FRCA Notes

Epilepsy in Pregnancy

Curriculum

This topic falls under the requirement for knowledge "...of concurrent medical diseases on pregnancy and the management of these patients"

Resources

  • Epilepsy complicates 0.5-1% of pregnancies
  • The risk of death is increased ten-fold in pregnant women with epilepsy; neurological conditions are the third commonest indirect cause of maternal death in the UK (MBRRACE 2021-23)
  • Most epilepsy-related maternal deaths are due to sudden unexpected death in epilepsy (SUDEP)
    • Uncontrolled tonic-clonic seizures are the strongest risk factor
    • Unwitnessed or nocturnal seizures add further risk

  • 1/3rd of patients experience worsening seizure frequency, owing to:
    • Hormonal changes
    • Altered pharmacokinetics of anti-epileptic drugs (AEDs); for example lamotrigine levels can fall by up to 70%
    • Poor concordance with anti-epileptics, often through concerns over fetal harm
  • 1/3rd of patients experience no change in seizure frequency
  • 1/3rd of patients experience an improvement in seizure frequency
  • The duration of seizure freedom prior to pregnancy is the best predictor of seizure control during it
  • There is an increased incidence of congenital abnormalities with anti-epileptic drugs
  • Valproate is the most teratogenic of the lot
  • Patients should have their medication altered by a Neurologist; the lowest effective dose of a single agent should be used
  • AEDs should never be stopped or changed abruptly

  • The Maternal Care Bundle requires that every pregnant woman with epilepsy has access to a local epilepsy in pregnancy team who lead the antenatal, intrapartum and postnatal care plans
  • More complex cases are referred to the regional maternal medicine network MDT, who may advise or take over care
  • The maternal medicine obstetrician coordinates the delivery plan, liaising with anaesthetists where required; obstetric anaesthetists are among the staff groups targeted for annual network teaching
  • The early postnatal period is highlighted as one of the highest risk times, and MBRRACE has identified gaps in early postnatal epilepsy care

Features identifying high risk women

  • Uncontrolled, frequent or nocturnal seizures (including clusters)
  • History of status epilepticus
  • Multiple AEDs, or high risk AEDs (particularly valproate and topiramate)
  • Poor adherence to treatment or antenatal care
  • Hyperemesis gravidarum: compromises oral AED intake
  • Sleeping alone; co-existing physical or mental health conditions; intellectual disability; alcohol or drug misuse

Peripartum management of the parturient with epilepsy


Place and mode of delivery

  • Women at risk of peripartum seizures should deliver in a consultant-led unit with one-to-one midwifery care and facilities for maternal and neonatal resuscitation
  • Epilepsy itself is not an indication for induction of labour or caesarean section
  • Elective caesarean section may be considered in the small group with recurrent, prolonged seizures at high risk of status epilepticus
  • Water birth is decided on an individual basis; generally reserved for those off AEDs and seizure-free for a significant period
  • Avoidable delays to planned induction or elective caesarean section should be minimised, as prolonged admission increases stress, insomnia and dehydration

The delivery plan

  • Should document the AED regimen (including any dose increases during pregnancy), seizure type and triggers, and a rescue plan should a seizure occur
  • Parenteral alternatives should be identified in advance for women who may be unable to take oral AEDs
  • Prophylactic clobazam may be considered where peripartum seizure risk is very high, e.g. recent convulsive seizures, seizures provoked by stress or sleep deprivation, or seizures in a previous labour
    • This must be balanced against neonatal respiratory depression

Minimising seizure risk

  • The risk is low: tonic-clonic seizures occur in 1-2% of women with epilepsy during labour, and in a further 1-2% within 24 hours of delivery
  • Precipitants include sleep deprivation, missed AED doses, pain, stress, dehydration and overbreathing
  • AEDs should be continued throughout labour; if oral intake is not tolerated, a parenteral alternative should be given (e.g. levetiracetam, sodium valproate, phenytoin or phenobarbital)
  • Maintain hydration and treat vomiting
  • One-to-one midwifery care; continuous fetal monitoring for women at high risk of seizures

Analgesia

  • Pain relief should be prioritised; TENS, Entonox and neuraxial techniques are all suitable
  • An early epidural is worth considering: it addresses several seizure precipitants:
    • Pain
    • Stress
    • Tachypnoea/over-breathing
    • Sleep deprivation
  • A well-working epidural also offers the advantage of rapid conversion to surgical anaesthesia in the event of a seizure
  • One should avoid pethidine, whose active metabolite norpethidine is pro-convulsant; diamorphine is the preferred parenteral opioid

Anaesthesia for operative delivery

  • Neuraxial anaesthesia is suitable and avoids the difficulties below
  • Should general anaesthesia be required, RCoG advise avoiding agents which lower seizure threshold (pethidine, ketamine) or which may be epileptogenic (sevoflurane)
  • Avoid hyperventilation and hypocapnia, which lower the seizure threshold
  • Chronic use of enzyme-inducing AEDs (e.g. phenytoin, carbamazepine) can cause resistance to non-depolarising neuromuscular blockers; monitor neuromuscular function appropriately

Differential diagnosis

  • Seizures in the second half of pregnancy which cannot clearly be attributed to epilepsy should be treated as eclampsia until proven otherwise
  • Differential diagnosis:

Immediate management

  • Call for help; airway, high flow oxygen and left lateral tilt or uterine displacement
  • Seizures should be terminated as soon as possible to avoid maternal hypoxia (from apnoea) and fetal hypoxia and acidosis (from uterine hypertonus)
  • A seizure lasting more than 5 minutes carries a high risk of progressing to convulsive status epilepticus
  • Pharmacotherapy is the same as for seizures in non-pregnant individuals

Fetal considerations

  • Persistent uterine hypertonus may be treated with tocolysis
  • Once the mother is stabilised, commence continuous fetal monitoring
  • If the fetal heart rate does not begin to recover within 5 minutes, or seizures recur, delivery should be expedited
  • Inform the neonatal team, given the risk of neonatal sedation and withdrawal from maternal benzodiazepines and AEDs

A high risk period

  • Seizure risk is relatively higher immediately after delivery than during pregnancy; the 3-day peripartum period is the time of maximal seizure exacerbation
  • This is driven by rapid hormonal shifts, fatigue and sleep deprivation, pain, stress and missed or altered medication

Management

  • Continue AEDs; treat nausea and vomiting, and use parenteral AEDs if oral intake is not possible
  • Women at reasonable risk of seizures should not be left unobserved; a single room is only appropriate if continuous observation by a partner, carer or staff is possible
  • Help with night feeds reduces sleep deprivation; breastfeeding should be encouraged
  • Where AED doses were increased during pregnancy, they should be reviewed within 10 days of delivery; reversal of pregnancy physiology can otherwise cause toxicity
  • The Maternal Care Bundle expects a follow-up review by the epilepsy in pregnancy team within 14 days of delivery, with a written postnatal plan shared with primary care and neurology

Analgesia

  • Good analgesia is important, as pain is itself a trigger; most standard post-operative analgesics are fair game
  • Avoid pethidine as above
  • Tramadol lowers the seizure threshold, especially in combination with SSRIs or TCAs, and is best avoided
  • Tranexamic acid can induce seizures, although this is unlikely in the 1-2g dosing regimen one might use in Obstetrics