Advertisement

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
  • 19 Downloads

Abstract

Purpose

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).

Methods

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.

Results

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.

Conclusions

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.

Keywords

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

Notes

Acknowledgements

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.

References

  1. 1.
    Goncalves LF, Chaiworapongsa T, Romero R (2002) Intrauterine infection and prematurity. Ment Retard Dev Disabil Res Rev 8(1):3–13CrossRefPubMedGoogle Scholar
  2. 2.
    Greig PC, Ernest JM, Teot L, Erikson M, Talley R (1993) Amniotic fluid interleukin-6 levels correlate with histologic chorioamnionitis and amniotic fluid cultures in patients in premature labor with intact membranes. Am J Obstet Gynecol 169 (4):1035–1044Google Scholar
  3. 3.
    Mueller-Heubach E, Rubinstein DN, Schwarz SS (1990) Histologic chorioamnionitis and preterm delivery in different patient populations. Obstet Gynecol 75(4):622–626PubMedGoogle Scholar
  4. 4.
    Wu YW, Colford JM Jr (2000) Chorioamnionitis as a risk factor for cerebral palsy: a meta-analysis. JAMA 284(11):1417–1424CrossRefPubMedGoogle Scholar
  5. 5.
    Yoon BH, Romero R, Kim CJ, Jun JK, Gomez R, Choi JH et al (1995) Amniotic fluid interleukin-6: a sensitive test for antenatal diagnosis of acute inflammatory lesions of preterm placenta and prediction of perinatal morbidity. Am J Obstet Gynecol 172(3):960–970CrossRefPubMedGoogle Scholar
  6. 6.
    Oh KJ, Park KH, Kim SN, Jeong EH, Lee SY, Yoon HY (2011) Predictive value of intra-amniotic and serum markers for inflammatory lesions of preterm placenta. Placenta 32(10):732–736CrossRefPubMedGoogle Scholar
  7. 7.
    Kim SA, Park KH, Lee SM (2016) Non-invasive prediction of histologic chorioamnionitis in women with preterm premature rupture of membranes. Yonsei Med J 57(2):461–468CrossRefPubMedGoogle Scholar
  8. 8.
    Miyazaki K, Furuhashi M, Ishikawa K, Tamakoshi K, Hayashi K, Kai A et al (2016) Impact of chorioamnionitis on short- and long-term outcomes in very low birth weight preterm infants: the Neonatal Research Network Japan. J Matern Fetal Neonatal Med 29(2):331–337CrossRefPubMedGoogle Scholar
  9. 9.
    Odibo AO, Rodis JF, Sanders MM, Borgida AF, Wilson M, Egan JF et al (1999) Relationship of amniotic fluid markers of intra-amniotic infection with histopathology in cases of preterm labor with intact membranes. J Perinatol 19 (6 Pt 1):407-412Google Scholar
  10. 10.
    Hillier SL, Witkin SS, Krohn MA, Watts DH, Kiviat NB, Eschenbach DA (1993) The relationship of amniotic fluid cytokines and preterm delivery, amniotic fluid infection, histologic chorioamnionitis, and chorioamnion infection. Obstet Gynecol 81(6):941–948PubMedGoogle Scholar
  11. 11.
    McNamara MF, Wallis T, Qureshi F, Jacques SM, Gonik B (1997) Determining the maternal and fetal cellular immunologic contributions in preterm deliveries with clinical or subclinical chorioamnionitis. Infect Dis Obstet Gynecol 5(4):273–279CrossRefPubMedGoogle Scholar
  12. 12.
    Skrablin S, Lovric H, Banovic V, Kralik S, Dijakovic A, Kalafatic D (2007) Maternal plasma interleukin-6, interleukin-1beta and C-reactive protein as indicators of tocolysis failure and neonatal outcome after preterm delivery. J Matern Fetal Neonatal Med 20(4):335–341CrossRefPubMedGoogle Scholar
  13. 13.
    Steinborn A, Sohn C, Scharf A, Geka F, Heger S, Kaufmann M (2000) Serum intercellular adhesion molecule-1 levels and histologic chorioamnionitis. Obstet Gynecol 95(5):671–676PubMedGoogle Scholar
  14. 14.
    Greig PC, Murtha AP, Jimmerson CJ, Herbert WN, Roitman-Johnson B, Allen J (1997) Maternal serum interleukin-6 during pregnancy and during term and preterm labor. Obstet Gynecol 90(3):465–469CrossRefPubMedGoogle Scholar
