A Rapid Amniotic Fluid Interleukin-6 Assessment for the Identification of Intra-Amniotic Inflammation in Women with Preterm Labor and Intact Membranes

Objectives: A multivariable predictive model has recently been developed with good accuracy to predict spontaneous preterm delivery within 7 days in women with preterm labor (PTL) and intact membranes. However, this model measures amniotic fluid (AF) interleukin (IL)-6 concentrations using the ELISA method, thereby limiting clinical implementation. The main objectives of this study were to validate the automated immunoassay as a quantitative method to measure AF IL-6 in women with PTL and to evaluate the diagnostic performance of AF IL-6 alone and as part of a multivariable predictive model to predict spontaneous delivery in 7 days with this automated method. Study Design: This is a retrospective observational study in women with PTL below 34 weeks who underwent amniocentesis to rule out microbial invasion of the amniotic cavity. Women with clinical signs of chorioamnionitis, cervical length measurement at admission >5th centile, maternal age <18 years, and no consent to perform amniocentesis for this indication were excluded. The local Institutional Review Boards approved the study (HCB/2019/0940). Analysis of AF IL-6 Concentrations: AF IL-6 concentrations were measured using an automated Cobas e602 electrochemiluminescence immunoanalyzer and Human IL-6 Quantikine ELISA kit. Results: Of the entire study group (n = 100), 38 women spontaneously delivered within 7 days after admission. Both laboratory methods showed good agreement (intraclass correlation coefficient: 0.937 (95% confidence interval [CI] 0.908–0.957); p < 0.001). Diagnostic performance of AF IL-6 to predict spontaneous delivery within 7 days when it was included in the multivariable predictive model showed an area under the receiver operating characteristic curve of 0.894 (95% CI 0.799–0.955), sensitivity of 97%, specificity of 74%, positive predictive value of 73%, negative predictive value of 97%, positive likelihood ratio (LR) of 3.7, and negative LR of 0.045. Conclusion: While both analytical methods were comparable for measuring AF IL-6 concentrations in women with PTL, the Cobas immunoanalyzer provided rapid diagnosis of intra-amniotic inflammation within minutes. The predictive model showed a good diagnostic performance to target women at high risk of spontaneous delivery within 7 days.

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Amniotic Fluid Infection in Preterm Pregnancies with Intact Membranes

Disease Markers ◽

10.1155/2017/8167276 ◽

2017 ◽

Vol 2017 ◽

pp. 1-9 ◽

Cited By ~ 8

Author(s):

Tarja Myntti ◽

Leena Rahkonen ◽

Irmeli Nupponen ◽

Anu Pätäri-Sampo ◽

Minna Tikkanen ◽

...

Keyword(s):

Amniotic Fluid ◽

Preterm Labor ◽

Molar Ratio ◽

Amniotic Cavity ◽

Culture Techniques ◽

Reactive Protein ◽

Molecular Microbiology ◽

Microbial Invasion ◽

Proteolytic Cascade ◽

Singleton Pregnancies

Introduction. Intra-amniotic infection (IAI) is a major cause of preterm labor and adverse neonatal outcome. We evaluated amniotic fluid (AF) proteolytic cascade forming biomarkers in relation to microbial invasion of the amniotic cavity (MIAC) and IAI in preterm pregnancies with intact membranes. Material and Methods. Amniocentesis was made to 73 women with singleton pregnancies; 27 with suspected IAI; and 46 controls. AF biomarkers were divided into three cascades: Cascade 1: matrix metalloproteinase-8 (MMP-8), MMP-9, myeloperoxidase (MPO), and interleukin-6; Cascade 2: neutrophil elastase (HNE), elafin, and MMP-9; Cascade 3: MMP-2, tissue inhibitor of matrix metalloproteinases-1 (TIMP-1), MMP-8/TIMP-1 molar ratio, and C-reactive protein (CRP). MMP-8 was measured by an immunoenzymometric assay and the others were measured by ELISA. Standard biochemical methods, molecular microbiology, and culture techniques were used. Results. MMP-8, MMP-9, MPO, elafin, and TIMP-1 concentrations were higher in IAI suspected cases compared to controls and also in IAI suspected cases with MIAC compared to those without MIAC when adjusted by gestational age at amniocentesis. All biomarkers except elafin and MMP-2 had the sensitivity of 100% with thresholds based on ROC-curve. Odd ratios of biomarkers for MIAC were 1.2-38 and 95% confidential intervals 1.0-353.6. Conclusions. Neutrophil based AF biomarkers were associated with IAI and MIAC.

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A comparative study of the diagnostic performance of amniotic fluid glucose, white blood cell count, interleukin-6, and Gram stain in the detection of microbial invasion in patients with preterm premature rupture of membranes

American Journal of Obstetrics and Gynecology ◽

10.1016/0002-9378(93)90014-a ◽

1993 ◽

Vol 169 (4) ◽

pp. 839-851 ◽

Cited By ~ 288

Author(s):

Roberto Romero ◽

Bo Hyun Yoon ◽

Moshe Mazor ◽

Ricardo Gomez ◽

Rogelio Gonzalez ◽

...

