{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T11:31:26Z","timestamp":1790163086238,"version":"4.1.0"},"reference-count":49,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2023,4,28]],"date-time":"2023-04-28T00:00:00Z","timestamp":1682640000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Preterm premature rupture of membranes, leading to preterm birth, is associated with neonatal and maternal morbidity and mortality. The study aimed to review the existing data on the best predictive value of pregnancy latency for known biomarkers in pregnancies after preterm premature rupture of membranes. The following databases were screened for the purposes of this systematic review: Pubmed\/MEDLINE, Web of Science, EMBASE, Scopus, and the Cochrane Library. The study was conducted according to the PRISMA guidelines for systematic reviews. Only a few studies assessed biomarkers predicting pregnancy duration after PPROM. IL-6, IL-8, CRP, IL1RA, s-endoglin, \u03b2hCG, AFP, PCT, urea, creatinine, oxygen radical absorbance capacity, MDA, lipocalin-2, endotoxin activity, MMP-8, MMP-9 and S100 A8\/A9 were found to have a positive predictive value for delivery timing prediction. Proinflammatory biomarkers, such as IL-6 or CRP, proved to be best correlated with delivery timing, independent of the occurrence of intrauterine infection.<\/jats:p>","DOI":"10.3390\/ijms24098027","type":"journal-article","created":{"date-parts":[[2023,4,28]],"date-time":"2023-04-28T10:51:52Z","timestamp":1682679112000},"page":"8027","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Biomarkers for Pregnancy Latency Prediction after Preterm Premature Rupture of Membranes\u2013A Systematic Review"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7746-8443","authenticated-orcid":false,"given":"Stepan","family":"Feduniw","sequence":"first","affiliation":[{"name":"Department of Gynecology, University Z\u00fcrich, Frauenklinikstrasse 10, 8091 Z\u00fcrich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2140-9732","authenticated-orcid":false,"given":"Michal","family":"Pruc","sequence":"additional","affiliation":[{"name":"Research Unit, Polish Society of Disaster Medicine, 05-806 Warsaw, Poland"},{"name":"Department of Public Health, International Academy of Ecology and Medicine, 02091 Kyiv, Ukraine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5780-5983","authenticated-orcid":false,"given":"Michal","family":"Ciebiera","sequence":"additional","affiliation":[{"name":"Second Department of Obstetrics and Gynecology, Centre of Postgraduate Medical Education, Inflancka 6, 00-189 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalia","family":"Zeber-Lubecka","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Hepatology and Clinical Oncology, Centre of Postgraduate Medical Education, Roentgena 5, 02-781 Warsaw, Poland"},{"name":"Department of Genetics, Maria Sklodowska-Curie National Research Institute of Oncology, 00-001 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diana","family":"Massalska","sequence":"additional","affiliation":[{"name":"Second Department of Obstetrics and Gynecology, Centre of Postgraduate Medical Education, Inflancka 6, 00-189 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magdalena","family":"Zgliczynska","sequence":"additional","affiliation":[{"name":"Department of Obstetrics, Perinatology and Neonatology, Centre of Postgraduate Medical Education, 01-813 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0893-1881","authenticated-orcid":false,"given":"Agnieszka","family":"Pawlowska","sequence":"additional","affiliation":[{"name":"Student Scientific Circle of Gynecology and Obstetrics \u201c\u017belazna\u201d, Warsaw Medical University, \u017bwirki i Wigury 61, 02-091 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0973-5455","authenticated-orcid":false,"given":"Lukasz","family":"Szarpak","sequence":"additional","affiliation":[{"name":"Henry JN Taub Department of Emergency Medicine, Baylor College of Medicine, Houston, TX 77030, USA"},{"name":"Institute of Outcomes Research, Maria Sklodowska-Curie Medical Academy, 00-136 Warsaw, Poland"},{"name":"Research Institute, Maria Sklodowska-Curie Bialystok Oncology Center, 15-027 Bialystok, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,4,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1111\/j.1471-0528.2005.00575.x","article-title":"The Epidemiology of Preterm Labour","volume":"112","author":"Steer","year":"2005","journal-title":"BJOG Int. J. Obstet. Gynaecol."},{"key":"ref_2","doi-asserted-by":"crossref","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":"ref_3","doi-asserted-by":"crossref","first-page":"2463","DOI":"10.1080\/14767058.2017.1344963","article-title":"US Trends in Abortion and Preterm Birth","volume":"31","author":"Saccone","year":"2018","journal-title":"J. Matern. Fetal Neonatal. Med."