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Valproate Embryopathy
Janice L. B. Byrne, MD
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KEY FACTS

  • Terminology

    • Imaging

      • Top Differential Diagnoses

        • Pathology

          • Clinical Issues

            TERMINOLOGY

            • Synonyms

              • Valproic acid (VPA) embryopathy, fetal valproate syndrome
            • Definitions

              • Fetal exposure to antiepileptic drug valproic acid (VPA), characterized by dysmorphic facial appearance, major and minor anomalies, central nervous system dysfunction

            IMAGING

            • General Features

              • Ultrasonographic Findings

                • Imaging Recommendations

                  DIFFERENTIAL DIAGNOSIS

                    PATHOLOGY

                    • General Features

                      CLINICAL ISSUES

                      • Presentation

                        • Demographics

                          • Natural History & Prognosis

                            • Treatment

                              Selected References

                              1. Veiby G et al: Fetal growth restriction and birth defects with newer and older antiepileptic drugs during pregnancy. J Neurol. 261(3):579-88, 2014
                              2. Vajda FJ et al: Dose dependence of fetal malformations associated with valproate. Neurology. 81(11):999-1003, 2013
                              3. Holmes LB et al: Fetal effects of anticonvulsant polytherapies: different risks from different drug combinations. Arch Neurol. 68(10):1275-81, 2011
                              4. Tomson T et al: Dose-dependent risk of malformations with antiepileptic drugs: an analysis of data from the EURAP epilepsy and pregnancy registry. Lancet Neurol. 10(7):609-17, 2011
                              5. Alessandri JL et al: Tibial developmental field defect in valproic acid embryopathy: Report on three cases. Am J Med Genet A. 152A(11):2805-9, 2010
                              6. Dawson JE et al: Folic acid and pantothenic acid protection against valproic acid-induced neural tube defects in CD-1 mice. Toxicol Appl Pharmacol. 211(2):124-32, 2006
                              7. Hrubec TC et al: Valproic acid-induced fetal malformations are reduced by maternal immune stimulation with granulocyte-macrophage colony-stimulating factor or interferon-gamma. Anat Rec A Discov Mol Cell Evol Biol. 288(12):1303-9, 2006
                              8. Padmanabhan R et al: Effect of maternal exposure to homocystine on sodium valproate-induced neural tube defects in the mouse embryos. Eur J Nutr. 45(6):311-9, 2006
                              9. Alsdorf R et al: Teratogenicity of sodium valproate. Expert Opin Drug Saf. 4(2):345-53, 2005
                              10. Schorry EK et al: Valproate embryopathy: clinical and cognitive profile in 5 siblings. Am J Med Genet A. 133A(2):202-6, 2005
                              11. Vajda FJ et al: Critical relationship between sodium valproate dose and human teratogenicity: results of the Australian register of anti-epileptic drugs in pregnancy. J Clin Neurosci. 11(8):854-8, 2004
                              12. Wide K et al: Major malformations in infants exposed to antiepileptic drugs in utero, with emphasis on carbamazepine and valproic acid: a nation-wide, population-based register study. Acta Paediatr. 93(2):174-6, 2004
                              13. Yonkers KA et al: Management of bipolar disorder during pregnancy and the postpartum period. Am J Psychiatry. 161(4):608-20, 2004
                              14. Malm H et al: Valproate embryopathy in three sets of siblings: further proof of hereditary susceptibility. Neurology. 59(4):630-3, 2002
                              15. Kozma C: Valproic acid embryopathy: report of two siblings with further expansion of the phenotypic abnormalities and a review of the literature. Am J Med Genet. 98(2):168-75, 2001
                              16. Moore SJ et al: A clinical study of 57 children with fetal anticonvulsant syndromes. J Med Genet. 37(7):489-97, 2000
                              Related Anatomy
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                              Related Differential Diagnoses
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                              References
                              Tables

