title: The role of infection in miscarriage.
abstract: BACKGROUND
  Miscarriage is the spontaneous loss of a pregnancy before 12 weeks (early miscarriage) or from 12 to 24 weeks (late miscarriage) of gestation. Miscarriage occurs in one in five pregnancies and can have considerable physiological and psychological implications for the patient. It is also associated with significant health care costs. There is evidence that potentially preventable infections may account for up to 15% of early miscarriages and up to 66% of late miscarriages. However, the provision of associated screening and management algorithms is inconsistent for newly pregnant women. Here, we review recent population-based studies on infections that have been shown to be associated with miscarriage.
  
  
  METHODS
  Our aim was to examine where the current scientific focus lies with regards to the role of infection in miscarriage. Papers dating from June 2009 with key words 'miscarriage' and 'infection' or 'infections' were identified in PubMed (292 and 327 papers, respectively, on 2 June 2014). Relevant human studies (meta-analyses, case-control studies, cohort studies or case series) were included. Single case reports were excluded. The studies were scored based on the Newcastle - Ottawa Quality Assessment Scale.
  
  
  RESULTS
  The association of systemic infections with malaria, brucellosis, cytomegalovirus and human immunodeficiency virus, dengue fever, influenza virus and of vaginal infection with bacterial vaginosis, with increased risk of miscarriage has been demonstrated. Q fever, adeno-associated virus, Bocavirus, Hepatitis C and Mycoplasma genitalium infections do not appear to affect pregnancy outcome. The effects of Chlamydia trachomatis, Toxoplasma gondii, human papillomavirus, herpes simplex virus, parvovirus B19, Hepatitis B and polyomavirus BK infections remain controversial, as some studies indicate increased miscarriage risk and others show no increased risk. The latest data on rubella and syphilis indicate increased antenatal screening worldwide and a decrease in the frequency of their reported associations with pregnancy failure. Though various pathogens have been associated with miscarriage, the mechanism(s) of infection-induced miscarriage are not yet fully elucidated.
  
  
  CONCLUSIONS
  Further research is required to clarify whether certain infections do increase miscarriage risk and whether screening of newly pregnant women for treatable infections would improve reproductive outcomes.
authors.affiliation: Centre for Reproductive Health, University of Edinburgh, Edinburgh EH16 4TJ, UK.
authors.forename: Sevi
authors.initials: S
authors.lastname: Giakoumelou
authors.affiliation: Moredun Research Institute, Pentlands Science Park, Bush Loan, Edinburgh EH26 0PZ, UK.
authors.forename: Nick
authors.initials: N
authors.lastname: Wheelhouse
authors.affiliation: Scottish HPV Reference Lab, Division of Lab Medicine, Royal Infirmary of Edinburgh, Edinburgh EH16 4SA, UK.
authors.forename: Kate
authors.initials: K
authors.lastname: Cuschieri
authors.affiliation: Moredun Research Institute, Pentlands Science Park, Bush Loan, Edinburgh EH26 0PZ, UK The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Easter Bush, Midlothian EH25 9RG, UK.
authors.forename: Gary
authors.initials: G
authors.lastname: Entrican
authors.affiliation: Centre for Inflammation Research, University of Edinburgh, Edinburgh EH16 4TJ, UK.
authors.forename: Sarah E M
authors.initials: SE
authors.lastname: Howie
authors.affiliation: Centre for Reproductive Health, University of Edinburgh, Edinburgh EH16 4TJ, UK Andrew.Horne@ed.ac.uk.
authors.forename: Andrew W
authors.initials: AW
authors.lastname: Horne
mesh_terms: D000022:Abortion, Spontaneous / Q000382:microbiology*; D001424:Bacterial Infections / Q000150:complications; D016022:Case-Control Studies; D015331:Cohort Studies; D005260:Female; D006801:Humans; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious; D011256:Pregnancy Outcome; D011296:Prenatal Diagnosis; D011528:Protozoan Infections / Q000150:complications; D014777:Virus Diseases / Q000150:complications
keywords: female tract; infection; miscarriage; pregnancy