Maternal B vitamins: effects on offspring weight and DNA methylation at genomically imprinted domains

• Type of Material: Article
• Authors: Lauren McCullough, Emory University; Erline E. Miller, University of North Carolina Chapel Hill; Michelle A. Mendez, University of North Carolina Chapel Hill; Amy P. Murtha, Duke University School of Medicine; Susan K. Murphy, Duke University School of Medicine; Cathrine Hoyo, North Carolina State University
• Language: English
• Date: 2016-01-22
• Publisher: BioMed Central
• Publication Version: Final Published Version
• Copyright Statement: © McCullough et al. 2016
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1186/s13148-016-0174-9
• Title of Journal or Parent Work: Clinical Epigenetics
• ISSN: 1868-7075
• Volume: 8
• Issue: 8
• Grant/Funding Information: This work was supported in part by grants from the National Institutes of Health (Grant no. R01-ES016772) via Cathrine Hoyo and National Cancer Institute (R25CA057726) via Lauren McCullough.
• Keywords: Childhood weight gain; Birth weight; B vitamins; DNA methylation; Epidemiology; Imprinted genes
• Research Categories: Health Sciences, Epidemiology; Health Sciences, Public Health

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.