Valproic acid use sparks pregnancy concerns, demanding careful choices.
Valproic acid (VPA), a common treatment for epilepsy and bipolar disorder, presents a complex dilemma for women of childbearing age due to significant risks during pregnancy. While effective in managing seizure control and mood stabilization, its teratogenic potential and association with neurodevelopmental disorders necessitate careful consideration.
### Fetal Development Under Threat
VPA exposure in early pregnancy is a major concern, with studies indicating a significantly higher risk of major congenital malformations (MCMs). Neural tube defects, such as spina bifida, are frequently cited, alongside cardiovascular anomalies, genitourinary malformations, and skeletal abnormalities. The characteristic “valproate syndrome,” featuring distinct facial features, is also associated with prenatal VPA exposure.
The risk of these malformations appears to be dose-dependent. Research suggests that even lower doses of VPA carry a heightened risk compared to many alternative antiepileptic drugs. For instance, a 2018 study analyzing data from the EURAP international registry found that VPA pregnancies had a 10.3% MCM prevalence, notably higher than that associated with phenobarbital, phenytoin, carbamazepine, topiramate, oxcarbazepine, lamotrigine, and levetiracetam.
### Balancing Risks and Treatment Needs
Despite guidelines recommending avoidance of VPA during pregnancy unless absolutely necessary, real-world data reveal variability in clinical practice. Some women discontinue VPA upon becoming pregnant, but a notable proportion may resume treatment due to a lack of efficacy with alternative medications or a risk of relapse. Switching medications can increase the likelihood of breakthrough seizures, posing direct risks to both mother and fetus.
For women with bipolar disorder, discontinuing VPA can also lead to a relapse of mood symptoms, potentially impacting maternal outcomes. This underscores the critical need for individualized treatment plans and close monitoring throughout pregnancy and the postpartum period.
### Global Perspectives and Guidance
International guidelines, including those from the American Academy of Neurology and the European Medicines Agency, strongly advise against VPA as a first-line treatment for women of childbearing potential. They recommend its use only when other medications fail to provide adequate seizure control.
Population-based studies from France and the United States indicate that while VPA prescription rates during pregnancy are relatively low (1.7% in France and around 5% in the US), concerns about fetal safety remain paramount. This highlights the ongoing challenge of balancing maternal health needs with fetal protection.
In October 2023, the UK’s Medicines and Healthcare products Regulatory Agency (MHRA) updated its guidance on valproate, reiterating the significant risks of developmental disorders and malformations in children exposed to the drug in the womb, and emphasizing the need for informed consent and exploration of alternatives.
### Ongoing Research and Future Directions
The review synthesized evidence from a comprehensive literature search, examining maternal and fetal outcomes, as well as neonatal considerations. The findings highlight the substantial risks associated with VPA during pregnancy, emphasizing the importance of shared decision-making between clinicians and patients. Further research is needed to improve outcomes for this vulnerable population, particularly regarding safer alternatives and optimized management strategies.
As of 2024, approximately 4.4% of pregnant women in the US who were taking valproic acid were reportedly prescribed it, a figure that continues to underscore the complex clinical decisions surrounding its use.
