Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2021 Apr:117:107688.
doi: 10.1016/j.yebeh.2020.107688. Epub 2021 Feb 23.

Folate fortification of food: Insufficient for women with epilepsy

Zahra Sadat-Hossieny  1 , Chelsea P Robalino  2 , Page B Pennell  3 , Morris J Cohen  4 , David W Loring  5 , Ryan C May  2 , Torin Block  6 , Travis Swiatlo  7 , Kimford J Meador  8 ; NEAD Investigator Group
Affiliations

Folate fortification of food: Insufficient for women with epilepsy

Zahra Sadat-Hossieny et al. Epilepsy Behav. 2021 Apr.

Abstract

Objective: Folic acid supplementation during the periconceptual period has been shown to improve cognitive outcomes in children of women with epilepsy taking anti-seizure medications (ASMs). The dose of folic acid necessary to provide positive cognitive outcomes is unclear. In many countries including the United States, food is fortified with folic acid, but no data exist on how food fortification may affect cognition in children with fetal-ASM exposure. This study evaluated the effect of dietary folate from natural folates plus folic acid fortification, separate from folic acid vitamin supplements, on age-6 year IQ in children with fetal-ASM exposure.

Methods: Data from the Neurodevelopmental Effects of Antiepileptic Drugs (NEAD) study were retrospectively analyzed for this investigation. Assessment of nutrient intake was conducted using the Block Food Frequency Questionnaire-98. The primary outcome of the present study was to assess association of maternal prepregnancy nutrient levels to child age-6 IQ.

Results: Folate from food alone without supplement was not associated with improvement of age-6 IQ in children with fetal ASM exposure (95% CI: -11.7-2.3, p = 0.187). Periconceptual folate supplement use was associated with a 10.1-point higher age-6 IQ (95% CI: 5.2-15.0, p < .001). Total combined folate from food plus supplement also showed that higher intake of folate was associated with higher age-6 IQ (Coefficient: 4.5, 95% CI: 2.0-6.9, p < .001). Six other nutrients from food and supplements were analyzed (Vitamin C, Vitamin D, Vitamin E, Omega 3, Gamma Tocopherol, and Vitamin B12) and had no significant association with age 6-IQ.

Significance: Dietary content of folate, even in a country where food is fortified with folic acid, is not sufficient to provide improved cognitive outcomes for children of women taking ASMs during pregnancy. Folate supplementation is needed for significant improvement in cognitive outcomes, specifically age-6 IQ.

Keywords: Antiepileptic drugs; Diet; Epilepsy; Folate; Pregnancy.

PubMed Disclaimer

Figures

Figure 1.
Figure 1.. Folate from Food and Supplements (log scale, mcg) by Age 6 IQ.
Figure depicts scatter plot with unadjusted regression lines by ASM. Includes 117 completers.
See this image and copyright information in PMC

References

    1. Hibbard BM. The role of folic acid in pregnancy with particular reference to anaemia, abruption and abortion. J Obstet Gynaecol Br Commonw 1964, 71: 529–42. - PubMed
    1. Hibbard ED, Smithells RW. Folic acid metabolism and human embryopathy. Lancet 1965; i: 1254.
    1. Smithells RW, Shephard S, Schorah CJ, et al. Possible prevention of neural-tube defects by periconceptional vitamin supplementation. Lancet 1980; i: 339–40. - PubMed
    1. MRC Vitamin Study Research Group. Prevention of neural tube defects: results of the Medical Research Council Vitamin Study. Lancet 1991;338:131–7. - PubMed
    1. Roth C, Magnus P, Schjølberg S, et al. Folic Acid Supplements in Pregnancy and Severe Language Delay in Children. JAMA. 2011;306(14):1566–1573. doi:10.1001/jama.2011.1433 - DOI - PMC - PubMed

Publication types