Neurosurgery notes/Paediatrics/Pregnancy and Neurosurgery/Pregnancy and seizures

Pregnancy and seizures

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Pregnancy and Neurosurgery

Before delivery

General
  • 2/3 patients will not have seizure deterioration in pregnancy.
  • Pregnant women who have experienced seizures in the year prior to conception require close monitoring for their epilepsy
  • All pregnant WWE should be provided with information about the UK Epilepsy and Pregnancy Register and invited to register.
Effects of AEDs and maternal seizures on
  • Mothers
    • Depression
    • Anxiety
    • Neuropsychiatric symptoms
    • AEDs can increase
      • Induction of labour (OR 1.40, 95% CI 1.05–1.85),
      • Fetal growth restriction (OR 3.51, 95% CI 1.23–10.01)
      • Postpartum haemorrhage (OR 1.33, 95% CI 1.16–1.54).
  • Foetus
    • Neurodevelopmental outcomes
      • Parents should be informed that evidence on long-term outcomes is based on small numbers of children.
      • Drugs that do not adversely affect neurodevelopment (IQ) of the offspring.
        • Levetiracetam
        • Phenytoin
        • Carbamazepine
        • Lamotrigine
      • Sodium valproate
        • Lowers
          • Intelligence quotient (IQ)
          • Verbal IQ
          • Performance IQ
        • Increased rates of childhood autism (adjusted hazard ratio 2.9)
      • Little is known about other new AEDs or combination therapies and the absence of data should not be taken as an indication of fetal safety.
    • Congenital abnormalities
      • General
        • More to do with drugs rather than epilepsy
          • The risk of recurrence for major congenital malformation was increased (16.8 per 100) in WWE with a previous child with major congenital malformation.
      • Congenital abnormalities form due to AED
        • Type
          • Lamotrigine, and carbamazepine monotherapy at lower doses have the least risk of major congenital malformation in the offspring
          • Sodium valproate
            • Neural tube defects
            • Facial cleft and hypospadias
          • Phenobarbital and phenytoin
            • Cardiac malformations
          • Phenytoin and carbamazepine
            • Cleft palate in the foetus
        • Number
        • Dose
      • WWE who are planning their pregnancy should have a clinician competent in the management of epilepsy take responsibility for sharing decisions around choice and dose of AEDs, based on the risk to the foetus and control of seizures.
      • Types of congenital abnormalities associated with AEDs
        • Neural tube defects
        • Congenital heart disorders
        • Urinary tract
        • Skeletal abnormalities and cleft palate
      • Mechanism
        • Lowering folate levels
          • AEDs can lower folate levels in the blood, especially those that induce the liver's P450 enzymes. This can lead to a higher risk of abnormal pregnancy outcomes, such as neural-tube defects, spontaneous abortion, and developmental anomalies.
          • Folate deficiency has been shown to affect the activity of certain CYP450 enzymes.
        • Increasing the risk of secondary cerebrovascular events
          • AEDs can also lower vitamin B12 levels, which can increase the risk of secondary cerebrovascular events.
        • Interaction with riboflavin
          • Folate metabolism interacts with riboflavin, which is a precursor to flavin adenine dinucleotide (FAD). FAD is a coenzyme that's required for the activity of the enzyme that metabolizes folate
How to reduce congenital abnormalities be minimised in WWE?
  • Take 5 mg/day of folic acid 3 months prior to conception and to continue the intake until at least the end of the first trimester
    • Reduce
      • Incidence of major congenital malformation.
      • Risk of AED-related cognitive deficits.
    • Improve long term cognitive outcome
  • Use lowest effective dose of the most appropriate AED
  • Reduce exposure to sodium valproate and other AED polytherapy
