epilepsy in relation to pregnancy and contraception
Last edited 03/2023
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Children with an epileptic parent have an increased risk of being epileptic; with one parent affected, the risk of the child becoming epileptic is 2.5 to 6%; with both parents affected, the risk increases to 15-20%(1).
Other conditions associated with epilepsy are also more likely - for example, neurofibromatosis, tuberous sclerosis, and the genetically determined epilepsies such as juvenile myoclonic epilepsy.
Epilepsy and anti-epileptic agents need to be considered in all stages of birth - from contraception to post-natal care.
The ideal regime is the lowest possible dose of a single anti-epileptic drug (1,2).
The majority of women with epilepsy have an uncomplicated delivery of a healthy child; however, due to the risks of complications and malformations, a specialist should be involved in management.
The woman should be counselled about the teratogenicity of anti-epileptic drugs (AEDs) and the need to continue treatment. The dose of drugs should be titrated against symptoms, the prime consideration being the control of seizures.
NICE state (3):
- discuss with women and girls of childbearing potential (including young girls who are likely to need treatment into their childbearing years), and their parents and/or carers if appropriate, the risk of AEDs causing malformations and possible neurodevelopmental impairments in an unborn child
- assess the risks and benefits of treatment with individual drugs. There are limited data on risks to the unborn child associated with newer drugs
- specifically discuss the risk of continued use of sodium valproate to the unborn child, being aware that higher doses of sodium valproate (more than 800 mg/day) and polytherapy, particularly with sodium valproate, are associated with greater risk. Follow the MHRA safety advice on sodium valproate
- be aware of the latest data on the risks to the unborn child associated with AED therapy when prescribing for women and girls of present and future childbearing potential
- all women and girls on AEDs should be offered 5 mg per day of folic acid before any possibility of pregnancy
- refer to the SPC and BNF for individual drug advice on the interactions between AEDs and hormonal replacement and contraception
- if a woman or girl taking enzyme-inducing AEDs chooses to take the combined oral contraceptive pill, guidance about dosage should be sought from the SPC and current edition of the BNF
- the progestogen-only pill is not recommended as reliable contraception in women and girls taking enzyme-inducing AEDs
- the progestogen implant is not recommended in women and girls taking enzyme-inducing AEDs
- the use of additional barrier methods should be discussed with women and girls taking enzyme-inducing AEDs and oral contraception or having depot injections of progestogen
- if emergency contraception is required for women and girls taking enzymeinducing AEDs, the type and dose of emergency contraception should be in line with the SPC and current edition of the BNF
- discuss with women and girls who are taking lamotrigine that the simultaneous use of any oestrogen-based contraceptive can result in a significant reduction of lamotrigine levels and lead to loss of seizure control. When a woman or girl starts or stops taking these contraceptives, the dose of lamotrigine may need to be adjusted
- summarised in the linked item below
A MHRA review states (4):
Summary of key conclusions of review
- Lamotrigine – Studies involving more than 12,000 pregnancies exposed to lamotrigine monotherapy consistently show that lamotrigine at maintenance doses is not associated with an increased risk of major congenital malformations
- Levetiracetam – Studies involving more than 1,800 pregnancies exposed to levetiracetam do not suggest an increased risk of major congenital malformations
- For both lamotrigine and levetiracetam, the data on neurodevelopmental outcomes are more limited than those for congenital malformations. The available studies do not suggest an increased risk of neurodevelopmental disorders or delay associated with in-utero exposure to either lamotrigine or levetiracetam; however, the data is inadequate to rule out definitively the possibility of an increased risk
- For the other key antiepileptic drugs, data show:
- an increased risk of major congenital malformations associated with carbamazepine, phenobarbital, phenytoin, and topiramate use during pregnancy
- the possibility of adverse effects on neurodevelopment of children exposed in utero to phenobarbital and phenytoin
- an increased risk of fetal growth restriction associated with phenobarbital, topiramate, and zonisamide use during pregnancy
Actions for prescribers
- At initiation and as part of the recommended annual review for patients with epilepsy, specialists should discuss with women the risks associated with antiepileptic drugs and with untreated epilepsy during pregnancy and review their treatment according to their clinical condition and circumstances – we have produced a safety information leaflet to assist with this discussion
- Urgently refer women who are planning to become pregnant for specialist advice on their antiepileptic treatment
- All women using antiepileptic drugs who are planning to become pregnant should be offered 5mg per day of folic acid before any possibility of pregnancy
- For lamotrigine, levetiracetam or any antiepileptic drugs that can be used during pregnancy, it is recommended to
- use monotherapy whenever possible
- use the lowest effective dose (see below for key dose monitoring advice, including for lamotrigine and levetiracetam)
- report any suspected adverse effects experienced by the mother or baby to the Yellow Card scheme
Reminder of advice to give to women with epilepsy
- Do not stop taking antiepileptic drugs without discussing it with your doctor
- If you are taking an antiepileptic drug and think you may be pregnant, seek urgent medical advice, including urgent referral to your specialist
- Read the patient information leaflets that accompany your medicines and other information provided by your healthcare professional
A systematic review and meta-analysis found that women with epilepsy are at increased odds of maternal death and increased odds of having offspring with congenital conditions compared with women who do not have epilepsy (6)
- women with epilepsy had increased odds of
- miscarriage ( OR (odds ratio), 1.62),
- stillbirth (pregnancies; OR, 1.37),
- preterm birth ( OR, 1.41) and
- maternal death (OR, 5.00
- neonates born to women with epilepsy had increased odds of congenital conditions (OR, 1.88), neonatal intensive care unit admission (OR, 1.99), and neonatal or infant death (OR, 1.87)
- increased odds of poor outcomes is associated with greater use of antiseizure medication
- O'Brien, (1993). Epilepsy and pregnancy. BMJ,307,492-5
- Consumers' Association, (1994). Epilepsy and pregnancy. Drug & Therapeutic Bulletin, 32:7, 49.
- NICE (April 2018). Epilepsies: diagnosis and management
- MHRA(January 2021).Antiepileptic drugs in pregnancy: updated advice following comprehensive safety review Drug Safety Update volume 14, issue 6: January 2021: 1.
- Mazzone PP, Hogg KM, Weir CJ, Stephen J, Bhattacharya S, Chin RFM. Comparison of Perinatal Outcomes for Women With and Without Epilepsy: A Systematic Review and Meta-analysis. JAMA Neurol. Published online March 13, 2023. doi:10.1001/jamaneurol.2023.01
maternal epilepsy in pregnancy