Skip to main content

Advertisement

SpringerLink
Log in

Antibody Microarray Analysis of Plasma Proteins for the Prediction of Histologic Chorioamnionitis in Women With Preterm Premature Rupture of Membranes

  • Published:
Reproductive Sciences Aims and scope Submit manuscript

Abstract

We aimed to identify maternal blood biomarkers predictive of histologic chorioamnionitis (HCA) in the plasma of women with preterm premature rupture of membranes (PPROM) and to determine whether the combination of these biomarkers with conventional clinical variables can improve the prediction of HCA. This retrospective cohort study included 82 consecutive women with PPROM (23-34 gestational weeks) who delivered within 96 hours of blood sampling. A membrane-based human antibody microarray was used to analyze the plasma proteome. The validation of 5 candidate biomarkers of interest was performed by enzyme-linked immunosorbent assay (ELISA) in the final cohort (n = 82). Serum C-reactive protein (CRP) levels were measured at sampling. Seventy-nine molecules studied exhibited intergroup differences. Validation by ELISA confirmed higher levels of plasma matrix metalloproteinase-9 (MMP-9), interleukin-6 (IL-6), S100 A8/A9, and insulin-like growth factor-binding protein 1 (IGFBP-1), but not tissue inhibitor of metalloproteinase 1 (TIMP-1), in women with HCA than in women without HCA. Using a stepwise regression analysis, a combined prediction model was developed, which included the plasma MMP-9, serum CRP levels, and gestational age (area under the curve [AUC], 0.932). The AUC for this model was significantly greater than that for any single variable included in the predictive model. Protein–antibody microarray technology can be useful in identifying plasma-based predictors for HCA. This study suggests that plasma MMP-9, IL-6, IGFBP-1, and S100 A8/A9 are important noninvasive predictors for HCA in women with PPROM and that the best predictive model, which combined these biomarkers with conventional clinical factors, can significantly improve the predictability for HCA.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Wu YW, Colford JM Jr. Chorioamnionitis as a risk factor for cerebral palsy: a meta-analysis. JAMA. 2000;284(11):1417–1424.

    Article  CAS  Google Scholar 

  2. Yoon BH, Romero R, Kim CJ, et al. 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. 1995;172(3):960–970.

    Article  CAS  Google Scholar 

  3. Oh KJ, Park KH, Kim SN, Jeong EH, Lee SY, Yoon HY. Predictive value of intra-amniotic and serum markers for inflammatory lesions of preterm placenta. Placenta. 2011;32(10):732–736.

    Article  CAS  Google Scholar 

  4. Kim SA, Park KH, Lee SM. Non-invasive predictionofhistologic chorioamnionitis in women with preterm premature rupture of membranes. Yonsei Med J. 2016;57(2):461–468.

    Article  CAS  Google Scholar 

  5. Miyazaki K, Furuhashi M, Ishikawa K, et al. Impact ofchorioam-nionitis on short- and long-term outcomes in very low birth weight preterm infants: the Neonatal Research Network Japan. JMatern Fetal Neonatal Med. 2016;29(2):331–337.

    Article  Google Scholar 

  6. Cobo T, Kacerovsky M, Palacio M, et al. A prediction model of histological chorioamnionitis and funisitis in preterm prelabor rupture of membranes: analyses of multiple proteins in the amniotic fluid. J Matern Fetal Neonatal Med. 2012;25(10):1995–2001.

    Article  CAS  Google Scholar 

  7. Park JW, Park KH, Jung EY. Clinical significance of histologic chorioamnionitis with a negative amniotic fluid culture inpatients with preterm labor and premature membrane rupture. PLoS One. 2017;12(3):e0173312.

    Article  Google Scholar 

  8. Buhimschi IA, Zambrano E, Pettker CM, et al. Using proteomic analysis of the human amniotic fluid to identify histologic chor-ioamnionitis. Obstet Gynecol. 2008;111(2 pt 1):403–412.

    Article  CAS  Google Scholar 

  9. McNamara MF, Wallis T, Qureshi F, Jacques SM, Gonik B. Determining the maternal and fetal cellular immunologic contributions in preterm deliveries with clinical or subclinical chor-ioamnionitis. Infect Dis Obstet Gynecol. 1997;5(4):273–279.

