Epigenetic aspects of preconceptional folate supplementation

Folates (vitamin B9) are essential for one-carbon metabolism, nucleotide synthesis, and DNA methylation, playing a central role in embryonic and placental development. Folate deficiency is associated with neural tube defects, pregnancy complications, and mental health disorders, including perinatal depression. Several studies have shown that inadequate dietary intake of folate may disrupt this pathway and reduce DNA methylation, a major epigenetic factor influencing gene activities. DNA methylation during fetal development plays a critical role in regulating fundamental biological processes such as imprinting, X-chromosome inactivation, differentiation, and pluripotency. Objective – to summarize recent evidence (2023–2025) on the role of folates during pregnancy, with a focus on epigenetic mechanisms, the Developmental Origins of Health and Disease (DOHaD) concept, offspring cognitive outcomes, and opportunities for personalized nutritional support. The review highlights experimental and clinical findings on the impact of folates on epigenetic regulation, placental function, and longterm offspring health. Supplementation is shown to reduce the risk of neural tube defects, preeclampsia, and intrauterine growth restriction. Associations between maternal folate status, child cognitive development, and perinatal depression are discussed. Special attention is given to monitoring biomarkers (red blood cell folate, homocysteine, vitamin B12) and genetic predictors (MTHFR polymorphisms) to justify a personalized approach. Adequate folate intake in the periconceptional period and throughout pregnancy is crucial for preventing obstetric and psychiatric complications and shaping favorable long-term offspring outcomes. Personalized supplementation strategies based on biomarkers and genetic data represent a promising avenue for clinical practice.

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