Welcome to Valproic Acid and Pregnancy

The drug valproic acid has been widely used as an anticonvulsant since the 1970s. It is routinely used to treat epilepsy or seizure disorder. It is also used to prevent migraine headaches and to treat various psychiatric illnesses, such as bipolar disorder and certain types of anxiety disorder.  During pregnancy, valproic acid is known to cross the placenta and to adversely affects the fetus causing a spectrum of congenital anomalies referred to as the  Fetal Valproate Syndrome (FVS) or Valproic Acid Embryopathy.  
 

Dr. Kozma has studied extensively the teratogenic effects of valproic acid. She described two affected siblings who were exposed to valproic acid prenatally and reviewed the English medical literature from 1978 to 2000.  She identified a total of 70 cases that were exposed solely to valproic acid with adequate clinical description.   She summarized the clinical manifestations of FVS; which encompass a wide spectrum of abnormalities including alteration in facial features, multiple systemic and orthopedic involvement, central nervous system dysfunction, and altered physical growth. The facial appearance is characterized by a small broad nose, small ears, a long upper lip with shallow philtrum (the ridges between the nose and the upper lip), and a small chin. In her review, Dr. Kozma found that 62% of the patients had musculoskeletal abnormalities, 30% had minor skin defects, 26% had cardiovascular abnormalities, 22% had genital abnormalities, and 16% had pulmonary abnormalities.  Less frequently encountered abnormalities included brain, eye, kidney, and hearing defects.  Neural tube defects or spina bifida were seen in 3% of the sample. Twelve percent of affected children died in infancy. Follow-up data on surviving patients in this study documented developmental delays in 20% and mental retardation in 9%.  While 15% of patients had growth retardation or were small, an overgrowth pattern was seen in 9%. Several animal models have been used to study the effects of prenatal exposure to valproic acid and have supported the teratogenic aspects of the drug.

Women of reproductive age who have seizure disorders should be counseled adequately before becoming pregnant regarding their risk of having a child with congenital abnormalities. All women with epilepsy should be advised that uncontrolled epilepsy is associated with maternal and fetal risk and that the incidence of malformations in their infants following treatment with anticonvulsants is 2-3 times higher than the general newborn population.  Furthermore, prenatal intake of valproic acid is associated with serious birth defects in the devolving fetus. The drug is not recommended for pregnant women unless the benefits of therapy clearly outweigh the risks. In fact, women in their childbearing years should take valproic acid only if it has been shown to be essential in the control of seizures. Valproic acid is excreted in breast milk; therefore nursing mothers should use only it with caution.

Reference:
Chahira Kozma.  Valproic Acid Embryopathy: Report of two siblings with further expansion of the phenotypic abnormalities and a review of the literature (2001).  The American Journal of Medical Genetics.  98: 168-175.