  15. 15.
    Park H, Park JW, Park KH, Kim YM, Kook SY, Jeon SJ (2017) An antibody microarray analysis of plasma proteins for the prediction of histologic chorioamnionitis in women with the preterm labor and intact membranes [abstract]. In: The 30th congress in Korean society of perinatology (abstract OB-6), 61Google Scholar
  16. 16.
    Park KH, Yoo H, Kook SY, Park H, Jeon SJ, Kim YM (2017) A comparison of immunoregulatory protein profile in plasma between women with and without histologic chorioamnionitis in preterm premature rupture of membranes. In: The 25th world congress on controversies in obstetrics gynecology and infertility (abstract P100-1095), 135Google Scholar
  17. 17.
    Lee SY, Park KH, Jeong EH, Oh KJ, Ryu A, Kim A (2013) Intra-amniotic infection/inflammation as a risk factor for subsequent ruptured membranes after clinically indicated amniocentesis in preterm labor. J Korean Med Sci 28(8):1226–1232CrossRefPubMedGoogle Scholar
  18. 18.
    Park JW, Park KH, Jung EY, Cho SH, Jang JA, Yoo HN (2017) Short cervical lengths initially detected in mid-trimester and early in the third trimester in asymptomatic twin gestations: association with histologic chorioamnionitis and preterm birth. PLoS One 12(4):e0175455CrossRefPubMedGoogle Scholar
  19. 19.
    Gibbs RS, Blanco JD, St Clair PJ, Castaneda YS (1982) Quantitative bacteriology of amniotic fluid from women with clinical intraamniotic infection at term. J Infect Dis 145(1):1–8CrossRefPubMedGoogle Scholar
  20. 20.
    DeLong ER, DeLong DM, Clarke-Pearson DL (1988) Comparing the areas under two or more correlated receiver operating characteristic curves: a nonparametric approach. Biometrics 44(3):837–845CrossRefPubMedGoogle Scholar
  21. 21.
    Murtha AP, Greig PC, Jimmerson CE, Roitman-Johnson B, Allen J, Herbert WN (1996) Maternal serum interleukin-6 concentrations in patients with preterm premature rupture of membranes and evidence of infection. Am J Obstet Gynecol 175(4 Pt 1):966–969CrossRefPubMedGoogle Scholar
  22. 22.
    Sayed Ahmed WA, Ahmed MR, Mohamed ML, Hamdy MA, Kamel Z, Elnahas KM (2016) Maternal serum interleukin-6 in the management of patients with preterm premature rupture of membranes. J Matern Fetal Neonatal Med 29(19):3162–3166PubMedGoogle Scholar
  23. 23.
    Gulati S, Bhatnagar S, Raghunandan C, Bhattacharjee J (2012) Interleukin-6 as a predictor of subclinical chorioamnionitis in preterm premature rupture of membranes. Am J Reprod Immunol 67(3):235–240CrossRefPubMedGoogle Scholar
  24. 24.
    Gargano JW, Holzman C, Senagore P, Thorsen P, Skogstrand K, Hougaard DM et al (2008) Mid-pregnancy circulating cytokine levels, histologic chorioamnionitis and spontaneous preterm birth. J Reprod Immunol 79(1):100–110CrossRefPubMedGoogle Scholar
  25. 25.
    Baricevic I, Jones DR, Nikolic JA, Nedic O (2006) Gastrointestinal inflammation and the circulating IGF system in humans. Horm Metab Res 38(1):22–27CrossRefPubMedGoogle Scholar
  26. 26.
    Shin M, Kang HS, Park JH, Bae JH, Song DK, Im SS (2017) Recent insights into insulin-like growth factor binding protein 2 transcriptional regulation. Endocrinol Metab (Seoul) 32(1):11–17CrossRefGoogle Scholar
  27. 27.
    Heald AH, Kaushal K, Siddals KW, Rudenski AS, Anderson SG, Gibson JM (2006) Insulin-like growth factor binding protein-2 (IGFBP-2) is a marker for the metabolic syndrome. Exp Clin Endocrinol Diabetes 114(7):371–376CrossRefPubMedGoogle Scholar
  28. 28.
    Han VK, Bassett N, Walton J, Challis JR (1996) The expression of insulin-like growth factor (IGF) and IGF-binding protein (IGFBP) genes in the human placenta and membranes: evidence for IGF-IGFBP interactions at the feto-maternal interface. J Clin Endocrinol Metab 81(7):2680–2693PubMedGoogle Scholar
