How do anti-seizure medications affect women during pregnancy?

IMPORTANT: Do not stop taking prescribed medication without consulting your doctor or epilepsy nurse. If you are concerned, please contact the helplines of Epilepsy Action (0808 800 5050) or Epilepsy Society (01494 601 400).

Dr Anita McGrogan at the University of Bath is using Big Data to assess the impact of anti-seizure medications (ASMs) during pregnancy. Anita’s Endeavour Project will support the use of anonymised healthcare data from around 40,000 women and assess children from birth into their early years. In this blog, Anita explains how the real-world experiences of women and their children will help evaluate the safety of ASMs.

Clinical trials test whether new medicines work for patients. While these trials may include thousands of people, women who are or may become pregnant are rarely eligible to take part. This means we have little information about how medicines work during pregnancy and whether they are safe for the mother and unborn child.

For chronic conditions like epilepsy, treatment is vital and often needs to be continued throughout pregnancy. Sometimes ASMs need to be changed during pregnancy – dosages may be increased or different combinations used in response to changes in seizure frequency.

To improve the safety of medicines in pregnancy, we need to know how frequently adverse outcomes occur and whether this varies between different ASMs and combinations of medications. We usually study important adverse outcomes such as major congenital malformations like cleft lip and palate, or heart or limb defects. These are rare outcomes and usually diagnosed before a child’s first birthday. We are also interested in neurodevelopmental disorders such as autism and attention deficit hyperactivity disorder (ADHD) which can take longer to diagnose – at least six years for many children. Other important outcomes include pregnancy loss, stillbirth and growth restriction.

This creates challenges to overcome when designing studies into which medications are safest to recommend using during pregnancy. One way to overcome these challenges is by using real world data from anonymous healthcare records collected during routine medical care. The records we use are from primary care with all patient identifying information removed. Not only can we include many thousands of women and their pregnancies, which helps in detecting any adverse outcomes, but we can also follow up their children’s progress into childhood to find outcomes diagnosed during primary years. Adverse outcomes can occur during any pregnancy, so we include a comparator group of women without epilepsy who go through pregnancy at a similar age and time. This allows us to identify increases of serious adverse outcomes in children who have been exposed to ASMs during pregnancy. By looking at all these outcomes, this will give us as full a picture as possible of the effects of ASMs during pregnancy.

In recent years we have learnt more about the effects of sodium valproate when used during pregnancy and the devastating impact valproate syndrome, major malformations and neurodevelopmental outcomes have on lives.

The safety of newer ASMs and combinations of medicines used in pregnancy remains uncertain. Women with epilepsy need to know more about medication safety when balancing the benefits of treating and preventing seizures with risks to their unborn child. Ultimately, this research will lead to safer pregnancies and healthier outcomes for babies and children born to women with epilepsy.