{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T23:58:29Z","timestamp":1781135909947,"version":"3.54.1"},"reference-count":37,"publisher":"Georg Thieme Verlag KG","issue":"03","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Z Geburtshilfe Neonatol"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Zonulin, a biomarker linked to intestinal barrier dysfunction, may contribute\n                        to fetal growth disorders such as intrauterine growth restriction (IUGR) and\n                        small-for-gestational-age (SGA) pregnancies. This study evaluated maternal\n                        serum zonulin levels as a diagnostic tool for distinguishing IUGR from SGA\n                        and investigated their associations with perinatal outcomes.<\/jats:p>\n                  <jats:p>This cross-sectional study included singleton pregnancies between 32 and 37\n                        weeks. Maternal blood samples collected at 16\u201318 weeks of gestation were\n                        analyzed for serum zonulin levels using ELISA, with measurements performed\n                        after group classification based on the final diagnosis (IUGR, SGA, and\n                        appropriate-for-gestational-age [AGA]). Demographic, obstetric, and neonatal\n                        data were analyzed. Diagnostic performance was assessed via receiver\n                        operating characteristic (ROC) curve analysis.<\/jats:p>\n                  <jats:p>Maternal serum zonulin levels were highest in the IUGR group, followed by SGA\n                        and AGA (p&lt;0.001). The optimal cutoff for diagnosing IUGR was 15.70\n                        ng\/mL, with a sensitivity of 86.7% and specificity of 62.5% (AUC: 0.779).\n                        For distinguishing IUGR from SGA, the cutoff was 20.28 ng\/mL (sensitivity:\n                        71.7%, specificity: 73.3%, AUC: 0.748). Zonulin levels negatively correlated\n                        with birth weight, gestational age, and Apgar scores (p&lt; 0.05).<\/jats:p>\n                  <jats:p>Maternal serum zonulin shows significant diagnostic potential for identifying\n                        IUGR and distinguishing it from SGA pregnancies. These findings suggest that\n                        zonulin could serve as a biomarker for pathological fetal growth\n                        restriction, warranting further studies to confirm its clinical utility.<\/jats:p>","DOI":"10.1055\/a-2764-1615","type":"journal-article","created":{"date-parts":[[2026,1,12]],"date-time":"2026-01-12T23:49:27Z","timestamp":1768261767000},"page":"192-200","source":"Crossref","is-referenced-by-count":0,"title":["Diagnostic Value of Maternal Zonulin Levels in Fetal Growth\n                    Disorders"],"prefix":"10.1055","volume":"230","author":[{"given":"Samettin","family":"\u00c7elik","sequence":"additional","affiliation":[{"name":"Obstetrics and Gynecology, Samsun University Faculty of\n                    Medicine, Canik, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8821-1835","authenticated-orcid":false,"given":"Sebati Sinan","family":"Urkmez","sequence":"additional","affiliation":[{"name":"Medical Biochemistry, Ondokuz Mayis University Faculty\n                    of Medicine, Atakum, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9662-244X","authenticated-orcid":false,"given":"Ye\u015fim","family":"Civil \u00dcrkmez","sequence":"additional","affiliation":[{"name":"Medical Biochemistry, Samsun University Faculty of\n                    Medicine, Canik, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"194","published-online":{"date-parts":[[2026,1,12]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"333","DOI":"10.1002\/uog.15884","article-title":"Consensus definition of fetal growth restriction: A Delphi procedure","volume":"48","author":"S J Gordijn","year":"2016","journal-title":"Ultrasound Obstet Gynecol"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"741","DOI":"10.1016\/S1701-2163(15)30865-3","article-title":"Intrauterine growth restriction: Screening, diagnosis, and management","volume":"35","author":"Maternal Fetal Medicine Committee","year":"2013","journal-title":"J Obstet Gynaecol Can"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1002\/uog.20854","article-title":"Validation of Delphi procedure consensus criteria for defining fetal growth\n                    restriction","volume":"56","author":"LC G Molina","year":"2020","journal-title":"Ultrasound Obstet Gynecol"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"S855","DOI":"10.1016\/j.ajog.2017.12.004","article-title":"Evidence-based national guidelines for the management of suspected fetal growth\n                    restriction: Comparison, consensus, and controversy","volume":"218","author":"L M McCowan","year":"2018","journal-title":"Am J Obstet 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Aris","year":"2019","journal-title":"Pediatrics"},{"key":"ref20","doi-asserted-by":"publisher","first-page":"1999","DOI":"10.1080\/14767058.2020.1846707","article-title":"Midregional pro-adrenomedullin and matrix metalloproteinase-2 levels in\n                    intrauterine growth restriction and small gestational age pregnancies:\n                    Biochemical diagnostic difference","volume":"34","author":"B \u015eahin","year":"2021","journal-title":"J Matern Fetal Neonatal Med"},{"key":"ref21","doi-asserted-by":"publisher","first-page":"521","DOI":"10.1080\/14767050701412263","article-title":"Maternal and umbilical venous adrenomedullin and nitric oxide levels in\n                    intrauterine growth restriction","volume":"20","author":"A Akturk","year":"2007","journal-title":"J Matern Fetal Neonatal Med"},{"key":"ref22","doi-asserted-by":"publisher","first-page":"3208","DOI":"10.1080\/14767058.2019.1680630","article-title":"Neonatal morbidity in late preterm small for 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restriction","volume":"32","author":"E Cakar","year":"2019","journal-title":"J Matern Fetal Neonatal Med"},{"key":"ref26","doi-asserted-by":"publisher","first-page":"3342","DOI":"10.3390\/ijms19113342","article-title":"The pathophysiology of gestational diabetes mellitus","volume":"19","author":"J F Plows","year":"2018","journal-title":"Int J Mol Sci"},{"key":"ref27","doi-asserted-by":"publisher","first-page":"5669","DOI":"10.3748\/wjg.v23.i31.5669","article-title":"Fluctuation of zonulin levels in blood vs stability of antibodies","volume":"23","author":"A Vojdani","year":"2017","journal-title":"World J Gastroenterol"},{"key":"ref28","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s40885-020-00139-x","article-title":"Zonulin as marker of pregnancy-induced hypertension: A case control study","volume":"26","author":"A T Bawah","year":"2020","journal-title":"Clin 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Couns"}],"container-title":["Zeitschrift f\u00fcr Geburtshilfe und Neonatologie"],"original-title":[],"language":"de","link":[{"URL":"http:\/\/www.thieme-connect.de\/products\/ejournals\/pdf\/10.1055\/a-2764-1615.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T23:28:59Z","timestamp":1781134139000},"score":1,"resource":{"primary":{"URL":"http:\/\/www.thieme-connect.de\/DOI\/DOI?10.1055\/a-2764-1615"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,12]]},"references-count":37,"journal-issue":{"issue":"03","published-online":{"date-parts":[[2026,6,5]]},"published-print":{"date-parts":[[2026,6]]}},"URL":"https:\/\/doi.org\/10.1055\/a-2764-1615","archive":["Portico","CLOCKSS"],"relation":{},"ISSN":["0948-2393","1439-1651"],"issn-type":[{"value":"0948-2393","type":"print"},{"value":"1439-1651","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,12]]}}}