Folic Acid Supplementation Throughout Pregnancy: Neurocognitive Developmental Benefits for Children

Sarfaroj Khan 


March 30, 2021


  • Continued folic acid (FA) supplementation in pregnancy beyond the early period currently recommended to prevent neural tube defects (NTD) is beneficial to neurocognitive development in the child.

  • Study also demonstrated the application of magnetoencephalography (MEG) as a non-invasive tool in paediatric research to objectively assess functional brain activity in response to nutrition and other interventions.

Why this matters

  • Findings add considerably to the existing evidence from observational studies and indicate that FA intervention throughout pregnancy will have beneficial effects on cognitive performance in the child up to 11 years.

  • Current recommendations for NTD prevention in the UK and most countries worldwide advise mothers to take FA supplements from before conceiving until the end of the 12th gestational week only.

Study design

  • This study was conducted as a follow-up investigation of children at 11 years whose mothers had participated in a randomised trial of Folic Acid Supplementation in the Second and Third Trimesters (FASSTT) in pregnancy and received FA (400 μg/day) or placebo from the 14th gestational week.

  • Of 119 mother-child pairs, 68 children were assessed for neurocognitive performance at 11-year follow-up (Dec 2017 to Nov 2018) (FA, n=37; placebo, n=31)

  • Cognitive performance and neuronal function were assessed using the Wechsler Intelligence Scale for Children and magnetoencephalographic (MEG) brain imaging, respectively.

  • Funding: Biotechnology and Biological Sciences Research Council and others.

Key results

  • Children of mothers randomised to FA vs placebo scored significantly higher in 2 processing speed tests:

    • symbol search (mean difference [MD], 2.9 points; 95% CI, 0.3-5.5; P=.03); and

    • cancellation (MD, 11.3 points; 95% CI, 2.5-20.1; P=.04).

  • The positive effect of prenatal FA on verbal comprehension was significant in girls only (MD, 6.5 points; 95% CI, 1.2-11.8; P=.03).

  • MEG assessment of neuronal responses to a language task showed increased power at the beta (13-30 Hz; MD, 83.2 points; 95% CI, 15.0-151.4; P=.01) and high gamma (49–70 Hz; MD, 70.7 points; 95% CI, 6.5-135.0; P=.04) bands in children of mothers who received FA, suggesting more efficient semantic processing of language.


  • Relatively small sample size.


Caffrey A, McNulty H, Rollins M, Prasad G, Gaur P, Talcott JB, Witton C, Cassidy T, Marshall B, Dornan J, Moore AJ, Ward M, Strain JJ, Molloy AM, McLaughlin M, Lees-Murdock DJ, Walsh CP, Pentieva K. Effects of maternal folic acid supplementation during the second and third trimesters of pregnancy on neurocognitive development in the child: an 11-year follow-up from a randomised controlled trial. BMC Med. 2021;19(1):73. doi: 10.1186/s12916-021-01914-9. PMID: 33750355.  View full text 

This clinical summary originally appeared on Univadis, part of the Medscape Professional Network.


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