The role of maternal choline, folate and one‐carbon metabolism in mediating the impact of prenatal alcohol exposure on placental and fetal development

Prenatal alcohol consumption (PAE) may be associated with a broad spectrum of impacts, ranging from no overt effects, to miscarriage, fetal growth restriction and fetal alcohol spectrum disorder. A major mechanism underlying the effects of PAE is considered to be altered DNA methylation and gene expression. Maternal nutritional status may be an important factor in determining the extent to which PAE impacts pregnancy outcomes, particularly the dietary micronutrients folate and choline because they provide methyl groups for DNA methylation via one carbon metabolism. This review summarises the roles of folate and choline in development of the blastocyst, the placenta and the fetal brain, and examines the evidence that maternal intake of these micronutrients can modify the effects of PAE on development. Studies of folate or choline deficiency have found reduced blastocyst development and implantation, reduced placental invasion, vascularisation and nutrient transport capability, impaired fetal brain development, and abnormal neurodevelopmental outcomes. PAE has been shown to reduce absorption and/or metabolism of folate and choline and to produce similar outcomes to maternal choline/folate deficiency. A few studies have demonstrated that the effects of PAE on brain development can be ameliorated by folate or choline supplementation; however, there is very limited evidence on the effects of supplementation in early pregnancy on the blastocyst and placenta. Further studies are required to support these findings and to determine optimal supplementation parameters. figure legend Summary of the proposed mechanism through which maternal nutrition and one carbon metabolism (1CM) mediate the impacts of prenatal alcohol exposure (PAE). Alcohol consumption is associated with poor nutrient intake and altered absorption and/or metabolism of many nutrients. Folate and choline are micronutrients with several important roles in fetal development including epigenetic programming. Both folate and choline contribute to the transfer of methyl groups for the remethylation of homocysteine (HCY) to methionine (MET), which is used to generate the universal methyl donor S‐adenosylmethionine (SAM) during one carbon metabolism (1CM). SAM is the substrate for the methylation of DNA (DNAm) (indicated by red circles on the DNA molecule), a key mechanism in the epigenetic regulation of gene expression. DNAm is important for epigenetic reprogramming of the blastocyst and for optimal placen