The U.S. Food and Drug Administration (FDA) lists Depakote and other forms of valproate in Pregnancy Category D. This indicates that there is clear evidence of risk to the human fetus, but the benefits may outweigh the risk for pregnant women who have a serious condition that cannot be treated effectively with a safer drug.

The babies of women taking Depakote have a greater than usual number of minor craniofacial abnormalities, organ malformations, limb deficiencies, or developmental delay. The risk of defects is higher for women who take more than one AED and for women with a family history of birth defects.

Spina bifida and other neural tube defects are estimated to affect at least 1-2% of infants whose mothers took valproate during the first trimester. This figure may be higher than for some other antiepileptic drugs. Advise women who are capable of becoming pregnant to take at least 400 mcg (0.4 mg) of folic acid (folate) daily to help prevent neural tube defects. Women at high risk, such as those with a history of a neural tube defect in a previous pregnancy, should take 4000 mcg (4 mg) daily, beginning before they become pregnant. The effectiveness of prophylactic folic acid use in preventing defects related to valproate has not been proven, however, so diagnostic ultrasonography at the 18th to 20th week is recommended, especially if pregnancy termination is an option.

Higher doses and peak blood levels of valproate appear to be associated with some defects, so preventive measures may include:

• Use of a different medication
• lower dosage of valproate
• prescribing smaller doses taken more often (or extended-release Depakote ER) to avoid high peak blood levels

About 20% to 35% of women have seizures more often during pregnancy because of changes in hormones or changes in how valproate is handled by the body. Check the blood levels of valproate regularly during pregnancy so that the dosage can be adjusted as needed.

Breast-feeding by mothers taking Depakote should be safe for healthy, full-term newborns, although a small amount (3-5%) of the medication will appear in the milk. The dose received is estimated to be less than 6% of the initial pediatric dose.