Epilepsy in pregnancy

Seizures may increase due to sleep deprivation, altered drug absorption (morning sickness/hyperemesis), altered drug metabolism, and difficulty taking medication around labour. A single seizure probably carries no fetal risk unless it causes abdominal trauma, but recurrent seizures are associated with increased risk. Status epilepticus is a medical emergency.

Most women with epilepsy get through pregnancy without seizures. In the EURAP study of 3784 pregnancies, 66.6% were seizure-free. Around a third experience an increase in seizure frequency.

The commonest way this goes wrong is a woman stopping or reducing her AED on her own out of fear of harming the baby — which raises seizure risk and the risk of SUDEP. Say this out loud early.

Pre-conception

Offer all women of childbearing age contraception counselling and pre-conception planning. Around 40% of pregnancies in women with epilepsy are still unplanned.

Pre-conception recommendations:

• Give comprehensive information about the course of epilepsy in pregnancy
• Use monotherapy wherever possible rather than combining AEDs
• Make any change of AED before pregnancy, not during it
• Folic acid 5 mg/day before and during the early stages of pregnancy
• Consider vitamin K in the last part of pregnancy for enzyme-inducing AEDs
• Report the pregnancy to an epilepsy and pregnancy registry

Refer to the patient’s neurologist to optimise medication. Use the least teratogenic but most effective AED for her epilepsy syndrome, at the lowest effective dose. Discontinuing AEDs may be considered after a three-year seizure-free period — always by taper, since rapid change can trigger seizures.

Counsel on prenatal screening, the genetics of her seizure disorder, AED teratogenicity, labour/breastfeeding/childcare planning (delivery at a base hospital), and diet/smoking/alcohol.

Enzyme-inducing AEDs (carbamazepine, oxcarbazepine, phenytoin, phenobarbitone, primidone, topiramate) increase oestrogen/progestogen metabolism and cause more oral contraceptive failures. AEDs that don’t affect hormonal contraception: gabapentin, lacosamide, lamotrigine, levetiracetam, sodium valproate, tiagabine, zonisamide. In women on enzyme-inducing AEDs, effective contraception options are depot, Mirena or copper IUD — the POP, implant and vaginal ring are not recommended (reduced efficacy), and standard-dose COCP may be ineffective (a 50 mcg ethinylestradiol preparation may help if an alternative method isn’t wanted).

Teratogenic risk

The risk of congenital malformation in women with epilepsy not taking AEDs is 1.1–3.3%, essentially the same as the general population (2.1–2.9%). With AEDs it rises to 4–9%, and rises further with valproate and with polytherapy. The risk is dose-dependent for a given drug.

• Valproate is the most dangerous. The Australian Pregnancy Register reported a malformation risk as high as 16% for first-trimester exposure above 1400 mg/day, against 6% below that. Avoid it in women of reproductive potential wherever possible; if unavoidable, use the lowest effective dose in divided doses.
• Levetiracetam and lamotrigine are considered relatively safe and have not been associated with an increased risk of birth defects.
• Data are still too thin to quantify risk for gabapentin, lacosamide, oxcarbazepine, pregabalin or topiramate as monotherapy, though newer-generation AEDs generally look more favourable than the older drugs.

Commonest malformations: cleft palate, neural tube defects, skeletal abnormalities, and congenital heart and urinary tract defects. In-utero valproate exposure is also associated with reduced IQ and neurodevelopmental problems.

First seizure in pregnancy

Rule out eclampsia, stroke and subarachnoid haemorrhage. A first seizure can occur at any point in pregnancy — consider metabolic disturbance, hypotension, CNS infection, stroke and vascular malformation. Refer to a consultant neurologist or make an urgent maternity referral. Consider MRI to look for a structural cause (e.g. a meningioma enlarging in pregnancy).

Management once pregnant

Make an urgent maternity referral once pregnancy is confirmed. Avoid altering AEDs in the first trimester.

Drug levels fall in pregnancy, by different amounts: lamotrigine to 50–60% of the pre-pregnancy level, levetiracetam 40–60%, oxcarbazepine 30–40%, topiramate 30–40%, zonisamide 20–40%. Most women on lamotrigine or levetiracetam will need a dose increase. Measure serum levels before pregnancy and at least once each trimester, and again if control is lost or toxicity appears.

Lamotrigine clearance rises steadily to about 32 weeks; postpartum the concentration rises again within a few days, so reduce the dose promptly to prevent toxicity. Correct dosing back to non-pregnant levels after delivery.

Arrange the detailed anatomy scan (18–20 weeks) and cardiac scan (26–28 weeks) at a specialist obstetric ultrasound practice. Pay attention to third-trimester fetal biometry — babies of mothers on AEDs are more likely to be small for gestational age.

Compared with women without epilepsy there is a slightly higher risk of spontaneous miscarriage, antepartum haemorrhage, hypertensive disorders, fetal growth restriction, preterm birth, induction, caesarean section and postpartum haemorrhage. Perinatal death rates are no different between the two groups.

Vitamin K: for women on enzyme-inducing AEDs (carbamazepine, phenytoin, phenobarbitone, primidone, oxcarbazepine, topiramate), give vitamin K 20 mg daily for the last two weeks before delivery, and 1 mg to the newborn.

Treat status epilepticus vigorously with benzodiazepines, give oxygen, and transfer to hospital immediately.

Labour and delivery

Epilepsy alone is not an indication for planned caesarean section or induction, and there is no reason to deliver early where seizures are well controlled and there are no obstetric risk factors. Caesarean may be considered for a woman with a marked increase in seizures, cluster seizures or high status-epilepticus risk.

The risk of a seizure during labour and immediately after is about 1–2%. Continue AEDs through labour, parenterally if oral is not possible. Early epidural analgesia reduces seizure triggers (pain, hyperventilation, sleep deprivation); pethidine is contraindicated because it lowers the seizure threshold.

Breastfeeding

Encourage breastfeeding in women with epilepsy taking AEDs. Cognitive outcomes are not worse in breastfed babies exposed to AEDs in milk — in the NEAD study breastfed children of mothers on AEDs had higher IQ at six years than non-breastfed children. Milk concentrations are well below maternal serum levels (valproate under 10%).

Watch for drowsiness where the mother is on high-dose phenobarbitone, primidone or benzodiazepines; consider suppressing lactation only in that situation. Stopping breastfeeding abruptly risks a neonatal withdrawal syndrome.