title: Sterile intra-amniotic inflammation in asymptomatic patients with a sonographic short cervix: prevalence and clinical significance.
abstract: OBJECTIVE
  To determine the frequency and clinical significance of sterile and microbial-associated intra-amniotic inflammation in asymptomatic patients with a sonographic short cervix.
  
  
  METHODS
  Amniotic fluid (AF) samples obtained by transabdominal amniocentesis from 231 asymptomatic women with a sonographic short cervix [cervical length (CL) ≤25 mm] were analyzed using cultivation techniques (for aerobic and anaerobic as well as genital mycoplasmas) and broad-range polymerase chain reaction (PCR) coupled with electrospray ionization mass spectrometry (PCR/ESI-MS). The frequency and magnitude of intra-amniotic inflammation [defined as an AF interleukin (IL)-6 concentration ≥2.6 ng/mL], acute histologic placental inflammation, spontaneous preterm delivery (sPTD), and the amniocentesis-to-delivery interval were examined according to the results of AF cultures, PCR/ESI-MS and AF IL-6 concentrations.
  
  
  RESULTS
  Ten percent (24/231) of patients with a sonographic short cervix had sterile intra-amniotic inflammation (an elevated AF IL-6 concentration without evidence of microorganisms using cultivation and molecular methods). Sterile intra-amniotic inflammation was significantly more frequent than microbial-associated intra-amniotic inflammation [10.4% (24/231) versus 2.2% (5/231); p < 0.001]. Patients with sterile intra-amniotic inflammation had a significantly higher rate of sPTD <34 weeks of gestation [70.8% (17/24) versus 31.6% (55/174); p < 0.001] and a significantly shorter amniocentesis-to-delivery interval than patients without intra-amniotic inflammation [median 35, (IQR: 10-70) versus median 71, (IQR: 47-98) days, (p < 0.0001)].
  
  
  CONCLUSIONS
  Sterile intra-amniotic inflammation is more common than microbial-associated intra-amniotic inflammation in asymptomatic women with a sonographic short cervix, and is associated with increased risk of sPTD (<34 weeks). Further investigation is required to determine the causes of sterile intra-amniotic inflammation and the mechanisms whereby this condition is associated with a short cervix and sPTD.
authors.affiliation: a 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 and Detroit , MI , USA.|b Department of Obstetrics and Gynecology , University of Michigan , Ann Arbor , MI , USA.|c Department of Epidemiology and Biostatistics , Michigan State University , East Lansing , MI , USA.
authors.forename: Roberto
authors.initials: R
authors.lastname: Romero
authors.affiliation: a 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 and Detroit , MI , USA.|d Department of Obstetrics and Gynecology , Wayne State University School of Medicine , Detroit , MI , USA.
authors.forename: Jezid
authors.initials: J
authors.lastname: Miranda
authors.affiliation: a 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 and Detroit , MI , USA.|d Department of Obstetrics and Gynecology , Wayne State University School of Medicine , Detroit , MI , USA.
authors.forename: Tinnakorn
authors.initials: T
authors.lastname: Chaiworapongsa
authors.affiliation: a 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 and Detroit , MI , USA.|d Department of Obstetrics and Gynecology , Wayne State University School of Medicine , Detroit , MI , USA.
authors.forename: Piya
authors.initials: P
authors.lastname: Chaemsaithong
authors.affiliation: a 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 and Detroit , MI , USA.|e Integrata Verona, Ostetricia Ginecologia, Azienda Ospedaliera Universitaria , Verona , Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Gotsch
authors.affiliation: a 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 and Detroit , MI , USA.|d Department of Obstetrics and Gynecology , Wayne State University School of Medicine , Detroit , MI , USA.
authors.forename: Zhong
authors.initials: Z
authors.lastname: Dong
authors.affiliation: a 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 and Detroit , MI , USA.|d Department of Obstetrics and Gynecology , Wayne State University School of Medicine , Detroit , MI , USA.
authors.forename: Ahmed I
authors.initials: AI
authors.lastname: Ahmed
authors.affiliation: f Department of Obstetrics and Gynecology , Seoul National University College of Medicine , Seoul , Korea.
authors.forename: Bo Hyun
authors.initials: BH
authors.lastname: Yoon
authors.affiliation: a 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 and Detroit , MI , USA.|d Department of Obstetrics and Gynecology , Wayne State University School of Medicine , Detroit , MI , USA.
authors.forename: Sonia S
authors.initials: SS
authors.lastname: Hassan
authors.affiliation: a 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 and Detroit , MI , USA.|g Department of Pathology , University of Ulsan College of Medicine, Asan Medical Center , Seoul , Korea , and.
authors.forename: Chong J
authors.initials: CJ
authors.lastname: Kim
authors.affiliation: a 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 and Detroit , MI , USA.|c Department of Epidemiology and Biostatistics , Michigan State University , East Lansing , MI , USA.|d Department of Obstetrics and Gynecology , Wayne State University School of Medicine , Detroit , MI , USA.
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Korzeniewski
authors.affiliation: a 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 and Detroit , MI , USA.|d Department of Obstetrics and Gynecology , Wayne State University School of Medicine , Detroit , MI , USA.
authors.forename: Lami
authors.initials: L
authors.lastname: Yeo
authors.affiliation: a 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 and Detroit , MI , USA.|h Department of Pathology , College of Medicine Inje University, Haeundae Paik Hospital , Busan , Democratic People's Republic of Korea.
authors.forename: Yeon Mee
authors.initials: YM
authors.lastname: Kim
keywords: Broad-range real-time polymerase chain reaction with electrospray ionization mass spectrometry; cervical length; infection; pregnancy; premature birth; prematurity; preterm delivery; ureaplasma urealyticim