title: The role of granulocyte colony-stimulating factor in the neutrophilia observed in the fetal inflammatory response syndrome.
abstract: Fetal neutrophilia is present in two-thirds of cases with the fetal inflammatory response syndrome (FIRS). The mechanisms responsible for this finding have not been elucidated. Granulocyte colony-stimulating factor (G-CSF) is the primary physiologic regulator of neutrophil production and plays a key role in the rapid generation and release of neutrophils in stressful conditions (i.e., infection). The objective of this study was to determine: 1) whether FIRS was associated with changes in fetal plasma G-CSF concentrations; and 2) if fetal plasma G-CSF concentrations correlated with fetal neutrophil counts, chorioamnionitis, neonatal morbidity/mortality and cordocentesis-to-delivery interval.
  
  
  
  Percutaneous umbilical cord blood sampling was performed in a population of patients with preterm labor (n=107). A fetal plasma interleukin-6 (IL-6) concentration >11 pg/mL was used to define FIRS. Cord blood G-CSF was measured by a sensitive and specific immunoassay. An absolute neutrophil count was determined and corrected for gestational age. Receiver operating characteristic (ROC) curve, survival analysis and Cox proportional hazard model were employed.
  
  
  
  1) G-CSF was detected in all fetal blood samples; 2) fetuses with FIRS had a higher median fetal plasma G-CSF concentration than those without FIRS (P<0.001); 3) a fetal plasma G-CSF concentration ≥134 pg/mL (derived from an ROC curve) was associated with a shorter cordocentesis-to-delivery interval, a higher frequency of chorioamnionitis (clinical and histological), intra-amniotic infection, and composite neonatal morbidity/mortality than a fetal plasma concentration below this cut-off; and 4) a fetal plasma G-CSF concentration ≥134 pg/mL was associated with a shorter cordocentesis-to-delivery interval (hazard ratio 3.2; 95% confidence interval 1.8-5.8) after adjusting for confounders.
  
  
  
  1) G-CSF concentrations are higher in the peripheral blood of fetuses with FIRS than in fetuses without FIRS; and 2) a subset of fetuses with FIRS with elevated fetal plasma G-CSF concentrations are associated with neutrophilia, a shorter procedure-to-delivery interval, chorio-amnionitis and increased perinatal morbidity and mortality.
authors.affiliation: Perinatology Research Branch, NICHD/NIH/DHHS, Bethesda, MD, USA.
authors.forename: Tinnakorn
authors.initials: T
authors.lastname: Chaiworapongsa
authors.forename: Roberto
authors.initials: R
authors.lastname: Romero
authors.forename: Stanley M
authors.initials: SM
authors.lastname: Berry
authors.forename: Sonia S
authors.initials: SS
authors.lastname: Hassan
authors.forename: Bo Hyun
authors.initials: BH
authors.lastname: Yoon
authors.forename: Samuel
authors.initials: S
authors.lastname: Edwin
authors.forename: Moshe
authors.initials: M
authors.lastname: Mazor
mesh_terms: D000328:Adult; D002821:Chorioamnionitis / Q000097:blood / Q000209:etiology; D003430:Cross-Sectional Studies; D005260:Female; D005312:Fetal Blood / Q000166:cytology / Q000378:metabolism; D005315:Fetal Diseases / Q000097:blood* / Q000209:etiology*; D005865:Gestational Age; D016179:Granulocyte Colony-Stimulating Factor / Q000097:blood*; D006801:Humans; D007231:Infant, Newborn; D007234:Infant, Premature; D015850:Interleukin-6 / Q000097:blood; D007958:Leukocyte Count; D009504:Neutrophils / Q000473:pathology*; D007752:Obstetric Labor, Premature / Q000097:blood; D011247:Pregnancy; D012189:Retrospective Studies; D018746:Systemic Inflammatory Response Syndrome / Q000097:blood* / Q000151:congenital / Q000209:etiology*; D055815:Young Adult
chemical_list: C508600:IL6 protein, human; D015850:Interleukin-6; D016179:Granulocyte Colony-Stimulating Factor