title: Dynamic Changes in DNA Methylation Occur during the First Year of Life in Preterm Infants.
abstract: Preterm birth associates with a substantially increased risk of later cardiovascular disease and neurodevelopmental disorders. Understanding underlying mechanisms will facilitate the development of screening and intervention strategies to reduce disease risk. Changes in DNA methylation have been proposed as one mechanism linking the early environment with later disease risk. We tested the hypothesis that preterm birth associates with altered DNA methylation in genes encoding insulin-like growth factor 2 (IGF2) and FK506-binding protein 5 (FKBP5), which appear particularly vulnerable to early life adversity.
  
  
  
  Fifty preterm infants were seen and assessed at birth, term equivalent age, 3 months and 1-year corrected ages; 40 term infants were seen at birth, 3 months and 1 year. Saliva was collected for DNA extraction at birth, term, and 1 year. Pyrosequencing of bisulfite-converted DNA was performed to measure DNA methylation at specific CpG sites within theIGF2andFKBP5loci.
  
  
  
  Weight and head circumference was reduced in preterm infants at all time points. Preterm infants had a higher percentage body fat at term-corrected age, but this difference was not persistent. DNA methylation at the differentially methylated region (DMR) ofIGF2(IGF2DMR2) andFKBP5was lower in preterm infants at birth- and term-corrected age compared to term infants at birth.IGF2DMR2andFKBP5methylation was related to birthweight SD score in preterm infants. Among preterm infants, social deprivation was an independent contributor toward reducing DNA methylation atIGF2DMR2at birth- and term-corrected age and maternal smoking was associated with reduced DNA methylation atFKBP5at birth. There were no persistent differences in DNA methylation at 1 year of age.
  
  
  
  Changes in DNA methylation were identified at key regions ofIGF2/H19andFKBP5in preterm infants in early life. Potential contributing factors include maternal smoking and social deprivation. However, these changes did not persist at 1 year of age and further longitudinal studies are required to determine any associations between altered DNA methylation in the perinatal period of individuals born preterm and their long-term health.
authors.affiliation: British Heart Foundation Centre for Cardiovascular Science, The Queen's Medical Research Institute, University of Edinburgh, Edinburgh, UK; Neonatal Unit, Simpson Centre for Reproductive Health, Royal Infirmary of Edinburgh, Edinburgh, UK.
authors.forename: Chinthika
authors.initials: C
authors.lastname: Piyasena
authors.affiliation: British Heart Foundation Centre for Cardiovascular Science, The Queen's Medical Research Institute, University of Edinburgh , Edinburgh , UK.
authors.forename: Jessy
authors.initials: J
authors.lastname: Cartier
authors.affiliation: Department of Translational Research in Psychiatry, Max-Planck Institute of Psychiatry , Munich , Germany.
authors.forename: Nadine
authors.initials: N
authors.lastname: Provençal
authors.affiliation: Department of Translational Research in Psychiatry, Max-Planck Institute of Psychiatry , Munich , Germany.
authors.forename: Tobias
authors.initials: T
authors.lastname: Wiechmann
authors.affiliation: British Heart Foundation Centre for Cardiovascular Science, The Queen's Medical Research Institute, University of Edinburgh , Edinburgh , UK.
authors.forename: Batbayar
authors.initials: B
authors.lastname: Khulan
authors.affiliation: Neonatal Unit, Simpson Centre for Reproductive Health, Royal Infirmary of Edinburgh , Edinburgh , UK.
authors.forename: Raju
authors.initials: R
authors.lastname: Sunderesan
authors.affiliation: Neonatal Unit, Simpson Centre for Reproductive Health, Royal Infirmary of Edinburgh , Edinburgh , UK.
authors.forename: Gopi
authors.initials: G
authors.lastname: Menon
authors.affiliation: British Heart Foundation Centre for Cardiovascular Science, The Queen's Medical Research Institute, University of Edinburgh , Edinburgh , UK.
authors.forename: Jonathan R
authors.initials: JR
authors.lastname: Seckl
authors.affiliation: British Heart Foundation Centre for Cardiovascular Science, The Queen's Medical Research Institute, University of Edinburgh , Edinburgh , UK.
authors.forename: Rebecca M
authors.initials: RM
authors.lastname: Reynolds
authors.affiliation: Department of Translational Research in Psychiatry, Max-Planck Institute of Psychiatry , Munich , Germany.
authors.forename: Elisabeth B
authors.initials: EB
authors.lastname: Binder
authors.affiliation: British Heart Foundation Centre for Cardiovascular Science, The Queen's Medical Research Institute, University of Edinburgh , Edinburgh , UK.
authors.forename: Amanda J
authors.initials: AJ
authors.lastname: Drake
keywords: DNA methylation; FKBP5; IGF2; glucocorticoids; prematurity