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Pedrini, L., Prefumo, F., Frusca, T., and Ghilardi, A. (2017). Counselling about the Risk of Preterm Delivery: A Systematic Review. Biomed. Res. Int., 2017.","DOI":"10.1155\/2017\/7320583"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1111\/1471-0528.14906","article-title":"Risk of Stillbirth, Preterm Delivery, and Fetal Growth Restriction Following Exposure in a Previous Birth: Systematic Review and Meta-Analysis","volume":"125","author":"Malacova","year":"2018","journal-title":"BJOG"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Feduniw, S., Gaca, Z., Malinowska, O., Brunets, W., Zgliczy\u0144ska, M., W\u0142odarczyk, M., W\u00f3jcikiewicz, A., and Ciebiera, M. (2022). The Management of Pregnancy Complicated with the Previable Preterm and Preterm Premature Rupture of the Membranes: What about a Limit of Neonatal Viability?\u2014A Review. Diagnostics, 12.","DOI":"10.3390\/diagnostics12082025"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1515\/jpm-2019-0163","article-title":"Preterm Premature Rupture of Membranes (PPROM)","volume":"47","author":"Skupski","year":"2019","journal-title":"J. Perinat. Med."},{"key":"ref_8","unstructured":"WHO (2015). WHO Recommendations on Interventions to Improve Preterm Birth Outcomes, WHO."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1097\/01.AOG.0000128172.71408.a0","article-title":"Preterm Premature Rupture of Membranes, Intrauterine Infection, and Oligohydramnios: Risk Factors for Placental Abruption","volume":"104","author":"Ananth","year":"2004","journal-title":"Obstet. Gynecol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1016\/S1701-2163(16)30711-3","article-title":"Prevalence, Management, and Outcomes of Preterm Prelabour Rupture of the Membranes of Women in Canada","volume":"27","author":"Smith","year":"2005","journal-title":"J. Obstet. Gynaecol. Can."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1216","DOI":"10.1016\/S0002-9378(99)70111-0","article-title":"The Preterm Prediction Study: Effect of Gestational Age and Cause of Preterm Birth on Subsequent Obstetric Outcome. National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network","volume":"181","author":"Mercer","year":"1999","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_12","first-page":"759","article-title":"Analysis of Cell-Cell Junctions in Human Amnion and Chorionic Plate Affected by Chorioamnionitis","volume":"31","author":"Licini","year":"2016","journal-title":"Histol. Histopathol."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Raba, G., and Tabarkiewicz, J. (2018). Cytokines in Preterm Delivery: Proposal of a New Diagnostic Algorithm. J. Immunol. Res., 2018.","DOI":"10.1155\/2018\/8073476"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1016\/j.ajog.2004.10.625","article-title":"Perinatal Outcomes in Women with Preterm Rupture of Membranes between 24 and 32 Weeks of Gestation and a History of Vaginal Bleeding","volume":"193","author":"Hnat","year":"2005","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"935","DOI":"10.1097\/AOG.0b013e3181da8d38","article-title":"First-Trimester Vaginal Bleeding and Complications Later in Pregnancy","volume":"115","author":"Lykke","year":"2010","journal-title":"Obstet. Gynecol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1097\/00001648-199805000-00011","article-title":"Risk Factors for Preterm Birth Subtypes","volume":"9","author":"Berkowitz","year":"1998","journal-title":"Epidemiology"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"574","DOI":"10.26574\/maedica.2021.16.4.574","article-title":"The Influence of Educational, Environmental and Social Factors in the Decision to Attend Prenatal Lectures among Pregnant Women in Romania","volume":"16","author":"Balasoiu","year":"2021","journal-title":"Maedica"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"3142","DOI":"10.3109\/14767058.2015.1115477","article-title":"Evaluation of Risk Factors Can Help to Predict Preterm Delivery within 7 Days in Women Hospitalized for Threatened Preterm Labour","volume":"29","author":"Raba","year":"2016","journal-title":"J. Matern. -Fetal Neonatal Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"622","DOI":"10.1111\/j.0001-6349.2004.00343.x","article-title":"Significance of Detecting Insulin-like Growth Factor Binding Protein-1 in Cervicovaginal Secretions: Comparison with Nitrazine Test and Amniotic Fluid Volume Assessment","volume":"83","author":"Erdemoglu","year":"2004","journal-title":"Acta Obstet. Gynecol. Scand."},{"key":"ref_20","first-page":"16","article-title":"Comparative Diagnosis of Premature Rupture of Membrane by Nitrazine Test, Urea, and Creatinine Estimation","volume":"15","author":"Olarinoye","year":"2021","journal-title":"Int. J. Health Sci."