title: Microbial invasion of the amniotic cavity in preeclampsia as assessed by cultivation and sequence-based methods.
abstract: 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.
  
  
  
  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.
  
  
  
  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).
  
  
  
  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.
authors.affiliation: Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA.
authors.forename: Daniel B
authors.initials: DB
authors.lastname: DiGiulio
authors.forename: Mariateresa
authors.initials: M
authors.lastname: Gervasi
authors.forename: Roberto
authors.initials: R
authors.lastname: Romero
authors.forename: Shali
authors.initials: S
authors.lastname: Mazaki-Tovi
authors.forename: Edi
authors.initials: E
authors.lastname: Vaisbuch
authors.forename: Juan Pedro
authors.initials: JP
authors.lastname: Kusanovic
authors.forename: Kimberley S
authors.initials: KS
authors.lastname: Seok
authors.forename: Ricardo
authors.initials: R
authors.lastname: Gómez
authors.forename: Pooja
authors.initials: P
authors.lastname: Mittal
authors.forename: Francesca
authors.initials: F
authors.lastname: Gotsch
authors.forename: Tinnakorn
authors.initials: T
authors.lastname: Chaiworapongsa
authors.forename: Enrique
authors.initials: E
authors.lastname: Oyarzún
authors.forename: Chong Jai
authors.initials: CJ
authors.lastname: Kim
authors.forename: David A
authors.initials: DA
authors.lastname: Relman
mesh_terms: D000328:Adult; D000650:Amnion / Q000382:microbiology*; D000653:Amniotic Fluid / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D001483:Base Sequence; D002821:Chorioamnionitis / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D015331:Cohort Studies; D017931:DNA Primers / Q000235:genetics; D019641:DNA, Archaeal / Q000235:genetics / Q000302:isolation & purification; D004269:DNA, Bacterial / Q000235:genetics / Q000302:isolation & purification; D004271:DNA, Fungal / Q000235:genetics / Q000302:isolation & purification; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D018836:Inflammation Mediators / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D020784:Matrix Metalloproteinase 8 / Q000378:metabolism; D008828:Microbiological Techniques; D016133:Polymerase Chain Reaction; D011225:Pre-Eclampsia / Q000276:immunology / Q000382:microbiology*; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000276:immunology / Q000378:metabolism / Q000382:microbiology*; D011256:Pregnancy Outcome; D012189:Retrospective Studies; D055815:Young Adult
chemical_list: D017931:DNA Primers; D019641:DNA, Archaeal; D004269:DNA, Bacterial; D004271:DNA, Fungal; C508600:IL6 protein, human; D018836:Inflammation Mediators; D015850:Interleukin-6; C488762:MMP8 protein, human; D020784:Matrix Metalloproteinase 8