Info: Zenodo’s user support line is staffed on regular business days between Dec 23 and Jan 5. Response times may be slightly longer than normal.

Published March 23, 2022 | Version v1
Journal article Open

THE FETAL INFLAMMATORY RESPONSE SYNDROME (CLINICAL LECTURE)

  • 1. Shupyk National Healthcare University of Ukraine, Kyiv, Ukraine

Description

The article highlights the problem of fetal inflammatory response syndrome (FIRS) in modern conditions. This term has been introduced into the clinical practice to describe the systemic activation of the innate or acquired immune system of the fetus. FIRS can occur in response to infection or inflammation and is divided into two types depending on the type of immune response. FIRS I and II types are different clinical syndromes and correspond to acute and chronic inflammatory processes.
The main pathophysiological mechanisms and clinical features of different variants of FIRS are described. Fetuses with this syndrome have signs of multiorgan damage. The consequences of FIRS are a high rate of complications in newborns: sepsis, congenital pneumonia, intraventricular hemorrhage, periventricular leukomalacia, cerebral palsy, neurosensory deafness, necrotic enterocolitis and others. The detailed description of fetal organs and systems damage by FIRS is presented. In further life, such children are at risk of long-term complications. This syndrome can also be the cause of unexplained antenatal fetal death.
Laboratory diagnostic criteria for FIRS type I include elevated levels of interleukin-6 and acute phase reagents. Histologically there are the signs of funiculitis or chorionic vasculitis.
The marker of FIRS type II is the chemotactic chemokine CXCL10, which simulates maternal antifetal rejection.
The article presents the basic mechanisms of the immune response in FIRS. In this type of pathology there are chronic inflammatory lesions of the placenta which are determined by histological study (chronic chorioamnionitis, vilitis of unknown etiology, chronic deciduitis).

Files

The Fetal Inflammatory Response Syndrome (Clinical lecture).pdf

Files (163.6 kB)

