{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T14:27:45Z","timestamp":1788532065570,"version":"build-2803163510"},"reference-count":27,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T00:00:00Z","timestamp":1788480000000},"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>Objective: Our objectives were to evaluate maternal serum YKL-40 levels in pregnancies complicated by preterm prelabor rupture of membranes (PPROM), compare them with healthy gestational age-comparable controls, and assess the association between YKL-40 levels and subsequent composite adverse neonatal outcomes (CANOs). Methods: This prospective observational study included 44 women with PPROM and 44 healthy pregnant controls between 24 and 37 weeks of gestation. Maternal serum YKL-40 concentrations were measured using an enzyme-linked immunosorbent assay (ELISA), with concentrations corrected for the manufacturer-specified 5-fold sample dilution. Multivariable Firth\u2019s penalized logistic regression was used to evaluate the independent association of YKL-40 with PPROM and, within the PPROM cohort only, subsequent CANO. Exploratory receiver operating characteristic (ROC) analysis was performed to assess the ability of YKL-40 to discriminate established PPROM cases from healthy controls. The study was powered a priori only for the primary between-group comparison of YKL-40; the ROC and CANO analyses were not separately powered and are reported as exploratory. Results: Maternal serum YKL-40 levels were significantly higher in the PPROM group than in the control group (5.87 \u00b1 2.64 vs. 2.44 \u00b1 0.96 ng\/mL, p &lt; 0.001). In multivariable analysis, YKL-40 remained independently associated with PPROM (adjusted odds ratio 5.61, 95% CI 2.07\u201315.23, p &lt; 0.001 per 1 ng\/mL increase). Within the PPROM cohort, YKL-40 was not independently associated with CANO (p = 0.775). Exploratory ROC analysis yielded an AUC of 0.935 (95% CI 0.881\u20130.989); a ROC-derived cut-off of &gt;3.3 ng\/mL provided 86.4% sensitivity and 84.1% specificity for discriminating established PPROM cases from healthy controls. Conclusions: Maternal serum YKL-40 levels were significantly elevated in women with established PPROM and remained independently associated with PPROM status, but were not associated with subsequent CANO. Because YKL-40 was measured after PPROM diagnosis, the observed ROC performance reflects case\u2013control discrimination rather than prospective prediction or established diagnostic utility. Larger prospective studies using clinically relevant comparison groups and independently validated assays are required to determine the potential clinical value of YKL-40 in PPROM.<\/jats:p>","DOI":"10.3390\/diagnostics16172845","type":"journal-article","created":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T13:50:44Z","timestamp":1788529844000},"page":"2845","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The Significance of YKL-40, a Marker Involved in Extracellular Matrix Remodeling, in Preterm Prelabor Rupture of Membranes: A Prospective Observational Study"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2564-2435","authenticated-orcid":false,"given":"G\u00fclten","family":"\u00c7irkin Teke\u015f","sequence":"first","affiliation":[{"name":"Perinatology Department, Etlik City Hospital, Ministry of Health, Varl\u0131k Mah. Halil Sezai Erkut Cad., Yenimahalle, Ankara 06170, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7034-6811","authenticated-orcid":false,"given":"Din\u00e7er","family":"S\u00fcmer","sequence":"additional","affiliation":[{"name":"Perinatology Department, Etlik City Hospital, Ministry of Health, Varl\u0131k Mah. Halil Sezai Erkut Cad., Yenimahalle, Ankara 06170, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Gunel","family":"Aliyeva","sequence":"additional","affiliation":[{"name":"Perinatology Department, Etlik City Hospital, Ministry of Health, Varl\u0131k Mah. Halil Sezai Erkut Cad., Yenimahalle, Ankara 06170, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-1134-9950","authenticated-orcid":false,"given":"\u00d6zge","family":"\u00d6zt\u00fcrk","sequence":"additional","affiliation":[{"name":"Perinatology Department, Etlik City Hospital, Ministry of Health, Varl\u0131k Mah. Halil Sezai Erkut Cad., Yenimahalle, Ankara 06170, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"}]},{"given":"Figen","family":"G\u00fcnday","sequence":"additional","affiliation":[{"name":"Perinatology Department, Etlik City Hospital, Ministry of Health, Varl\u0131k Mah. Halil Sezai Erkut Cad., Yenimahalle, Ankara 06170, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"}]},{"given":"Nurten","family":"\u00c7ilek","sequence":"additional","affiliation":[{"name":"Perinatology Department, Etlik City Hospital, Ministry of Health, Varl\u0131k Mah. Halil Sezai Erkut