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Complement and other immune-related factors in cervicovaginal fluid associated with intra-amniotic infection/inflammation and spontaneous preterm delivery in women with preterm labor

  • Maternal-Fetal Medicine
  • Published:
Archives of Gynecology and Obstetrics Aims and scope Submit manuscript

Abstract

Purpose

To investigate whether complement and other immune-related proteins in cervicovaginal fluid (CVF) can predict intra-amniotic infection and/or inflammation (IAI) and spontaneous preterm delivery (SPTD, < 34.0 weeks) in women with preterm labor (PTL) and to compare the predictive abilities of these biomarkers with that of amniotic fluid (AF) white blood cells (WBCs).

Methods

We designed a retrospective cohort study of 145 women with PTL at 23.0–33.6 weeks who underwent amniocentesis. AF was cultured and assayed for WBC count and interleukin-6 (IL-6). CVF samples were obtained at the time of amniocentesis. CVF was assayed for complement C3a and C5a, IGFBP-1, and MMP-9 by ELISA.

Results

In the multivariate analysis, elevated CVF levels of C5a and IGFBP-1 were significantly associated with IAI and SPTD at < 34 weeks, while those of C3a were associated with IAI, but not SPTD, even after adjusting for other baseline confounders. For C3a, C5a, and IGFBP-1 in the CVF, area under the curve (AUC) values were statistically similar to that of AF WBCs for detecting IAI, whereas these CVF biomarkers had similar or higher AUC values than AF WBCs for predicting SPTD at < 34 weeks. However, univariate analysis showed no significant correlation between high CVF MMP-9 and IAI or SPTD at < 34 weeks.

Conclusions

In women with PTL, the CVF levels of C3a, C5a, and IGFBP-1 may be useful as novel non-invasive predictors of IAI and SPTD at < 34 weeks. These biomarkers (especially IGFBP-1) have similar or better diagnostic performance compared to AF WBCs.

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References

  1. Combs CA, Gravett M, Garite TJ et al (2014) Amniotic fluid infection, inflammation, and colonization in preterm labor with intact membranes. Am J Obstet Gynecol 210(2):125 (e121–125 e115)

    Article  Google Scholar 

  2. Yoon BH, Romero R, Moon JB et al (2001) Clinical significance of intra-amniotic inflammation in patients with preterm labor and intact membranes. Am J Obstet Gynecol 185(5):1130–1136

    Article  CAS  Google Scholar 

  3. Jung EY, Park KH, Han BR et al (2017) Amniotic fluid infection, cytokine levels, and mortality and adverse pulmonary, intestinal, and neurologic outcomes in infants at 32 weeks’ gestation or less. J Korean Med Sci 32(3):480–487

    Article  Google Scholar 

  4. Bulletins-Obstetrics ACoP (2007) ACOG Practice Bulletin No. 80: premature rupture of membranes. Clinical management guidelines for obstetrician-gynecologists. Obstet Gynecol 109(4):1007–1019

    Article  Google Scholar 

  5. Soto E, Romero R, Richani K et al (2009) Evidence for complement activation in the amniotic fluid of women with spontaneous preterm labor and intra-amniotic infection. J Matern Fetal Neonatal Med 22(11):983–992

    Article  CAS  Google Scholar 

  6. Holst RM, Hagberg H, Wennerholm UB et al (2011) Prediction of microbial invasion of the amniotic cavity in women with preterm labour: analysis of multiple proteins in amniotic and cervical fluids. BJOG 118(2):240–249

    Article  Google Scholar 

  7. Holst RM, Hagberg H, Wennerholm UB et al (2009) Prediction of spontaneous preterm delivery in women with preterm labor: analysis of multiple proteins in amniotic and cervical fluids. Obstet Gynecol 114(2 Pt 1):268–277

