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. 2023 Mar;601(6):1061-1075. doi: 10.1113/JP283556. Epub 2023 Feb 21.

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 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.

Keywords: DNA methylation; blastocyst; fetal brain; maternal nutrition; one carbon metabolism; placenta; prenatal alcohol.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carbon / metabolism
  • Choline / metabolism
  • Choline / pharmacology
  • Female
  • Fetal Development
  • Folic Acid* / metabolism
  • Humans
  • Maternal-Fetal Exchange
  • Micronutrients / metabolism
  • Placenta / metabolism
  • Pregnancy
  • Prenatal Exposure Delayed Effects* / metabolism

Substances

  • Folic Acid
  • Choline
  • Micronutrients
  • Carbon