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Cited by 138Pharmacological Effects and Toxicity StudiesPrenatal Substance Exposure EffectsPregnancy and Medication Impact

Early Child Development and Exposure to Antiepileptic Drugs Prenatally and Through Breastfeeding: A Prospective Cohort Study on Children of Women With Epilepsy

Veiby, Gyri, Engelsen, Bernt A., Gilhus, Nils Erik·2013·JAMA Neurology
DOI 10.1001/jamaneurol.2013.4290
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Abstract

IMPORTANCE: Exposure to antiepileptic drugs during pregnancy is associated with adverse effects on psychomotor development. OBJECTIVES: To determine whether signs of impaired development appear already during the first months of life in children exposed prenatally to antiepileptic drugs, and to explore potential adverse effects of antiepileptic drug exposure through breastfeeding. DESIGN, SETTING, AND PARTICIPANTS: Mothers at 13 to 17 weeks of pregnancy were recruited in the population-based, prospective Norwegian Mother and Child Cohort Study from 1999 to 2009. The mothers reported on their child's motor and social skills, language, and behavior using items from standardized screening tools at 6 months (n = 78,744), 18 months (n = 61,351), and 36 months (n = 44,147) of age. The mothers also provided detailed information on breastfeeding during the first year. MAIN OUTCOMES AND MEASURES The risk of adverse development in children according to maternal or paternal epilepsy was estimated as the odds ratio with corresponding 95% confidence interval, adjusted for maternal age, parity, education, smoking, breastfeeding, depression/anxiety, folate supplementation, and congenital malformation in the child. RESULTS: At age 6 months, infants of mothers using antiepileptic drugs (n = 223) had a higher risk of impaired fine motor skills compared with the reference group (11.5% vs 4.8%, respectively; odds ratio = 2.1; 95% CI, 1.3-3.2). Use of multiple antiepileptic drugs compared with the reference group was associated with adverse outcome for both fine motor skills (25.0% vs 4.8%, respectively; odds ratio = 4.3; 95% CI, 2.0-9.1) and social skills (22.5% vs 10.2%, respectively; odds ratio = 2.6; 95% CI, 1.2-5.5). Continuous breastfeeding in children of women using antiepileptic drugs was associated with less impaired development at ages 6 and 18 months compared with those with no breastfeeding or breastfeeding for less than 6 months. At 36 months, prenatal antiepileptic drug exposure was associated with adverse development regardless of breastfeeding status during the first year. Children of women with epilepsy who did not use antiepileptic drugs and children of fathers with epilepsy had normal development at 6 months. CONCLUSIONS AND RELEVANCE: Prenatal exposure to antiepileptic drugs was associated with impaired fine motor skills already at age 6 months, especially when the child was exposed to multiple drugs. There were no harmful effects of breastfeeding. Women with epilepsy should be encouraged to breastfeed their children irrespective of antiepileptic drug treatment.

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Authors
Veiby, G., Engelsen, B. A., & Gilhus, N. E.
Affiliations
Haukeland University Hospital (NO)
Corresponding author
Veiby, Gyri
ORCID
Gilhus, Nils Erik
Venue
JAMA Neurology
Publisher
American Medical Association (AMA)
Published
2013-11-01
Volume
70
Issue
11
Pages
1367
ISSN
2168-6149 (ISSN-L)
DOI
10.1001/jamaneurol.2013.4290
OpenAlex
W2165824156
Cited by
138
References
59
Citations by year
2026: 3 · 2025: 5 · 2024: 12 · 2023: 12 · 2022: 15 · 2021: 11 · 2020: 9 · 2019: 12 · 2018: 12 · 2017: 8 · 2016: 12 · 2015: 11 · 2014: 14 · 2013: 2
FWCI
12.10
Type
journal article
Language
en
Open access
closed
Locations
  • JAMA Neurology (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health (n01es75558-11-0-1)
  • National Institute of Neurological Disorders and Stroke (UO1 NS 047537–01, U01NS047537, UO1 NS 047537-06A1)
  • National Institute of Environmental Health Sciences (N01ES75558)
Topics
  • Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Pharmacological Effects and Toxicity Studies
  • Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Prenatal Substance Exposure Effects
  • Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Pregnancy and Medication Impact
Keywords
antiepileptic drugs, prenatal drug exposure, breastfeeding, infant development, fine motor skills, social skills, maternal epilepsy, psychomotor development, Norwegian Mother and Child Cohort Study, congenital malformations, language development, folic acid supplementation, neurodevelopmental risk
MeSH terms
Age Factors, Anticonvulsants, Breast Feeding, Developmental Disabilities, Child, Preschool, Epilepsy, Female, Humans, Infant, Male, Norway, Parent-Child Relations, Pregnancy, Prenatal Exposure Delayed Effects, Surveys and Questionnaires, Retrospective Studies, Cohort Studies, Odds Ratio, Community Health Planning

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