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1007\/s10654-010-9491-z","article-title":"Critical Evaluation of the Newcastle-Ottawa Scale for the Assessment of the Quality of Nonrandomized Studies in Meta-Analyses","volume":"25","author":"Stang","year":"2010","journal-title":"Eur. J. Epidemiol."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Kim, H.J., Park, K.H., Kim, Y.M., Joo, E., Ahn, K., and Shin, S. (2020). 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. PLoS ONE, 15.","DOI":"10.1371\/journal.pone.0244720"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"3473","DOI":"10.1080\/14767058.2018.1465560","article-title":"Maternal Blood Endotoxin Activity in Pregnancies Complicated by Preterm Premature Rupture of Membranes","volume":"32","author":"Ronzoni","year":"2019","journal-title":"J. Matern. -Fetal Neonatal Med."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1266","DOI":"10.1177\/1933719118815590","article-title":"Cytokine Changes in Maternal Peripheral Blood Correlate With Time-to-Delivery in Pregnancies Complicated by Premature Prelabor Rupture of the Membranes","volume":"26","author":"Ronzoni","year":"2019","journal-title":"Reprod. Sci."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1002\/ijgo.12024","article-title":"Maternal C-Reactive Protein and Oxidative Stress Markers as Predictors of Delivery Latency in Patients Experiencing Preterm Premature Rupture of Membranes","volume":"136","author":"Ryu","year":"2017","journal-title":"Int. J. Gynecol. Obstet."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"772","DOI":"10.1080\/14767058.2016.1188072","article-title":"Use of Urea and Creatinine Levels in Vaginal Fluid for the Diagnosis of Preterm Premature Rupture of Membranes and Delivery Interval after Membrane Rupture","volume":"30","author":"Gezer","year":"2017","journal-title":"J. Matern. -Fetal Neonatal Med."},{"key":"ref_27","first-page":"1957","article-title":"Maternal Serum Concentrations of S-Endoglin and IL-6 in Pregnancy Complicated by Preterm Premature Membrane Rupture","volume":"29","author":"Zafer","year":"2016","journal-title":"J. Matern. Fetal Neonatal Med."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1070","DOI":"10.18203\/2320-1770.ijrcog20150429","article-title":"Comparative Analysis of Four Biomarkers in Diagnosing Premature Rupture of Membranes and Their Correlation with Onset of Labour","volume":"4","author":"Tigga","year":"2015","journal-title":"Int. J. Reprod. Contracept. Obstet. Gynecol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1079","DOI":"10.1002\/pd.2614","article-title":"Matrix Metalloproteinase-8 in Cervical Fluid in Early and Mid Pregnancy: Relation to Spontaneous Preterm Delivery","volume":"30","author":"Rahkonen","year":"2010","journal-title":"Prenat. Diagn."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1530\/REP-15-0211","article-title":"Role of the Endocannabinoid System in the Mechanisms Involved in the LPS-Induced Preterm Labor","volume":"150","author":"Bariani","year":"2015","journal-title":"Reproduction"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"e152","DOI":"10.1111\/1471-0528.15803","article-title":"Care of Women Presenting with Suspected Preterm Prelabour Rupture of Membranes from 24+0 Weeks of Gestation","volume":"126","author":"Thomson","year":"2019","journal-title":"BJOG: Int. J. Obstet. Gynaecol."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Bond, D.M., Middleton, P., Levett, K.M., van der Ham, D.P., Crowther, C.A., Buchanan, S.L., and Morris, J. (2017). Planned Early Birth versus Expectant Management for Women with Preterm Prelabour Rupture of Membranes Prior to 37 Weeks\u2019 Gestation for Improving Pregnancy Outcome. Cochrane Database Syst. Rev., 3.","DOI":"10.1002\/14651858.CD004735.pub4"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.ejogrb.2018.05.043","article-title":"Validation of Diagnostic Tests for Histologic Chorioamnionitis: Systematic Review and Meta-Analysis","volume":"228","author":"Fonseca","year":"2018","journal-title":"Eur. J. Obstet. Gynecol. Reprod. Biol."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Shi, H., Sun, L., Wang, Z., Zhang, A., Cao, H., Zhao, W., Wang, H., Yang, X., and Li, J. (2022). Non-invasive Prediction of Histologic Chorioamnionitis Using Maternal Serum Markers in Women with Preterm Prelabour Rupture of Membranes. Am. J. Rep. Immunol., 88.","DOI":"10.1111\/aji.13594"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1016\/j.ejogrb.2016.08.022","article-title":"Accuracy of Several Maternal Seric Markers for Predicting Histological Chorioamnionitis after Preterm Premature Rupture of Membranes: A Prospective and Multicentric Study","volume":"205","author":"Caloone","year":"2016","journal-title":"Eur. J. Obstet. Gynecol. Reprod. Biol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1159\/000488080","article-title":"Maternal Serum Interleukin-6: A Non-Invasive Predictor of Histological Chorioamnionitis in Women with Preterm-Prelabor Rupture of Membranes","volume":"45","year":"2019","journal-title":"Fetal Diagn. Ther."