Nutrition plays a fundamental role in supporting the structural and functional development of the human brain from conception, throughout early infancy and extending into later life. A growing body of evidence suggests that folate and the metabolically related B-vitamins are essential for brain health across all age groups, owing to their specific roles in C 1 metabolism and particularly in the production of S-adenosylmethionine, a universal methyl donor essential for the production of neurotransmitters. Emerging, though not entirely consistent, evidence suggests that maternal folate status throughout pregnancy may influence neurodevelopment and behaviour of the offspring. Furthermore optimal B-vitamin status is associated with better cognitive health in ageing. Of note, a recent clinical trial provided evidence that supplementation with folic acid and related B-vitamins over a 2-year-period reduced global and regional brain atrophy, as measured by MRI scan in older adults. In terms of potential mechanisms, the effects of these B-vitamins on cognitive health may be independent or may be mediated by nutrient-nutrient and/or relevant gene-nutrient interactions. Furthermore, a new area of research suggests that the in utero environment influences health in later life. Folate, an important cofactor in C 1 metabolism, is indirectly involved in DNA methylation, which in turn is considered to be one of the epigenetic mechanisms that may underlie fetal programming and brain development. The present review will explore the evidence that supports a role for folate and the related B-vitamins in brain health across the lifecycle, and potential mechanisms to explain such effects.

It is well established that folic acid supplementation in the early stages of pregnancy can reduce the risk of neural tube defects and some other congenital malformations (1) . Observational research also suggests that maternal folate intake may have a long-term effect on the neurocognitive development of the offspring (2)(3) , however, the evidence so far is inconclusive. The current study aimed to investigate the effect of folic acid supplementation during pregnancy on growth and cognitive development of young children.Mother-child pairs (n = 39) were recruited from a previously conducted randomized control trial which investigated the effect of folic acid supplementation (400 mg/day) in the second and third trimester of pregnancy (FASSTT) study. Anthropometric measurements including height, weight, and waist circumference were taken in order to assess the physical development of the children at the age of 2.8 years. Children of mothers who received folic acid supplementation during the second and third trimester of pregnancy compared to those that did not showed significantly higher scores in the cognitive domain of infant development assessment after adjustment for maternal age, socio-economic factors and birth weight. The differences between the two groups in the other developmental domains of BSITD were not found to be significant. In addition, no significant differences in anthropometric measurements were observed between children born to mothers in the placebo and folic acid treatment groups (not shown). This pilot study suggests that folic acid supplement use during later pregnancy may confer an enhanced effect on the cognitive ability of young children. However, further research in a larger scale study is required to confirm these findings.

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