Prevalence and Clinical Significance of Sterile Intra-amniotic Inflammation in Patients with Preterm Labor and Intact Membranes
Corresponding Author
Roberto Romero
Perinatology Research Branch, Program for Perinatal Research and Obstetrics, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, Bethesda, MD, USA
Perinatology Research Branch, Program for Perinatal Research and Obstetrics, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, Detroit, MI, USA
Department of Obstetrics and Gynecology, University of Michigan, Ann Arbor, MI, USA
Department of Epidemiology and Biostatistics, Michigan State University, East Lansing, MI, USA
Correspondence
Roberto Romero, Perinatology Research Branch, NICHD/NIH/DHHS, Wayne State University/Hutzel Women's Hospital, 3990 John R, Box 4, Detroit, MI 48201, USA.
E-mail: [email protected]
Search for more papers by this authorJezid Miranda
Perinatology Research Branch, Program for Perinatal Research and Obstetrics, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, Bethesda, MD, USA
Perinatology Research Branch, Program for Perinatal Research and Obstetrics, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, Detroit, MI, USA
Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI, USA
Search for more papers by this authorTinnakorn Chaiworapongsa
Perinatology Research Branch, Program for Perinatal Research and Obstetrics, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, Bethesda, MD, USA
Perinatology Research Branch, Program for Perinatal Research and Obstetrics, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, Detroit, MI, USA
Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI, USA
Search for more papers by this authorSteven J. Korzeniewski
Perinatology Research Branch, Program for Perinatal Research and Obstetrics, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, Bethesda, MD, USA
Perinatology Research Branch, Program for Perinatal Research and Obstetrics, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, Detroit, MI, USA
Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI, USA
Search for more papers by this authorPiya Chaemsaithong
Perinatology Research Branch, Program for Perinatal Research and Obstetrics, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, Bethesda, MD, USA
Perinatology Research Branch, Program for Perinatal Research and Obstetrics, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, Detroit, MI, USA
Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI, USA
Search for more papers by this authorFrancesca Gotsch
Perinatology Research Branch, Program for Perinatal Research and Obstetrics, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, Bethesda, MD, USA
Perinatology Research Branch, Program for Perinatal Research and Obstetrics, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, Detroit, MI, USA
Integrata Verona, Ostetricia Ginecologia, Azienda Ospedaliera Universitaria, Verona, Italy
Search for more papers by this authorZhong Dong
Perinatology Research Branch, Program for Perinatal Research and Obstetrics, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, Bethesda, MD, USA
Perinatology Research Branch, Program for Perinatal Research and Obstetrics, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, Detroit, MI, USA
Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI, USA
Search for more papers by this authorAhmed I. Ahmed
Perinatology Research Branch, Program for Perinatal Research and Obstetrics, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, Bethesda, MD, USA
Perinatology Research Branch, Program for Perinatal Research and Obstetrics, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, Detroit, MI, USA
Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI, USA
Search for more papers by this authorBo Hyun Yoon
Department of Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul, Korea
Search for more papers by this authorSonia S. Hassan
Perinatology Research Branch, Program for Perinatal Research and Obstetrics, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, Bethesda, MD, USA
Perinatology Research Branch, Program for Perinatal Research and Obstetrics, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, Detroit, MI, USA
Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI, USA
Search for more papers by this authorChong Jai Kim
Perinatology Research Branch, Program for Perinatal Research and Obstetrics, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, Bethesda, MD, USA
Perinatology Research Branch, Program for Perinatal Research and Obstetrics, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, Detroit, MI, USA
Department of Pathology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea
Search for more papers by this authorLami Yeo
Perinatology Research Branch, Program for Perinatal Research and Obstetrics, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, Bethesda, MD, USA
Perinatology Research Branch, Program for Perinatal Research and Obstetrics, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, Detroit, MI, USA
Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI, USA
Search for more papers by this authorCorresponding Author
Roberto Romero
Perinatology Research Branch, Program for Perinatal Research and Obstetrics, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, Bethesda, MD, USA
Perinatology Research Branch, Program for Perinatal Research and Obstetrics, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, Detroit, MI, USA
Department of Obstetrics and Gynecology, University of Michigan, Ann Arbor, MI, USA
Department of Epidemiology and Biostatistics, Michigan State University, East Lansing, MI, USA
Correspondence
Roberto Romero, Perinatology Research Branch, NICHD/NIH/DHHS, Wayne State University/Hutzel Women's Hospital, 3990 John R, Box 4, Detroit, MI 48201, USA.
