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Journal of Perinatal Medicine

Official Journal of the World Association of Perinatal Medicine

Editor-in-Chief: Dudenhausen, Joachim W.

Editorial Board Member: / Bancalari, Eduardo / Greenough, Anne / Genc, Mehmet R. / Chervenak, Frank A. / Chappelle, Joseph / Bergmann, Renate L. / Bernardes, J.F. / Bevilacqua, G. / Blickstein, Isaac / Cabero Roura, Luis / Carbonell-Estrany, Xavier / Carrera, Jose M. / D`Addario, Vincenzo / D'Alton, MD, Mary E. / Dimitrou, G. / Grunebaum, Amos / Hentschel, Roland / Köpcke, W. / Kawabata, Ichiro / Keirse, M.J.M.C. / Kurjak M.D., Asim / Lee, Ben H. / Levene, Malcolm / Lockwood, Charles J. / Marsal, Karel / Makatsariya, Alexander / Nishida, Hiroshi / Papp, Zoltán / Pejaver, Ranjan Kumar / Pooh, Ritsuko K. / Romero, Roberto / Saugstad, Ola D. / Schenker, Joseph G. / Sen, Cihat / Seri, Istvan / Vetter, Klaus / Winn, Hung N. / Young, Bruce K. / Zimmermann, Roland

6 Issues per year

IMPACT FACTOR 2013: 1.425

SCImago Journal Rank (SJR): 0.782
Source Normalized Impact per Paper (SNIP): 0.928



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

Tinnakorn Chaiworapongsa1, 2 / 1 / Stanley M. Berry3 / Sonia S. Hassan1, 2 / Bo Hyun Yoon4 / Samuel Edwin5 / Moshe Mazor6

1Perinatology Research Branch, NICHD/NIH/DHHS, Bethesda, MD and Detroit, MI, USA

2Department of Obstetrics and Gynecology, Wayne State University School of Medicine/Hutzel Women’s Hospital, Detroit, MI, USA

3William Beaumont Hospital, Royal Oak, MI, USA

4Seoul National University College of Medicine, Seoul, Korea

5Biosurety Division USARIID, Frederick, MD, USA

6Ben Gurion University, Soroka Medical Center, Beer Sheva, Israel

Corresponding author: Roberto Romero, MD Perinatology Research Branch NICHD, NIH, DHHS Wayne State University/Hutzel Women’s Hospital 3990 John R Box 4 Detroit MI 48201 USA Tel.: +1-313-993-2700 Fax: +1-313-993-2694

Citation Information: Journal of Perinatal Medicine. Volume 39, Issue 6, Pages 653–666, ISSN (Online) 1619-3997, ISSN (Print) 0300-5577, DOI: 10.1515/jpm.2011.072, September 2011

Publication History

Published Online:


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.

Keywords: Chorioamnionitis; cordocentesis; fetal infection; fetal plasma; FIRS; G-CSF; interleukin-6; pregnancy; prematurity; preterm labor

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