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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 / 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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Microbial invasion of the amniotic cavity in preeclampsia as assessed by cultivation and sequence-based methods

Daniel B. DiGiulio1, 2 / MariaTeresa Gervasi3 / Roberto Romero4–6, , / Shali Mazaki-Tovi4, 5 / Edi Vaisbuch4, 5 / Juan Pedro Kusanovic4, 5 / Kimberley S. Seok2 / Ricardo Gómez7, 8 / Pooja Mittal4, 5 / Francesca Gotsch4 / Tinnakorn Chaiworapongsa4, 5 / Enrique Oyarzún8 / Chong Jai Kim4, 9 / David A. Relman1, 2, 10

1Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA

2Veterans Affairs Palo Alto Health Care System, Palo Alto, CA, USA

3Department of Obstetrics and Gynecology, Azienda Ospedaliera of Padova, Padova, Italy

4Perinatology Research Branch, NICHD, NIH, Bethesda, MD, and Detroit, MI, USA

5Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Hutzel Women's Hospital, Detroit Medical Center, Detroit, MI, USA

6Center for Molecular Medicine and Genetics, Wayne State University School of Medicine, Detroit, MI, USA

7CEDIP (Center for Perinatal Diagnosis and Research), Department of Obstetrics and Gynecology, Sotero del Rio Hospital, Santiago, Chile

8Department of Obstetrics and Gynecology, P. Universidad Católica de Chile, Santiago, Chile

9Department of Pathology, Wayne State University School of Medicine, Detroit, MI, USA

10Department of Microbiology and Immunology, Stanford University, Stanford, CA, USA

Corresponding author: Roberto Romero, MD Perinatology Research Branch Intramural Division NICHD/NIH/DHHS Hutzel Women's Hospital Box No. 4, 3990 John R Detroit MI 48201 USA Tel.: +1 (313) 993-2700 Fax: +1 (313) 993-2694

Citation Information: Journal of Perinatal Medicine. Volume 38, Issue 5, Pages 503–513, ISSN (Online) 1619-3997, ISSN (Print) 0300-5577, DOI: 10.1515/jpm.2010.078, May 2010

Publication History

Received:
2010-03-05
Revised:
2010-03-26
Accepted:
2010-03-29
Published Online:
2010-05-20

Abstract

Objective: Infection has been implicated in the pathogenesis of preeclampsia, yet the association between microbial invasion of the amniotic cavity (MIAC) and preeclampsia has not been determined. The aim of this study was to determine the prevalence, and microbial diversity associated with MIAC, as well as the nature of the host response to MIAC in patients with preeclampsia.

Method of study: Amniotic fluid (AF) from 62 subjects with preeclampsia, not in labor, was analyzed with both cultivation and molecular methods. Broad-range and group-specific PCR assays targeting small subunit ribosomal DNA, or other gene sequences, from bacteria, fungi and archaea were used. Results were correlated with measurements of host inflammatory response, including AF white blood cell count and AF concentrations of glucose, interleukin-6 (IL-6) and MMP-8.

Results: 1) The rate of MIAC in preeclampsia was 1.6% (1/62) based on cultivation techniques, 8% (5/62) based on PCR, and 9.6% (6/62) based on the combined results of both methods; 2) among the six patients diagnosed with MIAC, three had a positive PCR for Sneathia/Leptotrichia spp.; and 3) patients with MIAC were more likely to have evidence of an inflammatory response in the amniotic cavity than those without MIAC, as determined by a higher median AF IL-6 [1.65 ng/mL interquartile range (IQR): 0.35–4.62 vs. 0.22 ng/mL IQR: 0.12–0.51; P=0.002).

Conclusion: The prevalence of MIAC in preeclampsia is low, suggesting that intra-amniotic infection plays only a limited role in preeclampsia. However, the unexpectedly high number of positive AF specimens for Sneathia/Leptotrichia warrants further investigation.

Keywords: IL-6; intra-amniotic infection; intra-amniotic inflammation; PCR; preeclampsia; pregnancy; 16S rRNA; Sneathia/Leptotrichia spp; Ureaplasma urealyticum

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