Cad., Yenimahalle, Ankara 06170, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"}]},{"given":"Zeynep Tu\u011f\u00e7e","family":"A\u015fan \u00d6zbek","sequence":"additional","affiliation":[{"name":"Perinatology Department, Etlik City Hospital, Ministry of Health, Varl\u0131k Mah. Halil Sezai Erkut Cad., Yenimahalle, Ankara 06170, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"}]},{"given":"Kadriye","family":"Yakut Y\u00fccel","sequence":"additional","affiliation":[{"name":"Perinatology Department, Etlik City Hospital, Ministry of Health, Varl\u0131k Mah. Halil Sezai Erkut Cad., Yenimahalle, Ankara 06170, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"supervision","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1061","DOI":"10.1097\/AOG.0000000000004142","article-title":"ACOG Practice Bulletin No. 217: Prelabor Rupture of Membranes","volume":"136","author":"Siegler","year":"2020","journal-title":"Obstet. Gynecol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1053\/j.semperi.2017.07.012","article-title":"Preterm prelabor rupture of the membranes: A disease of the fetal membranes","volume":"41","author":"Menon","year":"2017","journal-title":"Semin. Perinatol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"8705005","DOI":"10.1155\/2022\/8705005","article-title":"Analysis of Maternal and Neonatal Outcome of Patients with Preterm Prelabor Rupture of Membranes","volume":"2022","author":"Yan","year":"2022","journal-title":"J. Healthc. Eng."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"A\u011fao\u011flu, R.T., \u00d6zt\u00fcrk, \u00d6., Ulusoy, C.O., G\u00fcnday, F., Kurt, D.S., Aksu, M., Hizli, B., and Y\u00fccel, K.Y. (2025). Perinatal outcomes and predictors of neonatal mortality in preterm premature rupture of membranes: A tertiary center experience. BMC Pregnancy Childbirth, 25.","DOI":"10.1186\/s12884-025-07688-9"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"388","DOI":"10.48095\/cccg2022388","article-title":"Amniotic fluid soluble CD93 is elevated in the presence of intra-amniotic inflammation in preterm prelabor rupture of the fetal membranes","volume":"87","author":"Spacek","year":"2022","journal-title":"Ceska Gynekol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1007\/s00281-020-00808-x","article-title":"Novel pathways of inflammation in human fetal membranes associated with preterm birth and preterm pre-labor rupture of the membranes","volume":"42","author":"Menon","year":"2020","journal-title":"Semin. Immunopathol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"326","DOI":"10.1002\/ijgo.70408","article-title":"Maternal serum syndecan-1 levels in preterm prelabor rupture of membranes and potential predictor of adverse perinatal outcomes: A case-control study","volume":"171","author":"Bayrak","year":"2025","journal-title":"Int. J. Gynaecol. Obstet."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"3175","DOI":"10.1007\/s43032-024-01678-6","article-title":"Novel Biomarkers: Soluble Urokinase-Type Plasminogen Activator Receptor and Procalcitonin- and Histological Chorioamnionitis after Preterm Premature Rupture of Membranes","volume":"31","author":"Jalkanen","year":"2024","journal-title":"Reprod. Sci."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Saini, P., Kour, A., Sharma, R., and Lamba, J. (2025). Interleukin 6 (IL-6) in Cervico-Vaginal Fluid, A Diagnostic and Prognostic Tool for Intra Amniotic Infection\/Inflammation in Preterm Premature Rupture of Membranes (PPROM). J. Obstet. Gynecol. India.","DOI":"10.1007\/s13224-025-02276-5"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"16206","DOI":"10.1038\/s41598-024-67300-6","article-title":"Evaluating the predictive efficacy of first trimester biochemical markers (PAPP-A, f\u03b2-hCG) in forecasting preterm delivery incidences","volume":"14","author":"Swiercz","year":"2024","journal-title":"Sci. Rep."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"BSR20180323","DOI":"10.1042\/BSR20180323","article-title":"Chitinase: Diversity, limitations, and trends in engineering for suitable applications","volume":"38","author":"Oyeleye","year":"2018","journal-title":"Biosci. Rep."},{"key":"ref_12","first-page":"010502","article-title":"YKL-40 as a biomarker in various inflammatory diseases: A review","volume":"34","author":"Blazevic","year":"2024","journal-title":"Biochem. Medica"},{"key":"ref_13","first-page":"101908","article-title":"Heparin-binding of the human chitinase-like protein YKL-40 is allosterically modified by chitin oligosaccharides","volume":"41","author":"Magnusdottir","year":"2025","journal-title":"Biochem. Biophys. Rep."