Keyword(s):

Blood Cell ◽

Amniotic Fluid ◽

Interleukin 6 ◽

Diagnostic Performance ◽

Gram Stain ◽

Blood Cell Count ◽

Premature Rupture Of Membranes ◽

Premature Rupture ◽

Preterm Premature Rupture ◽

Microbial Invasion

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The diagnostic performance of the Mass Restricted (MR) score in the identification of microbial invasion of the amniotic cavity or intra-amniotic inflammation is not superior to amniotic fluid interleukin-6

The Journal of Maternal-Fetal & Neonatal Medicine ◽

10.3109/14767058.2013.844123 ◽

2013 ◽

Vol 27 (8) ◽

pp. 757-769 ◽

Cited By ~ 28

Author(s):

Roberto Romero ◽

Nicholas Kadar ◽

Jezid Miranda ◽

Steven J. Korzeniewski ◽

Alyse G. Schwartz ◽

...

Keyword(s):

Amniotic Fluid ◽

Interleukin 6 ◽

Diagnostic Performance ◽

Amniotic Cavity ◽

Microbial Invasion

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Interleukin-6 and interleukin-8 in cervical fluid in a population of Swedish women in preterm labor: relationship to microbial invasion of the amniotic fluid, intra-amniotic inflammation, and preterm delivery

Acta Obstetricia Et Gynecologica Scandinavica ◽

10.1111/j.0001-6349.2005.00708.x ◽

2005 ◽

Vol 84 (6) ◽

pp. 551-557 ◽

Cited By ~ 58

Author(s):

Rose-Marie Holst ◽

Inger Mattsby-Baltzer ◽

Ulla-Britt Wennerholm ◽

Henrik Hagberg ◽

Bo Jacobsson

Keyword(s):

Amniotic Fluid ◽

Preterm Delivery ◽

Interleukin 6 ◽

Preterm Labor ◽

Interleukin 8 ◽

Microbial Invasion ◽

Labor Relationship

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Predictive value of combined amniotic fluid proteomic biomarkers and interleukin-6 in preterm labor with intact membranes

American Journal of Obstetrics and Gynecology ◽

10.1016/j.ajog.2008.12.036 ◽

2009 ◽

Vol 200 (5) ◽

pp. 499.e1-499.e6 ◽

Cited By ~ 37

Author(s):

Teresa Cobo ◽

Montse Palacio ◽

Aleix Navarro-Sastre ◽

Antonia Ribes ◽

Jordi Bosch ◽

...

Keyword(s):

Amniotic Fluid ◽

Interleukin 6 ◽

Predictive Value ◽

Preterm Labor

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Antimicrobial peptides in amniotic fluid: defensins, calprotectin and bacterial/permeability-increasing protein in patients with microbial invasion of the amniotic cavity, intra-amniotic inflammation, preterm labor and premature rupture of membranes

The Journal of Maternal-Fetal & Neonatal Medicine ◽

10.1080/jmf.13.1.2.21 ◽

2003 ◽

Vol 13 (1) ◽

pp. 2-21 ◽

Cited By ~ 111

Author(s):

J. Espinoza ◽

T. Chaiworapongsa ◽

R. Romero ◽

S. Edwin ◽

C. Rathnasabapathy ◽

...

Keyword(s):

Antimicrobial Peptides ◽

Amniotic Fluid ◽

Preterm Labor ◽

Premature Rupture Of Membranes ◽

Premature Rupture ◽

Amniotic Cavity ◽

Microbial Invasion

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IgGFc-binding protein in pregnancies complicated by spontaneous preterm delivery: a retrospective cohort study

Scientific Reports ◽

10.1038/s41598-021-85473-2 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Jaroslav Stranik ◽

Marian Kacerovsky ◽

Ondrej Soucek ◽

Martina Kolackova ◽

Ivana Musilova ◽

...

Keyword(s):

Amniotic Fluid ◽

Preterm Labor ◽

Operating Characteristic ◽

Binding Protein ◽

Characteristic Curve ◽

Enzyme Linked Immunosorbent Assay ◽

Amniotic Cavity ◽

Spontaneous Preterm Delivery ◽

Microbial Invasion ◽

Prelabor Rupture Of Membranes

AbstractTo determine the IgGFc-binding protein (FcgammaBP) concentration in amniotic and cervical fluids in preterm prelabor rupture of membranes (PPROM) and preterm labor with intact membranes (PTL) and to assess the diagnostic indices of FcgammaBP to predict intra-amniotic infection (the presence of both microbial invasion of the amniotic cavity and intra-amniotic inflammation). In this study, we included 170 and 79 women with PPROM and PTL, respectively. Paired cervical and amniotic fluid samples were obtained using a Dacron polyester swab and transabdominal amniocentesis, respectively. The FcgammaBP concentrations in the samples were assessed using an enzyme-linked immunosorbent assay. The presence of intra-amniotic infection was associated with elevated FcgammaBP concentrations in pregnancies with PPROM and PTL [PPROM—presence: 86 ng/mL vs. absence: 13 ng/mL, p < 0.0001, area under receiver operating characteristic curve (AUC) = 0.94; PTL—presence: 140 ng/mL vs. absence: 22 ng/mL, p < 0.0001, AUC = 0.86]. In cervical fluid, the concentrations of FcgammaBP were elevated in the presence of intra-amniotic infection in pregnancies with PPROM only (presence: 345 ng/mL vs. absence: 60 ng/mL, p < 0.0001, AUC = 0.93). FcgammaBP in amniotic fluid might be a marker of intra-amniotic infection in women with both PPROM and PTL However, in cervical fluid, it is only observed in women with PPROM.

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