Skip to main content

Advertisement

Log in

Chorioamnionitis Occurring in Women With Preterm Rupture of the Fetal Membranes Is Associated With a Dynamic Increase in mRNAs Coding Cytokines in the Maternal Circulation

  • Original Article
  • Published:
Reproductive Sciences Aims and scope Submit manuscript

Abstract

Background:

Preterm prelabor rupture of the fetal membranes (PPROM) is a significant contributor to the morbidity and mortality of preterm birth, particularly in the setting of chorioamnionitis. No sensitive or specific diagnostic or predictive test currently exists for the accurate diagnosis of chorioamnionitis. Our aim was to measure messenger RNA (mRNA) coding cytokines in the maternal blood and examine whether they were increased in association with chorioamnionitis at delivery.

Methods/Results:

We performed a prospective cohort study of women recruited with PPROM at a mean gestational age of 28.9 weeks at risk of developing chorioamnionitis. Blood was sampled from participants, and the expression of mRNA coding for proinflammatory genes was measured in women with and without chorioamnionitis at the time of delivery as well as gestation-matched healthy controls. Expression was measured using quantitative polymerase chain reaction (PCR) and also digital PCR. Interleukin 1β (IL1B) mRNA expression in maternal blood was elevated in women with chorioamnionitis compared to gestation-matched controls. Importantly, among women admitted with PPROM, digital PCR confirmed a significant increase in IL1B expression in maternal blood in women with chorioamnionitis compared to women without chorioamnionitis. Polymerase chain reaction array revealed that CD14, nuclear factor of κ light polypeptide gene enhancer in B-cells 1 (NFKB1), and tumor necrosis factor receptor super family-interacting serine–threonine kinase 1 mRNA were significantly increased in women with chorioamnionitis compared to controls. Digital PCR confirmed that NFKB1 mRNA was significantly increased in patients with chorioamnionitis compared to controls and that CD14 levels increased over time in patients with PPROM having chorioamnionitis.

Conclusion:

Measuring circulating proinflammatory mRNA in women with PPROM may distinguish those with chorioamnionitis from those without, in turn providing better targeted therapies and appropriate timing of delivery.

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

Access this article

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. Goldenberg RL, Culhane JF, Lams JD, Romero R. Preterm Birth 1 Epidemiology and causes of preterm birth. Lancet. 2008; 371(9606):75–84.

    PubMed  PubMed Central  Google Scholar 

  2. Czikk MJ, McCarthy FP, Murphy KE. Chorioamnionitis: from pathogenesis to treatment. Clin Microbiol Infect. 2011; 17(9): 1304–1311. doi:10.1111/j.1469–0691.2011.03574.X.

    CAS  PubMed  Google Scholar 

  3. Ramsey PS, Lieman JM, Brumfield CG, Carlo W. Chorioamnionitis increases neonatal morbidity in pregnancies complicated by preterm premature rupture of membranes. Am J Obstet Gynecol. 2005; 192(4):1162–1166. doi:10.1016/j.ajog.2004.11.035.

    PubMed  Google Scholar 

  4. Andrews WW, Cliver SP, Biasini F, et al. Early preterm birth: association between in utero exposure to acute inflammation and severe neurodevelopmental disability at 6 years of age. Am J Obstet Gynecol. 2008; 198(4):466.e1–466.ell. doi:10.1016/j. ajog.2007.12.031.

    Google Scholar 

  5. Shatrov JG, Birch SCM, Lam LT. Chorioamnionitis and Cerebral Palsy. Obstet Gynecol. 2010;116(2):387–392.

    PubMed  Google Scholar 

  6. Kallapur SG, Presicce P, Chougnet CA, Rueda CM, Jobe AH. Fetal Immune Response to Chorioamnionitis. Semin Reprod Med. 2014;32(1):56–67.

    PubMed  PubMed Central  Google Scholar 

  7. Ng EKO, Tsui NBY, Lau TK, et al. mRNA of placental origin is readily detectable in maternal plasma. Proc Natl Acad Sci USA. 2003; 100(8):4748–4753.doi:10.1073/pnas.0637450100.

    CAS  PubMed  Google Scholar 

  8. Kim YM, Romero R, Chaiworapongsa T, et al. Toll-like receptor-2 and -4 in the chorioamniotic membranes in spontaneous labor at term and in preterm parturition that are associated with chorioamnionitis. Am J Obstet Gynecol. 2004; 191(4):1346–1355. doi:10. 1016/j.ajog.2004.07.009.

    CAS  PubMed  Google Scholar 

  9. Menon R, Taylor RN, Fortunato SJ. Chorioamnionitis-a complex pathophysiologic syndrome. Placenta. 2010; 31(2):113–120. doi: 10.1016/j.placenta.2009.11.012.

    CAS  PubMed  Google Scholar 

  10. Whale AS, Huggett JF, Cowen S, et al. Comparison of microfluidic digital PCR and conventional quantitative PCR for measuring copy number variation. Nucleic Acids Res. 2012; 40(11):e82. doi:10.1093/nar/gks203.

