Prospective assessment of autism traits in children exposed to antiepileptic drugs during pregnancy

Wood, Amanda G., Nadebaum, Caroline, Anderson, Vicki, Reutens, David, Barton, Sarah, O'Brien, Terence J. and Vajda, Frank (2015) Prospective assessment of autism traits in children exposed to antiepileptic drugs during pregnancy. Epilepsia, 56 7: 1047-1055. doi:10.1111/epi.13007

Author Wood, Amanda G.
Nadebaum, Caroline
Anderson, Vicki
Reutens, David
Barton, Sarah
O'Brien, Terence J.
Vajda, Frank
Title Prospective assessment of autism traits in children exposed to antiepileptic drugs during pregnancy
Journal name Epilepsia   Check publisher's open access policy
ISSN 0013-9580
Publication date 2015-01-01
Sub-type Article (original research)
DOI 10.1111/epi.13007
Open Access Status Not Open Access
Volume 56
Issue 7
Start page 1047
End page 1055
Total pages 9
Place of publication Hoboken, NJ, United States
Publisher Wiley-Blackwell
Language eng
Formatted abstract
Purpose: The association between autism spectrum disorders (ASDs) and prenatal anticonvulsant exposure is increasingly investigated, but comprehensive, blinded assessment using a validated instrument for autism within a well-characterized prospective cohort has not been conducted. Thus, existing studies may represent an underestimate of the true risk. Herein we present a prospective cohort study in children exposed to anticonvulsants during pregnancy, with all assessments conducted by examiners who were blinded to drug-exposure status.

Methods: Participants were 105 Australian children aged 6-8 years who were recruited via the Australian Pregnancy Register for Women on Antiepileptic Medication. Maternal epilepsy, pregnancy, and medical history data were obtained prospectively. Autism traits were assessed using the Childhood Autism Rating Scale (CARS).

Results: Eleven children (10.5%) had elevated CARS scores. Two were exposed to valproate monotherapy (2/26; 7.7%), two to carbamazepine monotherapy (2/34; 5.9%), and seven to valproate in polytherapy (7/15; 46.7%). Linear regression analysis showed that the mean valproate dose during pregnancy was a significant predictor of CARS scores after controlling for polytherapy, mean carbamazepine dose, folic acid use, seizures during pregnancy, tobacco and marijuana use, maternal intelligence quotient (IQ), and socioeconomic status. First trimester folic acid supplementation and marijuana use were also significant predictors of CARS scores.

Significance: Using direct assessment of children in our prospective study, we found an elevated rate of autism traits across the sample. The most important determinant of association with autistic traits was higher doses of sodium valproate exposure. The use of valproate in women who may become pregnant is now generally avoided; however, there are insufficient data regarding the risk of ASD with low-dose valproate. If this risk is no greater than with other antiepileptic drugs (AED)s, it may enable women with genetic generalized epilepsy to retain optimal seizure control as well as minimize harm to their unborn child.
Keyword Anticonvulsant
Autism spectrum
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2016 Collection
Centre for Advanced Imaging Publications
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Citation counts: TR Web of Science Citation Count  Cited 16 times in Thomson Reuters Web of Science Article | Citations
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Created: Tue, 29 Sep 2015, 23:26:22 EST by Lorine Wilkinson on behalf of Centre for Advanced Imaging