Immune biomarkers in maternal plasma to identify histologic chorioamnionitis in women with preterm labor

  • Jeong Woo Park
  • Kyo Hoon ParkEmail author
  • Song Yi Kook
  • Young Mi Jung
  • Yu Mi Kim
Maternal-Fetal Medicine



To determine whether various selected immune-related proteins in maternal plasma, alone or in combination, can predict histologic chorioamnionitis (HCA) in women with preterm labor, and to compare the predictive abilities of these biomarkers with that of serum C-reactive protein (CRP).


This retrospective cohort study included 74 consecutive women with preterm labor (23–34 gestational weeks) who delivered within 96 h of blood sampling. Their serum CRP levels were also measured. The stored maternal plasma was assayed for interleukin (IL)-6, matrix metalloproteinase (MMP)-9, tissue inhibitor of metalloproteinases (TIMP)-1, angiopoietin-2, S100 A8/A9, CXCL14, APRIL, and insulin-like growth factor-binding protein-2 (IGFBP-2), using ELISA kits. The primary outcome measure was HCA.


HCA was detected in 59.4% (44/74) of women. Women with HCA had a significantly lower median gestational age at sampling and plasma IGFBP-2 level, and higher median plasma IL-6 and S100 A8/A9 levels than those without HCA. In multivariable analysis, high plasma IL-6 and low plasma IGFBP-2 levels were independently associated with the occurrence of HCA. However, the sensitivities, specificities, and areas under the curve of plasma IL-6, S100 A8/A9, and IGFBP-2, alone or in combination, were similar to or lower than those of serum CRP, for detecting HCA.


Our data suggest that plasma IL-6, S100 A8/A9, and IGFBP-2 could be potential novel biomarkers for predicting HCA in women with PTL; however, elevated plasma levels of these biomarkers, alone or in combination, do not predict HCA better than serum CRP.


C-reactive protein Histologic chorioamnionitis Insulin-like growth factor-binding protein-2 Interleukin-6 Plasma Preterm labor 



This study was supported by a grant from the Korea Health Technology R&D Project, Ministry of Health and Welfare, Republic of Korea (Grant no. HI 14C1798).

Author contributions

JWP: protocol/project development, data analysis, and manuscript writing/editing. KHP: conceptualization, protocol/project development, supervision, funding acquisition, data analysis, and manuscript writing/editing. SYK: data collection or management and data analysis. YMJ: data collection or management and data analysis. YMK: data collection or management, data analysis, and ELISA assay.

Compliance with ethical standards

Conflict of interest

The authors report no conflict of interest.


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Obstetrics and GynecologySeoul National University College of Medicine, Seoul National University Bundang HospitalSeongnamsiKorea
  2. 2.Center for High Risk Pregnancy and NeonateSeoul National University Bundang HospitalSeongnamsiKorea

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