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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 / Ogata, Edward / 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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Evidence of changes in the immunophenotype and metabolic characteristics (intracellular reactive oxygen radicals) of fetal, but not maternal, monocytes and granulocytes in the fetal inflammatory response syndrome

Sun Kwon Kim1 / Roberto Romero1–3, , / Tinnakorn Chaiworapongsa1, 3 / Juan Pedro Kusanovic1, 3 / Shali Mazaki-Tovi1, 3 / Pooja Mittal1, 3 / Offer Erez1, 3 / Edi Vaisbuch1, 3 / Francesca Gotsch1 / Percy Pacora1 / Lami Yeo1, 3 / Maria Teresa Gervasi4 / Ronald F. Lamont1, 3 / Bo Hyun Yoon5 / Sonia S. Hassan1, 3

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

2Center for Molecular Medicine and Genetics, Wayne State University, Detroit, MI, USA

3Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI, USA

4Obstetrics and Gynecology Department, Azienda Ospedaliera of Padova, Padova, Italy

5Department of Obstetrics and Gynecology, Seoul National University, Seoul, Korea

Corresponding author: Roberto Romero, MD and Sun Kwon Kim, MD, PhD Perinatology Research Branch, NICHD, NIH, DHHS Wayne State University/Hutzel Women's Hospital 3990 John R, Box 4 Detroit, MI 48201 USA Tel.: +(313) 993-2700 Fax: +(313) 993-2694

Citation Information: Journal of Perinatal Medicine. Volume 37, Issue 5, Pages 543–552, ISSN (Online) 1619-3997, ISSN (Print) 0300-5577, DOI: 10.1515/JPM.2009.106, June 2009

Publication History

Published Online:


Objective: The fetal inflammatory response syndrome (FIRS) is present in a fraction of fetuses exposed to intra-amniotic infection and is associated with the impending onset of labor and multisystem organ involvement. Neonates born with funisitis, the histologic counterpart of fetal systemic inflammation, are at increased risk for cerebral palsy and bronchopulmonary dysplasia. The aim of this study was to determine whether fetal and maternal granulocytes and monocytes have the phenotypic and metabolic characteristics of activation in cases with FIRS.

Study design: A case-control study was conducted with umbilical cord and maternal blood samples obtained from patients who delivered preterm with (n=30) and without funisitis (n=15). The phenotypic characteristics of granulocytes and monocytes were examined using flow cytometry and monoclonal antibodies including CD11b, CD14, CD15, CD16, CD18, CD49d, CD62L, CD64, CD66b, and HLA-DR. Intracellular reactive oxygen species (iROS) were measured at the basal state and after stimulation (oxidative burst). A P<0.01 was considered statistically significant.

Results: (1) Funisitis was associated with a significant increase in the median mean channel brightness (MCB) of CD14, CD64, and CD66b on granulocytes and the MCB of CD64 on monocytes collected from umbilical cord blood. (2) The basal iROS production and oxidative burst were higher in the umbilical cord monocytes of neonates with funisitis than in those without funisitis. (3) There were no differences in the immunophenotype, basal iROS production, and oxidative burst in maternal granulocytes or monocytes between the study groups.

Conclusion: Fetal systemic inflammation is associated with phenotypic and metabolic changes consistent with activation in fetal immune cells but not in maternal blood.

Keywords: Chorioamnionitis; fetal inflammation; fetal inflammatory response syndrome; fetal monocyte-granulocyte activation; flow cytometry; funisitis; leukocyte phenotype; prematurity; preterm delivery

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