Periconceptional folic acid (FA) has an established protective effect in preventing neural tube defects (NTDs), leading to global recommendations for FA supplementation before and in early pregnancy. However, it is unclear whether there are any benefits for offspring brain health arising from continued maternal FA supplementation beyond the first trimester. The aim of this thesis was to investigate the role of maternal folate nutrition during pregnancy in relation to brain health in the offspring. As part of this work, an extensive review of the literature was conducted which highlighted that maternal folate during pregnancy may affect neurodevelopment and cognitive performance in the first decade of life, albeit the evidence at this time is predominantly observational. The children of mothers who had participated in a randomised trial of Folic Acid Supplementation in the Second and Third Trimesters (FASSTT) were investigated, providing a unique opportunity to more robustly examine offspring cognitive health in relation to maternal folate (the FASSTT Offspring trial; n
68). The findings showed improved performance in specific cognitive domains (but not Full Scale IQ) in children at 11 years whose mothers had been randomised to receive FA during pregnancy. Furthermore, girls from the FA group scored significantly higher in verbal IQ than those in the placebo group. The current results in the FASSTT offspring at 11 years provide further substantiation of earlier results from the same children at 3 and 7 years, which showed improved cognition and word reasoning (verbal IQ) scores, respectively, in response to maternal FA supplmentation through trimesters two and three of pregnancy. A unique feature of this thesis was the application of magnetoencephalography (MEG) to assess brain activity in a subset of these children (n
33). The results showed that offspring of the FA-treated mothers compared to placebo had better brain functioning at resting state and also demonstrated more efficient language processing abilities. Although the precise biological mechanism explaining the effect of FA during pregnancy on neurodevelopment of the child is unknown, it must involve the essential role of folate in one-carbon metabolism encompassing a network of pathways that support a variety of processes, including myelination, neurotransmitter synthesis and epigenetics. One of the studies within this thesis, indicated that continued maternal supplementation with FA after the first trimester of pregnancy leads to epigenetic changes in the offspring, via DNA methylation of genes related to brain development and function. There are potentially important impacts arising from this thesis. The findings provide scientific evidence that continuing FA supplementation beyond the early period that is protective against NTDs, may be beneficial for brain health in the offspring. Furthermore, this thesis demonstrates the application of MEG in nutrition research and specifically in children, as an objective measure of functional brain activity in response to nutrition intervention.
- Brain Imaging
- First 1,000 days