Folic Acid in Pregnancy and Neuropsychological Outcomes at Age 6-Years-Old in the MONEAD Study
Kimford Meador1, Morris Cohen2, David Loring3, Abigail Matthews4, Page Pennell5
1Stanford University School of Medicine, 2Pediatric Neuropsychology International, 3Neurology, Emory University, Dept of Neurology, 4The Emmes Company, LLC, 5University of Pittsburgh School of Medicine
Objective:
To assess the relation of folic acid supplementation during pregnancy and neuropsychological outcomes at age 6-years-old in children of women with epilepsy (WWE) and healthy women (HW).
Background:
Folic acid supplementation in pregnancy is known to reduce malformations and improve cognitive outcomes, but concerns have been raised over risks of higher folate doses.
Design/Methods:
The Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic Drugs (MONEAD) study is a prospective, observational, multi-center investigation which enrolled WWE and HW during pregnancy. The a priori primary neurodevelopmental outcome for children is age 6 Verbal Index score (VIS) calculated by averaging Differential Ability Scales-II Word Definitions and Verbal Similarities subtests, Expressive One-Word Picture Vocabulary Test-4, Peabody Picture Vocabulary Test-4, and Neuropsychological Assessment-2 Phonological Processing, Comprehension of Instructions, and Sentence Repetition subtests. The main behavioral outcome is the Adaptive Behavior Assessment System (ABAS-3) General Adaptive Composite Standard Score. We compared the outcomes in children as a function of folate supplementation using linear regression adjusting for potential confounders chosen via a stepwise selection algorithm.
Results:
Analyses include 345 children of WWE and HW. Adjusted LS Means (95% CI) for children’s VIS were higher in those using folic acid in the first 12 weeks of pregnancy (107.5 (106.5, 108.5)) vs. not (95.8 (86.8, 104.8)), p=0.012. Similarly, adjusted LS Means (95% CI) for ABAS-3 were higher when folic acid was used the first 12 weeks of pregnancy (102.4 (101.3, 103.4)) vs. not (82.2 (73.9, 90.5)), p<0.001. Outcomes were similar for low dose folic acid (>0-0.4mg/day) and high dose (>4.0mg/day) for VIS (109.8 (104.7, 114.9) vs. 108.1 (105.9, 110.3)) and for ABAS-3 (102.5 (97.3, 107.8) vs. 102.7 (100.4, 105.1)).
Conclusions:
Folic acid early in pregnancy was associated with improved verbal abilities and adaptive behavior of children at age 6-years-old. No risk of higher doses was apparent in this cohort.
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