title: An elevated fetal interleukin-6 concentration can be observed in fetuses with anemia due to Rh alloimmunization: implications for the understanding of the fetal inflammatory response syndrome.
abstract: OBJECTIVE
  The fetal inflammatory response syndrome (FIRS) has been described in the context of preterm labor and preterm prelabor rupture of the membranes and is often associated with intra-amniotic infection/inflammation. This syndrome is characterized by systemic fetal inflammation and operationally defined by an elevated fetal plasma interleukin (IL)-6. The objective of this study was to determine if FIRS can be found in fetuses with activation of their immune system, such as the one observed in Rh alloimmune-mediated fetal anemia.
  
  
  METHODS
  Fetal blood sampling was performed in sensitized Rh-D negative women with suspected fetal anemia (n=16). Fetal anemia was diagnosed according to reference range nomograms established for the assessment of fetal hematologic parameters. An elevated fetal plasma IL-6 concentration was defined using a cutoff of >11 pg/ml. Concentrations of IL-6 were determined by immunoassay. Non-parametric statistics were used for analysis.
  
  
  RESULTS
  (1) The prevalence of an elevated fetal plasma IL-6 was 25% (4/16); (2) there was an inverse relationship between the fetal hematocrit and IL-6 concentration -- the lower the hematocrit, the higher the fetal IL-6 (r=-0.68, p=0.004); (3) fetuses with anemia had a significantly higher plasma IL-6 concentration than those without anemia (3.74 pg/ml, interquartile range (IQR) 1.18-2.63 vs. 1.46 pg/ml, IQR 1.76-14.7; p=0.02); (4) interestingly, all fetuses with an elevated plasma IL-6 concentration had anemia (prevalence 40%, 4/10), while in the group without anemia, none had an elevated fetal plasma IL-6.
  
  
  CONCLUSIONS
  An elevation in fetal plasma IL-6 can be observed in a subset of fetuses with anemia due to Rh alloimmunization. This observation suggests that the hallmark of FIRS can be caused by non-infection-related insults. Further studies are required to determine whether the prognosis of FIRS caused by intra-amniotic infection/inflammation is different from that induced by alloimmunization.
authors.affiliation: Perinatology Research Branch, Intramural Division, NICHD/NIH/DHHS, Hutzel Women's Hospital, Detroit, MI 48201, USA.
authors.forename: Edi
authors.initials: E
authors.lastname: Vaisbuch
authors.forename: Roberto
authors.initials: R
authors.lastname: Romero
authors.forename: Ricardo
authors.initials: R
authors.lastname: Gomez
authors.forename: Juan Pedro
authors.initials: JP
authors.lastname: Kusanovic
authors.forename: Shali
authors.initials: S
authors.lastname: Mazaki-Tovi
authors.forename: Tinnakorn
authors.initials: T
authors.lastname: Chaiworapongsa
authors.forename: Sonia S
authors.initials: SS
authors.lastname: Hassan
mesh_terms: D000328:Adult; D000740:Anemia / Q000097:blood / Q000151:congenital / Q000209:etiology* / Q000276:immunology; D032882:Comprehension; D003430:Cross-Sectional Studies; D005260:Female; D005315:Fetal Diseases / Q000097:blood / Q000209:etiology* / Q000276:immunology; D005333:Fetus / Q000098:blood supply; D006400:Hematocrit; D006801:Humans; D015850:Interleukin-6 / Q000097:blood*; D009994:Osmolar Concentration; D011247:Pregnancy; D012189:Retrospective Studies; D012203:Rh Isoimmunization / Q000097:blood / Q000150:complications*; D018746:Systemic Inflammatory Response Syndrome / Q000097:blood / Q000151:congenital* / Q000209:etiology* / Q000276:immunology
chemical_list: D015850:Interleukin-6