title: Breastfeeding effects on DNA methylation in the offspring: A systematic literature review.
abstract: BACKGROUND
  Breastfeeding benefits both infants and mothers. Recent research shows long-term health and human capital benefits among individuals who were breastfed. Epigenetic mechanisms have been suggested as potential mediators of the effects of early-life exposures on later health outcomes. We reviewed the literature on the potential effects of breastfeeding on DNA methylation.
  
  
  METHODS
  Studies reporting original results and evaluating DNA methylation differences according to breastfeeding/breast milk groups (e.g., ever vs. never comparisons, different categories of breastfeeding duration, etc) were eligible. Six databases were searched simultaneously using Ovid, and the resulting studies were evaluated independently by two reviewers.
  
  
  RESULTS
  Seven eligible studies were identified. Five were conducted in humans. Studies were heterogeneous regarding sample selection, age, target methylation regions, methylation measurement and breastfeeding categorisation. Collectively, the studies suggest that breastfeeding might be negatively associated with promoter methylation of LEP (which encodes an anorexigenic hormone), CDKN2A (involved in tumour suppression) and Slc2a4 genes (which encodes an insulin-related glucose transporter) and positively with promoter methylation of the Nyp (which encodes an orexigenic neuropeptide) gene, as well as influence global methylation patterns and modulate epigenetic effects of some genetic variants.
  
  
  CONCLUSIONS
  The findings from our systematic review are far from conclusive due to the small number of studies and their inherent limitations. Further studies are required to understand the actual potential role of epigenetics in the associations of breastfeeding with later health outcomes. Suggestions for future investigations, focusing on epigenome-wide association studies, are provided.
authors.affiliation: Postgraduate Programme in Epidemiology, Federal University of Pelotas, Pelotas, Brazil.|MRC Integrative Epidemiology Unit, School of Social & Community Medicine, University of Bristol, Bristol, United Kingdom.
authors.forename: Fernando Pires
authors.initials: FP
authors.lastname: Hartwig
authors.affiliation: Postgraduate Programme in Epidemiology, Federal University of Pelotas, Pelotas, Brazil.
authors.forename: Christian
authors.initials: C
authors.lastname: Loret de Mola
authors.affiliation: MRC Integrative Epidemiology Unit, School of Social & Community Medicine, University of Bristol, Bristol, United Kingdom.|School of Social and Community Medicine, University of Bristol, United Kingdom.
authors.forename: Neil Martin
authors.initials: NM
authors.lastname: Davies
authors.affiliation: Postgraduate Programme in Epidemiology, Federal University of Pelotas, Pelotas, Brazil.
authors.forename: Cesar Gomes
authors.initials: CG
authors.lastname: Victora
authors.affiliation: MRC Integrative Epidemiology Unit, School of Social & Community Medicine, University of Bristol, Bristol, United Kingdom.|School of Social and Community Medicine, University of Bristol, United Kingdom.
authors.forename: Caroline L
authors.initials: CL
authors.lastname: Relton
mesh_terms: D001942:Breast Feeding; D019941:Cyclin-Dependent Kinase Inhibitor p16; D050763:Cyclin-Dependent Kinase Inhibitor p18 / Q000235:genetics / Q000378:metabolism; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D005260:Female; D051275:Glucose Transporter Type 4 / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007223:Infant; D008137:Longitudinal Studies; D008297:Male; D008895:Milk, Human / Q000737:chemistry* / Q000502:physiology
chemical_list: C000614131:CDKN2A protein, human; D019941:Cyclin-Dependent Kinase Inhibitor p16; D050763:Cyclin-Dependent Kinase Inhibitor p18; D051275:Glucose Transporter Type 4; C495692:SLC2A4 protein, human