{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T01:33:31Z","timestamp":1785548011566,"version":"3.56.0"},"reference-count":36,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,4,4]],"date-time":"2025-04-04T00:00:00Z","timestamp":1743724800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Infect. Microbiol."],"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>The objective of this study is to explore whether metagenomic next-generation sequencing (mNGS) and Epithelial Neutrophil Activating Peptide-78 (ENA-78) assays in the amniotic fluid (AF) of patients with preterm labor (PTL) could be employed for diagnosing intra-amniotic infection\/inflammation (IAI\/I) and predict the outcomes of emergency cerclage in women with cervical insufficiency(CI).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>AF samples from 40 patients were subjected to PTL were subjected to mNGS and microbial culture to diagnose intra-amniotic infection known as microbial invasion of the amniotic cavity (MIAC); ELISA was used to analyze ENA-78 levels for prediction of intra-amniotic inflammation (IAI). Pregnancy outcomes were compared, the predictive performance of mNGS and ENA-78 were assessed to evaluate the efficacy of emergency cervical cerclage.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The diagnosis rate of MIAC was higher with mNGS (17.5%) compared to microbial culture (2.5%). AF ENA-78 levels were significantly higher in IAI patients than in non-IAI\/I patients. ENA-78 demonstrated certain accuracy in identifying IAI, with sensitivity and specificity of 73.3% and 100%, respectively. Compared with non-IAI\/I patients, patients with MIAC or IAI exhibited poor pregnancy outcomes after cervical cerclage.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>mNGS and ENA-78 assays are valuable means for assessing the state of infection\/inflammation in the amniotic cavity and predicting the outcomes of emergency cerclage.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fcimb.2025.1510671","type":"journal-article","created":{"date-parts":[[2025,4,4]],"date-time":"2025-04-04T12:16:18Z","timestamp":1743768978000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["The clinic application of mNGS and ENA-78 assays to identify intra-amniotic infection\/inflammation"],"prefix":"10.3389","volume":"15","author":[{"given":"Di","family":"Shen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Ju","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongying","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xietong","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guangzhen","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,4,4]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"265","DOI":"10.1189\/jlb.5BT0615-234R","article-title":"At the Bedside: Neutrophil extracellular traps (NETs) as targets for biomarkers and therapies in autoimmune diseases","volume":"99","author":"Barnado","year":"2016","journal-title":"J. leukocyte Biol."},{"key":"B2","doi-asserted-by":"publisher","first-page":"1532","DOI":"10.1126\/science.1092385","article-title":"Neutrophil extracellular traps kill bacteria","volume":"303","author":"Brinkmann","year":"2004","journal-title":"science"},{"key":"B3","doi-asserted-by":"publisher","first-page":"241","DOI":"10.1159\/000480232","article-title":"Noninvasive sampling of the intrauterine environment in women with preterm labor and intact membranes","volume":"43","author":"Cobo","year":"2018","journal-title":"Fetal diagnosis Ther."},{"key":"B4","doi-asserted-by":"publisher","first-page":"583","DOI":"10.1016\/j.ajog.2014.07.047","article-title":"Prediction of preterm birth in twin gestations using biophysical and biochemical tests","volume":"211","author":"Conde-Agudelo","year":"2014","journal-title":"Am. J. Obstet Gynecol"},{"key":"B5","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1111\/brv.125220","article-title":"Preterm birth prevention","volume":"69","author":"da Fonseca","year":"2020","journal-title":"Best Pract. Res. Clin. Obstetrics Gynaecology"},{"key":"B6","doi-asserted-by":"publisher","first-page":"1685","DOI":"10.1111\/brv.125220","article-title":"Root extracellular traps versus neutrophil extracellular traps in host defence, a case of functional convergence","volume":"94","author":"Driouich","year":"2019","journal-title":"Biol. Rev."