{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,28]],"date-time":"2026-02-28T04:55:15Z","timestamp":1772254515503,"version":"3.50.1"},"reference-count":38,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2025,11,14]],"date-time":"2025-11-14T00:00:00Z","timestamp":1763078400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diagnostics"],"abstract":"<jats:p>Background\/Objective: Fetal growth restriction (FGR) is a condition in which the fetus fails to grow as expected for gestational age, and its growth is restricted. This study aimed to investigate the role of SCUBE-1, a new ischemia marker, in the diagnosis of late-onset FGR and its contribution to its pathophysiology. Methods: The data of 33 cases with late-onset fetal growth restriction were compared with the data of 33 cases without any pregnancy complications. Only cases beyond 32nd weeks of gestation were included. Fetal sonography and maternal\/fetal vascular Doppler parameters were recorded. Maternal serum SCUBE-1 and ischemia-modified albumin (IMA) levels were measured. Results: The mean maternal was 29.82 \u00b1 5.66 years old in the study group and 30.15 \u00b1 4.85 years old in the control group. The gestational ages in both groups were comparable. Maternal serum IMA levels were found to be similar in the late-onset FGR and control groups. However, serum SCUBE-1 levels were found to be statistically significantly higher in the study group than in the control group. In cases where the SCUBE-1 level was above 1.64, the sensitivity for predicting late-onset FGR was 93.9% and the specificity was 60.6% (AUC 0.891, p &lt; 0.001, 95% CI 0.811\u20130.970). Conclusions: This study reported a significant increase in SCUBE-1, which may be important in determining oxidative stress in late-onset FGR cases. SCUBE-1 was an effective and highly sensitive marker that could provide results in a maternal blood sample within an average of one hour and may be useful in the biochemical diagnosis of late-onset FGR. It may also be a useful serum marker for timing and planning delivery.<\/jats:p>","DOI":"10.3390\/diagnostics15222891","type":"journal-article","created":{"date-parts":[[2025,11,14]],"date-time":"2025-11-14T14:37:52Z","timestamp":1763131072000},"page":"2891","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Increased Serum Signal Peptide-Complement C1r\/C1s, Uegf, Bmp1 (CUB)-Epithelial Growth Factor Domain-Containing Protein-1 May Have a Role in the Pathophysiology of Late-Onset Fetal Growth Restriction"],"prefix":"10.3390","volume":"15","author":[{"given":"Gulseren","family":"Dinc","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology, Faculty of Medicine, Karadeniz Technical University, 61080 Trabzon, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Suleyman Caner","family":"Karahan","sequence":"additional","affiliation":[{"name":"Medical Biochemistry, Faculty of Medicine, Karadeniz Technical University, 61080 Trabzon, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4832-4525","authenticated-orcid":false,"given":"Suleyman","family":"Guven","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Faculty of Medicine, Karadeniz Technical University, 61080 Trabzon, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Society for Maternal-Fetal Medicine, Martins, J.G., Biggio, J.R., and Abuhamad, A. (2020). Society for Maternal-Fetal Medicine Consult Series #52: Diagnosis and management of fetal growth restriction: (Replaces Clinical Guideline Number 3, April 2012). Am. J. Obstet. Gynecol., 223, B2\u2013B17.","DOI":"10.1016\/j.ajog.2020.05.010"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1002\/uog.22134","article-title":"ISUOG Practice Guidelines: Diagnosis and management of small-for-gestational-age fetus and fetal growth restriction","volume":"56","author":"Lees","year":"2020","journal-title":"Ultrasound Obstet. Gynecol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1159\/000355525","article-title":"Evaluation of an optimal gestational age cut-off for the definition of early- and late-onset fetal growth restriction","volume":"36","author":"Savchev","year":"2014","journal-title":"Fetal Diagn. Ther."