OACS Ireland would like to thank all patients groups, Health Care Professional (HCP) involved, who have worked with the MHRA for many years on the Valproate Stakeholder Group. The New UK guidelines produced by the Royal College of Obstetricians and Gynaecologists, recommend women seek advice well before pregnancy on their care. Managing seizure control, fatigue and risks linked to some epilepsy medicines can make pregnancy a problematic time. But there are risks to the health of unborn babies from taking some anticonvulsant drugs (AEDs) during pregnancy, particularly Epilim. See the Irish Sodium Valproate (Epilim) Patient Booklet (HPRA)
Updated – Risk Acknowledgement Form Valproate (Epilim▼) and Risks in Pregnancy –2021.
The HPRA have updated the Risk Acknowledgement Form Valproate (Epilim▼) and Risks in Pregnancy. Children exposed to valproate in utero have a very high risk for congenital malformations and neurodevelopmental disorders. Valproate is therefore contraindicated in women of childbearing potential (i.e., a pre-menopausal female who is capable of becoming pregnant) unless the conditions of ‘prevent’, the valproate (Epilim) pregnancy prevention programme are fulfilled. : annual-risk-acknowledgement-form-valproate-(epilim-)-and-risks-in-pregnancy.pdf (hpra.ie)
AED use in pregnancy has received significant attention in both Ireland and the UK in recent months given developments in each jurisdiction regarding Sodium Valproate (Epilim).
This drug is known to have severe impacts on the child if prescribed in pregnancy. In the summer of 2020, the UK published the Cumberlege report (see more – https://bit.ly/3pOWx87 while towards the end of 2020 in Ireland, Minister for Health Stephen Donnelly announced that an inquiry will be held in Ireland on the historical use & licensing of the drug find out why here – https://bit.ly/2LgJYDx . The severe impacts this drug can have led the MHRA to conduct this review of currently available evidence on the safety of a wider range of AEDs in pregnancy. The review examined the following drugs:
The review considered information from clinical studies of women during pregnancy and from studies in animals. By reviewing this available information, the MHRA sought to establish the risk of the drugs in pregnancy in relation to:
- Physical birth abnormalities
- Harmful effects on the growth of the unborn baby
- Autism and attention deficit hyperactivity disorder (ADHD) and adverse effects on learning and thinking abilities.
A summary of the review’s findings based on available safety data is presented below under these three headings.
Physical birth abnormality
- Lamotrigine (Lamictal) and Levetiracetam (Keppra) medicines are safer to use during pregnancy than other epilepsy medicines. Information supports that they do not increase the risk of physical birth abnormalities compared with the general population
- Carbamazepine (Tegretol), phenobarbital or Topiramate (Topamax) use during pregnancy increases the risk of physical birth abnormalities compared with the general population
Epilepsy medicines where the data support an increased risk of having a baby born with a physical birth abnormality:
|General population||2 to 3 out of 100 babies|
|Carbamazepine||4 to 5 out of 100 babies|
|Phenobarbital||6 to 7 out of 100 babies|
|Phenytoin||about 6 out of 100 babies|
|Topiramate||4 to 5 out of 100 babies|
|Valproate||about 10 out of 100 babies|
- Gabapentin (Neurontin) and Pregabalin (Lyrica) – risks during pregnancy are not yet fully understood; some data suggest that taking pregabalin during pregnancy may slightly increase the risk of a baby being born with physical birth abnormalities
- Clobazam (Frisium) and Pregabalin (Lyrica) – some research suggests that these medicines may slightly increase the risk of a baby being born with physical birth abnormalities; however, the research that is available does not allow firm conclusions to be reached and further data are needed; the risk of harming a baby cannot be confirmed or ruled out.
- Zonisamide (Zonegran) – more data are needed to understand whether zonisamide use during pregnancy increases the chance of having a baby born with a birth abnormality.