Additional details

References

  • Madsen-Bouterse SA, Romero R, Tarca AL, Espinoza J, Kim CJ, Kim J-S, et al. The transcriptome of the fetal inflammatory response syndrome. Am J Reprod Immunol. 2010;63(1):73-92. doi: 10.1111/j.1600-0897.2009.00791.x.
  • Peng CC, Chang JH, Lin HY, Cheng P-J, Su B-H. Intrauterine inflammation, infection, or both (Triple I): A new concept for chorioamnionitis. Pediatr Neonatol. 2018;59(3):231-7. doi: 10.1016/j.pedneo.2017.09.001.
  • Wolfsberger CH, Bruckner M, Baik-Schneditz N, Schwaberger B, Mileder LP, Avian A, et al. Fetal Inflammatory Response Syndrome and Cerebral Oxygenation During Immediate Postnatal Transition in Preterm Neonates. Front Pediatr. 2020;8:401. doi: 10.3389/fped.2020.00401.
  • Fan SR, Liu P, Yan SM, Peng J-Y, Liu X-P. Diagnosis and Management of Intraamniotic Infection. Maternal-Fetal Med. 2020;2(4):223-30. doi: 10.1097/ FM9.0000000000000052.
  • Jung E, Romero R, Yeo L, Ramiro D-P, Julio M-C, Robert P, et al. The fetal inflammatory response syndrome: the origins of a concept, pathophysiology, diagnosis, and obstetrical implications. Semin Fetal Neonatal Med. 2020;25(4):101146. doi: 10.1016/j.siny.2020.101146.
  • Gomez R, Romero R, Ghezzi F, Yoon BH, Mazor M, Berry SM. The fetal inflammatory response syndrome. Am J Obstet Gynecol. 1998;179(1):194-202. doi: 10.1016/s0002-9378(98)70272-8.
  • Para R, Romero R, Miller D, Galaz J, Done B, Peyvandipour A. et al. The Distinct Immune Nature of the Fetal Inflammatory Response Syndrome Type I and Type II. ImmunoHorizons. 2021;5(9):735-51. doi: 10.4049/immunohorizons.2100047.
  • Romero R, Miranda J, Chaiworapongsa T, Chaemsaithong P, Gotsch F, Dong Z, et al. A novel molecular microbiologic technique for the rapid diagnosis of microbial invasion of the amniotic cavity and intra-amniotic infection in preterm labor with intact membranes. Am J Reprod Immunol. 2014;71(4):330-58. doi: 10.1111/aji.12189.
  • Leiby JS, McCormick K, Sherrill-Mix S, Clarke EL, Kessler LR, Taylor LJ, et al. Lack of detection of a human placenta microbiome in samples from preterm and term deliveries. Microbiome. 2018;6(1):196. doi: 10.1186/s40168-018-0575-4.
  • Combs CA, Gravett M, Garite TJ, Trofatter K, Lapidus J, Porreco R. Amniotic fluid infection, inflammation, and colonization in preterm labor with intact membranes. Am J Obstet Gynecol. 2014;210(2):125.e1-125.e15. doi: 10.1016/ j.ajog.2013.11.032.
  • Romero R, Savasan ZA, Chaiworapongsa T, Berry SM, Kusanovic JP, Hassan SS, et al. Hematologic profile of the fetus with systemic inflammatory response syndrome. J Perinat Med. 2011;40(1):19-32. doi: 10.1515/JPM.2011.100.
  • Romero R, Kadar N, Miranda J, Korzeniewski SJ, Schwartz AG, Chaemsaithong P, et al. The diagnostic performance of the Mass Restricted (MR) score in the identification of microbial invasion of the amniotic cavity or intra-amniotic inflammation is not superior to amniotic fluid interleukin-6. J Matern Fetal Neonatal Med. 2014;27(8):757-69. doi: 10.3109/14767058.2013.844123.
  • Ozalkaya E, Karatekin G, Topcuoglu S, Gursoy T, Ovalı F. Morbidity in preterm infants with fetal inflammatory response syndrome. Pediatr Int. 2016;58(9):850-4. doi: 10.1111/ped.12895.
  • Kim CJ, Romero R, Chaemsaithong P, Chaiyasit N, Yoon BH, Kim YM. Acute chorioamnionitis and funisitis: definition, pathologic features, and clinical significance. Am J Obstet Gynecol. 2015;213(4):29-52. doi: 10.1016/j.ajog.2015.08.040.
  • Di NE, Cromi A, Ghezzi F, Raio L, Uccella S, D'Addario V, et al. Fetal thymic involution: a sonographic marker of the fetal inflammatory response syndrome. Am J Obstet Gynecol. 2006;194(1):153-9. doi: 10.1016/j.ajog.2005.05.036.
  • Sciaky-Tamir Y, Hershkovitz R, Mazor M, Shelef I, Erez O. The use of imaging technology in the assessment of the fetal inflammatory response syndrome-imaging of the fetal thymus. Prenat Diagn. 2015;35(5):413-9. doi: 10.1002/pd.4560.
  • Jackson CM, Mukherjee S, Wilburn AN, Cates C, Lewkowich IP, Deshmukh H, et al. Pulmonary Consequences of Prenatal Inflammatory Exposures: Clinical Perspective and Review of Basic Immunological Mechanisms. Front Immunol. 2020;11:1285. doi: 10.3389/fimmu.2020.01285.
  • Goldstein JA, Gallagher K, Beck C, Kumar R, Gernand AD. Maternal-Fetal Inflammation in the Placenta and the Developmental Origins of Health and Disease. Front Immunol. 2020;11(2):2786. doi: 10.3389/fimmu.2020.531543.
  • Miao J, Ren Z, Rao Y, Xia X, Wang J, Xu Fang, Zhang X, et al. Pathological staging of chorioamnionitis contributes to complications in preterm infants. Ital J Pediatr. 2020;127(46):127. doi: 10.1186/s13052-020-00895-4.
  • Burd I, Balakrishnan B, Kannan S. Models of fetal brain injury, intrauterine inflammation, and preterm birth. Am J Reprod Immunol. 2012;67(4):287-94. doi: 10.1111/j.1600-0897.2012.01110.x.
  • Zaharie GC, Drugan T, Crivii C, Muresan D, Zaharie A, Hașmașanu MG, et al. Postpartum assessment of fetal inflammatory response syndrome in a preterm population with premature rupture of membranes: A Romanian study. Exp Ther Med. 2021;22(6):1427. doi: 10.3892/etm.2021.10862.
  • Mitchell T, MacDonald JW, Srinouanpranchanh S, Bammler TK, Merillat S, Boldenow E, et al. Evidence of cardiac involvement in the fetal inflammatory response syndrome: disruption of gene networks programming cardiac development in nonhuman primates. Am J Obstet Gynecol. 2018;218(4):438. doi: 10.1016/j.ajog.2018.01.009.
  • Sabic D, Koenig JM. A perfect storm: fetal inflammation and the developing immune system. Pediatr Res. 2020;87(2):319-26. doi: 10.1038/s41390-019-0582-6.
  • Shim YJ, Choi BY, Park KH, Lee H, Jung YM, Kim YM. Inflammatory and Immune Proteins in Umbilical Cord Blood: Association with Hearing Screening Test Failure in Preterm Neonates. Mediators Inflamm. 2018;19:4209359. doi: 10.1155/2018/4209359.
  • Lannaman K, Romero R, Chaiworapongsa T, Kim YM, Korzeniewski SJ, Eli Maymon et al. Fetal death: an extreme manifestation of maternal anti-fetal rejection. J Perinat Med. 2017;45(7):851-68. doi: 10.1515/jpm-2017-0073.