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Published in: BMC Medicine 1/2019

Open Access 01-12-2019 | Folic Acid | Research article

Effect of continued folic acid supplementation beyond the first trimester of pregnancy on cognitive performance in the child: a follow-up study from a randomized controlled trial (FASSTT Offspring Trial)

Authors: Helene McNulty, Mark Rollins, Tony Cassidy, Aoife Caffrey, Barry Marshall, James Dornan, Marian McLaughlin, Breige A. McNulty, Mary Ward, J. J. Strain, Anne M. Molloy, Diane J. Lees-Murdock, Colum P. Walsh, Kristina Pentieva

Published in: BMC Medicine | Issue 1/2019

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Abstract

Background

Periconceptional folic acid prevents neural tube defects (NTDs), but it is uncertain whether there are benefits for offspring neurodevelopment arising from continued maternal folic acid supplementation beyond the first trimester. We investigated the effect of folic acid supplementation during trimesters 2 and 3 of pregnancy on cognitive performance in the child.

Methods

We followed up the children of mothers who had participated in a randomized controlled trial in 2006/2007 of Folic Acid Supplementation during the Second and Third Trimesters (FASSTT) and received 400 μg/d folic acid or placebo from the 14th gestational week until the end of pregnancy. Cognitive performance of children at 7 years was evaluated using the Wechsler Preschool and Primary Scale of Intelligence (WPPSI-III) and at 3 years using the Bayley’s Scale of Infant and Toddler Development (BSITD-III).

Results

From a total of 119 potential mother-child pairs, 70 children completed the assessment at age 7 years, and 39 at age 3 years. At 7 years, the children of folic acid treated mothers scored significantly higher than the placebo group in word reasoning: mean 13.3 (95% CI 12.4–14.2) versus 11.9 (95% CI 11.0–12.8); p = 0.027; at 3 years, they scored significantly higher in cognition: 10.3 (95% CI 9.3–11.3) versus 9.5 (95% CI 8.8–10.2); p = 0.040. At both time points, greater proportions of children from folic acid treated mothers compared with placebo had cognitive scores above the median values of 10 (girls and boys) for the BSITD-III, and 24.5 (girls) and 21.5 (boys) for the WPPSI-III tests. When compared with a nationally representative sample of British children at 7 years, WPPSI-III test scores were higher in children from folic acid treated mothers for verbal IQ (p < 0.001), performance IQ (p = 0.035), general language (p = 0.002), and full scale IQ (p = 0.001), whereas comparison of the placebo group with British children showed smaller differences in scores for verbal IQ (p = 0.034) and full scale IQ (p = 0.017) and no differences for performance IQ or general language.

Conclusions

Continued folic acid supplementation in pregnancy beyond the early period recommended to prevent NTD may have beneficial effects on child cognitive development. Further randomized trials in pregnancy with follow-up in childhood are warranted.

Trial registration

ISRCTN ISRCTN19917787. Registered 15 May 2013.
Appendix
Available only for authorised users
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Metadata
Title
Effect of continued folic acid supplementation beyond the first trimester of pregnancy on cognitive performance in the child: a follow-up study from a randomized controlled trial (FASSTT Offspring Trial)
Authors
Helene McNulty
Mark Rollins
Tony Cassidy
Aoife Caffrey
Barry Marshall
James Dornan
Marian McLaughlin
Breige A. McNulty
Mary Ward
J. J. Strain
Anne M. Molloy
Diane J. Lees-Murdock
Colum P. Walsh
Kristina Pentieva
Publication date
01-12-2019
Publisher
BioMed Central
Keyword
Folic Acid
Published in
BMC Medicine / Issue 1/2019
Electronic ISSN: 1741-7015
DOI
https://doi.org/10.1186/s12916-019-1432-4

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