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Verbal abilities in children of mothers with epilepsy: Association to maternal folate status.
Neurology. 2018 08 28; 91(9):e811-e821.Neur

Abstract

OBJECTIVE

To examine the effect of maternal folic acid supplementation and maternal plasma folate and antiepileptic drug (AED) concentrations on language delay in AED-exposed children of mothers with epilepsy.

METHODS

Children of mothers with and without epilepsy enrolled from 1999 to 2008 in the Norwegian Mother and Child Cohort study were included. Information on medical history, AED use, and folic acid supplementation during pregnancy was collected from parent-completed questionnaires. Maternal plasma folate and maternal plasma and umbilical cord AED concentrations were measured in blood samples from gestational weeks 17 to 19 and immediately after birth, respectively. Language development at 18 and 36 months was evaluated by the Ages and Stages Questionnaires.

RESULTS

A total of 335 AED-exposed children of mothers with epilepsy and 104,222 children of mothers without epilepsy were surveyed. For those with no maternal periconceptional folic acid supplementation, the fully adjusted odds ratio (OR) for language delay in AED-exposed children compared to the controls at 18 months was 3.9 (95% confidence interval [CI] 1.9-7.8, p < 0.001) and at 36 months was 4.7 (95% CI 2.0-10.6, p < 0.001). When folic supplementation was used, the corresponding ORs for language delay were 1.7 (95% CI 1.2-2.6, p = 0.01) and 1.7 (95% CI 0.9-3.2, p = 0.13), respectively. The positive effect of folic acid supplement use on language delay in AED-exposed children was significant only when supplement was used in the period from 4 weeks before the pregnancy and until the end of the first trimester.

CONCLUSION

Folic acid use early in pregnancy may have a preventive effect on language delay associated with in utero AED exposure.

Authors+Show Affiliations

From the Department of Clinical Medicine (E.S.N.H., N.E.G., M.H.B.), Section for Neurology, Department of Clinical Science (B.R.), and Department of Global Public Health and Primary Care (A.K.D.), University of Bergen; Department of Neurology (E.S.N.H., N.E.G., M.H.B.) and Laboratory of Clinical Biochemistry (B.R.), Section of Clinical Pharmacology, Haukeland University Hospital, Bergen; Department of Clinical Pharmacology (O.S.), St. Olav University Hospital; Department of Clinical and Molecular Medicine (O.S.), Norwegian University of Science and Technology, Trondheim; and Department of Health Registries (A.K.D.), Norwegian Institute of Public Health, Bergen, Norway. elisabeth.husebye@uib.no.From the Department of Clinical Medicine (E.S.N.H., N.E.G., M.H.B.), Section for Neurology, Department of Clinical Science (B.R.), and Department of Global Public Health and Primary Care (A.K.D.), University of Bergen; Department of Neurology (E.S.N.H., N.E.G., M.H.B.) and Laboratory of Clinical Biochemistry (B.R.), Section of Clinical Pharmacology, Haukeland University Hospital, Bergen; Department of Clinical Pharmacology (O.S.), St. Olav University Hospital; Department of Clinical and Molecular Medicine (O.S.), Norwegian University of Science and Technology, Trondheim; and Department of Health Registries (A.K.D.), Norwegian Institute of Public Health, Bergen, Norway.From the Department of Clinical Medicine (E.S.N.H., N.E.G., M.H.B.), Section for Neurology, Department of Clinical Science (B.R.), and Department of Global Public Health and Primary Care (A.K.D.), University of Bergen; Department of Neurology (E.S.N.H., N.E.G., M.H.B.) and Laboratory of Clinical Biochemistry (B.R.), Section of Clinical Pharmacology, Haukeland University Hospital, Bergen; Department of Clinical Pharmacology (O.S.), St. Olav University Hospital; Department of Clinical and Molecular Medicine (O.S.), Norwegian University of Science and Technology, Trondheim; and Department of Health Registries (A.K.D.), Norwegian Institute of Public Health, Bergen, Norway.From the Department of Clinical Medicine (E.S.N.H., N.E.G., M.H.B.), Section for Neurology, Department of Clinical Science (B.R.), and Department of Global Public Health and Primary Care (A.K.D.), University of Bergen; Department of Neurology (E.S.N.H., N.E.G., M.H.B.) and Laboratory of Clinical Biochemistry (B.R.), Section of Clinical Pharmacology, Haukeland University Hospital, Bergen; Department of Clinical Pharmacology (O.S.), St. Olav University Hospital; Department of Clinical and Molecular Medicine (O.S.), Norwegian University of Science and Technology, Trondheim; and Department of Health Registries (A.K.D.), Norwegian Institute of Public Health, Bergen, Norway.From the Department of Clinical Medicine (E.S.N.H., N.E.G., M.H.B.), Section for Neurology, Department of Clinical Science (B.R.), and Department of Global Public Health and Primary Care (A.K.D.), University of Bergen; Department of Neurology (E.S.N.H., N.E.G., M.H.B.) and Laboratory of Clinical Biochemistry (B.R.), Section of Clinical Pharmacology, Haukeland University Hospital, Bergen; Department of Clinical Pharmacology (O.S.), St. Olav University Hospital; Department of Clinical and Molecular Medicine (O.S.), Norwegian University of Science and Technology, Trondheim; and Department of Health Registries (A.K.D.), Norwegian Institute of Public Health, Bergen, Norway.From the Department of Clinical Medicine (E.S.N.H., N.E.G., M.H.B.), Section for Neurology, Department of Clinical Science (B.R.), and Department of Global Public Health and Primary Care (A.K.D.), University of Bergen; Department of Neurology (E.S.N.H., N.E.G., M.H.B.) and Laboratory of Clinical Biochemistry (B.R.), Section of Clinical Pharmacology, Haukeland University Hospital, Bergen; Department of Clinical Pharmacology (O.S.), St. Olav University Hospital; Department of Clinical and Molecular Medicine (O.S.), Norwegian University of Science and Technology, Trondheim; and Department of Health Registries (A.K.D.), Norwegian Institute of Public Health, Bergen, Norway.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

