Effect of folic acid supplementation during pregnancy on growth and cognitive development of the offspring: a pilot follow-up investigation of children of FASSTT study participants

Pentieva, Kristina; McGarel, C.; McNulty, Breige; Ward, Mary; Elliott, Nadya T. Majette; Strain, James J.; Rollins, Mark D.; McNulty, Helene

doi:10.1017/s0029665112001966

Cited by 5 publications

(5 citation statements)

References 5 publications

(6 reference statements)

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“…A pilot study ( n 39), conducted by our group, examined the effect of folic acid supplementation in the second and third trimester of pregnancy and subsequent cognitive performance of the child. The novel results showed that children (aged 3 years) born to mothers supplemented with folic acid, scored significantly higher in the cognitive domain of the Bayley's development assessment ( 22 ) . These highly promising results from this RCT now need to be confirmed on a larger scale.…”

Section: C1 Metabolism B-vitamins and Early Brain Healthmentioning

confidence: 94%

Emerging roles for folate and related B-vitamins in brain health across the lifecycle

et al. 2014

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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.

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Section: C1 Metabolism B-vitamins and Early Brain Healthmentioning

confidence: 94%

Emerging roles for folate and related B-vitamins in brain health across the lifecycle

et al. 2014

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“…The only RCT to date to look at the specific effect of 0•4 mg/d FA in isolation was conducted at this centre, namely the FASSTT trial (ISRCTN19917787) (13) and provided a unique opportunity to specifically investigate the effect of FA supplementation in the second and third trimesters on subsequent cognitive performance of the child. The results showed that children of mothers supplemented with FA throughout pregnancy performed better in the cognitive domain at age 3 years (72) and the verbal domain at 7 years (73) . These findings are in agreement with the results of animal studies, whereby continuation of maternal FA supplementation increased serum folate concentrations in pregnant rat dams and improved neurodevelopment in their pups, from newborns to adulthood (74) .…”

Section: Maternal Folate and Offspring Cognitive Performancementioning

confidence: 96%

“…The only RCT to date to look at the specific effect of 0·4 mg/d FA in isolation was conducted at this centre, namely the FASSTT trial (ISRCTN19917787) ( 13 ) and provided a unique opportunity to specifically investigate the effect of FA supplementation in the second and third trimesters on subsequent cognitive performance of the child. The results showed that children of mothers supplemented with FA throughout pregnancy performed better in the cognitive domain at age 3 years ( 72 ) and the verbal domain at 7 years ( 73 ) .…”

Section: Maternal Folate and Offspring Cognitive Performancementioning

confidence: 99%

Maternal folate nutrition and offspring health: evidence and current controversies

et al. 2018

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Periconceptional folic acid (FA) is known to have a protective effect in the prevention of neural tube defects (NTD), leading to global recommendations for FA supplementation before and in early pregnancy. Maternal folate throughout pregnancy may have other roles in offspring health, including neurodevelopment and cognitive performance in childhood. Folate is essential for C1 metabolism, a network of pathways involved in several biological processes including nucleotide synthesis, DNA repair and methylation reactions. The evidence reviewed here shows a conclusive role for offspring health of maternal folate nutrition in early pregnancy and probable benefits in later pregnancy. Folate-mediated epigenetic changes in genes related to brain development and function offer a plausible biological basis to link maternal folate with effects in offspring brain, albeit this research is in its infancy. Mandatory FA fortification of food has proven to be highly effective in decreasing NTD cases in populations where it has been implemented, but this policy is controversial owing to concerns related to potential adverse effects of over-exposure to FA. In the absence of population-wide fortification, and given the generally poor compliance with current FA recommendations, optimising folate status of mothers in very early pregnancy for protection against NTD remains challenging. Thus, current policy in the UK, Ireland and elsewhere in Europe for the prevention of NTD (based on periconceptional FA supplementation only), has proven to be largely ineffective. This review addresses the evidence and the controversies that surround this area, as well as identifying the challenges in translating policy into practice.

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“…However, an intervention study from this centre, the Folic Acid Supplementation in the Second and Third Trimesters trial (9) , provided a unique opportunity to follow-up the children of trial participants and found direct evidence of beneficial effects of folic acid provided to mothers during pregnancy on the cognitive performance of their children at age 3 and 6 years (i.e. as measured by validated tools, the Bayley Scales of Infant and Toddler Development and Weschler Preschool and Primary Scale of Intelligence, respectively) (24,25) . Thus maintaining optimal maternal folate throughout pregnancy, well beyond the early period known to be protective against NTD, may be beneficial for brain development and functioning in the child.…”

Section: Health Impacts Of Folate and Related B Vitamins Through The mentioning

confidence: 99%

Addressing optimal folate and related B-vitamin status through the lifecycle: health impacts and challenges

et al. 2019

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The functional effects of folate within C1 metabolism involve interrelationships with vitamin B12, vitamin B6 and riboflavin, and related gene–nutrient interactions. These B vitamins have important roles throughout life, from pregnancy, through childhood, to middle and older age. Achieving optimal nutritional status for preventing folate-related disease is challenging, however, primarily as a result of the poor stability and incomplete bioavailability of folate from natural food sources when compared with the synthetic vitamin form, folic acid. Thus, in European countries, measures to prevent neural tube defects (NTD) have been largely ineffective because of the generally poor compliance of women with folic acid supplementation as recommended before and in early pregnancy. In contrast, countries worldwide with mandatory folic acid fortification policies have experienced marked reductions in NTD. Low vitamin B12 status is associated with increased risk of cognitive dysfunction, CVD and osteoporosis. Achieving optimal B12 status can be problematic for older people, however, primarily owing to food-bound B12 malabsorption which leads to sub-clinical deficiency even with high dietary B12 intakes. Optimising B-vitamin intake may be particularly important for sub-populations with impaired folate metabolism owing to genetic characteristics, most notably the 677C→T variant in the gene encoding the enzyme methylenetetrahydrofolate reductase (MTHFR). This common folate polymorphism is linked with several adverse health outcomes, including stroke, however, recent evidence has identified its novel interaction with riboflavin (the MTHFR cofactor) in relation to blood pressure and risk of developing hypertension. This review addresses why and how the optimal status of folate-related B vitamins should be achieved through the lifecycle.

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Effect of folic acid supplementation during pregnancy on growth and cognitive development of the offspring: a pilot follow-up investigation of children of FASSTT study participants

Cited by 5 publications

References 5 publications

Emerging roles for folate and related B-vitamins in brain health across the lifecycle

Emerging roles for folate and related B-vitamins in brain health across the lifecycle

Maternal folate nutrition and offspring health: evidence and current controversies

Addressing optimal folate and related B-vitamin status through the lifecycle: health impacts and challenges

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