{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T11:54:31Z","timestamp":1792065271453,"version":"4.4.0"},"reference-count":49,"publisher":"Public Library of Science (PLoS)","issue":"12","license":[{"start":{"date-parts":[[2020,12,31]],"date-time":"2020-12-31T00:00:00Z","timestamp":1609372800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Seoul National University Bundang Hospital Research Fund","award":["Grant No. 13-2020-011"],"award-info":[{"award-number":["Grant No. 13-2020-011"]}]},{"name":"National Research Foundation of Korea (NRF) grant funded by the Korea government","award":["No. 2020R1F1A1048362"],"award-info":[{"award-number":["No. 2020R1F1A1048362"]}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\"><jats:title>Objective<\/jats:title><jats:p>We sought to identify novel biomarkers in the amniotic fluid (AF) related to imminent spontaneous preterm delivery (SPTD) (\u2264 14 days after sampling) in women with early preterm premature rupture of membranes (PPROM), using a protein microarray.<\/jats:p><\/jats:sec><jats:sec id=\"sec002\"><jats:title>Method<\/jats:title><jats:p>This was a retrospective cohort study of a total of 88 singleton pregnant women with PPROM (23+0 to 30+6 weeks) who underwent amniocentesis. A nested case-control study for biomarker discovery was conducted using pooled AF samples from controls (non-imminent delivery, n = 15) and cases (imminent SPTD, n = 15), which were analyzed using an antibody microarray. Quantitative validation of four candidate proteins was performed, using ELISA, in the total cohort (n = 88). IL-8, MMP-9, and Fas levels were additionally measured for the comparison and to examine association of SPTD with the etiologic factors of PPROM.<\/jats:p><\/jats:sec><jats:sec id=\"sec003\"><jats:title>Results<\/jats:title><jats:p>Of all the proteins studied in the protein microarray, four showed significant intergroup differences. Analyses of the total cohort by ELISA confirmed the significantly elevated concentrations of AF lipocalin-2, MMP-9, and S100 A8\/A9, but not of endostatin and Fas, in women who delivered within 14 days of sampling. For inflammatory proteins showing a significant association, the odds of SPTD within 14 days increased significantly with an increase in baseline AF levels of the proteins (P for trend &lt;0.05 for each) in each quartile, especially in the 3rd and 4th quartile.<\/jats:p><\/jats:sec><jats:sec id=\"sec004\"><jats:title>Conclusions<\/jats:title><jats:p>We identified several potential novel biomarkers (i.e., lipocalin-2, MMP-9, and S100 A8\/A9) related to SPTD within 14 days of sampling, all of which are inflammation-related molecules. Furthermore, the SPTD risk increased with increasing quartiles of each of these inflammatory proteins, especially the 3rd and 4th quartile of each protein. The present findings may highlight the importance of inflammatory mechanisms and the degree of activated inflammatory response in developing SPTD in early PPROM.<\/jats:p><\/jats:sec>","DOI":"10.1371\/journal.pone.0244720","type":"journal-article","created":{"date-parts":[[2020,12,31]],"date-time":"2020-12-31T19:43:52Z","timestamp":1609443832000},"page":"e0244720","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":27,"title":["A protein microarray analysis of amniotic fluid proteins for the prediction of spontaneous preterm delivery in women with preterm premature rupture of membranes at 23 to 30 weeks of gestation"],"prefix":"10.1371","volume":"15","author":[{"given":"Hyeon Ji","family":"Kim","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3550-9686","authenticated-orcid":true,"given":"Kyo Hoon","family":"Park","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu Mi","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eunwook","family":"Joo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kwanghee","family":"Ahn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sue","family":"Shin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2020,12,31]]},"reference":[{"issue":"3","key":"pone.0244720.ref001","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1111\/jog.13886","article-title":"Incidence and risk factors of preterm premature rupture of membranes in singleton pregnancies at Siriraj Hospital","volume":"45","author":"P Sae-Lin","year":"2019","journal-title":"J Obstet Gynaecol Res"},{"issue":"7","key":"pone.0244720.ref002","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":"R Menon","year":"2017","journal-title":"Semin Perinatol"},{"issue":"1","key":"pone.0244720.ref003","first-page":"178","article-title":"Preterm premature rupture of the membranes","volume":"101","author":"BM Mercer","year":"2003","journal-title":"Obstet Gynecol"},{"issue":"4","key":"pone.0244720.ref004","doi-asserted-by":"crossref","first-page":"1007","DOI":"10.1097\/01.AOG.0000263888.69178.1f","article-title":"ACOG Practice Bulletin No. 80: premature rupture of membranes. 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