},{"key":"B7","doi-asserted-by":"publisher","first-page":"177","DOI":"10.1053\/j.semperi.2014.03.002","article-title":"Prediction and prevention of ischemic placental disease","author":"Friedman","year":"2014","journal-title":"Semin. perinatology; 2014: Elsevier;"},{"key":"B8","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1155\/2015\/435014","article-title":"Predicting preterm labour: current status and future prospects","volume":"2015","author":"Georgiou","year":"2015","journal-title":"Dis. Markers"},{"key":"B9","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1016\/j.jri.2018.06.029","article-title":"Inflammation induced preterm labor and birth","volume":"129","author":"Gilman-Sachs","year":"2018","journal-title":"J. Reprod. Immunol."},{"key":"B10","doi-asserted-by":"publisher","first-page":"544","DOI":"10.1097\/OGX.0000000000001182","article-title":"Cervical cerclage: A comprehensive review of major guidelines","volume":"78","author":"Giouleka","year":"2023","journal-title":"Obstetrical Gynecological Survey"},{"key":"B11","doi-asserted-by":"publisher","first-page":"e01888","DOI":"10.1128\/mBio.01888-15","article-title":"Making the leap from research laboratory to clinic: challenges and opportunities for next-generation sequencing in infectious disease diagnostics","volume":"6","author":"Goldberg","year":"2015","journal-title":"MBio"},{"key":"B12","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1016\/S0140-6736(08)60074-4","article-title":"Epidemiology and causes of preterm birth","volume":"371","author":"Goldenberg","year":"2008","journal-title":"Lancet"},{"key":"B13","doi-asserted-by":"publisher","first-page":"R11","DOI":"10.1530\/REP-22-0046","article-title":"The immunobiology of preterm labor and birth: intra-amniotic inflammation or breakdown of maternal\u2013fetal homeostasis","volume":"164","author":"Gomez-Lopez","year":"2022","journal-title":"Reproduction"},{"key":"B14","doi-asserted-by":"publisher","first-page":"e12723","DOI":"10.1111\/aji.2017.78.issue-4","article-title":"Amniotic fluid neutrophils can phagocytize bacteria: a mechanism for microbial killing in the amniotic cavity","volume":"78","author":"Gomez-Lopez","year":"2017","journal-title":"Am. J. Reprod. Immunol."},{"key":"B15","doi-asserted-by":"publisher","first-page":"1139","DOI":"10.1177\/1933719116678690","article-title":"Neutrophil extracellular traps in the amniotic cavity of women with intra-amniotic infection: a new mechanism of host defense","volume":"24","author":"Gomez-Lopez","year":"2017","journal-title":"Reprod. Sci."},{"key":"B16","doi-asserted-by":"publisher","first-page":"1325","DOI":"10.1067\/mob.2001.115119","article-title":"Does cervical cerclage prevent preterm delivery in patients with a short cervix","volume":"184","author":"Hassan","year":"2001","journal-title":"Am. J. obstetrics gynecology"},{"key":"B17","doi-asserted-by":"publisher","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":"B18","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1155\/2014\/185758","article-title":"Chemokines profiling of patients with preterm birth","volume":"2014","author":"Laudanski","year":"2014","journal-title":"Mediators Inflammation"},{"key":"B19","doi-asserted-by":"publisher","first-page":"313","DOI":"10.1159\/000514898","article-title":"Interleukin-6 in amniotic fluid: A reliable marker for adverse outcomes in women in preterm labor and intact membranes","volume":"48","author":"Lea\u00f1os-Miranda","year":"2021","journal-title":"Fetal Diagnosis Ther."},{"key":"B20","doi-asserted-by":"publisher","first-page":"633. e631","DOI":"10.1016\/j.ajog.2007.11.047","article-title":"The frequency and significance of intraamniotic inflammation in patients with cervical insufficiency","volume":"198","author":"Lee","year":"2008","journal-title":"Am. J. obstetrics gynecology"},{"key":"B21","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1080\/07853890.2016.1211789","article-title":"Early- or mid-trimester amniocentesis biomarkers for predicting preterm delivery: a meta-analysis","volume":"49","author":"Liu.","year":"2016","journal-title":"Ann. Med."},{"key":"B22","doi-asserted-by":"publisher","first-page":"R237","DOI":"10.1093\/hmg\/ddx210","article-title":"Placental biomarkers for assessing fetal health","volume":"26","author":"Manokhina","year":"2017","journal-title":"Hum. Mol. Genet."},{"key":"B23","doi-asserted-by":"publisher","first-page":"523","DOI":"10.1515\/jpm-2016-0225","article-title":"Clinical chorioamnionitis at term VII: the amniotic fluid cellular immune response","volume":"45","author":"Martinez-Varea","year":"2017","journal-title":"J. perinatal Med."