title: Chorioamnionitis Occurring in Women With Preterm Rupture of the Fetal Membranes Is Associated With a Dynamic Increase in mRNAs Coding Cytokines in the Maternal Circulation.
abstract: BACKGROUND
  Preterm prelabor rupture of the fetal membranes (PPROM) is a significant contributor to the morbidity and mortality of preterm birth, particularly in the setting of chorioamnionitis. No sensitive or specific diagnostic or predictive test currently exists for the accurate diagnosis of chorioamnionitis. Our aim was to measure messenger RNA (mRNA) coding cytokines in the maternal blood and examine whether they were increased in association with chorioamnionitis at delivery.
  
  
  RESULTS
  We performed a prospective cohort study of women recruited with PPROM at a mean gestational age of 28.9 weeks at risk of developing chorioamnionitis. Blood was sampled from participants, and the expression of mRNA coding for proinflammatory genes was measured in women with and without chorioamnionitis at the time of delivery as well as gestation-matched healthy controls. Expression was measured using quantitative polymerase chain reaction (PCR) and also digital PCR. Interleukin 1β (IL1B) mRNA expression in maternal blood was elevated in women with chorioamnionitis compared to gestation-matched controls. Importantly, among women admitted with PPROM, digital PCR confirmed a significant increase in IL1B expression in maternal blood in women with chorioamnionitis compared to women without chorioamnionitis. Polymerase chain reaction array revealed that CD14, nuclear factor of κ light polypeptide gene enhancer in B-cells 1 (NFKB1), and tumor necrosis factor receptor super family-interacting serine-threonine kinase 1 mRNA were significantly increased in women with chorioamnionitis compared to controls. Digital PCR confirmed that NFKB1 mRNA was significantly increased in patients with chorioamnionitis compared to controls and that CD14 levels increased over time in patients with PPROM having chorioamnionitis.
  
  
  CONCLUSIONS
  Measuring circulating proinflammatory mRNA in women with PPROM may distinguish those with chorioamnionitis from those without, in turn providing better targeted therapies and appropriate timing of delivery.
authors.affiliation: Department of Obstetrics and Gynaecology, Translational Obstetrics Group, University of Melbourne, Mercy Hospital for Women, Heidelberg, Victoria, Australia owen.stock@unimelb.edu.au.
authors.forename: Owen
authors.initials: O
authors.lastname: Stock
authors.affiliation: Murdoch Children's Research Institute, The Royal Children's Hospital, Parkville, Victoria, Australia Australian Genome Research Facility Ltd, The Walter and Eliza Hall Institute, Parkville, Victoria, Australia.
authors.forename: Lavinia
authors.initials: L
authors.lastname: Gordon
authors.affiliation: Department of Obstetrics and Gynaecology, Translational Obstetrics Group, University of Melbourne, Mercy Hospital for Women, Heidelberg, Victoria, Australia.
authors.forename: Jada
authors.initials: J
authors.lastname: Kapoor
authors.affiliation: Department of Obstetrics and Gynaecology, Translational Obstetrics Group, University of Melbourne, Mercy Hospital for Women, Heidelberg, Victoria, Australia.
authors.forename: Susan P
authors.initials: SP
authors.lastname: Walker
authors.affiliation: Department of Obstetrics and Gynaecology, Translational Obstetrics Group, University of Melbourne, Mercy Hospital for Women, Heidelberg, Victoria, Australia.
authors.forename: Clare
authors.initials: C
authors.lastname: Whitehead
authors.affiliation: Department of Obstetrics and Gynaecology, Translational Obstetrics Group, University of Melbourne, Mercy Hospital for Women, Heidelberg, Victoria, Australia.
authors.forename: Tu'uhevaha J
authors.initials: TJ
authors.lastname: Kaitu'u-Lino
authors.affiliation: Department of Obstetrics and Gynaecology, Translational Obstetrics Group, University of Melbourne, Mercy Hospital for Women, Heidelberg, Victoria, Australia.
authors.forename: Gabrielle
authors.initials: G
authors.lastname: Pell
authors.affiliation: Department of Obstetrics and Gynaecology, Translational Obstetrics Group, University of Melbourne, Mercy Hospital for Women, Heidelberg, Victoria, Australia.
authors.forename: Natalie J
authors.initials: NJ
authors.lastname: Hannan
authors.affiliation: Department of Obstetrics and Gynaecology, Translational Obstetrics Group, University of Melbourne, Mercy Hospital for Women, Heidelberg, Victoria, Australia.
authors.forename: Stephen
authors.initials: S
authors.lastname: Tong
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D002821:Chorioamnionitis / Q000097:blood / Q000175:diagnosis / Q000235:genetics*; D015331:Cohort Studies; D016207:Cytokines / Q000097:blood / Q000235:genetics*; D005260:Female; D005322:Premature Rupture of Fetal Membranes / Q000097:blood / Q000175:diagnosis / Q000235:genetics*; D006801:Humans; D053583:Interleukin-1beta / Q000097:blood / Q000235:genetics; D018950:Lipopolysaccharide Receptors / Q000097:blood / Q000235:genetics; D052002:NF-kappa B p50 Subunit / Q000097:blood / Q000235:genetics; D021041:Placental Circulation / Q000235:genetics*; D011247:Pregnancy; D011446:Prospective Studies; D012333:RNA, Messenger / Q000097:blood / Q000235:genetics*; D014409:Tumor Necrosis Factor-alpha / Q000097:blood / Q000235:genetics
chemical_list: D015415:Biomarkers; D016207:Cytokines; C508585:IL1B protein, human; D053583:Interleukin-1beta; D018950:Lipopolysaccharide Receptors; D052002:NF-kappa B p50 Subunit; C489548:NFKB1 protein, human; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha
keywords: IL1B; PCR; chorioamnionitis; digital PCR; inflammation; intrauterine infection; mRNA; preterm birth; preterm prelabor rupture of the fetal membranes