title: Placental 11-beta hydroxysteroid dehydrogenase methylation is associated with newborn growth and a measure of neurobehavioral outcome.
abstract: BACKGROUND
  There is growing evidence that the intrauterine environment can impact the neurodevelopment of the fetus through alterations in the functional epigenome of the placenta. In the placenta, the HSD11B2 gene encoding the 11-beta hydroxysteroid dehydrogenase enzyme, which is responsible for the inactivation of maternal cortisol, is regulated by DNA methylation, and has been shown to be susceptible to stressors from the maternal environment.
  
  
  RESULTS
  We examined the association between DNA methylation of the HSD11B2 promoter region in the placenta of 185 healthy newborn infants and infant and maternal characteristics, as well as the association between this epigenetic variability and newborn neurobehavioral outcome assessed with the NICU Network Neurobehavioral Scales. Controlling for confounders, HSD11B2 methylation extent is greatest in infants with the lowest birthweights (P = 0.04), and this increasing methylation was associated with reduced scores of quality of movement (P = 0.04).
  
  
  CONCLUSIONS
  These results suggest that factors in the intrauterine environment which contribute to birth outcome may be associated with placental methylation of the HSD11B2 gene and that this epigenetic alteration is in turn associated with a prospectively predictive early neurobehavioral outcome, suggesting in some part a mechanism for the developmental origins of infant neurological health.
authors.affiliation: Department of Pharmacology, Dartmouth Medical School, Hanover, New Hampshire, United States of America. Carmen.J.Marsit@dartmouth.edu
authors.forename: Carmen J
authors.initials: CJ
authors.lastname: Marsit
authors.forename: Matthew A
authors.initials: MA
authors.lastname: Maccani
authors.forename: James F
authors.initials: JF
authors.lastname: Padbury
authors.forename: Barry M
authors.initials: BM
authors.lastname: Lester
mesh_terms: D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2 / Q000235:genetics / Q000378:metabolism*; D001288:Attention; D001519:Behavior; D019175:DNA Methylation / Q000235:genetics*; D003710:Demography; D005260:Female; D018507:Gene Expression Regulation, Developmental; D015971:Gene Expression Regulation, Enzymologic; D048788:Growth and Development / Q000235:genetics*; D006801:Humans; D007231:Infant, Newborn / Q000254:growth & development*; D016014:Linear Models; D008297:Male; D009420:Nervous System / Q000378:metabolism*; D010920:Placenta / Q000201:enzymology*; D011247:Pregnancy; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
chemical_list: D012333:RNA, Messenger; D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2; C468387:HSD11B2 protein, human