TY - JOUR
T1 - In utero exposure to valproic acid and autism - A current review of clinical and animal studies
AU - Roullet, Florence I.
AU - Lai, Jonathan K.Y.
AU - Foster, Jane A.
N1 - Funding Information:
Operating funds from the National Science and Engineering Research Council of Canada (NSERC , to JAF), and equipment funds from the Canadian Foundation for Innovation (to JAF) in the conduct of published work related to this review were acknowledged. Graduate stipend support (to JKYL) was provided by the Canadian Institute of Health Research — Vanier Scholarship .
PY - 2013/3
Y1 - 2013/3
N2 - Valproic acid (VPA) is both an anti-convulsant and a mood stabilizer. Clinical studies over the past 40. years have shown that exposure to VPA in utero is associated with birth defects, cognitive deficits, and increased risk of autism. Two recent FDA warnings related to use of VPA in pregnancy emphasize the need to reevaluate its use clinically during child-bearing years. The emerging clinical evidence showing a link between VPA exposure and both cognitive function and risk of autism brings to the forefront the importance of understanding how VPA exposure influences neurodevelopment. In the past 10. years, animal studies have investigated anatomical, behavioral, molecular, and physiological outcomes related to in utero VPA exposure. Behavioral studies show that VPA exposure in both rats and mice leads to autistic-like behaviors in the offspring, including social behavior deficits, increased repetitive behaviors, and deficits in communication. Based on this work VPA maternal challenge in rodents has been proposed as an animal model to study autism. This model has both face and construct validity; however, like all animal models there are limitations to its translation to the clinical setting. Here we provide a review of clinical studies that examined pregnancy outcomes of VPA use as well as the related animal studies.
AB - Valproic acid (VPA) is both an anti-convulsant and a mood stabilizer. Clinical studies over the past 40. years have shown that exposure to VPA in utero is associated with birth defects, cognitive deficits, and increased risk of autism. Two recent FDA warnings related to use of VPA in pregnancy emphasize the need to reevaluate its use clinically during child-bearing years. The emerging clinical evidence showing a link between VPA exposure and both cognitive function and risk of autism brings to the forefront the importance of understanding how VPA exposure influences neurodevelopment. In the past 10. years, animal studies have investigated anatomical, behavioral, molecular, and physiological outcomes related to in utero VPA exposure. Behavioral studies show that VPA exposure in both rats and mice leads to autistic-like behaviors in the offspring, including social behavior deficits, increased repetitive behaviors, and deficits in communication. Based on this work VPA maternal challenge in rodents has been proposed as an animal model to study autism. This model has both face and construct validity; however, like all animal models there are limitations to its translation to the clinical setting. Here we provide a review of clinical studies that examined pregnancy outcomes of VPA use as well as the related animal studies.
KW - Anti-epileptic drugs
KW - Autism
KW - Behavior
KW - Neurodevelopment
KW - Pregnancy registries
KW - Teratogen
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U2 - 10.1016/j.ntt.2013.01.004
DO - 10.1016/j.ntt.2013.01.004
M3 - Review article
C2 - 23395807
AN - SCOPUS:84875666213
SN - 0892-0362
VL - 36
SP - 47
EP - 56
JO - Neurotoxicology and Teratology
JF - Neurotoxicology and Teratology
ER -