russian Federation, 117997 Moscow, Russia"},{"name":"Project Center of Omics Technologies and Advanced Mass Spectrometry, 121205 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evgeny","family":"Nikolaev","sequence":"additional","affiliation":[{"name":"Project Center of Omics Technologies and Advanced Mass Spectrometry, 121205 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gennady","family":"Sukhikh","sequence":"additional","affiliation":[{"name":"V.I. Kulakov National Medical Research Center for Obstetrics Gynecology and Perinatology, Ministry of Healthcare of Russian Federation, 117997 Moscow, Russia"},{"name":"Department of Obstetrics, Gynecology, Perinatology and Reproductology, Institute of Professional Education, Federal State Autonomous Educational Institution of Higher Education I.M. 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