title: Maternal B vitamins: effects on offspring weight and DNA methylation at genomically imprinted domains.
abstract: BACKGROUND
  Inadequate maternal nutrition during early fetal development can create permanent alterations in the offspring, leading to poor health outcomes. While nutrients involved in one-carbon cycle metabolism are important to fetal growth, associations with specific nutrients remain inconsistent. This study estimates associations between maternal vitamins B12, B6 (pyridoxal phosphate [PLP] and 4-pyridoxic acid [PA]), and homocysteine (Hcy) concentrations, offspring weight (birth weight and 3-year weight gain), and DNA methylation at four differentially methylated regions (DMRs) known to be involved in fetal growth and development (H19, MEG3, SGCE/PEG10, and PLAGL1).
  
  
  METHODS
  Study participants (n = 496) with biomarker and birth weight data were enrolled as part of the Newborn Epigenetics STudy. Weight gain data were available for 273 offspring. Among 484 mother-infant pairs, DNA methylation at regulatory sequences of genomically imprinted genes was measured in umbilical cord blood DNA using bisulfite pyrosequencing. We used generalized linear models to estimate associations.
  
  
  RESULTS
  Multivariate adjusted regression models revealed an inverse association between maternal Hcy concentration and male birth weight (β = -210.40, standard error (SE) = 102.08, p = 0.04). The offspring of the mothers in the highest quartile of B12 experienced lower weight gain between birth and 3 years compared to the offspring of the mothers in the lowest (β = -2203.03, SE = 722.49, p = 0.003). Conversely, maternal PLP was associated with higher weight gain in males; higher maternal PLP concentrations were also associated with offspring DNA methylation levels at the MEG3 DMR (p < 0.01).
  
  
  CONCLUSIONS
  While maternal concentrations of B12, B6, and Hcy do not associate with birth weight overall, they may play an important role in 3-year weight gain. This is the first study to report an association between maternal PLP and methylation at the MEG3 DMR which may be an important epigenetic tag for maternal B vitamin adequacy.
authors.affiliation: Department of Epidemiology, University of North Carolina Chapel Hill, Chapel Hill, NC USA ; Lineberger Comprehensive Cancer Center, University of North Carolina Chapel Hill, Chapel Hill, NC USA ; Rollins School of Public Health, Emory University, 1518 Clifton Rd NE, CNR 3037, Atlanta, GA 30322 USA.
authors.forename: Lauren E
authors.initials: LE
authors.lastname: McCullough
authors.affiliation: Department of Epidemiology, University of North Carolina Chapel Hill, Chapel Hill, NC USA.
authors.forename: Erline E
authors.initials: EE
authors.lastname: Miller
authors.affiliation: Department of Nutrition, University of North Carolina Chapel Hill, Chapel Hill, NC USA.
authors.forename: Michelle A
authors.initials: MA
authors.lastname: Mendez
authors.affiliation: Department of Obstetrics and Gynecology, Duke University School of Medicine, Durham, NC USA.
authors.forename: Amy P
authors.initials: AP
authors.lastname: Murtha
authors.affiliation: Department of Obstetrics and Gynecology, Duke University School of Medicine, Durham, NC USA.
authors.forename: Susan K
authors.initials: SK
authors.lastname: Murphy
authors.affiliation: Department of Biological Sciences, North Carolina State University, Raleigh, NC USA.
authors.forename: Cathrine
authors.initials: C
authors.lastname: Hoyo
mesh_terms: D000328:Adult; D001724:Birth Weight / Q000235:genetics* / Q000502:physiology; D018797:Cell Cycle Proteins / Q000235:genetics; D002675:Child, Preschool; D019175:DNA Methylation / Q000502:physiology; D005260:Female; D006710:Homocysteine / Q000097:blood; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D011247:Pregnancy / Q000097:blood; D062085:RNA, Long Noncoding / Q000235:genetics; D049031:Sarcoglycans / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics; D025521:Tumor Suppressor Proteins / Q000235:genetics; D014805:Vitamin B 12 / Q000097:blood*; D025101:Vitamin B 6 / Q000097:blood*; D015430:Weight Gain / Q000235:genetics* / Q000502:physiology; D055815:Young Adult
chemical_list: D018797:Cell Cycle Proteins; C094335:H19 long non-coding RNA; C498907:MEG3 non-coding RNA, human; C106464:PLAGL1 protein, human; D062085:RNA, Long Noncoding; C526572:SGCE protein, human; D049031:Sarcoglycans; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; D006710:Homocysteine; D025101:Vitamin B 6; D014805:Vitamin B 12
keywords: B vitamins; Birth weight; Childhood weight gain; DNA methylation; Epidemiology; Imprinted genes