1. Exposure to levetiracetam in utero was not associated with increased developmental or language delays in children at ages 3-4.5 years.
2. Children exposed to valproic acid in utero scored lower on gross motor, comprehension and language skill assessments at 3-4.5 years compared to those exposed to levetiracetam.
Evidence Rating Level: 2 (Good)
Study Rundown: This study found that exposure to levetiracetam, an anti-epileptic drug, in utero was not associated with developmental or language delays in preschool aged children but that valproic acid was associated with delays. This is one of the first studies to look at the long-term effects of in utero levetiracetam exposure.
A limitation of the current study is the difference in the prevalence of pregnant mothers on levetiracetam (83%) versus valproic acid (35%). Additionally, seizure exposure in utero was not reported in the initial prospective database and had to be collected retrospectively. Future studies might try to replicate results in a prospective, inception cohort that controls for type, frequency, and duration of seizures to better separate the long term effects of seizure and anti-epileptic exposure in utero.
Relevant Reading: Comparative safety of antiepileptic drugs during pregnancy
In-Depth [prospective observational study]: Researchers recruited children ages 36-54 months born to women with epilepsy who used either levetiracetam (Keppra) (n=53) or valproic acid (Depakote) (n=44) from a prospective UK register. Children born to women without epilepsy who did not take medication, controls, (n=131) were recruited from a separate database. Children were assessed for cognitive and language development using the Griffiths Mental Development Scales (GMDS) and the Reynell Language Development Scale (RLDS) respectively.
Children exposed to levetiracetam in utero did not differ in cognitive or language development skills compared with controls. On average, children exposed to valproic acid scored 15.8 points lower on gross motor skills (p<0.001), 6.4 points lower on language comprehension (p=0.005), and 9.5 points lower on language expression (p<0.001) than children exposed to levetiracetam. Maternal seizures during pregnancy were associated with lower scores on all cognitive and the majority of language assessments.
By Maren Shapiro and Leah Hawkins, MD, MPH
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