{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T12:13:14Z","timestamp":1785413594818,"version":"3.56.0"},"reference-count":80,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T00:00:00Z","timestamp":1778198400000},"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":["24-64-000006"],"award-info":[{"award-number":["24-64-000006"]}],"id":[{"id":"10.13039\/501100006769","id-type":"DOI","asserted-by":"publisher"}]},{"award":["24-64-000006"],"award-info":[{"award-number":["24-64-000006"]}],"id":[{"id":"https:\/\/ror.org\/03y2gwe85","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>This prospective study evaluated first-trimester markers in pregnancies with isolated and combined forms of fetal growth disorders and gestational diabetes mellitus (GDM). Among 1869 screened women, the analysis included 83 controls, 55 GDM, 22 isolated intrauterine growth restriction (iIUGR), and 33 isolated large-for-gestational-age (iLGA) cases, with GDM subgroups stratified by fetal growth (GDM with normal fetal weight, GDM + IUGR, and GDM + LGA). First-trimester clinical and routine biochemical parameters were recorded, and serum concentrations of 80 proteins were measured using targeted LC-MRM-MS proteomics. Different trajectories emerged: IUGR phenotypes showed low PAPP-A\/PlGF and high TSH (p &lt; 0.01), indicating early placental insufficiency, while macrosomia showed opposite trends. GDM + IUGR represented the most severe \u201cdouble hit\u201d phenotype (lowest PlGF, earliest delivery), whereas GDM + LGA showed increased umbilical artery resistance despite excessive growth, suggesting endothelial dysfunction. Targeted proteomics revealed characteristic signatures: iIUGR featured low complement (C4A|C4B) and IGF proteins (IGFALS, IGFBP3) versus GDM and iLGA (p &lt; 0.001); GDM + IUGR showed elevated PZP and CD5L versus iIUGR (p &lt; 0.05); GDM + LGA was marked by high C4BPA and low RBP4, SERPINA7 versus iLGA (p &lt; 0.05). Complement and IGF pathways were consistently implicated. Machine learning achieved 77% sensitivity for IUGR prediction using clinical parameters and 88% sensitivity for LGA prediction using proteomic data. These findings demonstrate that fetal growth disorders represent pathophysiologically unique entities detectable in the first trimester, enabling early risk stratification and personalized management.<\/jats:p>","DOI":"10.3390\/ijms27104192","type":"journal-article","created":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T19:10:52Z","timestamp":1778267452000},"page":"4192","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Integrated Clinical and Molecular Profiling of Fetal Growth Disorders in the First Trimester"],"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. Kulakov National Medical Research Center for Obstetrics Gynecology and Perinatology, Ministry of Healthcare of Russian Federation, Oparina Str. 4, 117997 Moscow, Russia"},{"name":"Moscow Center for Advanced Studies, 123592 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alisa","family":"Tokareva","sequence":"additional","affiliation":[{"name":"V.I. Kulakov National Medical Research Center for Obstetrics Gynecology and Perinatology, Ministry of Healthcare of Russian Federation, Oparina Str. 4, 117997 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalia","family":"Frankevich","sequence":"additional","affiliation":[{"name":"V.I. Kulakov National Medical Research Center for Obstetrics Gynecology and Perinatology, Ministry of Healthcare of Russian Federation, Oparina Str. 4, 117997 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexey","family":"Kononikhin","sequence":"additional","affiliation":[{"name":"V.I. Kulakov National Medical Research Center for Obstetrics Gynecology and Perinatology, Ministry of Healthcare of Russian Federation, Oparina Str. 4, 117997 Moscow, Russia"},{"name":"The Center for Bio- and Medical Technologies, 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, Oparina Str. 4, 117997 Moscow, Russia"},{"name":"Emanuel Institute of Biochemical Physics, Russian Academy of Sciences, Kosygina Str. 4, 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":"The Center for Bio- and Medical Technologies, 121205 Moscow, Russia"},{"name":"Emanuel Institute of Biochemical Physics, Russian Academy of Sciences, Kosygina Str. 4, 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, Oparina Str. 4, 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, Leninsky Av.38\/2, 119334 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Derenko","sequence":"additional","affiliation":[{"name":"V.I. Kulakov National Medical Research Center for Obstetrics Gynecology and Perinatology, Ministry of Healthcare of Russian Federation, Oparina Str. 4, 117997 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vladimir","family":"Frankevich","sequence":"additional","affiliation":[{"name":"V.I. Kulakov National Medical Research Center for Obstetrics Gynecology and Perinatology, Ministry of Healthcare of Russian Federation, Oparina Str. 4, 117997 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evgeny","family":"Nikolaev","sequence":"additional","affiliation":[{"name":"The Center for Bio- and Medical Technologies, 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, Oparina Str. 4, 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. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation, Trubetskaya Str. 8\/2, 119991 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1038\/s41572-019-0098-8","article-title":"Gestational Diabetes Mellitus","volume":"5","author":"McIntyre","year":"2019","journal-title":"Nat. Rev. Dis. Prim."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1016\/j.pcl.2018.12.009","article-title":"Intrauterine Growth Restriction: Postnatal Monitoring and Outcomes","volume":"66","author":"Kesavan","year":"2019","journal-title":"Pediatr. Clin. N. 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