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1002\/uog.15884","article-title":"Consensus definition of fetal growth restriction: A Delphi procedure","volume":"48","author":"Gordijn","year":"2016","journal-title":"Ultrasound Obstet. Gynecol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"S790","DOI":"10.1016\/j.ajog.2017.12.003","article-title":"Diagnosis and surveillance of late-onset fetal growth restriction","volume":"218","author":"Figueras","year":"2018","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"452.e1","DOI":"10.1016\/j.ajog.2024.01.008","article-title":"First trimester risk of preeclampsia and rate of spontaneous birth in patients without preeclampsia","volume":"231","author":"Cavoretto","year":"2024","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2505774","DOI":"10.1080\/14767058.2025.2505774","article-title":"Maternal factors and perinatal outcomes associated with early-onset versus late-onset fetal growth restriction: A meta-analysis","volume":"38","author":"Tedyanto","year":"2025","journal-title":"J. Matern. Fetal Neonatal Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1016\/j.placenta.2024.06.018","article-title":"Oxidative stress biomarkers for fetal growth restriction in umbilical cord blood: A scoping review","volume":"154","author":"Blok","year":"2024","journal-title":"Placenta"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1063","DOI":"10.1007\/s00404-025-08133-0","article-title":"Oxidative stress biomarkers in fetal growth restriction: A systematic review and meta-analysis","volume":"312","author":"Li","year":"2025","journal-title":"Arch. Gynecol. Obstet."},{"key":"ref_10","unstructured":"Hypertension in pregnancy (2013). Report of the American College of Obstetricians and Gynecologists\u2019 Task Force on Hypertension in Pregnancy. Obstet. Gynecol., 122, 1122\u20131131."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1016\/S0736-4679(00)00255-9","article-title":"A novel assay for cobalt-albumin binding and its potential as a marker for myocardial ischemia-a preliminary report","volume":"19","author":"Lau","year":"2000","journal-title":"J. Emerg. Med."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Lin, Y.C., Sahoo, B.K., Gau, S.S., and Yang, R.B. (2023). The biology of SCUBE. J. Biomed. Sci., 30.","DOI":"10.1186\/s12929-023-00925-3"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Dinc, G., Karahan, S.C., and Guven, S. (2024). Maternal Serum SCUBE-1: A Novel Ischemic Marker in Preeclampsia. J. Pers. Med., 14.","DOI":"10.3390\/jpm14111102"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"76","DOI":"10.5114\/pm.2021.106089","article-title":"Serum ischemia-modified albumin level returns to its premenopausal level with 1-year hormone therapy in healthy menopausal women","volume":"20","author":"Cetin","year":"2021","journal-title":"Menopause Rev."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1159\/000367787","article-title":"Is the measurement of serum ischemia-modified albumin the best test to diagnose ovarian torsion?","volume":"79","author":"Guven","year":"2015","journal-title":"Gynecol. Obstet. Investig."},{"key":"ref_16","first-page":"846531","article-title":"The Diagnostic Value of beta-Human Chorionic Gonadotropin, Progesterone, and Ischemia-Modified Albumin and Their Combined Use in the Prediction of First Trimester Abortions","volume":"2014","author":"Osmanagaoglu","year":"2014","journal-title":"Int. Sch. Res. Not."},{"key":"ref_17","first-page":"389","article-title":"The effects of hormone therapy on ischemia modified albumin and soluble CD40 ligand levels in obese surgical menopausal women","volume":"40","author":"Osmanagaoglu","year":"2013","journal-title":"Clin. Exp. Obstet. Gynecol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1016\/j.ejogrb.2011.11.027","article-title":"Carbon dioxide pneumoperitoneum induces systemic oxidative stress: A clinical study","volume":"161","author":"Aran","year":"2012","journal-title":"Eur. J. Obstet. Gynecol. Reprod. Biol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1515\/jpm.2010.062","article-title":"Occult inflammation and\/or ischemia may be responsible for the false positivity of biochemical Down syndrome screening test","volume":"38","author":"Guven","year":"2010","journal-title":"J. Perinat. Med."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1016\/j.ejogrb.2010.01.006","article-title":"Serum ischemia-modified albumin as a novel marker of ovarian torsion: An experimental study","volume":"150","author":"Aran","year":"2010","journal-title":"Eur. J. Obstet. Gynecol. Reprod. Biol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1016\/j.rbmo.2009.05.012","article-title":"Elevated concentrations of serum ischaemia-modified albumin in PCOS, a novel ischaemia marker of coronary artery disease","volume":"19","author":"Guven","year":"2009","journal-title":"Reprod. Biomed. Online"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1080\/00016340902777517","article-title":"The novel ischemia marker \u2018ischemia-modified albumin\u2019 is increased in normal pregnancies","volume":"88","author":"Guven","year":"2009","journal-title":"Acta Obstet. Gynecol. Scand."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1080\/09513590.2019.1683537","article-title":"Evaluation of SCUBE-1 levels as a placental dysfunction marker at gestational diabetes mellitus","volume":"36","author":"Yilmaz","year":"2020","journal-title":"Gynecol. Endocrinol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"94","DOI":"10.5653\/cerm.2018.45.2.94","article-title":"A new biomarker for the early diagnosis of ovarian torsion: SCUBE-1","volume":"45","author":"Uyanikoglu","year":"2018","journal-title":"Clin. Exp. Reprod. Med."