Medline ® Abstract for Reference 111
of 'Risks associated with epilepsy and pregnancy'
111
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IQ at 6 years after in utero exposure to antiepileptic drugs: a controlled cohort study.
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Baker GA, Bromley RL, Briggs M, Cheyne CP, Cohen MJ, García-Fiñana M, Gummery A, Kneen R, Loring DW, Mawer G, Meador KJ, Shallcross R, Clayton-Smith J, Liverpool and Manchester Neurodevelopment Group
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Neurology. 2015;84(4):382. Epub 2014 Dec 24.
OBJECTIVE:
To delineate the risk to child IQ associated with frequently prescribed antiepileptic drugs.
METHODS:
Children born to women with epilepsy (n = 243) and women without epilepsy (n = 287) were recruited during pregnancy and followed prospectively. Of these, 408 were blindly assessed at 6 years of age. Maternal and child demographics were collected and entered into statistical models.
RESULTS:
The adjusted mean IQ was 9.7 points lower (95% confidence interval [CI]-4.9 to -14.6; p<0.001) for children exposed to high-dose (>800 mg daily) valproate, with a similar significant effect observed for the verbal, nonverbal, and spatial subscales. Children exposed to high-dose valproate had an 8-fold increased need of educational intervention relative to control children (adjusted relative risk, 95% CI 8.0, 2.5-19.7; p<0.001). Valproate at doses<800 mg daily was not associated with reduced IQ, but was associated with impaired verbal abilities (-5.6, 95% CI -11.1 to -0.1; p = 0.04) and a 6-fold increase in educational intervention (95% CI 1.4-18.0; p = 0.01). In utero exposure to carbamazepine or lamotrigine did not have a significant effect on IQ, but carbamazepine was associated with reduced verbal abilities (-4.2, 95% CI -0.6 to -7.8; p = 0.02) and increased frequency of IQ<85.
CONCLUSIONS:
Consistent with data from younger cohorts, school-aged children exposed to valproate at maternal doses more than 800 mg daily continue to experience significantly poorer cognitive development than control children or children exposed to lamotrigine and carbamazepine.
AD
From the Departments of Molecular and Clinical Pharmacology (G.A.B.), Biostatistics (C.P.C., M.G.-F.), and Clinical Psychology (R.S.), Institute of Infection and Global Health (M.J.C., A.G.), and Alder Hey Children's Hospital&Institute of Infection&Global Health (R.K.), University of Liverpool; Institute of Human Development (R.L.B., J.C.-S.), University of Manchester; Manchester Academic Health Sciences Centre (R.L.B., M.B., G.M., J.C.-S.), Central Manchester University Hospitals Foundation Trust, UK; Department of Neurology (M.J.C.), Georgia Regents University, Augusta; Department of Neurology&Pediatrics (D.W.L.), Emory University, Atlanta, GA; and Department of Neurology&Neurological Sciences (K.J.M.), Stanford University, CA.
PMID