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Abstract
Objective Emerging evidence suggests potential positive neuropsychological effects of periconceptional folate in both healthy children and children exposed in utero to antiseizure medications (ASMs). In this report, we test the hypothesis that periconceptional folate improves neurodevelopment in children of women with epilepsy by re-examining data from the Neurodevelopmental Effects of Antiepileptic Drugs (NEAD) study.
Methods The NEAD study was an NIH-funded, prospective, observational, multicenter investigation of pregnancy outcomes in 311 children of 305 women with epilepsy treated with ASM monotherapy. Missing data points were imputed with Markov chain Monte Carlo methods. Multivariate analyses adjusted for multiple factors (e.g., maternal IQ, ASM type, standardized ASM dose, and gestational birth age) were performed to assess the effects of periconceptional folate on cognitive outcomes (i.e., Full Scale Intelligence Quotient [FSIQ], Verbal and Nonverbal indexes, and Expressive and Receptive Language indexes at 3 and 6 years of age, and executive function and memory function at 6 years of age).
Results Periconceptional folate was associated with higher FSIQ at both 3 and 6 years of age. Significant effects for other measures included Nonverbal Index, Expressive Language Index, and Developmental Neuropsychological Assessment Executive Function at 6 years of age, and Verbal Index and Receptive Language Index at 3 years of age. Nonsignificant effects included Verbal Index, Receptive Index, Behavior Rating Inventory of Executive Function–Parent Questionnaire Executive Function, and General Memory Index at 6 years of age, and Nonverbal Index and Expressive Index at 3 years of age.
Conclusions Use of periconceptional folate in pregnant women with epilepsy taking ASMs is associated with better cognitive development.
ClinicalTrials.gov identifier: NCT00021866.
Glossary
- ASM=
- antiseizure medication;
- CI=
- confidence interval;
- DAS=
- Differential Ability Scales;
- DTVMI-5=
- Developmental Test of Visual-Motor Integration–5th Edition;
- FSIQ=
- Full Scale Intelligence Quotient;
- ITT=
- intent-to-treat;
- MTHFR=
- methyl tetrahydrofolate dihydrofolate reductase;
- NEAD=
- Neurodevelopmental Effects of Antiepileptic Drugs;
- NEPSY=
- Developmental Neuropsychological Assessment;
- PLS-4=
- Preschool Language Scale–4th Edition;
- PPVT-4=
- Peabody Picture Vocabulary Test–4th Edition
Footnotes
Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.
The NEAD Investigator Group is listed in Appendix 2.
CME Course: NPub.org/cmelist
- Received March 8, 2019.
- Accepted in final form August 21, 2019.
- © 2019 American Academy of Neurology
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