Steane, S.E., Cuffe, J.S.M. and Moritz, K.M. (2023), The role of maternal choline, folate and one-carbon metabolism in mediating the impact of prenatal alcohol exposure on placental and fetal development. J Physiol. Accepted Author Manuscript. https://doi.org/10.1113/JP283556
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Abstract
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 thought to be altered DNA methylation (DNAm) 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 as they provide methyl groups for DNAm via one carbon metabolism (1CM). 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.
Key points
- Prenatal alcohol exposure (PAE) can result in alterations to the growth and development of the placenta and the fetus leading to long term physical and neurological abnormalities.
- A major mechanism through which alcohol is thought to impact fetal development is by altering DNA methylation, an important process in the epigenetic regulation of gene expression.
- Maternal intake of micronutrients, particularly folate and choline, may be an important factor in modifying the effects of PAE as these nutrients supply methyl groups for DNA methylation.
- Clinical and preclinical studies have demonstrated that maternal supplementation with folate and choline can ameliorate the effects of alcohol on fetal brain development. However, there is limited evidence for the effects of supplementation in early pregnancy on the preimplantation embryo and, later in pregnancy, on the placenta.
- Further studies are required to determine threshold concentrations of both choline and folate to support optimal fetal and placental development.
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