    • Change medication prior to conception
    • If cannot change to maintain seizure control then will have to let mother decide
Monitoring during pregnancy
  • Mother
    • In the antenatal period:
      • risk factors for seizures,
        • such as sleep deprivation and stress;
        • High risk of seizures need to be monitored
          • Sleep in same room as partner
          • Never left alone
        • Individuals with unwitnessed seizures are at high risk of SUDEP, with nocturnal seizures being an independent risk factor.
      • adherence to AEDs;
      • seizure type and frequency
  • Foetus
    • USS Screen for structural abnormalities.
      • The fetal anomaly scan at 18+0–20+6 weeks of gestation can identify major cardiac defects in addition to neural tube defects.
      • National Health Service Fetal Anomaly Screening Programme standards.
    • Biochemical screening
      • Maternal serum alpha-fetoprotein
        • when combined with ultrasonography increases the detection rate for neural tube defects to 94–100%
What to do when WWE becomes pregnant unexpectedly
  • Discuss therapy with an epilepsy specialist on an urgent basis.
  • Do not stop or change AEDs abruptly without an informed discussion.
  • Ask patient to register themselves to the UK Epilepsy and Pregnancy Register
What is the effect of pregnancy on seizures in WWE?
  • 2/3 patients will not have seizure deterioration in pregnancy.
  • Pregnant women who have experienced seizures in the year prior to conception require close monitoring for their epilepsy.
    • The seizure-free duration is the most important factor in assessing the risk of seizure deterioration.
      • In women who were seizure free for at least 9 months to 1 year prior to pregnancy, 74–92% continued to be seizure free in pregnancy.
  • Idiopathic generalised epilepsies were more likely to remain seizure free (74%) than those with focal epilepsies (60%).
  • There is insufficient evidence to assess whether the rates of status epilepticus are increased in pregnant WWE compared with non-pregnant women.
  • Currently, there are no tests to predict the risk of seizure deterioration in pregnancy.
How should women taking AEDs be monitored to avoid worsening of seizures? For WWE taking AEDs, is dose escalation better than expectant management?
  • Based on current evidence, routine monitoring of serum AED levels in pregnancy is not recommended although individual circumstances may be taken into account.
WWE should be assessed if they truly have seizures and a cause could be found to help plan
anti-epileptic medication
  • Imaging modalities such as magnetic resonance imaging (MRI) and computerised tomography (CT) scans are considered safe in pregnancy to assess women presenting with seizures.
    • The risk to the fetus from a single exposure is minimal.
  • If there is doubt whether the seizure is secondary to epilepsy or eclampsia,
    • magnesium sulfate, which is the drug of choice for the treatment of eclamptic seizures, should be administered until a definitive diagnosis is made.
  • The other differential diagnoses for seizures in pregnancy include cerebral venous sinus thrombosis, posterior reversible leucoencephalopathy syndrome, space-occupying lesions and reversible cerebral vasoconstriction syndrome. Other conditions, such as syncope associated with cardiac arrhythmia, aortic stenosis, carotid sinus sensitivity, vasovagal syncope and metabolic conditions such as hypoglycaemia, hyponatraemia and Addisonian crisis will need to be ruled out for first presentation of seizures in pregnancy
WWE should be informed of the effect of changing the dose of AED on seizures and its impact on driving privileges.
  • The general driving regulations for individuals with epilepsy apply to pregnant WWE.
  • Mothers will need to be informed that stopping or reducing the dose of AED in pregnancy may result in seizure deterioration, including the first episode of seizures.
  • This will have an impact on driving privileges and may affect parenting and work plans.

