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Observational Study
. 2020 Jun;267(6):1724-1736.
doi: 10.1007/s00415-020-09764-w. Epub 2020 Feb 28.

Neurocognition after prenatal levetiracetam, lamotrigine, carbamazepine or valproate exposure

Yfke Huber-Mollema  1   2 , Loretta van Iterson  1 , Frans J Oort  2 , Dick Lindhout  1   3 , Roos Rodenburg  4   5
Affiliations
Observational Study

Neurocognition after prenatal levetiracetam, lamotrigine, carbamazepine or valproate exposure

Yfke Huber-Mollema et al. J Neurol. 2020 Jun.

Abstract

Objective: To examine neurocognitive functioning of children exposed prenatally to carbamazepine, lamotrigine, levetiracetam or valproate monotherapy.

Methods: In a prospective observational study, children aged 6 or 7 years, identified from the European Registry of Antiepileptic Drugs and Pregnancy database in The Netherlands, were assessed using the Wechsler Intelligence Scale for Children and the developmental neuropsychological assessment. Maternal IQ was measured using Wechsler Adult Intelligence Scale. Assessors were blinded to drug exposures.

Results: One hundred and sixty-one children (one set of twins and 21 sibling pairs) of 139 mothers were included. As a group, children achieved average scores on neurocognitive outcomes. Children exposed to valproate (n = 22) performed lower on all six neurocognitive domains, especially language, than those exposed to carbamazepine (n = 32), lamotrigine (n = 82) or levetiracetam (n = 25). After controlling for maternal IQ and drug dose, the verbal IQ of valproate-exposed children was on average 9.1 points lower than those exposed to carbamazepine (95% confidence interval [CI] 1.3-17.0; p = 0.023), 10.3 lower than lamotrigine-exposed children (CI 3.4-17.3; p = 0.004) and 13.4 lower than levetiracetam-exposed children (CI 5.2-21.6; p = 0.002). No significant dose-effect was found. Virtually no significant differences were found between lamotrigine and levetiracetam or lamotrigine and carbamazepine exposed children.

Conclusions: Consistent with previous research, valproate-exposed children experienced more problems compared to three other common antiepileptic drugs, while children exposed to lamotrigine, carbamazepine or levetiracetam revealed little to no problems. This illustrates the need for systematic follow-up of prenatally exposed children, to support pre-pregnancy counseling and treatment decisions in women of reproductive age.

Keywords: Antiepileptic drugs; Cognition; EURAP & development; Epilepsy; Neuropsychological assessment; Pregnancy.

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Conflict of interest statement

YH-M, FO, LvI and RR have no disclosures to report. DL has received—in the past (2000–2002)—research grants from Janssen-Cilag, GlaxoSmithKline, Pfizer, and The Netherlands Epilepsy Foundation, to start-up the basic EURAP study in The Netherlands.

Figures

Fig. 1
Fig. 1
Flowchart inclusion Dutch EURAP & Development study
Fig. 2
Fig. 2
Distribution of verbal IQ scores of exposed children across the four AED groups
See this image and copyright information in PMC

References

    1. Hauser W, Hesdorffer D. Epilepsy: frequency, causes and consequences. New York: Demos publications; 1990.
    1. Yerby MS. Pregnancy, teratogenesis, and epilepsy. Neurol Clin. 1994;12:749–771. doi: 10.1016/S0733-8619(18)30075-6. - DOI - PubMed
    1. Lindhout D, Omtzigt JGC. Pregnancy and the risk of teratogenicity. Epilepsia. 1992;33:41–48. doi: 10.1111/j.1528-1157.1992.tb06226.x. - DOI - PubMed
    1. Pennell PB. Pregnancy in women who have epilepsy. Neurol Clin. 2004;22:799–820. doi: 10.1016/j.ncl.2004.07.004. - DOI - PubMed
    1. Meador KJ, Baker GA, Browning N, et al. Fetal antiepileptic drug exposure and cognitive outcomes at age 6 years (NEAD study): a prospective observational study. Lancet Neurol. 2013;12:244–252. doi: 10.1016/S1474-4422(12)70323-X. - DOI - PMC - PubMed

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