                              Tables

                              KEY FACTS

                              • Terminology

                                • Imaging

                                  • Top Differential Diagnoses

                                    • Pathology

                                      • Clinical Issues

                                        TERMINOLOGY

                                        • Synonyms

                                          • Valproic acid (VPA) embryopathy, fetal valproate syndrome
                                        • Definitions

                                          • Fetal exposure to antiepileptic drug valproic acid (VPA), characterized by dysmorphic facial appearance, major and minor anomalies, central nervous system dysfunction

                                        IMAGING

                                        • General Features

                                          • Ultrasonographic Findings

                                            • Imaging Recommendations

                                              DIFFERENTIAL DIAGNOSIS

                                                PATHOLOGY

                                                • General Features

                                                  CLINICAL ISSUES

                                                  • Presentation

                                                    • Demographics

                                                      • Natural History & Prognosis

                                                        • Treatment

                                                          Selected References

                                                          1. Veiby G et al: Fetal growth restriction and birth defects with newer and older antiepileptic drugs during pregnancy. J Neurol. 261(3):579-88, 2014
                                                          2. Vajda FJ et al: Dose dependence of fetal malformations associated with valproate. Neurology. 81(11):999-1003, 2013
                                                          3. Holmes LB et al: Fetal effects of anticonvulsant polytherapies: different risks from different drug combinations. Arch Neurol. 68(10):1275-81, 2011
                                                          4. Tomson T et al: Dose-dependent risk of malformations with antiepileptic drugs: an analysis of data from the EURAP epilepsy and pregnancy registry. Lancet Neurol. 10(7):609-17, 2011
                                                          5. Alessandri JL et al: Tibial developmental field defect in valproic acid embryopathy: Report on three cases. Am J Med Genet A. 152A(11):2805-9, 2010
                                                          6. Dawson JE et al: Folic acid and pantothenic acid protection against valproic acid-induced neural tube defects in CD-1 mice. Toxicol Appl Pharmacol. 211(2):124-32, 2006
                                                          7. Hrubec TC et al: Valproic acid-induced fetal malformations are reduced by maternal immune stimulation with granulocyte-macrophage colony-stimulating factor or interferon-gamma. Anat Rec A Discov Mol Cell Evol Biol. 288(12):1303-9, 2006
                                                          8. Padmanabhan R et al: Effect of maternal exposure to homocystine on sodium valproate-induced neural tube defects in the mouse embryos. Eur J Nutr. 45(6):311-9, 2006
                                                          9. Alsdorf R et al: Teratogenicity of sodium valproate. Expert Opin Drug Saf. 4(2):345-53, 2005
                                                          10. Schorry EK et al: Valproate embryopathy: clinical and cognitive profile in 5 siblings. Am J Med Genet A. 133A(2):202-6, 2005
                                                          11. Vajda FJ et al: Critical relationship between sodium valproate dose and human teratogenicity: results of the Australian register of anti-epileptic drugs in pregnancy. J Clin Neurosci. 11(8):854-8, 2004
                                                          12. Wide K et al: Major malformations in infants exposed to antiepileptic drugs in utero, with emphasis on carbamazepine and valproic acid: a nation-wide, population-based register study. Acta Paediatr. 93(2):174-6, 2004
                                                          13. Yonkers KA et al: Management of bipolar disorder during pregnancy and the postpartum period. Am J Psychiatry. 161(4):608-20, 2004
                                                          14. Malm H et al: Valproate embryopathy in three sets of siblings: further proof of hereditary susceptibility. Neurology. 59(4):630-3, 2002
                                                          15. Kozma C: Valproic acid embryopathy: report of two siblings with further expansion of the phenotypic abnormalities and a review of the literature. Am J Med Genet. 98(2):168-75, 2001
                                                          16. Moore SJ et al: A clinical study of 57 children with fetal anticonvulsant syndromes. J Med Genet. 37(7):489-97, 2000