At delivery

What is the optimal timing and mode of delivery for WWE based on seizure control?
  • Most WWE will have an uncomplicated labour and delivery.
    • Pregnant WWE should be counselled that the risk of seizures in labour is low.
  • Epilepsy per se is not an indication for planned caesarean section or induction of labour.
Reduce seizure risk just before delivery
  • Adequate analgesia and appropriate care in labour should be provided to minimise risk factors for seizures such as insomnia, stress and dehydration.
  • Long-acting benzodiazepines such as clobazam can be considered if there is a very high risk of seizures in the peripartum period.
  • AED intake should be continued during labour. If this cannot be tolerated orally, a parenteral alternative should be administered.
Seizures during labour
  • Every obstetric unit should have written guidelines on the management of seizures in labour.
    • Any seizure lasting more than 5 minutes is unusual and represents a high risk of progressing to convulsive status epilepticus, a life-threatening medical emergency which affects around 1% of pregnancies in WWE.
      • Treatment should be initiated as soon as reasonably possible before status epilepticus and pharmacoresistance is established.
      • Left lateral tilt should be established alongside maintenance of airway and oxygenation at all times
  • Seizures in labour should be terminated as soon as possible to avoid
    • Maternal and foetal hypoxia
    • Foetal acidosis
  • Benzodiazepines are the drugs of choice.
After delivery
  • Neonates born to WWE taking AEDs should be monitored for adverse effects associated with AED exposure in utero.
  • WWE who are taking AEDs in pregnancy should be encouraged to breastfeed.
    • Based on current evidence, mothers should be informed that the risk of adverse cognitive outcomes is not increased in children exposed to AEDs through breast milk.
  • If the AED dose was increased in 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 of intramuscular P vitamin K to prevent haemorrhagic disease of the newborn.
    • Given to baby not mum
    • There is insufficient evidence to recommend routine maternal use of oral vitamin K to prevent haemorrhagic disease of the newborn in WWE taking enzyme-inducing AEDs.
    • There is insufficient evidence to recommend giving vitamin K to WWE to prevent postpartum P haemorrhage.
    • Mech
      • Enzyme-inducing AEDs (carbamazepine, phenytoin, phenobarbital, primidone, oxcarbazepine, topiramate and eslicarbazepine) are considered to competitively inhibit the precursors of clotting factors and affect fetal microsomal enzymes that degrade vitamin K, thereby increasing the risk of haemorrhagic disease of the newborn.
What is the optimum management of epileptic seizures in labour?
  • Every obstetric unit should have written guidelines on the management of seizures in labour.
  • Seizures in labour should be terminated as soon as possible to avoid
    • maternal and foetal hypoxia
    • foetal acidosis.
  • Benzodiazepines are the drugs of choice.
  • Continuous foetal monitoring is recommended in women at high risk of a seizure in labour, and following an intrapartum seizure.
Status epilepticus
in Pregnancy
  • 1st line
    • lorazepam given as an intravenous dose of 0.1 mg/kg (usually a 4 mg bolus, with a further dose after 10−20 minutes) is preferred. Diazepam 5–10 mg administered slowly intravenously is an alternative.
    • If there is no intravenous access, diazepam 10−20 mg rectally repeated once 15 minutes later if there is a continued risk of status epilepticus, or midazolam 10 mg as a buccal preparation are suitable.
  • 2nd line
    • Phenytoin or fosphenytoin.
      • The loading dose of phenytoin is 10–15 mg/kg by intravenous infusion, with the usual dosage for Evidence an adult of about 1000 mg.
      • Guidance on the management of seizures is available in the NICE guideline on epilepsy.
  • If there is persistent uterine hypertonus, consider administration of tocolytic agents. After the mother is stabilised, continuous electronic foetal monitoring should be commenced. If the foetal heart rate does not begin to recover within 5 minutes or if the seizures are recurrent, expedite delivery. This may require caesarean delivery if vaginal delivery is not imminent.
  • The neonatal team should be informed, as there is a risk of neonatal withdrawal syndrome Evidence with the maternal use of benzodiazepines and AEDs.85