E-mail: [email protected]
Search for more papers by this authorJezid Miranda
Perinatology Research Branch, Program for Perinatal Research and Obstetrics, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, Bethesda, MD, USA
Perinatology Research Branch, Program for Perinatal Research and Obstetrics, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, Detroit, MI, USA
Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI, USA
Search for more papers by this authorTinnakorn Chaiworapongsa
Perinatology Research Branch, Program for Perinatal Research and Obstetrics, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, Bethesda, MD, USA
Perinatology Research Branch, Program for Perinatal Research and Obstetrics, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, Detroit, MI, USA
Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI, USA
Search for more papers by this authorSteven J. Korzeniewski
Perinatology Research Branch, Program for Perinatal Research and Obstetrics, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, Bethesda, MD, USA
Perinatology Research Branch, Program for Perinatal Research and Obstetrics, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, Detroit, MI, USA
Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI, USA
Search for more papers by this authorPiya Chaemsaithong
Perinatology Research Branch, Program for Perinatal Research and Obstetrics, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, Bethesda, MD, USA
Perinatology Research Branch, Program for Perinatal Research and Obstetrics, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, Detroit, MI, USA
Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI, USA
Search for more papers by this authorFrancesca Gotsch
Perinatology Research Branch, Program for Perinatal Research and Obstetrics, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, Bethesda, MD, USA
Perinatology Research Branch, Program for Perinatal Research and Obstetrics, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, Detroit, MI, USA
Integrata Verona, Ostetricia Ginecologia, Azienda Ospedaliera Universitaria, Verona, Italy
Search for more papers by this authorZhong Dong
Perinatology Research Branch, Program for Perinatal Research and Obstetrics, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, Bethesda, MD, USA
Perinatology Research Branch, Program for Perinatal Research and Obstetrics, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, Detroit, MI, USA
Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI, USA
Search for more papers by this authorAhmed I. Ahmed
Perinatology Research Branch, Program for Perinatal Research and Obstetrics, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, Bethesda, MD, USA
Perinatology Research Branch, Program for Perinatal Research and Obstetrics, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, Detroit, MI, USA
Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI, USA
Search for more papers by this authorBo Hyun Yoon
Department of Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul, Korea
Search for more papers by this authorSonia S. Hassan
Perinatology Research Branch, Program for Perinatal Research and Obstetrics, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, Bethesda, MD, USA
Perinatology Research Branch, Program for Perinatal Research and Obstetrics, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, Detroit, MI, USA
Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI, USA
Search for more papers by this authorChong Jai Kim
Perinatology Research Branch, Program for Perinatal Research and Obstetrics, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, Bethesda, MD, USA
Perinatology Research Branch, Program for Perinatal Research and Obstetrics, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, Detroit, MI, USA
Department of Pathology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea
Search for more papers by this authorLami Yeo
Perinatology Research Branch, Program for Perinatal Research and Obstetrics, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, Bethesda, MD, USA
Perinatology Research Branch, Program for Perinatal Research and Obstetrics, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, Detroit, MI, USA
Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI, USA
Search for more papers by this authorAbstract
Problem
Inflammation and infection play a major role in preterm birth. The purpose of this study was to (i) determine the prevalence and clinical significance of sterile intra-amniotic inflammation and (ii) examine the relationship between amniotic fluid (AF) concentrations of high mobility group box-1 (HMGB1) and the interval from amniocentesis to delivery in patients with sterile intra-amniotic inflammation.
Method of study
AF samples obtained from 135 women with preterm labor and intact membranes were analyzed using cultivation techniques as well as broad-range PCR and mass spectrometry (PCR/ESI-MS). Sterile intra-amniotic inflammation was defined when patients with negative AF cultures and without evidence of microbial footprints had intra-amniotic inflammation (AF interleukin-6 ≥ 2.6 ng/mL).
Results
(i) The frequency of sterile intra-amniotic inflammation was significantly greater than that of microbial-associated intra-amniotic inflammation [26% (35/135) versus 11% (15/135); (P = 0.005)], (ii) patients with sterile intra-amniotic inflammation delivered at comparable gestational ages had similar rates of acute placental inflammation and adverse neonatal outcomes as patients with microbial-associated intra-amniotic inflammation, and (iii) patients with sterile intra-amniotic inflammation and high AF concentrations of HMGB1 (≥8.55 ng/mL) delivered earlier than those with low AF concentrations of HMGB1 (P = 0.02).
Conclusion
(i) Sterile intra-amniotic inflammation is more frequent than microbial-associated intra-amniotic inflammation, and (ii) we propose that danger signals participate in sterile intra-amniotic inflammation in the setting of preterm labor.
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