title: Intrauterine Candida albicans Infection Causes Systemic Fetal Candidiasis With Progressive Cardiac Dysfunction in a Sheep Model of Early Pregnancy.
abstract: BACKGROUND
  Several recent studies have identified a potential role for intrauterine Candida albicans in adverse pregnancy outcomes, including preterm birth. There is, however, a limited understanding of the impact of intrauterine candida infection on fetal well-being in early pregnancy. Using a sheep model of early pregnancy, the aims of this study were to determine (1) the ability of experimentally induced intrauterine C albicans to infect the fetus and (2) whether C albicans exposure in early pregnancy is associated with alterations in fetal cardiac function, as measured by spectral tissue Doppler imaging analysis of fetal cardiac function.
  
  
  METHODS
  Merino ewes carrying singleton pregnancies at 89 days' gestation (term is ∼150 days) received C albicans (n = 8) via ultrasound-guided intra-amniotic injection. Saline-exposed fetuses served as controls (n = 6). Spectral tissue Doppler imaging echocardiography and amniotic fluid collection were performed at baseline and 24 and 72 hours after intrauterine C albicans injection. Fetal tissues were collected at postmortem for analysis of infection and inflammation.
  
  
  RESULTS
  Relative to saline control, intrauterine C albicans infection resulted in pronounced increases in amniotic fluid tumor necrosis factor α (TNF-α; P < .05) and cytokine/chemokine messenger RNA (interleukin [IL] 1β, IL-6, TNF-α, and monocyte chemoattractant protein 1; P < .05) in the fetal myocardium, lung, skin, and liver at 72 and 96 hours postinfection. Spectral tissue Doppler imaging showed diastolic dysfunction at 24 hours and severe biventricular diastolic dysfunction 72 hours postinfection.
  
  
  CONCLUSIONS
  Intrauterine C albicans infection in a sheep model of early pregnancy causes systemic fetal candidiasis, which is associated with a robust systemic inflammatory response and progressive cardiac dysfunction detectable by spectral tissue Doppler imaging.
authors.affiliation: 1 Tommy's Centre for Maternal and Fetal Health, MRC Centre for Reproductive Health, University of Edinburgh Queen's Medical Research Institute, Edinburgh, Scotland.|2 School of Women's and Infants' Health, University of Western Australia, Perth, Western Australia, Australia.
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: Stock
authors.affiliation: 3 Fetal Medicine Unit, St George's, University of London, London, United Kingdom.
authors.forename: Olga
authors.initials: O
authors.lastname: Patey
authors.affiliation: 3 Fetal Medicine Unit, St George's, University of London, London, United Kingdom.
authors.forename: Basky
authors.initials: B
authors.lastname: Thilaganathan
authors.affiliation: 2 School of Women's and Infants' Health, University of Western Australia, Perth, Western Australia, Australia.
authors.forename: Scott
authors.initials: S
authors.lastname: White
authors.affiliation: 2 School of Women's and Infants' Health, University of Western Australia, Perth, Western Australia, Australia.
authors.forename: Lucy L
authors.initials: LL
authors.lastname: Furfaro
authors.affiliation: 2 School of Women's and Infants' Health, University of Western Australia, Perth, Western Australia, Australia.
authors.forename: Matthew S
authors.initials: MS
authors.lastname: Payne
authors.affiliation: 4 Institute of Molecular and Experimental Medicine, Cardiff University, Cardiff, United Kingdom.
authors.forename: Owen B
authors.initials: OB
authors.lastname: Spiller
authors.affiliation: 2 School of Women's and Infants' Health, University of Western Australia, Perth, Western Australia, Australia.
authors.forename: Andres
authors.initials: A
authors.lastname: Noé
authors.affiliation: 2 School of Women's and Infants' Health, University of Western Australia, Perth, Western Australia, Australia.
authors.forename: Rory
authors.initials: R
authors.lastname: Watts
authors.affiliation: 2 School of Women's and Infants' Health, University of Western Australia, Perth, Western Australia, Australia.
authors.forename: Sean
authors.initials: S
authors.lastname: Carter
authors.affiliation: 2 School of Women's and Infants' Health, University of Western Australia, Perth, Western Australia, Australia.
authors.forename: Demelza J
authors.initials: DJ
authors.lastname: Ireland
authors.affiliation: 5 Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, OH, USA.
authors.forename: Alan H
authors.initials: AH
authors.lastname: Jobe
authors.affiliation: 2 School of Women's and Infants' Health, University of Western Australia, Perth, Western Australia, Australia.
authors.forename: John P
authors.initials: JP
authors.lastname: Newnham
authors.affiliation: 2 School of Women's and Infants' Health, University of Western Australia, Perth, Western Australia, Australia.
authors.forename: Matthew W
authors.initials: MW
authors.lastname: Kemp
keywords: TDI echocardiography; candidiasis; fetal heart; fetal inflammation; preterm birth; sheep