title: Amniotic fluid infection, inflammation, and colonization in preterm labor with intact membranes.
abstract: OBJECTIVE
  The purpose of this study was to compare intraamniotic inflammation vs microbial invasion of the amniotic cavity (MIAC) as predictors of adverse outcome in preterm labor with intact membranes.
  
  
  METHODS
  Interleukin-6 (IL-6) was measured in prospectively collected amniotic fluid from 305 women with preterm labor. MIAC was defined by amniotic fluid culture and/or detection of microbial 16S ribosomal DNA. Cases were categorized into 5 groups: infection (MIAC; IL-6, ≥11.3 ng/mL); severe inflammation (no MIAC; IL-6, ≥11.3 ng/mL); mild inflammation (no MIAC; IL-6, 2.6-11.2 ng/mL); colonization (MIAC; IL-6, <2.6 ng/mL); negative (no MIAC; IL-6, <2.6 ng/mL).
  
  
  RESULTS
  The infection (n = 27) and severe inflammation (n = 36) groups had similar latency (median, <1 day and 2 days, respectively) and similar rates of composite perinatal morbidity and mortality (81% and 72%, respectively). The colonization (n = 4) and negative (n = 195) groups had similar outcomes (median latency, 23.5 and 25 days; composite morbidity and mortality rates, 21% and 25%, respectively). The mild inflammation (n = 47) groups had outcomes that were intermediate to the severe inflammation and negative groups (median latency, 7 days; composite morbidity and mortality rates, 53%). In logistic regression adjusting for gestational age at enrollment, IL-6 ≥11.3 and 2.6-11.2 ng/mL, but not MIAC, were associated significantly with composite morbidity and mortality rates (odds ratio [OR], 4.9; 95% confidence interval [CI], 2.2-11.2, OR, 3.1; 95% CI, 1.5-6.4, and OR, 1.8; 95% CI, 0.6-5.5, respectively).
  
  
  CONCLUSIONS
  We confirmed previous reports that intraamniotic inflammation is associated with adverse perinatal outcomes whether or not intraamniotic microbes are detected. Colonization without inflammation appears relatively benign. Intraamniotic inflammation is not simply present or absent but also has degrees of severity that correlate with adverse outcomes. We propose the designation amniotic inflammatory response syndrome to denote the adverse outcomes that are associated with intraamniotic inflammation.
authors.affiliation: Center for Research, Education, and Quality, Mednax, Inc., Sunrise, FL; Obstetrix Medical Group, San Jose, CA.
authors.forename: C Andrew
authors.initials: CA
authors.lastname: Combs
authors.affiliation: University of Washington Medical Center, Seattle, WA.
authors.forename: Michael
authors.initials: M
authors.lastname: Gravett
authors.affiliation: Center for Research, Education, and Quality, Mednax, Inc., Sunrise, FL.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Garite
authors.affiliation: ProteoGenix, Inc., Costa Mesa, CA.
authors.forename: Durlin E
authors.initials: DE
authors.lastname: Hickok
authors.affiliation: Oregon Health and Science University, Portland, OR.
authors.forename: Jodi
authors.initials: J
authors.lastname: Lapidus
authors.affiliation: Obstetrix Medical Group of Colorado, Denver, CO.
authors.forename: Richard
authors.initials: R
authors.lastname: Porreco
authors.affiliation: Center for Research, Education, and Quality, Mednax, Inc., Sunrise, FL; Obstetrix Medical Group of Colorado, Denver, CO.
authors.forename: Julie
authors.initials: J
authors.lastname: Rael
authors.affiliation: ProteoGenix, Inc., Costa Mesa, CA.
authors.forename: Thomas
authors.initials: T
authors.lastname: Grove
authors.affiliation: Oregon Health and Science University, Portland, OR.
authors.forename: Terry K
authors.initials: TK
authors.lastname: Morgan
authors.affiliation: Obstetrix Medical Group, Phoenix Perinatal Associates, Phoenix, AZ.
authors.forename: William
authors.initials: W
authors.lastname: Clewell
authors.affiliation: Obstetrix Medical Group of Arizona, Tucson, AZ.
authors.forename: Hugh
authors.initials: H
authors.lastname: Miller
authors.affiliation: Obstetrix Medical Group of Washington, Seattle, WA.
authors.forename: David
authors.initials: D
authors.lastname: Luthy
authors.affiliation: Oregon Health and Science University, Portland, OR.
authors.forename: Leonardo
authors.initials: L
authors.lastname: Pereira
authors.affiliation: Obstetrix Medical Group, Southern California, Long Beach, CA.
authors.forename: Michael
authors.initials: M
authors.lastname: Nageotte
authors.affiliation: University of Washington Medical Center, Seattle, WA.
authors.forename: Peter A
authors.initials: PA
authors.lastname: Robilio
authors.affiliation: Perinatal Research Group, Nashville, TN.
authors.forename: Stephen
authors.initials: S
authors.lastname: Fortunato
authors.affiliation: University of Pittsburgh, Pittsburgh, PA.
authors.forename: Hyagriv
authors.initials: H
authors.lastname: Simhan
authors.affiliation: Thomas Jefferson University, Philadelphia, PA.
authors.forename: Jason K
authors.initials: JK
authors.lastname: Baxter
authors.affiliation: St. Louis University School of Medicine, St. Louis, MO.
authors.forename: Erol
authors.initials: E
authors.lastname: Amon
authors.affiliation: Carolinas Medical Center, Charlotte, NC.
authors.forename: Albert
authors.initials: A
authors.lastname: Franco
authors.affiliation: University Medical Center, Greenville, SC.
authors.forename: Kenneth
authors.initials: K
authors.lastname: Trofatter
authors.affiliation: Obstetrix Medical Group of Colorado, Denver, CO.
authors.forename: Kent
authors.initials: K
authors.lastname: Heyborne
mesh_terms: D000328:Adult; D000653:Amniotic Fluid / Q000737:chemistry / Q000276:immunology / Q000382:microbiology*; D002821:Chorioamnionitis / Q000382:microbiology; D004275:DNA, Ribosomal / Q000032:analysis; D005260:Female; D006801:Humans; D015850:Interleukin-6 / Q000032:analysis; D016015:Logistic Models; D007752:Obstetric Labor, Premature; D016133:Polymerase Chain Reaction; D011247:Pregnancy; D011256:Pregnancy Outcome; D012307:Risk Factors
chemical_list: D004275:DNA, Ribosomal; D015850:Interleukin-6
keywords: chorioamnionitis; intraamniotic infection; intraamniotic inflammation; microbial invasion of the amniotic cavity; morbidity; preterm birth; preterm labor