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It is well known that prenatal exposure of valproic acid (VPA) may be associated with the occurrence of neural tube defects (Robert and Gibaud, 1982). Additional adverse effects related to VPA exposure include craniofacial abnormalities, skeletal defects, brain defects, cardiovascular defects, and urogenital defects (DiLiberti et al., 1984; Winter et al., 1987; Huot et al., 1987; Jager-Roman et al., 1986; Martinez-Frias, 1990). Recently, radial ray reduction has been reported as a severe type of skeletal defect associated with VPA exposure (Jager-Roman et al., 1986; Huot et al., 1987; Verloes et al., 1990). We report two additional cases of this severe limb reduction defect as part of a broader pattern of altered morphogenesis in fetuses exposed to VPA and to confirm an association between such severe specific skeletal defects and VPA exposure. We briefly review teratologic studies in experimental animals which document the biologic plausibility of this association, and suggest that fetuses exposed to VPA undergo detailed prenatal ultrasonographic evaluation of the limbs.
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