After delivery

What is the risk of seizure deterioration postpartum and how can this be minimised?
  • WWE and their caregivers need to be aware that although the overall chance of seizures during and immediately after delivery is low, it is relatively higher than during pregnancy.
  • WWE should be advised to continue their AEDs postnatally.
  • Mothers should be well supported in the postnatal period to ensure that triggers of seizure deterioration such as sleep deprivation, stress and pain are minimised.
  • The immediate postpartum period is a high-risk period for exacerbation of seizure frequency due to
    • increased stress,
    • sleep deprivation,
    • missed medication
    • Anxiety
  • A prospective study of 1297 pregnancies in WWE showed that the period of maximal seizure exacerbation was the 3-day peripartum period in women with generalised and partial seizures.
    • The risk was highest in women who had seizures in the month prior to pregnancy compared with those who were free of seizures during the same period (OR 3.7, 95% CI 2.4–5.9).
  • Women should ensure that they take their AEDs as prescribed in the postnatal period. Nausea and vomiting should be treated and if there is no oral intake, consideration should be given to parenteral administration of AEDs. Sleep deprivation-related seizures could be reduced by arranging help for the mother, especially for night-time feeds. If the mother breastfeeds, storage of breast milk pumped during the day might be beneficial. Reviewing the daily activities of the mother and identifying high-risk situations can reduce the risks to the mother and baby due to seizures
Is there a need to modify the dose of AED after delivery?
  • If the AED dose was increased in pregnancy, it should be reviewed within 10 days of delivery to avoid postpartum toxicity.
  • Many women are on higher doses of AEDs at the end of pregnancy compared with their prepregnancy dose.
  • In the postpartum period, the physiological changes that occurred in pregnancy, such as increased renal and hepatic clearance and haemodilution, are reversed level 3 and these women become at risk of toxicity from high AED doses.
  • The increase in the dose of AED that occurred in pregnancy should be clearly documented in the notes, with a comprehensive plan to liaise with the neurological team to taper the dose in the first 10 days after delivery. If symptoms of AED toxicity develop in the puerperium (e.g. drowsiness, diplopia or unsteadiness), urgent neurological review is needed.
Effects of AED exposure on the newborn through placental and breast mild transfer and babies of WWE taking AEDs be monitored?
  • Placenta
    • The rates of transfer of AEDs to the neonate through the placenta and breast milk vary.
      • Many of the old generation AEDs, such as phenobarbital, carbamazepine and phenytoin, and the new generation drugs, such as lamotrigine, oxcarbazepine and topiramate, have an umbilical cord to maternal serum AED concentration (U/S) that is close to one, suggesting free transfer of AED across the placenta.
      • The fetal accumulation is mildly increased for levetiracetam, sodium valproate and gabapentin.
      • Babies born to mothers taking AEDs may have adverse effects such as lethargy, difficulty in feeding, excessive sedation and withdrawal symptoms with inconsolable crying.
      • Individualised assessment should be made for the level of post-delivery monitoring required for withdrawal symptoms, and for any signs of toxicity.
      • This is especially important in premature babies, and serum levels of AEDs in the baby should be checked where appropriate.
  • Breast milk
    • Breast mild does not cause adverse cognitive outcomes
    • The magnitude of AED transfer to the baby through breast milk that is required to affect neonatal and childhood outcomes is not known.
      • The American Academy of Neurology/ American Epilepsy Society panel considered an AED transfer rate of 0.6 (neonatal to maternal plasma concentration ratio or a milk to maternal serum [M/S] concentration ratio) or increasing concentrations of AED in the neonate by 25% during the follow-up period (3 days up to 1 month) to be clinically important.61
    • Lamotrigine (M/S 0.6), levetiracetam (M/S 1–3.09) and topiramate (M/S 0.66–1.1) transfer to a larger extent to the child from breast milk compared with sodium valproate (M/S 0.01–0.1), carbamazepine (M/S 0.36–0.41) and phenytoin (M/S 0.06–0.19), which have minimal transfer.96
    • Breastfeeding has not been shown to affect the cognitive outcomes at 3 years of age in children who were exposed in utero to lamotrigine, sodium valproate, phenytoin or carbamazepine monotherapy.98
    • A prospective study on babies who were exposed to AEDs in utero showed that the psychomotor development of the breastfed children was better at 6 and 18 months compared with those who were not breastfed or were breastfed for less than 6 months.99 Other options such as alternating breast and bottle milk could be considered if there are any concerns about AED exposure.

Contraception

  • WWE should be offered effective contraception to avoid unplanned pregnancies.
  • Options
    • If taking enzyme inducing AEDs
      • Enzyme-inducing AEDs (carbamazepine, phenytoin, phenobarbital, primidone, oxcarbazepine, topiramate and eslicarbazepine) try to avoid hormonal contraceptives.
      • Not affected by enzyme-inducing AEDs (preferred)
        • Copper intrauterine devices (IUDs),
        • the levonorgestrel-releasing intrauterine system (LNG-IUS)
        • medroxyprogesterone acetate injections
    • If not taking enzyme inducing AEDs
      • All methods of contraception may be offered to women taking non-enzyme-inducing AEDs (e.g. sodium valproate, levetiracetam, gabapentin, vigabatrin, tiagabine and pregabalin)
  • Emergency contraception
    • WWE taking enzyme-inducing AEDs should be informed that a copper IUD is the preferred choice for emergency contraception.
    • Emergency contraception pills with levonorgestrel and ulipristal acetate are affected by enzyme-inducing AEDs.
  • Women taking lamotrigine monotherapy and oestrogen-containing contraceptives should be informed of the potential increase in seizures due to a fall in the levels of lamotrigine.