Most Cochrane Reviews focus primarily on the intended effects of interventions, but some are designed to investigate the potential harms. One such review was published in November 2016 to examine the effects of anti-epileptic drugs during pregnancy. The lead author, Rebecca Bromley from the Institute of Human Development at the University of Manchester in the UK tells us more in this podcast.
John: Hello, I'm John Hilton, editor of the Cochrane Editorial unit. Most Cochrane Reviews focus primarily on the intended effects of interventions, but some are designed to investigate the potential harms. One such review was published in November 2016 to examine the effects of anti-epileptic drugs during pregnancy. The lead author, Rebecca Bromley from the Institute of Human Development at the University of Manchester in the UK tells us more in this podcast.
Rebecca: Women of reproductive age make up about a third of the people with epilepsy and approximately one in every 250 pregnant women take an antiepileptic drug. We know that there are important decisions that need to be made by these women and their healthcare providers to maximize maternal health whilst minimizing the risk to the fetus. To be able to do this it’s important to know about the risks associated with commonly used antiepileptic drugs so that women can make informed decisions about their treatment options.
We set out, therefore, to look for studies that had investigated these harms. This meant that designs such as cohort studies, as well as randomised trials were eligible. In the cohort studies, there were two usual types of control group: women without epilepsy and women with epilepsy who were not taking the drugs during pregnancy.
We included 50 studies with 31 contributing to our meta-analyses, which allowed us to quantify the effects of individual drugs compared with the control groups and with other drugs as monotherapy.
We found that children exposed to valproate had the highest prevalence risk of a major congenital malformation, with an overall risk of around 10%. Children exposed in the womb to carbamazepine, phenobarbital, phenytoin and topiramate were all found to have a raised risk of malformation in comparison to one or both the control groups. But children exposed to lamotrigine or levetiracetam were not found to be at an increased risk of malformation in comparison to either control group and in fact there was a reduction in risk of malformation when exposed to these drugs in comparison to others.
We found associations between valproate exposure and a wide range of specific malformation types, whilst phenobarbital was associated with an increased risk of cardiac malformations. However, the data on specific malformations was limited, as several studies didn’t provide detailed information about the types of malformation in their control groups.
In conclusion, although these results are concerning with regards to malformation prevalence in children exposed to valproate, it’s important to remember that valproate is an effective drug at controlling seizures for some women and that uncontrolled seizures may pose a risk to maternal health, and possibly to fetal health. Currently, exposure to lamotrigine and levetiracetam appear to be associated with the lowest level of risk; however treatment decisions are complex and should be made as a collaboration between the woman and her prescriber.
John: If you would like to learn more about the associations between the use of these antiepileptic drugs during pregnancy and malformations in the child, you can find Rebecca’s full review online. Just go to Cochrane Library dot com and search ‘epilepsy in pregnancy and congenital malformations’.