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Original Investigation |

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

Gyri Veiby, MD1,2; Bernt A. Engelsen, MD, PhD1,2; Nils Erik Gilhus, MD, PhD1,2
[+] Author Affiliations
1Department of Clinical Medicine, Section for Neurology, University of Bergen, Bergen, Norway
2Department of Neurology, Haukeland University Hospital, Bergen, Norway
JAMA Neurol. 2013;70(11):1367-1374. doi:10.1001/jamaneurol.2013.4290.
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Published online

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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Figure 1.
Exclusive or Mixed Breastfeeding at Ages 0 to 6 Months

Frequency of breastfeeding in epilepsy groups and the reference group at 0 to 6 months after delivery. AED indicates antiepileptic drug.

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Figure 2.
Risk of Adverse Development Score at 6 Months in Children of Mothers With Epilepsy According to Breastfeeding

Epilepsy groups with no maternal antiepileptic drug use (A), maternal antiepileptic drug use (B), maternal antiepileptic drug polytherapy (C), and maternal lamotrigine monotherapy (D) were examined. Odds ratios (ORs) with 95% CIs were adjusted for maternal age, parity, smoking, folate use, education, anxiety/depression, and child malformation.

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