The Role of High Dose Maternal Folic Acid Supplementation on the Association of Antiseizure Medication Use in Pregnancy with Standardized Test Scores of Danish School-aged Children
Abstract number :
2.158
Submission category :
4. Clinical Epilepsy / 4E. Women's Issues
Year :
2022
Submission ID :
2204285
Source :
www.aesnet.org
Presentation date :
12/4/2022 12:00:00 PM
Published date :
Nov 22, 2022, 05:24 AM
Authors :
Julie Dreier, PhD – Aarhus University, Denmark; Betina Trabjerg, MSc – Aarhus University, Denmark; Jakob Christensen, MD, DrMedSci – Aarhus University, Denmark
Rationale: Maternal supplementation with high doses of folic acid is generally recommended for pregnant women using antiseizure medication (ASM) for the prevention of ASM-associated birth defects. Recently, it has been proposed that supplementation may reduce the negative effects of some ASMs on child neurodevelopment as well. In this study, we explored whether the associations of prenatal exposure to valproate and other ASMs with performance in standardized tests among school-aged children, were modified by maternal use of high dose folic acid in pregnancy.
Methods: This was a nationwide register-based cohort study of children born in Denmark between January 1, 1997, and December 31, 2009, who participated in the Danish National Test Program between 2010 and 2019. The age range of eligible schoolchildren was 7 to 17 years. Maternal prescription fill for ASM and high-dose folic acid (1-5 mg) during pregnancy was obtained from the Danish National Prescription Register. Using linear regression models, we estimated the difference (∆) in mean standardized scores (scale 1-100, higher scores indicate better results) between children with no prenatal ASM exposure (reference group) and children with ASM monotherapy exposure with or without high-dose folic acid, adjusted for relevant confounders.
Results: Among 552,965 children included, 2,452 (0.4%) were born to mothers using ASM in pregnancy, and of these 685 (27.9%) also used high-dose folic acid supplements. The mean score was 56.3 for all language tests and 57.2 for all mathematics tests. Children with prenatal valproate monotherapy exposure performed worse in the standardized tests compared to children with no prenatal ASM exposure, regardless of whether the mother used high-dose folic acid supplements in pregnancy (n=118; language ∆adj=-6.5, 95% CI: -10.6; -2.5; mathematics ∆adj =-3.0, 95% CI: -7.4; 1.5) or not (n = 153; language ∆adj=-5.8, 95% CI: -9.3; -2.2; mathematics ∆adj =-3.9, 95% CI: -8.2; 0.4). Similarly, associations between prenatal ASM exposure and school performance did not differ in children of mothers using high dose folic acid and children of mothers not using high dose folic acid, for lamotrigine (n=771 [25% with high dose folic acid]), carbamazepine (n=290, [41% with high dose folic acid]), oxcarbazepine (n=259, [25% with high dose folic acid]), or clonazepam (n=214, [12% with high dose folic acid]), all p-values > 0.05.
Conclusions: In this nationwide study of Danish school-aged children, we found no evidence that maternal use of high dose folic acid supplements in pregnancy reduces the negative influence of prenatal valproate exposure on performance in standardized language and mathematics tests or modifies the association with other ASMs.
Funding: The study was supported by the Danish Epilepsy Association, the Central Denmark Region, the Novo Nordisk Foundation (NNF16OC0019126, NNF22OC0075033), and the Independent Research Fund Denmark (1133-00026B).
Clinical Epilepsy