The Impact of Amniotic Fluid Interleukin-6, Interleukin-8, and Metalloproteinase-9 on Preterm Labor: A Narrative Review

Background/objectives: Preterm labor is a leading cause of neonatal morbidity and mortality worldwide. Previous research has indicated that an inflammatory response or microbial invasion of the amniotic cavity is a pathological condition linked to preterm birth; hence, inflammatory markers such as m...

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Main Authors: Theodoros Karampitsakos, Despoina Mavrogianni, Nikolaos Machairiotis, Anastasios Potiris, Periklis Panagopoulos, Sofoklis Stavros, Panos Antsaklis, Peter Drakakis
Format: Article
Language:English
Published: MDPI AG 2025-01-01
Series:Biomedicines
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Online Access:https://www.mdpi.com/2227-9059/13/1/118
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author Theodoros Karampitsakos
Despoina Mavrogianni
Nikolaos Machairiotis
Anastasios Potiris
Periklis Panagopoulos
Sofoklis Stavros
Panos Antsaklis
Peter Drakakis
author_facet Theodoros Karampitsakos
Despoina Mavrogianni
Nikolaos Machairiotis
Anastasios Potiris
Periklis Panagopoulos
Sofoklis Stavros
Panos Antsaklis
Peter Drakakis
author_sort Theodoros Karampitsakos
collection DOAJ
description Background/objectives: Preterm labor is a leading cause of neonatal morbidity and mortality worldwide. Previous research has indicated that an inflammatory response or microbial invasion of the amniotic cavity is a pathological condition linked to preterm birth; hence, inflammatory markers such as metalloproteinase-9 (MMP-9), interleukin-6 (IL-6), and interleukin-8 (IL-8) have been utilized to predict preterm delivery. The identification of reliable biomarkers for early prediction is critical for improving maternal, fetal, and neonatal outcomes. Methods: To address this issue, a literature review has been conducted on PubMed/Medline and Scopus databases for articles investigating the possible correlation between IL6, IL8, and MMP9 and preterm labor. Results: Using a comprehensive search of the PubMed and Scopus databases, 12 studies were analyzed to identify the correlation between these biomarkers and preterm labor. Seven studies point the impact of increased IL-6 levels or polymorphisms of the gene and higher incidence of preterm labor. Two of the included studies identified the increased risk for preterm birth in elevated levels of IL-8 in amniotic fluid. Six studies highlight the increased incidence of preterm birth in women with polymorphisms of the MMP-9 gene. Conclusions: Elevated IL-6 levels and specific gene polymorphisms are strongly associated with preterm delivery risk, with IL-8 concentrations correlating with systemic inflammation and histologic chorioamnionitis. MMP-9 gene variations and protein levels showed significant predictive value for membrane rupture and labor onset. The findings emphasize integrating these biomarkers into diagnostic tools for routine prenatal care, enhancing early detection, risk stratification, and timely interventions to improve maternal and neonatal outcomes.