    Article  CAS  Google Scholar 

  10. Kim MA, Lee YS, Seo K. Assessment of predictive markers for placental inflammatory response in preterm births. PLoS One. 2014;9(10):e107880.

    Article  Google Scholar 

  11. Greig PC, Murtha AP, Jimmerson CJ, Herbert WN, Roitman-Johnson B, Allen J. Maternal serum interleukin-6 during pregnancy and during term and preterm labor. Obstet Gynecol. 1997;90(3):465–469.

    Article  CAS  Google Scholar 

  12. Boggess KA, Greig PC, Murtha AP, Jimmerson CE, Herbert WN. Maternal serum granulocyte-colony stimulating factor in preterm birth with subclinical chorioamnionitis. JReprod Immunol. 1997;33(1):45–52.

    Article  CAS  Google Scholar 

  13. Le Ray I, Mace G, Sediki M, et al. Changes in maternal blood inflammatory markers as a predictor of chorioamnionitis: a prospective multicenter study. Am J Reprod Immunol. 2015;73(1): 79–90.

    Article  CAS  Google Scholar 

  14. Chan KY, Leung FW, Lam HS, et al. Immunoregulatory protein profiles of necrotizing enterocolitis versus spontaneous intestinal perforation in preterm infants. PLoS One. 2012;7(5):e36977.

    Article  CAS  Google Scholar 

  15. Kim HB, Kim CK, Iijima K, Kobayashi T, Kita H. Protein micro-array analysis in patients with asthma: elevation of the chemokine PARC/CCL18 in sputum. Chest. 2009;135(2):295–302.

    Article  CAS  Google Scholar 

  16. Cha DM, Woo SJ, Kim HJ, Lee C, Park KH. Comparative analysis of aqueous humor cytokine levels between patients with exudative age-related macular degeneration and normal controls. Invest Ophthalmol Vis Sci. 2013;54(10):7038–7044.

    Article  CAS  Google Scholar 

  17. Park JW, Park KH, Jung EY, Cho SH, Jang JA, Yoo HN. 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. 2017;12(4):e0175455.

    Article  Google Scholar 

  18. Ryu A, Park KH, Oh KJ, Lee SY, Jeong EH, Park JW. Predictive value of combined cervicovaginal cytokines and gestational age at sampling for intra-amniotic infection in preterm premature rupture of membranes. Acta Obstet Gynecol Scand. 2013;92(5): 517–524.

    Article  Google Scholar 

  19. Park KH, Kim SN, Oh KJ, Lee SY, Jeong EH, Ryu A. Noninva- sive prediction of intra-amniotic infection and/or inflammation in preterm premature rupture of membranes. Reprod Sci. 2012;19(6):658–665.

    Article  CAS  Google Scholar 

  20. DeLong ER, DeLong DM, Clarke-Pearson DL. Comparing the areas under two or more correlated receiver operating characteristic curves: a nonparametric approach. Biometrics. 1988;44(3): 837–845.

    Article  CAS  Google Scholar 

  21. Murtha AP, Greig PC, Jimmerson CE, Roitman-Johnson B, Allen J, Herbert WN. Maternal serum interleukin-6 concentrations in patients with preterm premature rupture of membranes and evidence of infection. Am J Obstet Gynecol. 1996;175(4 pt 1): 966–969.

    Article  CAS  Google Scholar 

  22. Sayed Ahmed WA, Ahmed MR, Mohamed ML, Hamdy MA, Kamel Z, Elnahas KM. Maternal serum interleukin-6 in the management of patients with preterm premature rupture of membranes. JMatern Fetal Neonatal Med. 2016;29(19):3162–3166.

    Article  CAS  Google Scholar 

  23. Gulati S, Bhatnagar S, Raghunandan C, Bhattacharjee J. Interleukin-6 as a predictor of subclinical chorioamnionitis in preterm premature rupture of membranes. Am J Reprod Immunol. 2012;67(3):235–240.

    Article  CAS  Google Scholar 

  24. van de Laar R, van der Ham DP, Oei SG, Willekes C, Weiner CP, Mol BW. Accuracy of C-reactive protein determination in predicting chorioamnionitis and neonatal infection in pregnant women with premature rupture of membranes: a systematic review. Eur J Obstet Gynecol Reprod Biol. 2009;147(2):124–129.