  29. 29.
    Hill DJ, Clemmons DR (1992) Similar distribution of insulin-like growth factor binding proteins-1, -2, -3 in human fetal tissues. Growth Factors 6(4):315–326CrossRefPubMedGoogle Scholar
  30. 30.
    Ryckman C, Vandal K, Rouleau P, Talbot M, Tessier PA (2003) Proinflammatory activities of S100: proteins S100A8, S100A9, and S100A8/A9 induce neutrophil chemotaxis and adhesion. J Immunol 170(6):3233–3242CrossRefPubMedGoogle Scholar
  31. 31.
    Pergialiotis V, Prodromidou A, Pappa E, Vlachos GD, Perrea DN, Papantoniou N (2016) An evaluation of calprotectin as serum marker of preeclampsia: a systematic review of observational studies. Inflamm Res 65(2):95–102CrossRefPubMedGoogle Scholar
  32. 32.
    Terrin G, Passariello A, De Curtis M, Paludetto R, Berni Canani R (2012) S100 A8/A9 protein as a marker for early diagnosis of necrotising enterocolitis in neonates. Arch Dis Child 97(12):1102CrossRefPubMedGoogle Scholar
  33. 33.
    Bealer JF, Colgin M (2010) S100A8/A9: a potential new diagnostic aid for acute appendicitis. Acad Emerg Med 17(3):333–336CrossRefPubMedGoogle Scholar
  34. 34.
    Terrin G, Passariello A, Manguso F, Salvia G, Rapacciuolo L, Messina F et al (2011) Serum calprotectin: an antimicrobial peptide as a new marker for the diagnosis of sepsis in very low birth weight newborns. Clin Dev Immunol 2011:291085CrossRefPubMedGoogle Scholar
  35. 35.
    Athayde N, Romero R, Gomez R, Maymon E, Pacora P, Mazor M et al (1999) Matrix metalloproteinases-9 in preterm and term human parturition. J Matern Fetal Med 8(5):213–219CrossRefPubMedGoogle Scholar
  36. 36.
    Stygar D, Wang H, Vladic YS, Ekman G, Eriksson H, Sahlin L (2002) Increased level of matrix metalloproteinases 2 and 9 in the ripening process of the human cervix. Biol Reprod 67(3):889–894CrossRefPubMedGoogle Scholar
  37. 37.
    Tu FF, Goldenberg RL, Tamura T, Drews M, Zucker SJ, Voss HF (1998) Prenatal plasma matrix metalloproteinase-9 levels to predict spontaneous preterm birth. Obstet Gynecol 92(3):446–449PubMedGoogle Scholar
  38. 38.
    Caloone J, Rabilloud M, Boutitie F, Traverse-Glehen A, Allias-Montmayeur F, Denis L et al (2016) Accuracy of several maternal seric markers for predicting histological chorioamnionitis after preterm premature rupture of membranes: a prospective and multicentric study. Eur J Obstet Gynecol Reprod Biol 205:133–140CrossRefPubMedGoogle Scholar
  39. 39.
    Sorokin Y, Romero R, Mele L, Wapner RJ, Iams JD, Dudley DJ et al (2010) Maternal serum interleukin-6, C-reactive protein, and matrix metalloproteinase-9 concentrations as risk factors for preterm birth < 32 weeks and adverse neonatal outcomes. Am J Perinatol 27(8):631–640CrossRefPubMedGoogle Scholar
  40. 40.
    Arpino V, Brock M, Gill SE (2015) The role of TIMPs in regulation of extracellular matrix proteolysis. Matrix Biol 44–46:247–254CrossRefPubMedGoogle Scholar
  41. 41.
    Locksmith GJ, Clark P, Duff P, Saade GR, Schultz GS (2001) Amniotic fluid concentrations of matrix metalloproteinase 9 and tissue inhibitor of metalloproteinase 1 during pregnancy and labor. Am J Obstet Gynecol 184(2):159–164CrossRefPubMedGoogle Scholar
  42. 42.
    Roy-Lacroix ME, Guerard M, Berthiaume M, Rola-Pleszczynski M, Crous-Tsanaclis AM, Pasquier JC (2013) Time-dependent effect of in utero inflammation: a longitudinal study in rats. J Matern Fetal Neonatal Med 26(8):789–794CrossRefPubMedGoogle Scholar
  43. 43.
    Geva E, Ginzinger DG, Zaloudek CJ, Moore DH, Byrne A, Jaffe RB (2002) Human placental vascular development: vasculogenic and angiogenic (branching and nonbranching) transformation is regulated by vascular endothelial growth factor-A, angiopoietin-1, and angiopoietin-2. J Clin Endocrinol Metab 87(9):4213–4224CrossRefPubMedGoogle Scholar

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

Personalised recommendations