    CAS  PubMed  PubMed Central  Google Scholar 

  11. Trochez-Martinez RD, Smith P, Lamont RF. Use of C-reactive protein as a predictor of chorioamnionitis in preterm prelabour rupture of membranes: a systematic review. BJOG. 2007; 114(7):796–801.doi:10.1111/j.1471–0528.2007.01385.x.

    CAS  PubMed  Google Scholar 

  12. 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 Obs Gynecol Reprod Biol. 2009; 147(2): 124–129. doi:10.1016/j.ejogrb.2009.09.017.

    Google Scholar 

  13. Gulati S, Agrawal S, Raghunandan C, et al. Maternal serum interleukin-6 and its association with clinicopathological infectious morbidity in preterm premature rupture of membranes: a prospective cohort study. J Matern Fetal Neonatal Med. 2012; 25(8): 1428–1432. doi: 10.3109/14767058.2011.638952.

    CAS  PubMed  Google Scholar 

  14. Holst RM, Laurini R, Jacobsson B, et al. Expression of cytokines and chemokines in cervical and amniotic fluid: relationship to histological chorioamnionitis. J Matern Fetal Neonatal Med. 2007; 20(12):885–893.doi:10.1080/14767050701752601.

    CAS  PubMed  Google Scholar 

  15. Lacerte M, Bujold E, Audibert F, Mayrand M-H. Amniocentesis for PPROM management: a feasibility study. J Obstet Gynaecol Can. 2008; 30(8):659–664. Web site, http://www.ncbi.nlm.nih.gov/pubmed/18786287. Accessed July 15, 2014.

    PubMed  Google Scholar 

  16. Mcintosh JJ, McHugh K, Haas DM. Difficulties in establishing routine amniocentesis for preterm labor evaluation. J Matern Fetal Neonatal Med. 2012; 25(3):313–314. doi:10.3109/14767058.2011. 573826.

    PubMed  Google Scholar 

  17. Dinarello CA. Immunological and inflammatory functions of the interleukin-1 family. Annu Rev Immunol. 2009;27:519–550. doi: 10.1146/annurev.immunol.021908.132612.

    CAS  PubMed  Google Scholar 

  18. Van de Veerdonk FL, Netea MG, Dinarello CA, Joosten LA. Inflammasome activation and IL-1β and IL-18 processing during infection. Trends Immunol. 2011; 32(3):110–116. doi:10.1016/j.it. 2011.01.003.

    PubMed  Google Scholar 

  19. Bowen JM, Chamley L, Keelan JA, Mitchell MD. Cytokines of the placenta and extra-placental membranes: roles and regulation during human pregnancy and parturition. Placenta. 2002; 23(4): 257–273. doi:10.1053/plac.2001.0782.

    CAS  PubMed  Google Scholar 

  20. Sadowsky DW, Adams KM, Gravett MG, Witkin SS, Novy MJ. Preterm labor is induced by intraamniotic infusions of interleukin-1 beta and tumor necrosis factor-alpha but not by interleukin-6 or interleukin-8 in a nonhuman primate model. Am J Obstet Gynecol. 2006; 195(6):1578–1589. doi:10.1016/j.ajog. 2006.06.072.

    CAS  PubMed  Google Scholar 

  21. Ashur-Fabian O, Yerushalmi GM, Mazaki-Tovi S, et al. Cell free expression of hifl alpha and p21 in maternal peripheral blood as a marker for preeclampsia and fetal growth restriction. PLoS One. 2012; 7(5):e37273. doi:10.1371/journal.pone. 0037273.

    CAS  PubMed  PubMed Central  Google Scholar 

  22. Hahn S, Rusterholz C, Hosli I, Lapaire O. Cell-free nucleic acids as potential markers for preeclampsia. Placenta. 2011;32 suppl: S17–S20. doi:10.1016/j.placenta.2010.06.018.

    CAS  PubMed  Google Scholar 

  23. Pang WW, Tsui MH, Sahota D, et al. A strategy for identifying circulating placental RNA markers for fetal growth assessment. Prenat Diagn. 2009; 29(5):495–504. doi:10.1002/pd.2230.

    CAS  PubMed  Google Scholar 

  24. Whitehead C, Teh WT, Walker SP, et al. Quantifying circulating hypoxia-induced RNA transcripts in maternal blood to determine in utero fetal hypoxic status. BMC Med. 2013;11:256.

    PubMed  PubMed Central  Google Scholar 

  25. Lanoix D, Lacasse A-A, St-Pierre J, et al. Quantitative PCR pitfalls: the case of the human placenta. Mol Biotechnol. 2012; 52(3):234–243. doi:10.1007/s12033-012-9539-2.

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Owen Stock BMSc, MBBS.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Stock, O., Gordon, L., Kapoor, J. et al. Chorioamnionitis Occurring in Women With Preterm Rupture of the Fetal Membranes Is Associated With a Dynamic Increase in mRNAs Coding Cytokines in the Maternal Circulation. Reprod. Sci. 22, 852–859 (2015). https://doi.org/10.1177/1933719114565034

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1177/1933719114565034

Keywords

Navigation