Epilepsy in Pregnancy

2016; a second edition was noted as in development at time of writing — verify current edition before citing in new content)

Background

• Epilepsy affects 0.5-1% of pregnancies; about 2,500 infants are born to women with epilepsy (WWE) each year in the UK.
• The risk of death is increased ten-fold in pregnant WWE compared with women without epilepsy. Of 14 epilepsy-related maternal deaths in the 2009-2012 MBRRACE-UK enquiry, 12 were classified as SUDEP (sudden unexpected death in epilepsy), with poorly controlled seizures the main contributory factor — the guideline's central safety message is that under-treatment (through fear of AED harm) is at least as dangerous as the drugs themselves.

Pre-Pregnancy Counselling and AED Management

• WWE planning pregnancy should have a clinician competent in epilepsy management share decisions on AED choice and dose, balancing fetal risk against seizure control.
• Most mothers with epilepsy have normal, healthy babies; the risk of congenital malformation is low if the fetus is not exposed to AEDs in the periconception period (Grade C). Malformation risk is dependent on the type, number, and dose of AEDs (Grade B) — polytherapy and higher doses carry greater risk than monotherapy at the lowest effective dose.
• Sodium valproate carries a recognised adverse impact on long-term neurodevelopment of the child after in utero exposure, and WWE and their partners should be informed of this (Grade C).
• Based on limited evidence, in utero exposure to carbamazepine and lamotrigine does not appear to adversely affect offspring neurodevelopment; evidence for levetiracetam and phenytoin is very limited. Parents should be told that long-term outcome evidence overall is based on small numbers of children.
• Exposure to sodium valproate and other AED polytherapy should be minimised by changing medication before conception, as recommended by an epilepsy specialist after weighing risks and benefits — but if switching carries a high risk of seizure deterioration, continuing valproate or polytherapy may still be the safer course for that individual.
• The lowest effective dose of the most appropriate AED should be used (Grade B).
• Two-thirds of WWE will not experience seizure deterioration in pregnancy (Grade C); those who have had a seizure in the year before conception need close monitoring (Grade D).
• It is never recommended to stop or change AEDs abruptly without an informed specialist discussion — WWE who become unexpectedly pregnant while on AEDs should be able to access urgent specialist review rather than self-discontinuing.

Folic Acid

• All WWE should be advised to take 5 mg/day of folic acid before conception and to continue it until at least the end of the first trimester, to reduce the incidence of major congenital malformation.
• Pre-pregnancy folic acid 5 mg/day may also help reduce the risk of AED-related cognitive deficits in the child (Grade C).

Antenatal Management

• Routine monitoring of serum AED levels in pregnancy is not recommended based on current evidence, though individual circumstances may warrant it (Grade C).
• Detailed ultrasound anomaly scanning (18+0-20+6 weeks) should be offered per the NHS Fetal Anomaly Screening Programme, as it can detect major cardiac defects as well as neural tube defects.
• Serial growth scans are recommended, as obstetric risks (including small-for-gestational-age babies) are slightly but significantly increased in WWE and those exposed to AEDs (Grade B). There is no role for routine antepartum cardiotocography surveillance in WWE taking AEDs (Grade D).
• In WWE on enzyme-inducing AEDs at risk of preterm birth, doubling the antenatal corticosteroid dose for RDS prophylaxis is not recommended (Grade D).
• Seizures presenting for the first time in the second half of pregnancy that cannot be clearly attributed to epilepsy should be treated immediately per existing eclampsia-management protocols until a definitive diagnosis is reached by full neurological assessment.

Intrapartum Care

• The risk of seizures in labour is low, and epilepsy alone is not an indication for planned caesarean section or induction of labour (Grade D).
• AED intake should be continued through labour; if oral intake is not tolerated, a parenteral alternative should be given.
• Benzodiazepines are the drugs of choice to terminate a seizure in labour as quickly as possible, to avoid maternal and fetal hypoxia and fetal acidosis (Grade D). Long-acting benzodiazepines (e.g. clobazam) can be considered where the peripartum seizure risk is very high.
• Every obstetric unit should have written local guidelines for managing seizures in labour, and continuous fetal monitoring is recommended for women at high risk of a seizure in labour or following an intrapartum seizure.
• Pethidine should be used with caution for labour analgesia in WWE; diamorphine is preferred (Grade D). There are no known contraindications to any induction agents in WWE on AEDs.
• WWE at risk of peripartum seizures should deliver in a consultant-led unit with one-to-one midwifery care and maternal/neonatal resuscitation facilities available.

Postpartum and Neonatal Considerations

• The overall chance of seizures during and immediately after delivery is low but relatively higher than during pregnancy; WWE should continue their AEDs postnatally, and triggers such as sleep deprivation, stress, and pain should be minimised.
• If the AED dose was increased during pregnancy, it should be reviewed within 10 days of delivery to avoid postpartum toxicity.
• All babies born to WWE taking enzyme-inducing AEDs should be offered 1 mg intramuscular vitamin K to prevent haemorrhagic disease of the newborn. Evidence is insufficient to recommend routine maternal oral vitamin K for this purpose, or maternal vitamin K to prevent postpartum haemorrhage.
• Neonates born to WWE taking AEDs should be monitored for adverse effects associated with in utero AED exposure.
• WWE taking AEDs should be encouraged to breastfeed (Grade C) — current evidence indicates the risk of adverse cognitive outcomes is not increased in children exposed to AEDs through breast milk (Grade C).
• WWE should be screened for postpartum depressive disorder, with information on symptoms and contact details for support (Grade D).

High-Yield Exam Points

• 5 mg/day folic acid pre-conception through the first trimester — the same high dose used for other high-risk indications, not the standard 400 microgram dose.
• Sodium valproate is the AED most strongly associated with adverse long-term neurodevelopmental outcome; the guideline explicitly frames minimising valproate/polytherapy exposure as a specialist-led medication change made before conception, not something stopped abruptly by the patient.
• The core safety tension the exam likes to probe: uncontrolled seizures (SUDEP risk) vs. AED teratogenicity — the guideline consistently favours seizure control and warns against abrupt self-discontinuation.
• Vitamin K 1 mg IM for the neonate is specifically tied to maternal use of enzyme-inducing AEDs (e.g. carbamazepine, phenytoin, phenobarbital, primidone, oxcarbazepine, topiramate, eslicarbazepine), which also reduce efficacy of hormonal contraception — a copper IUD is the preferred emergency contraception in these women.
• Epilepsy alone is not an indication for caesarean section or induction of labour; benzodiazepines are first-line for terminating an intrapartum seizure.
• Breastfeeding is encouraged on AEDs — a commonly tested "safe, not contraindicated" fact that contradicts intuitive assumptions about drug transfer in breast milk.

Source: RCOG Green-top Guideline No. 68 (1st edition) (June 2016 (RCOG lists this as "last reviewed" 20 June)

Read the original on rcog.org.uk

Clinically reviewed by NHS obstetricians and gynaecologists · Source last updated June 2016 (RCOG lists this as "last reviewed" 20 June

MRCOG AI is an independent educational tool. It is not affiliated with, endorsed by, or connected to the Royal College of Obstetricians and Gynaecologists (RCOG).