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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

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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

Received:
2011-05-18
Revised:
2011-06-03
Accepted:
2011-06-20
Published Online:
2011-09-15

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.

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

Citing Articles

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[1]
Joon-Seok Hong, Roberto Romero, Deug-Chan Lee, Nandor Gabor Than, Lami Yeo, Piya Chaemsaithong, Soyeon Ahn, Jung-Sun Kim, Chong Jai Kim, and Yeon Mee Kim
The Journal of Maternal-Fetal & Neonatal Medicine, 2015, Page 1
[2]
Roberto Romero, Nicholas Kadar, Jezid Miranda, Steven J. Korzeniewski, Alyse G. Schwartz, Piya Chaemsaithong, Wade Rogers, Eleazar Soto, Francesca Gotsch, Lami Yeo, Sonia S. Hassan, and Tinnakorn Chaiworapongsa
Journal of Maternal-Fetal and Neonatal Medicine, 2014, Volume 27, Number 8, Page 757
[3]
JoonHo Lee, Roberto Romero, Tinnakorn Chaiworapongsa, Zhong Dong, Adi L. Tarca, Yi Xu, Po Jen Chiang, Juan Pedro Kusanovic, Sonia S. Hassan, Lami Yeo, Bo Hyun Yoon, Nandor Gabor Than, and Chong Jai Kim
American Journal of Reproductive Immunology, 2013, Volume 70, Number 4, Page 265
[4]
Tamara Stampalija, Tinnakorn Chaiworapongsa, Roberto Romero, Adi L. Tarca, Gaurav Bhatti, Po Jen Chiang, Nandor Gabor Than, Enrico Ferrazzi, Sonia S. Hassan, and Lami Yeo
Journal of Maternal-Fetal and Neonatal Medicine, 2014, Volume 27, Number 2, Page 111
[5]
Tamara Stampalija, Roberto Romero, Steven J. Korzeniewski, Piya Chaemsaithong, Jezid Miranda, Lami Yeo, Zhong Dong, Sonia S. Hassan, and Tinnakorn Chaiworapongsa
Journal of Maternal-Fetal and Neonatal Medicine, 2013, Volume 26, Number 14, Page 1384
[6]
B. D. Taylor, C. B. Holzman, R. N. Fichorova, Y. Tian, N. M. Jones, W. Fu, and P. K. Senagore
Human Reproduction, 2013, Volume 28, Number 4, Page 942
[7]
Marian Kacerovsky, Teresa Cobo, Ctirad Andrys, Ivana Musilova, Marcela Drahosova, Helena Hornychova, Petr Janku, and Bo Jacobsson
Journal of Maternal-Fetal and Neonatal Medicine, 2013, Volume 26, Number 8, Page 795
[8]
Vincenzo Zanardo, Carla Peruzzetto, Daniele Trevisanuto, Francesco Cavallin, Stefania Vedovato, Gianluca Straface, and Silvia Chiarelli
Journal of Maternal-Fetal and Neonatal Medicine, 2012, Volume 25, Number 12, Page 2769
[9]
Seung Mi Lee, Roberto Romero, Jeong Woo Park, Sun Min Kim, Chan-Wook Park, Steven J. Korzeniewski, Tinnakorn Chaiworapongsa, and Bo Hyun Yoon
Journal of Maternal-Fetal and Neonatal Medicine, 2012, Volume 25, Number 9, Page 1690
[10]
Sun Young Kim, Roberto Romero, Adi L. Tarca, Gaurav Bhatti, Chong Jai Kim, JoonHo Lee, Amelia Elsey, Nandor Gabor Than, Tinnakorn Chaiworapongsa, Sonia S. Hassan, Gyeong Hoon Kang, and Jung-Sun Kim
American Journal of Reproductive Immunology, 2012, Volume 68, Number 1, Page 8

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