title: Epigenetic modifications of human placenta associated with preterm birth: a systematic review.
abstract: OBJECTIVE
  Preterm birth (PTB) is one of the leading causes of neonatal mortality and morbidity around the world. Epigenetic alterations of the human placenta may be involved in the causal chain of adverse pregnancy outcomes specifically PTB. In this systematic review, we investigated whether epigenetic dysregulation of the human placenta is associated with PTB.
  
  
  METHODS
  We searched MEDLINE and EMBASE and systematically reviewed all relevant studies on epigenetic placental modifications in PTB. Two independent reviewers selected controlled human studies published in any language, evaluated their quality, and graded them using the Newcastle-Ottawa Quality Assessment Scale. We resolved disagreements by consensus with a third reviewer.
  
  
  RESULTS
  Eleven observational studies of low to moderate quality met the eligibility criteria out of 60 unique studies. Most studies reported an association between placental epigenetic changes (methylation, mRNA and miRNA) and PTB, although research methods were highly heterogeneous.
  
  
  CONCLUSIONS
  Studies reported various associations between specific epigenetic findings and PTB, although methodological concerns limited results' validity. Additional high quality studies are needed to assess the repeatability of these findings. The STROBE guidelines can be used to improve the quality of reporting.
authors.affiliation: a Department of Health Promotion, Social and Behavioral Health , College of Public Health, University of Nebraska Medical Center , Omaha , NE , USA.
authors.forename: Drissa M
authors.initials: DM
authors.lastname: Toure
authors.affiliation: b Department of Environmental, Agricultural and Occupational Health , College of Public Health, University of Nebraska Medical Center , Omaha , NE , USA.
authors.forename: Wael
authors.initials: W
authors.lastname: ElRayes
authors.affiliation: c Department of Epidemiology , College of Public Health, University of Nebraska Medical Center , Omaha , NE , USA.
authors.forename: Debora
authors.initials: D
authors.lastname: Barnes-Josiah
authors.affiliation: d McGoogan Library of Medicine , University of Nebraska Medical Center , Omaha , NE , USA.
authors.forename: Teresa
authors.initials: T
authors.lastname: Hartman
authors.affiliation: e Department of Biochemistry and Molecular Biology , University of Nebraska Epigenomics Core Facility , Omaha , NE , USA.
authors.forename: David
authors.initials: D
authors.lastname: Klinkebiel
authors.affiliation: c Department of Epidemiology , College of Public Health, University of Nebraska Medical Center , Omaha , NE , USA.
authors.forename: Lorena
authors.initials: L
authors.lastname: Baccaglini
mesh_terms: D016022:Case-Control Studies; D044127:Epigenesis, Genetic; D005260:Female; D006801:Humans; D008745:Methylation; D035683:MicroRNAs / Q000378:metabolism; D064887:Observational Studies as Topic; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy; D047928:Premature Birth / Q000209:etiology / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism
chemical_list: D035683:MicroRNAs; D012333:RNA, Messenger
keywords: DNA; Epigenetics; methylation; miRNA; preterm birth