{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T20:38:42Z","timestamp":1772138322621,"version":"3.50.1"},"reference-count":29,"publisher":"Oxford University Press (OUP)","issue":"13","license":[{"start":{"date-parts":[[2025,4,23]],"date-time":"2025-04-23T00:00:00Z","timestamp":1745366400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100007165","name":"University of Missouri","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007165","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,6,18]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Background: Early diagnosis, close follow-up and timely delivery constitute the main elements for appropriate detection and management of Fetal Growth Disorders (FGD). We hypothesized that fetoplacental FGD-associated alterations can be detected in circulating DNA (cirDNA) samples isolated from maternal blood, as early as the first gestational trimester. Methods: Plasma cirDNA was isolated from samples prospectively collected during first trimester gestation (n\u2009=\u200956). Small, Large and Appropriate for Gestational Age (SGA n\u2009=\u200911, LGA n\u2009=\u200918, and AGA n\u2009=\u200929, respectively) status was determined at birth according to weight and gestational age. cirDNA amount, fragmentation, mitochondrial\/nuclear ratio and cirDNA methylation profiles were quantified using qPCR-based assays. Machine learning approaches were applied to build a molecular signature for prediction of LGA and SGA. Prediction accuracy was assessed by Receiver-Operating Curve (ROC) analysis, and Positive and Negative Predictive values (PPV and NPV, respectively) were calculated. Results: Total concentration of plasma cirDNA, cirDNA fragmentation and ratio of mitochondrial\/nuclear cirDNA were increased in SGA and LGA compared to AGA pregnancies. Out of the 10 selected loci, we detected 5 genes (HSD2, RASSF1, CYP19A1, IL10, and LEP) showing significant differential methylation differences (p\u2009&amp;lt;\u20090.05) across the SGA, AGA and LGA samples at first trimester. cirDNA marker signature discriminated between FGD and AGA pregnancies with high accuracy (AUC\u2009&amp;gt;\u20090.95), achieving 88.8% PPV and 85.7% NPV. Conclusions: Maternal blood cirDNA profiles accurately detects early gestation FGD. The proposed novel marker panel hold great potential for implementation of low invasive approaches for reliable prediction of FGDs, enabling a disruptive path toward precision medicine in FGD.<\/jats:p>","DOI":"10.1093\/hmg\/ddaf055","type":"journal-article","created":{"date-parts":[[2025,4,10]],"date-time":"2025-04-10T07:40:54Z","timestamp":1744270854000},"page":"1089-1096","source":"Crossref","is-referenced-by-count":1,"title":["Fetal growth disorders detection during first trimester gestation through comprehensive maternal circulating DNA profiling"],"prefix":"10.1093","volume":"34","author":[{"given":"Rene","family":"Cortese","sequence":"first","affiliation":[{"name":"Department of Gynecology, Obstetrics and Women\u2019s Health, University of Missouri , 1 Hospital Dr. Columbia, MO 65212 ,","place":["United States"]},{"name":"Department of Pediatrics, School of Medicine, University of Missouri , 1 Hospital Dr. Columbia, MO 65212 ,","place":["United States"]},{"name":"Institute for Data Science and Informatics, University of Missouri , Columbia, 22 Heinkel Building, MO 6521 1","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kylie","family":"Cataldo","sequence":"additional","affiliation":[{"name":"Department of Gynecology, Obstetrics and Women\u2019s Health, University of Missouri , 1 Hospital Dr. Columbia, MO 65212 ,","place":["United States"]},{"name":"Department of Pediatrics, School of Medicine, University of Missouri , 1 Hospital Dr. Columbia, MO 65212 ,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Justin","family":"Hummel","sequence":"additional","affiliation":[{"name":"Institute for Data Science and Informatics, University of Missouri , Columbia, 22 Heinkel Building, MO 6521 1","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gracie","family":"Smith","sequence":"additional","affiliation":[{"name":"Department of Gynecology, Obstetrics and Women\u2019s Health, University of Missouri , 1 Hospital Dr. Columbia, MO 65212 ,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Madison","family":"Ortega","sequence":"additional","affiliation":[{"name":"Department of Gynecology, Obstetrics and Women\u2019s Health, University of Missouri , 1 Hospital Dr. Columbia, MO 65212 ,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Madison","family":"Richey","sequence":"additional","affiliation":[{"name":"Department of Gynecology, Obstetrics and Women\u2019s Health, University of Missouri , 1 Hospital Dr. Columbia, MO 65212 ,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hung","family":"Winn","sequence":"additional","affiliation":[{"name":"Department of Gynecology, Obstetrics and Women\u2019s Health, University of Missouri , 1 Hospital Dr. Columbia, MO 65212 ,","place":["United 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