Development of the brain
- Phenobarbital or phenytoin use during pregnancy increases the risk the child may have difficulties with learning and thinking ability. Although the exact risk is not known it is not as high as for valproate (Epilim).
- For carbamazepine (Tegretol), lamotrigine (Lamictal) and levetiracetam (Keppra) the available information does not suggest an increased risk of the child having difficulties with learning and thinking ability; however, the limited data for lamotrigine and levetiracetam mean an increased risk cannot be ruled out
- For gabapentin (Neurontin), oxcarbazepine (Trileptal), pregabalin (Lyrica), topiramate (Topamax) and zonisamide (Zonegran) more data are needed to understand whether use of these epilepsy medicines during pregnancy increases the chance of having a baby born with a learning or thinking disability.
Growth of the baby in the womb
- Phenobarbital, topiramate (Topamax), or zonisamide (Zonegran) use during pregnancy increases the risk of the baby being born smaller than expected compared with the general population
- For lamotrigine (Lamictal) and levetiracetam (Keppra) the information supports that use of these medicines during pregnancy does not increase the risk of the baby being born small for gestational age
- For carbamazepine (Tegretol), gabapentin (Neurontin), oxcarbazepine (Trileptal), phenytoin and pregabalin (Lyrica) the data are either limited or report inconsistent findings and therefore the possibility of an increased risk cannot be confirmed or ruled out
Lack of evidence on some medications
For the medicines listed below there is not enough information on their use in pregnancy to make any conclusions about their safety when used during pregnancy. This means the risk of harming a baby cannot be confirmed or ruled out.
- Brivaracetam (brand name Briviact)
- Clonazepam (brand name Rivotril)
- Eslicarbazepine (brand name Zebinix)
- Ethosuximide (brand name Zarontin)
- Lacosamide (brand name Vimpat)
- Rufinamide (brand name Inovelon)
- Perampanel (brand name Fycompa)
- Primidone (brand name Mysoline)
- Tiagabine (brand name Gabitril)
- Vigabatrin (brand name Sabril)
Questions you may have…
We know that this may lead to questions from women who are on these drugs – particularly those who may be see a drug they are currently taking showing an increased risk. We have listed some questions that you may have and further advice for you below.
A drug I am taking is listed as showing an increased risk in the review. Should I stop taking it?
DO NOT stop taking your prescribed epilepsy medication without first consulting with your medical team. If you have any concerns with the information listed above, please contact your healthcare professional regarding same.
I am planning on starting a family and I’m concerned about the AED I’m on. What should I do?
You should contact your healthcare professionals to discuss this. It is important for all women with epilepsy to have a discussion with their team when planning a family given the nature of the condition. Therefore, if you are planning a family, link in with your local Epilepsy Nurse Specialist, Medical professional or local Community Resource Officer.
Is this new information?
It is important to stress that the review consists of information that was already available and is a review of existing evidence in order to give women and health professionals further guidance and advice. The review highlights the importance of collaborative communication between healthcare professionals and their patients on potential risks. If you have concerns about the medication you are on, ensure that you discuss this with your medical team.
Are there figures on the specific risk of each drug?
With regard to the drugs that have recorded an increased risk of birth defects, the MHRA have published the relative risk of each (see table above). It is important to note that for all drugs assessed in the review, the risk of birth defects is lower compared to valproate. It should also be noted that there is a 2-3% background risk of birth defects occurring in children who have not been exposed to ANY medication during pregnancy.
Comparative data is not included in the review in relation to neurodevelopmental delay or other effects. . You can read the full MHRA findings HERE and it is also available for download at the end of this article.
I think my child has potentially been affected by exposure to AED’s during pregnancy. Who can I contact?
If you think your child has been impacted, you should contact your healthcare professional and to discuss this further. You can also contact our colleagues in Epilepsy Ireland.
If you need further support or advice with regard to epilepsy when planning a pregnancy, feel free to contact your Epilepsy Ireland local Community Resource Officer or visit the Women section of our website HERE.