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

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.

The Impact of Oxidative Stress on the Epigenetics of Fetal Alcohol Spectrum Disorders

“…Current treatment options for FASD involve supportive approaches such as motivational interviewing and the community-reinforcement approach. There is potential for proactive maternal nutritional intervention, including prenatal administration of antioxidant supplements, folic acid, choline, neuroactive peptides, and neurotrophic growth factors [20,128,129]. Recent suggestions indicate that targeting specific epigenetic mechanisms involved in regulating gene expression could hold significant clinical relevance for individuals with FASD [114].…”

Neurobehavioral alterations induced by third‐trimester gestation‐equivalent ethanol exposure are inhibited by folate administration

“…Pharmacological (Krahe et al, 2009) (Naseer et al, 2011) and vitamin E (Wentzel et al, 2006), and choline-rich diets (Baker et al, 2023) have shown promising outcomes. Folate, a member of the vitamin B family, is crucial for cellular homeostasis, DNA synthesis, and amino acid metabolism (Steane et al, 2023). Folate heightens antioxidant defenses by increas-ing glutathione levels and reducing lipid oxidation.…”

Nutrition and Metabolism in the First 1000 Days of Life

“…During gestation, maternal nutrition affects fetal growth and development via the mother-to-fetus interface. Folic acid and choline, essential nutrients during pregnancy, are involved in the synthesis of nucleotides and phospholipids, as well as methylation [2]. 5,10-methylenetetrahydrofolate dehydrogenase (MTHFD1) is the key enzyme in folic acid metabolism and participates in choline metabolism.…”