Maternal B vitamins: effects on offspring weight and DNA methylation at genomically imprinted domains.
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).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.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).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.
McCullough, LE; Miller, EE; Mendez, MA; Murtha, AP; Murphy, SK; Hoyo, C
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