    Article  CAS  Google Scholar 

  8. Myntti T, Rahkonen L, Nupponen I et al (2017) Amniotic fluid infection in preterm pregnancies with intact membranes. Dis Markers 2017:8167276

    Article  Google Scholar 

  9. Lee J, Lee SM, Oh KJ et al (2011) Fragmented forms of insulin-like growth factor binding protein-1 in amniotic fluid of patients with preterm labor and intact membranes. Reprod Sci 18(9):842–849

    Article  CAS  Google Scholar 

  10. Di Quinzio MK, Georgiou HM, Holdsworth-Carson SJ et al (2008) Proteomic analysis of human cervico-vaginal fluid displays differential protein expression in association with labor onset at term. J Proteome Res 7(5):1916–1921

    Article  Google Scholar 

  11. Goncalves LF, Chaiworapongsa T, Romero R (2002) Intrauterine infection and prematurity. Ment Retard Dev Disabil Res Rev 8(1):3–13

    Article  Google Scholar 

  12. Park JW, Park KH, Lee SY (2013) Noninvasive prediction of intra-amniotic infection and/or inflammation in women with preterm labor: various cytokines in cervicovaginal fluid. Reprod Sci 20(3):262–268

    Article  Google Scholar 

  13. Jung EY, Park JW, Ryu A et al (2016) Prediction of impending preterm delivery based on sonographic cervical length and different cytokine levels in cervicovaginal fluid in preterm labor. J Obstet Gynaecol Res 42(2):158–165

    Article  CAS  Google Scholar 

  14. Combs CA, Garite TJ, Lapidus JA et al (2015) Detection of microbial invasion of the amniotic cavity by analysis of cervicovaginal proteins in women with preterm labor and intact membranes. Am J Obstet Gynecol 212(4):48 (e481–482 e412)

    Article  Google Scholar 

  15. Kacerovsky M, Celec P, Vlkova B et al (2013) Amniotic fluid protein profiles of intraamniotic inflammatory response to Ureaplasma spp. and other bacteria. PLoS One 8(3):e60399

    Article  CAS  Google Scholar 

  16. Lee SY, Park KH, Jeong EH et al (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):1226–1232

    Article  CAS  Google Scholar 

  17. Yoon BH, Romero R, Kim CJ 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):960–970

    Article  CAS  Google Scholar 

  18. Gibbs RS, Blanco JD, St Clair PJ et al (1982) Quantitative bacteriology of amniotic fluid from women with clinical intraamniotic infection at term. J Infect Dis 145(1):1–8

    Article  CAS  Google Scholar 

  19. 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):837–845

    Article  CAS  Google Scholar 

  20. Fowler DJ, Nicolaides KH, Miell JP (2000) Insulin-like growth factor binding protein-1 (IGFBP-1): a multifunctional role in the human female reproductive tract. Hum Reprod Update 6(5):495–504

    Article  CAS  Google Scholar 

  21. Shi L, Banerjee D, Dobierzewska A et al (2016) Direct regulation of IGF-binding protein 1 promoter by interleukin-1beta via an insulin- and FoxO-1-independent mechanism. Am J Physiol Endocrinol Metab 310(8):E612–E623

    Article  CAS  Google Scholar 

  22. Rutanen EM (2000) Insulin-like growth factors in obstetrics. Curr Opin Obstet Gynecol 12(3):163–168

    Article  CAS  Google Scholar 

  23. Conde-Agudelo A, Romero R (2016) Cervical phosphorylated insulin-like growth factor binding protein-1 test for the prediction of preterm birth: a systematic review and metaanalysis. Am J Obstet Gynecol 214(1):57–73

    Article  CAS  Google Scholar 

  24. Hitti J, Lapidus JA, Lu X et al (2010) Noninvasive diagnosis of intraamniotic infection: proteomic biomarkers in vaginal fluid. Am J Obstet Gynecol 203(1):32 (e31–32. e38)

