What is the prevalence of epilepsy
0.5%
Most common neurological condition affecting childbearing women
What are the types of epilepsy
- Primary generalised epilepsy: tonic-clonic seizures, absences, myoclonic jerks
- Partial (focal) seizures with or without loss of consciousness or secondary generalisation (complex partial seizures)
- Temporal lobe seizures (a type of partial seizure) often associated with an aura, duration of 1 minute or more and confusion after the event
What is the pathogenesis of epilepsy?
Primary
- idiopathic, no underlying cause found, 30% have family history
Secondary
- previous surgery to cerebral hemispheres
- intracranial mass lesions (meningiomas and AVMs) enlarge during pregnancy. Should be considered if first seizure is in pregnancy
- Antiphospholipid syndrome
What are the causes of seizures in pregnancy?
A - Alcohol and Drug Withdrawal
C - Cerebral vein thrombosis
E - Eclampsia
S - Stroke (increased risk in pregnancy)
S - Subarachnoid haemorrhage
I - Infection
G - Gestational epilepsy
H - Hypoglycaemia (diabetes, hypoadrenalism, hypopituitarism, liver failure)
H - Hypocalcaemia (magnesium surface therapy, hypoparathyroidism)
H - Hyponatraemia (hyperemesis, hypoadrenalism, pre-eclampsia)
T - Thrombotic thrombocytopenia purpura (TTP)
What investigations would you do for someone who has a first seizure in pregnancy
Eclampsia until proven otherwise
- Blood pressure, urinalysis
- PET bloods (FBC, urea and creatinine, sodium, LFTs, calcium, clotting screen)
- Serum glucose
- EEG
- CT / MRI of brain
What is the impact of pregnancy on epilepsy
- in most women, pregnancy does not affect frequency of seizures
- those with poorly controlled epilepsy are more likely to deteriorate in pregnancy
- risk of seizures is highest peripartum
What is the effect of epilepsy on pregnancy?
- The fetus is relatively resistant to short episodes of hypoxia.
- NO evidence of adverse effect of single seizure on the fetus
- no increased risk of miscarriage or obstetric complications unless a seizure results in abdominal trauma
- status epilepticus (rare, affecting <2% pregnancies) is dangerous for both mother and fetus and should be treated vigorously.
- increased risk of the fetus having epilepsy: 4-5% if either parent has epilepsy, increased with maternal epilepsy, 10% if there’s a previously affected sibling 15-20% if both parents have epilepsy
What is the likelihood of congenital anomaly with different AED agents?
What are the major anomalies caused by anti-epileptic drugs?
All AEDS cross placenta and are teratogenic
Most AEDs the risk is roughly 5% (2-3 times background risk)
Levetiracetam and carbamazepine are slightly lower
Sodium valproate is twice as likely to cause anomalies (up to 10%)
Neural tube defects (particularly valproate, 1-3.8%, but NOT phenytoin) Orofacial clefts (particularly phenobarbitone) Congenital heart defects (particularly phenytoin phenobarbitone and valproate) Fetal anticonvulsant syndrome
What are the features of fetal anticonvulsant syndrome
Minor malformations associated with anticonvulsant use in pregnancy
Dysmorphic features (V-shaped eyebrows, low-set ears, broad nasal bridge, irregular teeth)
Hypertelorism
Hypoplastic nails and distal digits
Hypoplasia of the midface could be a marker for cognitive dysfunction
Outline your approach to anti-epileptic medications preconceptually:
- If seizure free > 2 years consider weaning off AED prior to conception OR coming off at least preconceptually and for first trimester
- Most women ALL cases of juvenile myoclonic epilepsy should be advised to continue AEDs
- Avoid polytherapy - cumulative risk of teratogenicity
- Aim for lowest possible dose to achieve symptom control - many AEDs have dose dependent effect on teratogenicity
- If possible, change to less teratogenic AEDs: carbamazepine, lamotrigine (partial seizures), levetiracetam (primary generalised/complex partial).
- Sodium valproate is at least twice as teratogenic as other AEDS, possible approaches:
- If possible, stop sodium valproate and switch to another AED
- OR reduce dose to <=600 mg
- OR Change to long acting formulation or give in 3-4 divided doses daily to minimise peak levels
- Start 5mg folic acid 12 weeks prior to conception
How would your antenatal care differ from routine care for a woman taking carbamazepine for epilepsy?
- Ideally have pre-conceptual counselling to discuss risks in pregnancy and congenital anomalies
- Where possible stop or reduce dose prior to pregnancy, but do not do this in pregnancy due to the likelihood that higher doses are often required in pregnancy, and due to the risk of precipitating seizure
- Start 5mg folic acid from 12 weeks prior to conception and continue through pregnancy due to higher risk of anaemia second to folate deficiency
- Consider baseline serum AED trough level to help guide therapy in pregnancy if required (especially for lamotrigine)
- It is common that AED dose needs to be increased for women in pregnancy who have regular seizures, and this is most marked for lamotrigine (due to increase hepatic metabolism and renal clearance being increased in pregnancy)
- Detailed tertiary anatomy scan including cardiac views
- For women taking hepatic enzyme inducing AEDS (carbamazepine, phenobarbitone, phenytoin) - take 10-20mg vitamin K daily from 36 weeks due to a reduction in vitamin K dependent clotting factors, and increased risk of early vitamin K dependent bleeding (VKDB) of the newborn.
What advice should be given to postnatal, breast feeding mothers taking AEDs?
- Neonate should receive IM vitamin K prophylaxis (especially if taking a hepatic enzyme inducing AEDS)
- Breast feeding should be encouraged
- All AEDS present in small amounts in breast milk, but much lower than in utero, and well below treatment dose for neonate
- Aim to feed prior to taking AED
- Be careful with phenobarbitone and lamotrigine which require glucuronidation prior to clearance, which newborns are unable to do, and are at higher risk of toxic build up
- AEDs should gradually be reduced down to pre-pregancy doses, this can happen more rapidly with lamotrigine
- Safety advice should be given - change baby on floor, bathe baby with someone present and in shallow water
How do AEDs cause congenital anomalies?
- Interfere with folate metabolism
- Accumulation of toxic metabolites and cytotoxic free radicals
What should women know about contraception and AEDS?
- Hepatic enzyme inducing AEDS (phenytoin, carbamazepine, phenobarbital) all increase clearance of most systemically administered hormonal contraceptions
- POP - double dose
- COCP - double dose, or higher oestrogen (50mcg) formulation
- Jadelle/nexplanon - affected too
- Depo-provera - unaffected (cleared by first pass effect, not affected by CP450 activity
- Mirena - not affected, local effect of progesterone
- CuIUCD - not affected, non-hormonal
- Tubal ligation - not affected, non-hormonal
What are the specific risks to a baby when the mother takes sodium valproate?
- Congenital anomaly - cardiac defect, NTD
- Impaired neurodevelopment
- Lower IQ
- Autism
- ADHD
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Epilepsy15
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VTE38
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Cardiovascular67
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Skin32
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Pituitary And Adrenal Disease31
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Thyroid Disease32
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Renal Disease31
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Neurological Disease47
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Hypertension And PET33
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Respiratory Disease28
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Connective Tissue Disease28
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Haematological Disease58
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Gastrointestinal Disease33
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Liver Disease66
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Differential Dx Of Presenting Complaints In Pregnancy4
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Diabetes38
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Thyroid disease COPY21
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Cancer in pregnancy49