30068633

Citation

Husebye, Elisabeth Synnøve Nilsen, et al. "Verbal Abilities in Children of Mothers With Epilepsy: Association to Maternal Folate Status." Neurology, vol. 91, no. 9, 2018, pp. e811-e821.
Husebye ESN, Gilhus NE, Riedel B, et al. Verbal abilities in children of mothers with epilepsy: Association to maternal folate status. Neurology. 2018;91(9):e811-e821.
Husebye, E. S. N., Gilhus, N. E., Riedel, B., Spigset, O., Daltveit, A. K., & Bjørk, M. H. (2018). Verbal abilities in children of mothers with epilepsy: Association to maternal folate status. Neurology, 91(9), e811-e821. https://doi.org/10.1212/WNL.0000000000006073
Husebye ESN, et al. Verbal Abilities in Children of Mothers With Epilepsy: Association to Maternal Folate Status. Neurology. 2018 08 28;91(9):e811-e821. PubMed PMID: 30068633.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Verbal abilities in children of mothers with epilepsy: Association to maternal folate status. AU - Husebye,Elisabeth Synnøve Nilsen, AU - Gilhus,Nils Erik, AU - Riedel,Bettina, AU - Spigset,Olav, AU - Daltveit,Anne Kjersti, AU - Bjørk,Marte Helene, Y1 - 2018/08/01/ PY - 2017/10/05/received PY - 2018/05/24/accepted PY - 2018/8/3/pubmed PY - 2019/8/20/medline PY - 2018/8/3/entrez SP - e811 EP - e821 JF - Neurology JO - Neurology VL - 91 IS - 9 N2 - OBJECTIVE: To examine the effect of maternal folic acid supplementation and maternal plasma folate and antiepileptic drug (AED) concentrations on language delay in AED-exposed children of mothers with epilepsy. METHODS: Children of mothers with and without epilepsy enrolled from 1999 to 2008 in the Norwegian Mother and Child Cohort study were included. Information on medical history, AED use, and folic acid supplementation during pregnancy was collected from parent-completed questionnaires. Maternal plasma folate and maternal plasma and umbilical cord AED concentrations were measured in blood samples from gestational weeks 17 to 19 and immediately after birth, respectively. Language development at 18 and 36 months was evaluated by the Ages and Stages Questionnaires. RESULTS: A total of 335 AED-exposed children of mothers with epilepsy and 104,222 children of mothers without epilepsy were surveyed. For those with no maternal periconceptional folic acid supplementation, the fully adjusted odds ratio (OR) for language delay in AED-exposed children compared to the controls at 18 months was 3.9 (95% confidence interval [CI] 1.9-7.8, p < 0.001) and at 36 months was 4.7 (95% CI 2.0-10.6, p < 0.001). When folic supplementation was used, the corresponding ORs for language delay were 1.7 (95% CI 1.2-2.6, p = 0.01) and 1.7 (95% CI 0.9-3.2, p = 0.13), respectively. The positive effect of folic acid supplement use on language delay in AED-exposed children was significant only when supplement was used in the period from 4 weeks before the pregnancy and until the end of the first trimester. CONCLUSION: Folic acid use early in pregnancy may have a preventive effect on language delay associated with in utero AED exposure. SN - 1526-632X UR - https://www.unboundmedicine.com/medline/citation/30068633/Verbal_abilities_in_children_of_mothers_with_epilepsy:_Association_to_maternal_folate_status_ L2 - http://www.neurology.org/cgi/pmidlookup?view=long&amp;pmid=30068633 DB - PRIME DP - Unbound Medicine ER -