Abstract
BackgroundMaternal folic acid (FA) supplementation before and in early pregnancy prevents neural tube defects (NTD), but it is uncertain whether continuing FA after the first trimester has benefits on offspring health. We aimed to evaluate the effect of FA supplementation throughout pregnancy on cognitive performance and brain function in the child.MethodsFollow-up investigation of 11-year-old children, residing in Northern Ireland, whose mothers had participated in a randomised trial of Folic Acid Supplementation in the Second and Third Trimesters (FASSTT) in pregnancy and received 400 μg/day FA or placebo from the 14th gestational week. Cognitive performance (Full Scale Intelligence Quotient, Verbal Comprehension, Working Memory, Perceptual Reasoning, and Processing Speed) was assessed using the Wechsler Intelligence Scale for Children. Neuronal function was assessed using magnetoencephalographic (MEG) brain imaging.ResultsOf 119 mother-child pairs in the FASSTT trial, 68 children were assessed for neurocognitive performance at 11-year follow-up (Dec 2017 to Nov 2018). Children of mothers randomised to FA compared with placebo scored significantly higher in two Processing Speed tests, i.e. symbol search (mean difference 2.9 points, 95% CI 0.3 to 5.5, p = 0.03) and cancellation (11.3 points, 2.5 to 20.1, p = 0.04), whereas the positive effect on Verbal Comprehension was significant in girls only (6.5 points, 1.2 to 11.8, p = 0.03). MEG assessment of neuronal responses to a language task showed increased power at the Beta (13–30 Hz, p = 0.01) and High Gamma (49–70 Hz, p = 0.04) bands in children from FA-supplemented mothers, suggesting more efficient semantic processing of language.ConclusionsContinued FA supplementation in pregnancy beyond the early period currently recommended to prevent NTD can benefit neurocognitive development of the child. MEG provides a non-invasive tool in paediatric research to objectively assess functional brain activity in response to nutrition and other interventions.Trial registrationISRCTN ISRCTN19917787. Registered on 15 May 2013.
Highlights
Maternal folic acid (FA) supplementation before and in early pregnancy prevents neural tube defects (NTD), but it is uncertain whether continuing FA after the first trimester has benefits on offspring health
There were no significant differences between the treatment groups in serum or Red blood cell (RBC) folate at the 14th gestational week (GW), but after FA intervention for 26 weeks, these folate biomarkers were significantly higher in the FA group in maternal and in cord blood samples (Table 2)
Mean dietary folate and B-vitamin intakes compared favourably with European Food Safety Authority (EFSA) population reference intake (PRI) values for children 11–14 years [24], and B-vitamin biomarker concentrations were in good agreement with those reported in population-based surveys in children from Norway [25], the UK [26] and the USA [27]
Summary
Maternal folic acid (FA) supplementation before and in early pregnancy prevents neural tube defects (NTD), but it is uncertain whether continuing FA after the first trimester has benefits on offspring health. Folate is essential in early life, with conclusive evidence that periconceptional supplementation with folic acid (FA; the synthetic vitamin form) is effective in preventing the first occurrence [1] and recurrence [2] of neural tube defects (NTD). This evidence has led to recommendations that are in place worldwide for women to take FA from before conceiving until the end of the first trimester. Another study of note used magnetic resonance imaging (MRI) of the child’s brain along with cognitive tests and found that maternal folate deficiency in later pregnancy was associated with, lower language and visuospatial abilities, and reduced brain volumes in children aged 6–8 years [9]
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