OBJECTIVES: 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. STUDY DESIGN: 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. RESULTS: 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. CONCLUSIONS: 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.
OBJECTIVES: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. STUDY DESIGN: 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. RESULTS: 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. CONCLUSIONS: 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: R Romero; J Espinoza; L F Gonçalves; R Gomez; L Medina; M Silva; T Chaiworapongsa; B H Yoon; F Ghezzi; W Lee; M Treadwell; S M Berry; E Maymon; M Mazor; G DeVore Journal: J Matern Fetal Neonatal Med Date: 2004-09
Authors: R L Goldenberg; W W Andrews; B M Mercer; A H Moawad; P J Meis; J D Iams; A Das; S N Caritis; J M Roberts; M Miodovnik; K Menard; G Thurnau; M P Dombrowski; D McNellis Journal: Am J Obstet Gynecol Date: 2000-03 Impact factor: 8.661
Authors: Alice R Goepfert; William W Andrews; Waldemar Carlo; Patrick S Ramsey; Suzanne P Cliver; Robert L Goldenberg; John C Hauth Journal: Am J Obstet Gynecol Date: 2004-10 Impact factor: 8.661
Authors: Neil Hamill; Roberto Romero; Francesca Gotsch; Juan Pedro Kusanovic; Sam Edwin; Offer Erez; Nandor Gabor Than; Pooja Mittal; Jimmy Espinoza; Lara A Friel; Edi Vaisbuch; Shali Mazaki-Tovi; Sonia S Hassan Journal: J Perinat Med Date: 2008 Impact factor: 1.901
Authors: Seung Mi Lee; Roberto Romero; Jeong Woo Park; Sun Min Kim; Chan-Wook Park; Steven J Korzeniewski; Tinnakorn Chaiworapongsa; Bo Hyun Yoon Journal: J Matern Fetal Neonatal Med Date: 2012-04-25
Authors: K Motomura; R Romero; V Garcia-Flores; Y Leng; Y Xu; J Galaz; R Slutsky; D Levenson; N Gomez-Lopez Journal: Mol Hum Reprod Date: 2020-09-01 Impact factor: 4.025
Authors: Roberto Romero; Piya Chaemsaithong; Steven J Korzeniewski; Juan P Kusanovic; Nikolina Docheva; Alicia Martinez-Varea; Ahmed I Ahmed; Bo Hyun Yoon; Sonia S Hassan; Tinnakorn Chaiworapongsa; Lami Yeo Journal: J Perinat Med Date: 2016-01 Impact factor: 1.901