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

Abstract

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: Tinnakorn Chaiworapongsa, Roberto Romero, Stanley M Berry, Sonia S Hassan, Bo Hyun Yoon, Samuel Edwin, Moshe Mazor
• Journal: Journal of perinatal medicine (J Perinat Med) Vol. 39 Issue 6 Pg. 653-66 (11 2011) ISSN: 1619-3997 [Electronic] Germany
• PMID: 21801092 (Publication Type: Journal Article, Research Support, N.I.H., Intramural, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• IL6 protein, human
• Interleukin-6
• Granulocyte Colony-Stimulating Factor

Topics

• Adult
• Chorioamnionitis (blood, etiology)
• Cross-Sectional Studies
• Female
• Fetal Blood (cytology, metabolism)
• Fetal Diseases (blood, etiology)
• Gestational Age
• Granulocyte Colony-Stimulating Factor (blood)
• Humans
• Infant, Newborn
• Infant, Premature
• Interleukin-6 (blood)
• Leukocyte Count
• Neutrophils (pathology)
• Obstetric Labor, Premature (blood)
• Pregnancy
• Retrospective Studies
• Systemic Inflammatory Response Syndrome (blood, congenital, etiology)
• Young Adult