Language Development of Children of Women With Epilepsy Similar to Those of Healthy Women

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Investigators compared 2-year-old children of women with epilepsy to those of healthy women to evaluate their cognitive abilities based on antiseizure medication exposure.

Language development of children of women with epilepsy (WWE) taking antiseizure medications do not tend to differ from children of healthy women when assessed at 2 years of age, according to study findings published in JAMA Neurology.

The prospective, observational Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic Drugs (MONEAD) study ( Identifier: NCT01730170) assessed pregnancy outcomes in healthy women from 2012 to 2016 at 20 epilepsy centers in the United States.

This study included a total of 292 children of WWE (median age, 2.1 years) as well as 90 children of healthy women (median age, 2.1 years). The researchers followed children from birth to 6 years of age, and conducted assessments of the children at 2 years of age.

The assessments focused on improvements in the language domain score, based on the Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III). This score incorporates 5 domain scores, including those involved in language, motor, cognitive, social-emotional, and general adaptive.

There was no significant difference between the children of WWE vs those of healthy women regarding the outcome of language domain at 2 years of age (parameter estimate, -0.5; 95% CI, -4.1 to 3.2; P =.81). In the adjusted analysis, there was also no difference between the 2 groups concerning the other 4 BSID-III domains at 2 years of age.

The majority of WWE received lamotrigine and/or levetiracetam during the study period. The study investigators found no association between exposure to antiseizure medicines and the language domain in children of WWE.

Secondary analyses showed higher maximum observed blood levels of antiseizure medications during the third trimester correlated with significantly lower BSID-III scores for the motor domain (-5.6; 95% CI, -10.7 to -0.5; P =.03). There was also an association between higher maximum ratio of defined daily dose of antiseizure medications in the third trimester and lower scores in the general adaptive domain (-1.4; 95% CI, -2.8 to -0.05; P =.049).

A limitation of this study included the lack of randomization (a randomized protocol has ethical concerns when implemented in pregnancy). Additionally, the study researchers note that the associations yielded from cognitive and behavioral assessments at 2 years of age are not as strong as those produced when used at older ages.

The study researchers concluded additional research in the “cohort in children of older ages and in other cohorts are needed to fully delineate the effects of [antiseizure medication] exposure on the immature brain.”


Meador KJ, Cohen MJ, Loring DW, et al. Two-year-old cognitive outcomes in children of pregnant women with epilepsy in the maternal outcomes and neurodevelopmental effects of antiepileptic drugs study. Published online June 7, 2021. JAMA Neurol. doi:10.1001/jamaneurol.2021.1583