},{"key":"B24","doi-asserted-by":"publisher","first-page":"652","DOI":"10.1016\/s0029-7844(99)00633-x","article-title":"Amniocentesis for selection before rescue cerclage","volume":"95","author":"Mays","year":"2000","journal-title":"Obstetrics Gynecology"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2013.00058","article-title":"Bacterial aetiological agents of intra-amniotic infections and preterm birth in pregnant women","volume":"3","author":"Mendz","year":"2013","journal-title":"Front. Cell. infection Microbiol."},{"key":"B26","doi-asserted-by":"publisher","first-page":"S231","DOI":"10.1093\/cid\/ciy693","article-title":"Microbiological diagnostic performance of metagenomic next-generation sequencing when applied to clinical practice","volume":"67","author":"Miao","year":"2018","journal-title":"Clin. Infect. Dis."},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.00454","article-title":"The red blood cell\u2014inflammation vicious circle in sickle cell disease","volume":"11","author":"Nader","year":"2020","journal-title":"Front. Immunol."},{"key":"B28","doi-asserted-by":"publisher","first-page":"261","DOI":"10.1515\/jpm.2010.040","article-title":"Detection of ureaplasmas by the polymerase chain reaction in the amniotic fluid of patients with cervical insufficiency","volume":"38","author":"Oh","year":"2010"},{"key":"B29","doi-asserted-by":"publisher","first-page":"52.e51","DOI":"10.1016\/j.ajog.2007.11.068","article-title":"Colonization of second-trimester placenta parenchyma","volume":"199","author":"Onderdonk","year":"2008","journal-title":"Am. J. Obstet Gynecol"},{"key":"B30","doi-asserted-by":"publisher","first-page":"760","DOI":"10.1126\/science.1251816","article-title":"Preterm labor: one syndrome, many causes","volume":"345","author":"Romero","year":"2014","journal-title":"Science"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1515\/jpm-2022-0604","article-title":"Are bacteria, fungi, and archaea present in the midtrimester amniotic fluid","volume":"51","author":"Romero","year":"2023","journal-title":"J Perinat Med"},{"key":"B32","doi-asserted-by":"publisher","first-page":"1086","DOI":"10.1016\/s0002-9378(12)80043-3","article-title":"Infection and labor: VIII. Microbial invasion of the amniotic cavity in patients with suspected cervical incompetence: prevalence and clinical significance","volume":"167","author":"Romero","year":"1992","journal-title":"Am. J. obstetrics gynecology"},{"key":"B33","doi-asserted-by":"publisher","first-page":"458","DOI":"10.1111\/aji.2014.72.issue-5","article-title":"Prevalence and clinical significance of sterile intra-amniotic inflammation in patients with preterm labor and intact membranes","volume":"72","author":"Romero","year":"2014","journal-title":"Am. J. Reprod. Immunol."},{"key":"B34","doi-asserted-by":"publisher","first-page":"3888","DOI":"10.4049\/jimmunol.158.8.3888","article-title":"Neutrophil-activating protein ENA-78 and IL-8 exhibit different patterns of expression in lipopolysaccharide-and cytokine-stimulated human monocytes","volume":"158","author":"Schnyder-Candrian","year":"1997","journal-title":"J. Immunol. (Baltimore Md: 1950)"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.735324","article-title":"The role of innate immune system in the human amniotic membrane and human amniotic fluid in protection against intra-amniotic infections and inflammation","volume":"12","author":"\u0160ket","year":"2021","journal-title":"Front. Immunol."},{"key":"B36","doi-asserted-by":"publisher","first-page":"L342","DOI":"10.1152\/ajplung.00151.2012","article-title":"HMGB1 promotes neutrophil extracellular trap formation through interactions with Toll-like receptor 4","volume":"304","author":"Tadie","year":"2013","journal-title":"Am. J. Physiology-Lung Cell. Mol. Physiol."}],"container-title":["Frontiers in Cellular and Infection Microbiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcimb.2025.1510671\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,4]],"date-time":"2025-04-04T12:16:21Z","timestamp":1743768981000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcimb.2025.1510671\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4,4]]},"references-count":36,"alternative-id":["10.3389\/fcimb.2025.1510671"],"URL":"https:\/\/doi.org\/10.3389\/fcimb.2025.1510671","relation":{},"ISSN":["2235-2988"],"issn-type":[{"value":"2235-2988","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,4,4]]},"article-number":"1510671"}}