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Mandal\u00e0, M. (2025). Oxidative Stress and Inflammation in Uterine\u2013Vascular Adaptation During Pregnancy. Antioxidants, 14.","DOI":"10.3390\/antiox14091051"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Zhang, C., Guo, Y., Yang, Y., Du, Z., Fan, Y., Zhao, Y., and Yuan, S. (2023). Oxidative stress on vessels at the maternal-fetal interface for female reproductive system disorders: Update. Front. Endocrinol., 14.","DOI":"10.3389\/fendo.2023.1118121"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2173","DOI":"10.1016\/j.jacc.2008.01.060","article-title":"Plasma concentration of SCUBE1, a novel platelet protein, is elevated in patients with acute coronary syndrome and ischemic stroke","volume":"51","author":"Dai","year":"2008","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1016\/j.cardiores.2006.04.010","article-title":"Localization and characterization of a novel secreted protein SCUBE1 in human platelets","volume":"71","author":"Tu","year":"2006","journal-title":"Cardiovasc. Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1159\/000359969","article-title":"Placental pathology in early-onset and late-onset fetal growth restriction","volume":"36","author":"Mifsud","year":"2014","journal-title":"Fetal Diagn. Ther."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Voros, C., Stavros, S., Sapantzoglou, I., Mavrogianni, D., Daskalaki, M.A., Theodora, M., Antsaklis, P., Drakakis, P., Loutradis, D., and Daskalakis, G. (2025). The Role of Placental Mitochondrial Dysfunction in Adverse Perinatal Outcomes: A Systematic Review. J. Clin. Med., 14.","DOI":"10.3390\/jcm14113838"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1016\/j.placenta.2021.09.003","article-title":"Hypoxic effects on the mitochondrial content and functions of the placenta in fetal growth restriction","volume":"114","author":"Xu","year":"2021","journal-title":"Placenta"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Long, J., Huang, Y., Wang, G., Tang, Z., Shan, Y., Shen, S., and Ni, X. (2023). Mitochondrial ROS Accumulation Contributes to Maternal Hypertension and Impaired Remodeling of Spiral Artery but Not IUGR in a Rat PE Model Caused by Maternal Glucocorticoid Exposure. Antioxidants, 12.","DOI":"10.3390\/antiox12050987"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"106199","DOI":"10.1016\/j.earlhumdev.2025.106199","article-title":"Prenatal human brain development is not spared by IUGR: A systematic review","volume":"201","author":"Honorio","year":"2025","journal-title":"Early Hum. Dev."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1016\/j.bpobgyn.2018.02.007","article-title":"Prophylaxis and treatment of foetal growth restriction","volume":"49","author":"Nawathe","year":"2018","journal-title":"Best Pract. Res. Clin. Obstet. Gynaecol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2526111","DOI":"10.1080\/14767058.2025.2526111","article-title":"Clinical practice guidance for the management of fetal growth restriction: An expert review","volume":"38","author":"Villalain","year":"2025","journal-title":"J. Matern. Fetal Neonatal Med."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Cobanoglu, U., Birge, O., Cetin, M., and Guven, E.S.G. (2024). Evaluation of Maternal Ischemia-Modified Albumin Levels during Pregnancy and Their Effect on Fetal Birth Weight. Medicina, 60.","DOI":"10.3390\/medicina60091530"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Zhong, X., Sun, Y., Lu, Y., and Xu, L. (2023). Immunomodulatory role of estrogen in ischemic stroke: Neuroinflammation and effect of sex. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1164258"},{"key":"ref_38","unstructured":"Feingold, K.R., Ahmed, S.F., Anawalt, B., Blackman, M.R., Boyce, A., Chrousos, G., Corpas, E., de Herder, W.W., Dhatariya, K., and Dungan, K. (2000). Endocrinology of Pregnancy. Endotext [Internet], MDText.com Inc."}],"container-title":["Diagnostics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-4418\/15\/22\/2891\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,14]],"date-time":"2025-11-14T14:50:36Z","timestamp":1763131836000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-4418\/15\/22\/2891"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,14]]},"references-count":38,"journal-issue":{"issue":"22","published-online":{"date-parts":[[2025,11]]}},"alternative-id":["diagnostics15222891"],"URL":"https:\/\/doi.org\/10.3390\/diagnostics15222891","relation":{},"ISSN":["2075-4418"],"issn-type":[{"value":"2075-4418","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,14]]}}}