Valproate teratogenicity and epilepsy syndrome.
Maternal valproate (VPA) use is associated with a significant risk for congenital malformations in the exposed fetus. Since VPA is commonly used in epilepsy syndromes with a presumed genetic cause (idiopathic epilepsies), it is possible that maternal genetic background contributes to this outcome. We reviewed responses to telephone questionnaires and medical records, when available, of enrollees in the North American Antiepileptic Drug Pregnancy Registry, classifying reason for treatment as idiopathic generalized epilepsy (IGE), partial epilepsy (PE), nonclassifiable epilepsy (NCE), or not epilepsy (NE). Of 284 VPA-exposed pregnancies, 30 (11.0%) were associated with malformations: IGE = 15/126 (12%), PE = 4/28 (14%), NCE = 9/105 (9%), NE = 2/25 (8%) (p > 0.7 for all comparisons). There was a trend toward increased malformation risk with higher VPA doses (p = 0.07). VPA, and not the underlying genetic syndrome, seems to be associated with the elevated risk for malformations in the drug-exposed fetus.
Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA. ebromfield@partners.org
Edward B
EB
Bromfield
Barbara A
BA
Dworetzky
Diego F
DF
Wyszynski
Caitlin R
CR
Smith
Elizabeth J
EJ
Baldwin
Lewis B
LB
Holmes
D000014:Abnormalities, Drug-Induced / Q000209:etiology*; D017668:Age of Onset; D000704:Analysis of Variance; D000927:Anticonvulsants / Q000009:adverse effects*; D004305:Dose-Response Relationship, Drug; D004827:Epilepsy / Q000145:classification / Q000188:drug therapy; D005260:Female; D006801:Humans; D008297:Male; D018811:Maternal Exposure / Q000009:adverse effects*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D012042:Registries; D011795:Surveys and Questionnaires; D014635:Valproic Acid / Q000009:adverse effects*
D000927:Anticonvulsants; D014635:Valproic Acid