    Article  Google Scholar 

  25. Caloone J, Rabilloud M, Boutitie F, et al; ICAMs Study Group. Accuracy of several maternal seric markers for predicting histo-logical chorioamnionitis after preterm premature rupture ofmem-branes: a prospective and multicentric study. Eur J Obstet Gynecol Reprod Biol. 2016;205:133–140.

    Article  Google Scholar 

  26. Stamenkovic I. Extracellular matrix remodelling: the role of matrix metalloproteinases. J Pathol. 2003;200(4):448–464.

    Article  CAS  Google Scholar 

  27. Guzel S, Serin O, Guzel EC, Buyuk B, Yilmaz G, Guvenen G. Interleukin-33, matrix metalloproteinase-9, and tissue inhibitor [corrected] of matrix metalloproteinase-1 in myocardial infarction. Korean J Intern Med. 2013;28(2):165–173.

    Article  CAS  Google Scholar 

  28. Tayebjee MH, Lip GY, Blann AD, Macfadyen RJ. Effects of age, gender, ethnicity, diurnal variation and exercise on circulating levels of matrix metalloproteinases (MMP)-2 and -9, and their inhibitors, tissue inhibitors of matrix metalloproteinases (TIMP)-1 and-2. Thromb Res. 2005;115(3):205–210.

    Article  CAS  Google Scholar 

  29. Murtha AP, Sinclair T, Hauser ER, Swamy GK, Herbert WN, Heine RP. Maternal serum cytokines in preterm premature rupture of membranes. Obstet Gynecol. 2007;109(1):121–127.

    Article  CAS  Google Scholar 

  30. Canzoneri BJ, Grotegut CA, Swamy GK, et al. Maternal serum interleukin-6 levels predict impending funisitis in preterm premature rupture of membranes after completion of antibiotics. JMatern Fetal Neonatal Med. 2012;25(8):1329–1332.

    Article  CAS  Google Scholar 

  31. Ryckman C, Vandal K, Rouleau P, Talbot M, Tessier PA. Proin- flammatory activities of S100: proteins S100A8, S100A9, and S100A8/A9 induce neutrophil chemotaxis and adhesion. JImmu-nol. 2003;170(6):3233–3242.

    Article  CAS  Google Scholar 

  32. Garcia-Rodriguez S, Callejas-Rubio JL, Ortego-Centeno N, et al. Altered AKT1 and MAPK1 gene expression on peripheral blood mononuclear cells and correlation with T-helper-transcription factors in systemic lupus erythematosus patients. Mediators Inflamm. 2012;2012:495934.

    PubMed  PubMed Central  Google Scholar 

  33. Bealer JF, Colgin M. S100A8/A9: a potential new diagnostic aid for acute appendicitis. Acad Emerg Med. 2010;17(3):333–336.

    Article  Google Scholar 

  34. Terrin G, Passariello A, De Curtis M, Paludetto R, Berni Canani R. S100 A8/A9 protein as a marker for early diagnosis of necrotising enterocolitis in neonates. Arch Dis Child. 2012;97(12):1102.

    Article  Google Scholar 

  35. Fisk NM, Fysh J, Child AG, Gatenby PA, Jeffery H, Bradfield AH. Is C-reactive protein really useful in preterm premature rupture of the membranes?. Br J Obstet Gynaecol. 1987;94(12): 1159–1164.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, Korea

    Jeong Woo Park, Kyo Hoon Park, Yu Mi Kim & Se Jin Lee

  2. Center for Theragnosis, Biomedical Research Institute, Korea Institute of Science and Technology, Seoul, Korea

    Ji Eun Lee & Dong Huey Cheon

  3. Department of Biomedical Engineering, Sogang University, Seoul, Korea

    Dong Huey Cheon

Authors
  1. Jeong Woo Park
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Kyo Hoon Park
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ji Eun Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yu Mi Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Se Jin Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Dong Huey Cheon
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Kyo Hoon Park.

Supplemental Material

Supplemental Material

Supplemental material for this article is available online.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Park, J.W., Park, K.H., Lee, J.E. et al. Antibody Microarray Analysis of Plasma Proteins for the Prediction of Histologic Chorioamnionitis in Women With Preterm Premature Rupture of Membranes. Reprod. Sci. 26, 1476–1484 (2019). https://doi.org/10.1177/1933719119828043

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1177/1933719119828043

Keywords

Search

Navigation