title: Cesarean delivery and hematopoietic stem cell epigenetics in the newborn infant: implications for future health?
abstract: OBJECTIVE
  Cesarean section (CS) has been associated with a greater risk for asthma, diabetes, and cancer later in life. Although elective CS continues to rise, it is unclear whether and how it may contribute to compromised future health. Our aim was to investigate the influence of mode of delivery on the epigenetic state in neonatal hematopoietic stem cells.
  
  
  METHODS
  This was an observational study of 64 healthy, singleton, newborn infants (33 boys) born at term. Cord blood was sampled after elective CS (n = 27) and vaginal delivery. Global deoxyribonucleic acid (DNA) methylation in hematopoietic stem cells (CD34+) was determined by luminometric methylation assay, and genome-wide, locus-specific DNA methylation analysis was performed by Illumina Infinium 450K (Illumina, San Diego, CA), validated by bisulfite-pyrosequencing.
  
  
  RESULTS
  CD34+ cells from infants delivered by CS were globally more DNA methylated (+2%) than DNA from infants delivered vaginally (P = .02). In relation to mode of delivery, a locus-specific analysis identified 343 loci with a difference in DNA methylation of 10% or greater (P < .01). A majority of the differentially methylated loci in neonatal CD34+ cells (76%) were found to be hypermethylated after vaginal delivery. In these infants, the degree of DNA methylation in 3 loci correlated to the duration of labor. The functional relevance of differentially methylated loci involved processes such as immunoglobulin biosynthetic process, regulation of glycolysis and ketone metabolism, and regulation of the response to food.
  
  
  CONCLUSIONS
  A possible interpretation is that mode of delivery affects the epigenetic state of neonatal hematopoietic stem cells. Given the functional relevance indicated, our findings may have important implications for health and disease in later life.
authors.affiliation: Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; The Center for Molecular Medicine, Stockholm, Sweden.
authors.forename: Malin
authors.initials: M
authors.lastname: Almgren
authors.affiliation: Department of Clinical Science, Intervention, and Technology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Titus
authors.initials: T
authors.lastname: Schlinzig
authors.affiliation: Department of Medicine, Karolinska Institutet, Stockholm, Sweden; The Center for Molecular Medicine, Stockholm, Sweden.
authors.forename: David
authors.initials: D
authors.lastname: Gomez-Cabrero
authors.affiliation: Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; The Center for Molecular Medicine, Stockholm, Sweden.
authors.forename: Agneta
authors.initials: A
authors.lastname: Gunnar
authors.affiliation: Department of Clinical Science, Intervention, and Technology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Mikael
authors.initials: M
authors.lastname: Sundin
authors.affiliation: Department of Medicine, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Stefan
authors.initials: S
authors.lastname: Johansson
authors.affiliation: Department of Clinical Science, Intervention, and Technology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Mikael
authors.initials: M
authors.lastname: Norman
authors.affiliation: Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; The Center for Molecular Medicine, Stockholm, Sweden. Electronic address: tomas.ekstrom@ki.se.
authors.forename: Tomas J
authors.initials: TJ
authors.lastname: Ekström
mesh_terms: D000328:Adult; D018952:Antigens, CD34 / Q000378:metabolism; D002585:Cesarean Section; D019175:DNA Methylation / Q000235:genetics*; D036861:Delivery, Obstetric / Q000379:methods; D044127:Epigenesis, Genetic / Q000235:genetics*; D005260:Female; D005312:Fetal Blood / Q000166:cytology; D006412:Hematopoietic Stem Cells / Q000378:metabolism*; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D011247:Pregnancy; D055815:Young Adult
chemical_list: D018952:Antigens, CD34
keywords: cesarean section; delivery; epigenetics; methylation