Folate fortification of food: Insufficient for women with epilepsy

Zahra Sadat-Hossieny; Chelsea P Robalino; Page B Pennell; Morris J Cohen; David W Loring; Ryan C May; Torin Block; Travis Swiatlo; Kimford J Meador; NEAD Investigator Group

doi:10.1016/j.yebeh.2020.107688

Folate fortification of food: Insufficient for women with epilepsy

Epilepsy Behav. 2021 Apr:117:107688. doi: 10.1016/j.yebeh.2020.107688. Epub 2021 Feb 23.

Authors

Zahra Sadat-Hossieny¹, Chelsea P Robalino², Page B Pennell³, Morris J Cohen⁴, David W Loring⁵, Ryan C May², Torin Block⁶, Travis Swiatlo⁷, Kimford J Meador⁸; NEAD Investigator Group

Affiliations

¹ Department of Neurology and Neurological Sciences, Stanford University, Stanford, CA, USA. Electronic address: zahra.x.sadat-hossieny@kp.org.
² The Emmes Company, LLC, Rockville, MD, USA.
³ Department of Neurology, Brigham & Women's Hospital, Harvard Medical School, Boston, MA, USA.
⁴ Pediatric Neuropsychology International, Augusta, GA, USA.
⁵ Departments of Neurology and Pediatrics, Emory University, Atlanta, GA, USA.
⁶ NutritionQuest, Berkley, CA, USA.
⁷ Department of Clinical Nutrition, Stanford Hospitals and Clinics, Stanford, CA, USA.
⁸ Department of Neurology and Neurological Sciences, Stanford University, Stanford, CA, USA.

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.

Publication types

Research Support, N.I.H., Extramural

MeSH terms

Child
Dietary Supplements
Epilepsy* / drug therapy
Female
Folic Acid* / therapeutic use
Humans
Pregnancy
Retrospective Studies
United States
Vitamin B 12

Substances

Folic Acid
Vitamin B 12

Abstract

Publication types

MeSH terms

Substances

Grants and funding