The role of granulocyte colony-stimulating factor in the neutrophilia observed in the fetal inflammatory response syndrome

• Published in: Journal of perinatal medicine Vol. 39; no. 6; pp. 653 - 666
• Main Authors: Chaiworapongsa, Tinnakorn, Romero, Roberto, Berry, Stanley M., Hassan, Sonia S., Yoon, Bo Hyun, Edwin, Samuel, Mazor, Moshe
• Format: Journal Article
• Language: English
• Published: Berlin Walter de Gruyter 01.11.2011; De Gruyter
• Subjects: Adult; Biological and medical sciences; Chorioamnionitis; Chorioamnionitis - blood; Chorioamnionitis - etiology; cordocentesis; Cross-Sectional Studies; Delivery. Postpartum. Lactation; Diseases of mother, fetus and pregnancy; Disorders; Female; Fetal Blood - cytology; Fetal Blood - metabolism; Fetal Diseases - blood; Fetal Diseases - etiology; fetal infection; fetal plasma; FIRS; G-CSF; Gestational Age; Granulocyte Colony-Stimulating Factor - blood; Gynecology. Andrology. Obstetrics; Humans; Infant, Newborn; Infant, Premature; interleukin-6; Interleukin-6 - blood; Leukocyte Count; Medical sciences; Neutrophils - pathology; Obstetric Labor, Premature - blood; Pregnancy; Pregnancy. Fetus. Placenta; prematurity; preterm labor; Retrospective Studies; Systemic Inflammatory Response Syndrome - blood; Systemic Inflammatory Response Syndrome - congenital; Systemic Inflammatory Response Syndrome - etiology; Young Adult; Fetal inflammatory response syndrome; Biological fluid; Chorioamnionitis; Pregnancy disorders; Cordocentesis; Neonatology; interleukin-6; Blood plasma; Interleukin 6; Fetal diseases; Granulocyte colony stimulating factor; Delivery disorders; Female; Fetus; Woman; fetal plasma; Human; FIRS; fetal infection; Cytokine; Premature delivery; preterm labor; Inflammation; Placenta diseases; G-CSF; Pregnancy; Infection; Prenatal diagnosis; Maturity; pre-maturity
• ISSN: 0300-5577; 1619-3997
• DOI: 10.1515/JPM.2011.072

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.