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. 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.
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.
Authors: Torbjörn Tomson; Dina Battino; Erminio Bonizzoni; John Craig; Dick Lindhout; Emilio Perucca; Anne Sabers; Sanjeev V Thomas; Frank Vajda Journal: Lancet Neurol Date: 2018-04-18 Impact factor: 44.182
Authors: Kimford J Meador; Gus A Baker; Nancy Browning; Morris J Cohen; Rebecca L Bromley; Jill Clayton-Smith; Laura A Kalayjian; Andres Kanner; Joyce D Liporace; Page B Pennell; Michael Privitera; David W Loring Journal: Lancet Neurol Date: 2013-01-23 Impact factor: 44.182
Authors: Kimford J Meador; Gus A Baker; Nancy Browning; Jill Clayton-Smith; Deborah T Combs-Cantrell; Morris Cohen; Laura A Kalayjian; Andres Kanner; Joyce D Liporace; Page B Pennell; Michael Privitera; David W Loring Journal: N Engl J Med Date: 2009-04-16 Impact factor: 91.245
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