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


Background: 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. We aimed to evaluate the effect of FA supplementation throughout pregnancy on cognitive performance and brain function in the child. Methods: Follow-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. Results: Of 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. 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. Trial registration: ISRCTN ISRCTN19917787. Registered on 15 May 2013.

Publication DOI: https://doi.org/10.1186/s12916-021-01914-9
Divisions: College of Health & Life Sciences > School of Psychology
College of Health & Life Sciences > Clinical and Systems Neuroscience
College of Health & Life Sciences
College of Health & Life Sciences > School of Optometry > Vision, Hearing and Language
Funding Information: The authors wish to thank the children and families of the FASSTT Offspring Trial for their participation and commitment.
Additional Information: © The Author(s). 2021 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
Uncontrolled Keywords: Child cognition,Magnetoencephalographic brain imaging,Neuronal function,Pregnancy,Prenatal folic acid,Randomised controlled trial,Wechsler Intelligence Scale for Children,Medicine(all)
Publication ISSN: 1741-7015
Last Modified: 14 May 2024 07:22
Date Deposited: 22 Mar 2021 11:51
Full Text Link:
Related URLs: http://www.scop ... tnerID=8YFLogxK (Scopus URL)
https://bmcmedi ... 916-021-01914-9 (Publisher URL)
PURE Output Type: Article
Published Date: 2021-03-10
Accepted Date: 2021-01-14
Authors: Caffrey, Aoife
McNulty, Helene
Rollins, Mark
Prasad, Girijesh
Gaur, Pramod
Talcott, Joel B. (ORCID Profile 0000-0001-7958-8369)
Witton, Caroline (ORCID Profile 0000-0002-5610-4234)
Cassidy, Tony
Marshall, Barry
Dornan, James
Moore, Adrian J.
Ward, Mary
Strain, J. J.
Molloy, Anne M.
McLaughlin, Marian
Lees-Murdock, Diane J.
Walsh, Colum P.
Pentieva, Kristina



Version: Published Version

License: Creative Commons Attribution

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