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1038\/s41392-020-00303-7","article-title":"Chitinase-3 like-protein-1 function and its role in diseases","volume":"5","author":"Zhao","year":"2020","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Chang, M.C., Chen, C.T., Chiang, P.F., and Chiang, Y.C. (2024). The Role of Chitinase-3-like Protein-1 (YKL40) in the Therapy of Cancer and Other Chronic-Inflammation-Related Diseases. Pharmaceuticals, 17.","DOI":"10.3390\/ph17030307"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Mizoguchi, E., Sadanaga, T., Nanni, L., Wang, S., and Mizoguchi, A. (2024). Recently Updated Role of Chitinase 3-like 1 on Various Cell Types as a Major Influencer of Chronic Inflammation. Cells, 13.","DOI":"10.20944\/preprints202402.1627.v1"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"e13697","DOI":"10.1111\/aji.13697","article-title":"Expression of inflammatory, angiogenic, and extracellular matrix-related mediators in the cervicovaginal fluid of women with preterm premature rupture of membranes: Relationship with acute histological chorioamnionitis","volume":"89","author":"Kim","year":"2023","journal-title":"Am. J. Reprod. Immunol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1080\/14767058.2017.1281904","article-title":"Comparison of rapid MMP-8 and interleukin-6 point-of-care tests to identify intra-amniotic inflammation\/infection and impending preterm delivery in patients with preterm labor and intact membranes","volume":"31","author":"Chaemsaithong","year":"2018","journal-title":"J. Matern.-Fetal Neonatal Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"e13642","DOI":"10.1111\/aji.13642","article-title":"Matrix metalloproteinases in preterm prelabor rupture of membranes in the setting of chorioamnionitis: A scoping review","volume":"89","author":"Nguyen","year":"2023","journal-title":"Am. J. Reprod. Immunol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"e13656","DOI":"10.1111\/aji.13656","article-title":"NETs promote ROS production to induce human amniotic epithelial cell apoptosis via ERK1\/2 signaling in spontaneous preterm birth","volume":"89","author":"Hu","year":"2023","journal-title":"Am. J. Reprod. Immunol."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Cho, H.Y., Park, K.H., Oh, E., Lee, M.J., Choi, B.Y., and Im, E.M. (2024). Plasma acute phase proteins as potential predictors of intra-amniotic inflammation and infection in preterm premature rupture of membranes. Innate Immun., 17534259241306237.","DOI":"10.1177\/17534259241306237"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Neam\u021bu, S.I., Sava, M., Bereanu, A.S., B\u0103dil\u0103, R.M., Codru, I.R., Vintil\u0103, B.I., Must\u0103\u021bea, S., Stoia, O., and Chicea, R. (2025). Evaluation of Maternal Inflammatory Biomarkers in Preterm Prelabor Rupture of Membranes: A Systematic Review and Meta-Analysis. Medicina, 62.","DOI":"10.3390\/medicina62010020"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"98","DOI":"10.4274\/tjod.galenos.2022.94884","article-title":"Elevated serum YKL-40 levels as a diagnostic and prognostic marker in the placenta accreta spectrum","volume":"19","author":"Bayramoglu","year":"2022","journal-title":"Turk. J. Obstet. Gynecol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2211681","DOI":"10.1080\/01443615.2023.2211681","article-title":"YKL-40 promotes proliferation and invasion of HTR-8\/SVneo cells by activating akt\/MMP9 signalling in placenta accreta spectrum disorders","volume":"43","author":"Liu","year":"2023","journal-title":"J. Obstet. Gynaecol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"e20231574","DOI":"10.1590\/1806-9282.20231574","article-title":"The role of the Chitinase 3-Like 1 (CHI3L1) genes in the preeclampsia pathophysiology","volume":"70","author":"Mammadova","year":"2024","journal-title":"Rev. Assoc. Med. Bras."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1080\/09513590.2018.1563889","article-title":"Inflammatory marker YKL-40 levels in intrahepatic cholestasis of pregnancy","volume":"35","author":"Erdem","year":"2019","journal-title":"Gynecol. Endocrinol."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Mlodawska, M., Zmelonek-Znamirowska, A., Swiercz, G., Mehta, J., and Mlodawski, J. (2026). Neonatal Respiratory Outcomes in Placenta Previa with Histopathologically Confirmed Placenta Accreta Spectrum. J. Clin. Med., 15.","DOI":"10.3390\/jcm15155891"}],"container-title":["Diagnostics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-4418\/16\/17\/2845\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T14:03:25Z","timestamp":1788530605000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-4418\/16\/17\/2845"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,4]]},"references-count":27,"journal-issue":{"issue":"17","published-online":{"date-parts":[[2026,9]]}},"alternative-id":["diagnostics16172845"],"URL":"https:\/\/doi.org\/10.3390\/diagnostics16172845","relation":{},"ISSN":["2075-4418"],"issn-type":[{"value":"2075-4418","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,4]]}}}