Effects of continued folic acid supplementation during the second and third trimesters of pregnancy on children’s neurocognitive development at 11 years

Background:
Peri-conceptional folic acid (FA) supplementation is known to prevent neural tube defects. It remains uncertain whether continuing FA after the first trimester has benefits for offspring neurodevelopment. A previously published follow up study of Mothers who had participated in a randomized trialof FA Supplementation in the Second and Third Trimesters (FASSTT) in pregnancy and who had received 400 micrograms/day FA or placebo from the 14th gestational week until the end of pregnancy showed their offspring at both 3 and 7 years scored significantly higher than the placebo group in word reasoning and cognition.
Objectives:
Follow up investigation of 11 year old children, whose Mothers had participated in a randomized trial of FA Supplementation in the Second and Third Trimesters (FASSTT) in pregnancy and received 400 micrograms/day FA or placebo from the 14th gestational week to determine if previous improvement in Cognitive performance and brain function
persists in this age group.
Methods:
Mother - child pairs who undertook the FASSTT trial (healthy pregnant women aged 18–35 years with singleton pregnancy) and who had taken 400 micrograms/day of FA
in the first trimester were randomized to receive FA supplements or placebo until the end of pregnancy. When the child was 11 years old Mother-child pairs were recruited by invitation to undergo assessment of the child`s Cognitive performance by the Wechsler Intelligence Scale for Children (WISCIV). Assessors were blinded to the treatment allocation of theMother during the FASSTT trial. In a sub sample of participants, magnetoencephalographic(MEG)brain imaging was performed to assess brain functioning through estimating neuronal activity in relation to semantic processing of language. Related covariates including general health and lifestyle measures, socioeconomic status, anthropometry including BMI status, B-vitamin biomarkers and nutritional dietary analysis were evaluated. Statistical analysis was performed using the Statistical package for the Social Services software.
Results:
Of the 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 randomized 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.
Conclusions:
Continued 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. Our findings add considerably to the existing evidence that have linked maternal folate status in pregnancy with neurocognitive outcomes in the older child. This evidence reinforces our previous findings in these children and suggest that continued FA intervention in pregnancy beyond the early period is beneficial to future neurocognitive development.