title: Funisitis and chorionic vasculitis: the histological counterpart of the fetal inflammatory response syndrome.
abstract: OBJECTIVE
  To determine whether there is a relationship between the presence of histological signs of inflammation in the extraplacental membranes and umbilical cord and the concentrations of fetal plasma interleukin-6 (IL-6).
  
  
  METHODS
  The study examined a cohort of patients who were admitted with preterm labor or preterm premature rupture of the membranes (PROM) and who underwent cordocentesis. Inclusion criteria included fetal plasma available for IL-6 determination, histological examination of the umbilical cord and placenta, and delivery within 48 h of the procedure. This last criterion was used to preserve a meaningful temporal relationship between fetal plasma IL-6 and the results of histological examination of the placenta. Fetal plasma IL-6 was determined by a high sensitivity ELISA. Forty-five patients were available for study: 18 patients had preterm labor with intact membranes and 27 had preterm PROM.
  
  
  RESULTS
  The incidence of funisitis was 44.4% (20/45): 27.8% (5/18) in patients with preterm labor and intact membranes and 55.6% (15/27) in patients with preterm PROM. The median values of fetal plasma IL-6 in patients with funisitis, chorioamnionitis without funisitis, and non-inflamed membranes were 51.4, 18.4 and 5.2 pg/ml, respectively. After log transformation of the fetal plasma IL-6 concentration, the means differed significantly from each other (ANOVA, p < 0.02). There was no difference in log fetal plasma IL-6 concentration between patients with funisitis and those with chorioamnionitis without funisitis. The difference in mean concentration of log fetal plasma IL-6 between patients with funisitis or chorionic vasculitis and those without inflammation was highly significant (post-hoc test, p = 0.01 and p < 0.01, respectively). Fetuses with fetal plasma IL-6 > 11 pg/ml had a significantly higher rate of histological signs of inflammation in the extra-placental membranes and umbilical cord than those with fetal plasma IL-6 < 11 pg/ml (funisitis: 55.6% (15/27) vs. 27.8% (5/18), p < 0.05; chorionic vasculitis: 55.6% (15/27) vs. 12.5% (2/16), p < 0.01; chorioamnionitis only: 25.9% (7/27) vs. 16.7% (3/18), p < 0.05; no inflammation: 18.5% (5/27) vs. 55.6% (10/18), p < 0.05, respectively). Fetuses with funisitis had significantly higher rates of clinical and histological chorioamnionitis, and neonatal infectious morbidity (proven + suspected sepsis) than fetuses without funisitis (40% (8/20) vs. 8% (2/25), 90% (18/20) vs. 36% (9/25), and 40% (8/20) vs. 4% (1/25), respectively; p < 0.01 for each). Fetuses with chorionic vasculitis had significantly higher rates of clinical and histological chorioamnionitis as well as neonatal infectious morbidity (proven + suspected sepsis) than fetuses without chorionic vasculitis (100% (17/17) vs. 42.3% (11/26), p < 0.01; 82.4% (14/17) vs. 50.0% (13/26), p = 0.05; and 41.2% (7/17) vs. 7.7% (2/26), p = 0.01).
  
  
  CONCLUSIONS
  Fetal plasma IL-6 concentration is significantly associated with the presence of inflammatory lesions in the extraplacental membranes and umbilical cord. Fetuses with fetal plasma IL-6 > 11 pg/ml had a significantly higher rate of funisitis and/or chorionic vasculitis than fetuses with fetal plasma IL-6 < 11 pg/ml. These findings suggest that funisitis/chorionic vasculitis is the histological manifestation of the fetal inflammatory response syndrome.
authors.affiliation: The Perinatology Research Branch, National Institute of Child Health and Human Development, Bethesda, Maryland, USA.
authors.forename: P
authors.initials: P
authors.lastname: Pacora
authors.forename: T
authors.initials: T
authors.lastname: Chaiworapongsa
authors.forename: E
authors.initials: E
authors.lastname: Maymon
authors.forename: Y M
authors.initials: YM
authors.lastname: Kim
authors.forename: R
authors.initials: R
authors.lastname: Gomez
authors.forename: B H
authors.initials: BH
authors.lastname: Yoon
authors.forename: F
authors.initials: F
authors.lastname: Ghezzi
authors.forename: S M
authors.initials: SM
authors.lastname: Berry
authors.forename: F
authors.initials: F
authors.lastname: Qureshi
authors.forename: S M
authors.initials: SM
authors.lastname: Jacques
authors.forename: J C
authors.initials: JC
authors.lastname: Kim
authors.forename: N
authors.initials: N
authors.lastname: Kadar
authors.forename: R
authors.initials: R
authors.lastname: Romero
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D002821:Chorioamnionitis / Q000276:immunology* / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005312:Fetal Blood / Q000276:immunology*; D005322:Premature Rupture of Fetal Membranes / Q000276:immunology / Q000473:pathology; D005865:Gestational Age; D006801:Humans; D015850:Interleukin-6 / Q000097:blood*; D016015:Logistic Models; D007752:Obstetric Labor, Premature / Q000276:immunology / Q000473:pathology; D011247:Pregnancy; D012372:ROC Curve; D012680:Sensitivity and Specificity; D013577:Syndrome; D014470:Umbilical Cord / Q000473:pathology*
chemical_list: D015850:Interleukin-6