Managing Epilepsy in Pregnancy
National Maternity Hospital, Holles Street, Dublin 2
Epilepsy is one of the commonest medical conditions affecting women of childbearing age1. In the most recent triennial report into maternal deaths in Ireland and the UK, two thirds of women who died had a medical condition. In this report, 14 maternal deaths during pregnancy and up to 42 days postpartum were attributable to epilepsy or seizures; a rate of 0.4 per 100,000 maternities. In 12 of these women’ the cause was sudden unexplained death in epilepsy. Thus, epilepsy remains a high-risk condition in pregnancy. The gold standard of care is a multidisciplinary approach involving obstetricians, a neurologist and an epilepsy nurse specialist2. Like other units in Ireland this multidisciplinary service is currently provided in the National Maternity Hospital’s maternal medicine clinic, in conjunction with neurology services in Beaumont Hospital.
Pre-conceptual counselling should be offered to all women with epilepsy (WWE). High dose folic acid should be taken by women considering pregnancy for three months prior to conception and until the end of the first trimester. Studies have shown that folic acid supplementation is taken by <50% of Irish women. This is in part due to lack of knowledge about folic acid supplementation and unplanned pregnancies3-5. Prior to pregnancy it is also important to review antiepileptic drugs (AEDs). If possible, women considering pregnancy should avoid sodium valproate due to a 10-fold increased risk in teratogenicity. While monotherapy is preferable, more than one medication may be needed to control seizure activity. The EURAP study group suggests that the lowest rates of malformation are observed in WWE taking lamotrigine (2 per 100, 95% CI 1.19–3.24), carbamazepine (3.4 per 100, 95% CI 1.11–7.71) and levetiracetam monotherapy (0.7 per 100; 95% CI 0.19–2.51).6 Furthermore, there appears to be no effect on neurodevelopmental outcomes in children of women taking lamotrigine and carbamazepine in pregnancy. However, newer AED drug levels can fluctuate during pregnancy necessitating monitoring of drug levels at least once a trimester. At our clinic, written information is provided by our dedicated pharmacist, to all our patients and a copy placed in their chart for each AED, which can be reassuring for women and healthcare providers.
Women with epilepsy can be reassured that at least two thirds will not have any increase in seizure frequency during pregnancy. Potential causes of increased seizure frequency include poor compliance with AEDs, altered drug levels during pregnancy and stress or sleep deprivation1. Women will often put the wellbeing of their unborn child ahead of their own health and wellbeing and stop their AEDs when they have a positive pregnancy test. In fact, the risk of stopping an AED and having a seizure probably has a higher adverse effect on pregnancy than the small potential teratogenic effect. It is important to reinforce this point both pre-conceptually and at the first antenatal visit. WWE should be offered review appointments with an epilepsy nurse specialist in early pregnancy and again in the third trimester to discuss lifestyle safety advice including the use of buccal midazolam for seizure control and so that they have the opportunity to discuss pregnancy specific concerns. All women should be offered an anatomy scan between 18 and 22 weeks gestation and consider a third trimester growth scan as epilepsy and AEDs are associated with intrauterine growth restriction7.
WWE can be reassured that spontaneous labour and delivery of a healthy baby is the most common outcome. Labour and delivery can be managed according to obstetric indications. However, pethidine should be avoided as it lowers the seizure threshold and an early epidural may be required. Avoiding prolonged sleep deprivation, a potential trigger for a seizure, can be difficult around this time. Induction of labour can be considered on a case basis where prolonged sleep deprivation due to pains is putting a WWE at risk of a seizure. If a seizure occurs in the second half of pregnancy and there is any possibility that the seizure is eclamptic rather than epileptic in origin treatment with magnesium sulphate to reduce the risk of further seizures should be given. A guideline for emergency management of seizures in WWE is placed in our hospital charts. Medications included in this guideline are intravenous lorazepam to treat epileptic seizures in hospital followed by a phenytoin infusion. Seizures during labour affect about 1% of WWE and can cause fetal hypoxia and acidosis, therefore WWE should continue to take their AEDs during labour and postpartum.
Postpartum advice given by both the obstetric team and epilepsy nurse specialist includes advice that breastfeeding is safe with AEDs and WWE can breastfeed if they choose to do so. Again it is important to minimize sleep deprivation and involve their partner and all supports available to the new mother in the first few weeks postpartum. Other safety precautions for caring for a newborn baby such as include not bathing the baby alone are discussed during pregnancy and postpartum. Contraception should be discussed with all women with epilepsy. Some AEDs are enzyme inducers (carbamazepine, phenytoin and topiramate) and will interfere with oestrogen and progesterone containing contraception including progesterone implants and injections. Lamotrigine levels are reduced in women taking oestrogen containing contraceptive pills because of hepatic metabolism. Other options include intrauterine contraceptive devices (IUCDs). A recent study showed that only one third of WWE receive counseling about contraception and those counseled about IUCDs were more likely to choose this than other methods of contraception8.
Finally, standardization of management of WWE in pregnancy is needed. The RCOG has recently published a guideline for the management of epilepsy in pregnancy6. There is also an Irish guideline on epilepsy in pregnancy in development, which will hopefully be published, in the not to distant future.
Correspondence: Dr. Vicky O’Dwyer, National Maternity Hospital, Holles street, Dublin 2
Ph: 016373100 / 0876824664
- National Institute for Health and Care Excellence. The epilepsies: the diagnosis and management of the epilepsies in adults and children in primary and secondary care.NICE clinical guideline 137.[Manchester]: NICE; 2012.
- Knight M, Tuffnell D, Kenyon S, Shakespeare J, Gray R, Kurinczuk JJ (Eds.) on behalf of MBRRACE-UK. Saving Lives, Improving Mothers’ Care – Surveillance of maternal deaths in the UK 2011-13 and lessons learned to inform maternity care from the UK and Ireland Confidential Enquiries into Maternal Deaths and Morbidity 2009-13. Oxford: National Perinatal Epidemiology Unit, University of Oxford 2015.
- McKeating A, Farren M, Cawley S, Daly N, McCartney D, Turner MJ. Maternal folic acid supplementation trends 2009-2013. Acta Obstet Gynecol Scand.2015; 94:727-33.
- Cawley S, Mullaney L, McKeating A, Farren M, McCartney D, TurnerMJ. Knowledge about folic acidsupplementation in women presenting for antenatal care. Eur J Clin Nutr. 2016;70:1285-1290.
- Cawley S, Mullaney L, Kennedy R, Farren M, McCartney D, TurnerMJ. Duration of periconceptional folic acidsupplementation in women booking for antenatal care. Public Health Nutr. 2016: 1-9. [Epub ahead of print]
- Royal College of Obstetricians and Gynaecologists. Epilepsy in Pregnancy. RCOG Guideline 68. London: RCOG; 2016
- Farmen AH, Grundt J, Tomson T, Nakken KO, Nakling J, Mowinchel P6, Lossius M. Intrauterine growth retardation in foetuses of women with epilepsy. Seizure.2015; 28: 76-80.
- Espinera AR, Gavvala J, Bellinski I, Kennedy J, Macken MP, Narechania A, Templer J, VanHaerents S, Schuele SU, Gerard EE. Counseling by epileptologists affects contraceptive choices of women with epilepsy. Epilepsy Behav.2016; 65:1-6.