Children of Women With Epilepsy Do Not Face Worse Neurodevelopmental Outcomes

Verbal abilities do not differ among children of women with epilepsy who used antiseizure medications (ASMs) in pregnancy vs those born to healthy women, according to study findings published in JAMA Neurology.

ASMs are known teratogens that have been associated with neurodevelopmental effects.

Researchers of The Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic Drugs (MONEAD; ClinicalTrials.gov Identifier: NCT01730170) study recruited pregnant women with epilepsy (n=351) and healthy women (n=105) at 20 sites between 2012 and 2016. In this study, the researchers assessed the verbal abilities of the participants’ offspring (n=387) at age 6 years using the Differential Ability Scales-2^nd Edition (DAS-2), Expressive One-Word Picture Vocabulary Test-4^th Edition (EOWPVT-4), Neuropsychological Assessment-2^nd Edition (NEPSY-2), and Peabody Picture Vocabulary Test-4^th Edition (PPVT-4).

The children of a women with epilepsy (n=298; girls, 53.0%; White, 80.2%) and healthy women (n=89; girls, 46.1%; White, 67.4%) were age 6.4 years at the verbal assessment.

Verbal Index Score (VIS) did not differ between children born to women with epilepsy and healthy women (adjusted estimate, -0.6; P =.64).

The VIS outcome associated positively with mother’s intellectual quotient (IQ) score (adjusted estimate, 0.3; P <.001) and negatively with the child being small-for-gestational age (adjusted estimate, -8.2; P =.002), the mother having no college degree (adjusted estimate, -5.7; P =.002) or a college degree (adjusted estimate, -2.9; P =.03) compared with an advanced degree, exposure to acetaminophen in pregnancy (adjusted estimate, -3.9; P =.003), Hispanic ethnicity (adjusted estimate, -3.2; P <.001), and male gender (adjusted estimate, -2.6; P =.02).

The VIS outcome did not depend on the mother’s ASM blood concentration in the 3^rd trimester (adjusted estimate, 1.9; P =.44). When accounting for ASM blood concentration, VIS was positively related with unclassified or mixed epilepsy compared with focal epilepsy (adjusted estimate, 5.2; P =.04), mother’s IQ score (adjusted estimate, 0.4; P <.001), and mother’s age at enrollment (adjusted estimate, 0.4; P =.003) and negatively related with the child being small-for-gestational age (adjusted estimate, -9.6; P =.02) and Hispanic ethnicity (adjusted estimate, -4.1; P =.02).

A significant interaction was observed for ASM category (P =.007), in which VIS was positively related with use of lamotrigine monotherapy (adjusted estimate, 13.2; P =.02) and negatively related with levetiracetam monotherapy (adjusted estimate, -8.6; P =.02) but unrelated with other monotherapy, lamotrigine plus levetiracetam, and other polytherapy.

The results of secondary, exploratory, and sensitivity analyses were consistent with the main findings.

In the explanatory analysis, compared with no use, folate use in the first 12 weeks of pregnancy significantly associated with VIS (adjusted least-squares [aLS] mean, 107.5 vs 95.8; P =.01) and Adaptive Behavior Assessment System-3^rd Edition (ABAS-3) score (aLS mean, 102.4 vs 82.2; P <.001). Both outcomes depended on folate dose, but higher doses were not associated with worse outcomes (both P £.008).

This study may have been limited by not standardizing the time-of-day serum samples were collected.

“Results of this nonrandomized clinical trial suggest that there are presently 2 ASMs (lamotrigine and levetiracetam) with established relative safety for fetal exposure,” the researchers concluded.

Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.