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spelling doaj-art-7d419a837f934462abaa1b6511fc03222025-01-24T13:24:04ZengMDPI AGBiomedicines2227-90592025-01-0113111810.3390/biomedicines13010118The Impact of Amniotic Fluid Interleukin-6, Interleukin-8, and Metalloproteinase-9 on Preterm Labor: A Narrative ReviewTheodoros Karampitsakos0Despoina Mavrogianni1Nikolaos Machairiotis2Anastasios Potiris3Periklis Panagopoulos4Sofoklis Stavros5Panos Antsaklis6Peter Drakakis7Third Department of Obstetrics and Gynecology, University General Hospital “ATTIKON”, Medical School, National and Kapodistrian University of Athens, 124 62 Athens, GreeceFirst Department of Obstetrics and Gynecology, Alexandra Hospital, Medical School, National and Kapodistrian University of Athens, 115 28 Athens, GreeceThird Department of Obstetrics and Gynecology, University General Hospital “ATTIKON”, Medical School, National and Kapodistrian University of Athens, 124 62 Athens, GreeceThird Department of Obstetrics and Gynecology, University General Hospital “ATTIKON”, Medical School, National and Kapodistrian University of Athens, 124 62 Athens, GreeceThird Department of Obstetrics and Gynecology, University General Hospital “ATTIKON”, Medical School, National and Kapodistrian University of Athens, 124 62 Athens, GreeceThird Department of Obstetrics and Gynecology, University General Hospital “ATTIKON”, Medical School, National and Kapodistrian University of Athens, 124 62 Athens, GreeceFirst Department of Obstetrics and Gynecology, Alexandra Hospital, Medical School, National and Kapodistrian University of Athens, 115 28 Athens, GreeceThird Department of Obstetrics and Gynecology, University General Hospital “ATTIKON”, Medical School, National and Kapodistrian University of Athens, 124 62 Athens, GreeceBackground/objectives: Preterm labor is a leading cause of neonatal morbidity and mortality worldwide. Previous research has indicated that an inflammatory response or microbial invasion of the amniotic cavity is a pathological condition linked to preterm birth; hence, inflammatory markers such as metalloproteinase-9 (MMP-9), interleukin-6 (IL-6), and interleukin-8 (IL-8) have been utilized to predict preterm delivery. The identification of reliable biomarkers for early prediction is critical for improving maternal, fetal, and neonatal outcomes. Methods: To address this issue, a literature review has been conducted on PubMed/Medline and Scopus databases for articles investigating the possible correlation between IL6, IL8, and MMP9 and preterm labor. Results: Using a comprehensive search of the PubMed and Scopus databases, 12 studies were analyzed to identify the correlation between these biomarkers and preterm labor. Seven studies point the impact of increased IL-6 levels or polymorphisms of the gene and higher incidence of preterm labor. Two of the included studies identified the increased risk for preterm birth in elevated levels of IL-8 in amniotic fluid. Six studies highlight the increased incidence of preterm birth in women with polymorphisms of the MMP-9 gene. Conclusions: Elevated IL-6 levels and specific gene polymorphisms are strongly associated with preterm delivery risk, with IL-8 concentrations correlating with systemic inflammation and histologic chorioamnionitis. MMP-9 gene variations and protein levels showed significant predictive value for membrane rupture and labor onset. The findings emphasize integrating these biomarkers into diagnostic tools for routine prenatal care, enhancing early detection, risk stratification, and timely interventions to improve maternal and neonatal outcomes.https://www.mdpi.com/2227-9059/13/1/118interleukin-6 (IL-6)interleukin-8 (IL-8)metalloproteinase-9 (MMP-9)preterm laboramniotic fluid
spellingShingle Theodoros Karampitsakos
Despoina Mavrogianni
Nikolaos Machairiotis
Anastasios Potiris
Periklis Panagopoulos
Sofoklis Stavros
Panos Antsaklis
Peter Drakakis
The Impact of Amniotic Fluid Interleukin-6, Interleukin-8, and Metalloproteinase-9 on Preterm Labor: A Narrative Review
Biomedicines
interleukin-6 (IL-6)
interleukin-8 (IL-8)
metalloproteinase-9 (MMP-9)
preterm labor
amniotic fluid
title The Impact of Amniotic Fluid Interleukin-6, Interleukin-8, and Metalloproteinase-9 on Preterm Labor: A Narrative Review
title_full The Impact of Amniotic Fluid Interleukin-6, Interleukin-8, and Metalloproteinase-9 on Preterm Labor: A Narrative Review
title_fullStr The Impact of Amniotic Fluid Interleukin-6, Interleukin-8, and Metalloproteinase-9 on Preterm Labor: A Narrative Review
title_full_unstemmed The Impact of Amniotic Fluid Interleukin-6, Interleukin-8, and Metalloproteinase-9 on Preterm Labor: A Narrative Review
title_short The Impact of Amniotic Fluid Interleukin-6, Interleukin-8, and Metalloproteinase-9 on Preterm Labor: A Narrative Review
title_sort impact of amniotic fluid interleukin 6 interleukin 8 and metalloproteinase 9 on preterm labor a narrative review
topic interleukin-6 (IL-6)
interleukin-8 (IL-8)
metalloproteinase-9 (MMP-9)
preterm labor
amniotic fluid
url https://www.mdpi.com/2227-9059/13/1/118
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