Valproate-induced biochemical abnormalities in pregnancy corrected by vitamins: A case report

Purpose: Valproate (VPA) is a teratogenic anticonvulsant (AED), but vitamin supplementation has been suggested to limit the effect of VPA on the fetus. Maternal urinary metabolites were monitored to assess the metabolic effects of VPA before and after vitamin supplementation. Methods: A pregnant woman with epilepsy receiving VPA and ethosuximide (ESM) was given high-dose multivitamins from 13 to 28 weeks' gestation. Maternal urinary metabolites were measured throughout the pregnancy by gas chromatography/mass spectrometry. Results: Before multivitamin supplementation began, the patient bad significantly increased excretion rates of alpha-ketoglutarate, beta-lactate, pyruvate, lactate, methylmalonate, and other metabolites compared with normal pregnant women. During multivitamin supplementation, many previously increased excretion rates decreased significantly. Fetal head growth was normal up to 30 weeks, but then lagged. Bitemporal narrowing was noted at birth. Conclusions: VPA may cause metabolic abnormalities in pregnancy. Many biochemical abnormalities attributable to VPA in this patient were corrected with high-dose multivitamin supplementation. The specific oration between biochemical abnormalities and VPA teratogenesis remains to be determined.