    Article  Google Scholar 

  25. Dunkelberger JR, Song WC (2010) Complement and its role in innate and adaptive immune responses. Cell Res 20(1):34–50

    Article  CAS  Google Scholar 

  26. Lockwood CJ (1994) Recent advances in elucidating the pathogenesis of preterm delivery, the detection of patients at risk, and preventative therapies. Curr Opin Obstet Gynecol 6(1):7–18

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  28. Locksmith GJ, Clark P, Duff P et al (1999) Amniotic fluid matrix metalloproteinase-9 levels in women with preterm labor and suspected intra-amniotic infection. Obstet Gynecol 94(1):1–6

    CAS  PubMed  Google Scholar 

  29. Boots AB, Sanchez-Ramos L, Bowers DM et al (2014) The short-term prediction of preterm birth: a systematic review and diagnostic metaanalysis. Am J Obstet Gynecol 210(1):54 (e51–54 e10)

    PubMed  Google Scholar 

  30. Lee SM, Romero R, Park JW et al (2012) The clinical significance of a positive Amnisure test in women with preterm labor and intact membranes. J Matern Fetal Neonatal Med 25(9):1690–1698

    Article  CAS  Google Scholar 

  31. Rizzo G, Capponi A, Vlachopoulou A et al (1997) The diagnostic value of interleukin-8 and fetal fibronectin concentrations in cervical secretions in patients with preterm labor and intact membranes. J Perinat Med 25(6):461–468

    Article  CAS  Google Scholar 

  32. Spong CY, Ghidini A, Ossandon M et al (1998) Are the cytokines interleukin-6 and angiogenin stable in frozen amniotic fluid? Am J Obstet Gynecol 178(4):783–786

    Article  CAS  Google Scholar 

  33. Park KH, Kim SN, Oh KJ et al (2012) Noninvasive prediction of intra-amniotic infection and/or inflammation in preterm premature rupture of membranes. Reprod Sci 19(6):658–665

    Article  CAS  Google Scholar 

  34. Romero R, Chaemsaithong P, Chaiyasit N et al (2017) CXCL10 and IL-6: Markers of two different forms of intra-amniotic inflammation in preterm labor. Am J Reprod Immunol 78(1):e12685

    Article  Google Scholar 

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Acknowledgements

This study was supported by a grant from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (Grant number: HI18C0063). The funders had no role in the design of this study; data collection, analysis, and interpretation; or the writing of the manuscript.

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Author notes

  1. Subeen Hong and Young Mi Jung contributed equally to this work.

Authors and Affiliations

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

    Subeen Hong, Young Mi Jung & Kyo Hoon Park

  2. Department of Obstetrics and Gynecology, Seoul National University Bundang Hospital, 82, Gumi-ro 173 Beon-gil, Bundang-gu, Seongnam, 463-707, Korea

    Subeen Hong, Young Eun Lee, Yehyon Park, Yu Mi Kim & Kyo Hoon Park

  3. Department of Obstetrics and Gynecology, Seoul National University Hospital, Seoul, Korea

    Young Mi Jung

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  1. Subeen Hong
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Contributions

SH: protocol/project development, data analysis, manuscript writing/editing. YMJ: protocol/project development, data analysis, manuscript writing/editing. YEL: data collection or management, data analysis. YP: data collection or management, data analysis. YMK: data collection or management, data analysis, ELISA. KHP: conceptualization, protocol/project development, supervision, funding acquisition, data analysis, manuscript writing/editing.

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Correspondence to Kyo Hoon Park.

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Hong, S., Jung, Y.M., Lee, Y.E. et al. Complement and other immune-related factors in cervicovaginal fluid associated with intra-amniotic infection/inflammation and spontaneous preterm delivery in women with preterm labor. Arch Gynecol Obstet 301, 1431–1439 (2020). https://doi.org/10.1007/s00404-020-05560-z

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  • DOI: https://doi.org/10.1007/s00404-020-05560-z

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