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1476","DOI":"10.1177\/1933719119828043","article-title":"Antibody Microarray Analysis of Plasma Proteins for the Prediction of Histologic Chorioamnionitis in Women With Preterm Premature Rupture of Membranes","volume":"26","author":"Park","year":"2019","journal-title":"Reprod. Sci."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1428","DOI":"10.3109\/14767058.2011.638952","article-title":"Maternal Serum Interleukin-6 and Its Association with Clinicopathological Infectious Morbidity in Preterm Premature Rupture of Membranes: A Prospective Cohort Study","volume":"25","author":"Gulati","year":"2012","journal-title":"J. Matern. Fetal Neonatal Med."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"385.e1","DOI":"10.1016\/j.ajog.2014.03.069","article-title":"Bedside Assessment of Amniotic Fluid Interleukin-6 in Preterm Prelabor Rupture of Membranes","volume":"210","author":"Kacerovsky","year":"2014","journal-title":"AJOG"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"392","DOI":"10.3109\/14767058.2014.917625","article-title":"Vaginal Fluid IL-6 and IL-8 Levels in Pregnancies Complicated by Preterm Prelabor Membrane Ruptures","volume":"28","author":"Kacerovsky","year":"2015","journal-title":"J. Matern. Fetal Neonatal. Med."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1995","DOI":"10.3109\/14767058.2012.666592","article-title":"A Prediction Model of Histological Chorioamnionitis and Funisitis in Preterm Prelabor Rupture of Membranes: Analyses of Multiple Proteins in the Amniotic Fluid","volume":"25","author":"Cobo","year":"2012","journal-title":"J. Matern. Fetal Neonatal Med."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1159\/000499482","article-title":"Pentraxin 3 in Noninvasively Obtained Cervical Fluid Samples from Pregnancies Complicated by Preterm Prelabor Rupture of Membranes","volume":"46","author":"Janku","year":"2019","journal-title":"Fetal Diagn. Ther."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Musilova, I., Andrys, C., Krejsek, J., Drahosova, M., Zednikova, B., Pliskova, L., Zemlickova, H., Jacobsson, B., and Kacerovsky, M. (2017). Amniotic Fluid Pentraxins: Potential Early Markers for Identifying Intra-Amniotic Inflammatory Complications in Preterm Pre-Labor Rupture of Membranes. Am. J. Reprod. Immunol., 79.","DOI":"10.1111\/aji.12789"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"e279","DOI":"10.3346\/jkms.2021.36.e279","article-title":"Maternal Plasma and Amniotic Fluid LBP, Pentraxin 3, Resistin, and IGFBP-3: Biomarkers of Microbial Invasion of Amniotic Cavity and\/or Intra-Amniotic Inflammation in Women with Preterm Premature Rupture of Membranes","volume":"36","author":"Joo","year":"2021","journal-title":"J. Korean Med. Sci."},{"key":"ref_45","first-page":"345","article-title":"Prediction of Preterm Birth","volume":"65","author":"Borg","year":"2013","journal-title":"Minerva Ginecol."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Zhou, S., Mei, L., Zhou, W., Yang, Y., Zhang, X., Mu, X., Quan, Q., and Wang, L. (2022). Clinical Factors and Perinatal Outcomes Associated With Short Latency Period in Twin Pregnancies With Preterm Premature Rupture of Membranes Before 34 Weeks: A Retrospective Study. Front. Med., 9.","DOI":"10.3389\/fmed.2022.839240"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Feduniw, S., Golik, D., Kajdy, A., Pruc, M., Modzelewski, J., Sys, D., Kwiatkowski, S., Makomaska-Szaroszyk, E., and Rabijewski, M. (2022). Application of Artificial Intelligence in Screening for Adverse Perinatal Outcomes\u2014A Systematic Review. Healthcare, 10.","DOI":"10.3390\/healthcare10112164"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1016\/j.jclinepi.2021.03.001","article-title":"The PRISMA 2020 Statement: An Updated Guideline for Reporting Systematic Reviews","volume":"134","author":"Page","year":"2021","journal-title":"J. Clin. Epidemiol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"359","DOI":"10.2147\/CLEP.S66677","article-title":"Quality Assessment of Observational Studies in a Drug-Safety Systematic Review, Comparison of Two Tools: The Newcastle-Ottawa Scale and the RTI Item Bank","volume":"6","author":"Margulis","year":"2014","journal-title":"Clin. Epidemiol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/9\/8027\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T19:25:52Z","timestamp":1760124352000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/9\/8027"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,4,28]]},"references-count":49,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2023,5]]}},"alternative-id":["ijms24098027"],"URL":"https:\/\/doi.org\/10.3390\/ijms24098027","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,4,28]]}}}