Pregnancy with Epilepsy

Dr.Bhagirathi Kayastha
Lecturer,OBGYN
2022/05/17
Tuesday
Contents
• Definition
• Introduction
• Effects on fetus and mother
• Different AEDs
• Management – pre-pregnancy counselling
- Antenatal period
- Delivery
- Postpartum period and contraception
Conclusion and take home message
 Definition of Seizure
• Recurrent Paroxysmal disorder of CNS characterized by an abnormal
neuronal discharge with or without loss of consciousness.
• Types:
i) Partial seizures
ii) Generalized seizures
 Partial seizures
• These originate in one localized area of the brain and affects a
correspondingly localized area of neurological function.
• Consciousness usually not lost & recovery is rapid
• Causes:
• Trauma
• Abscess
• Tumor/A V Malformation
• Perinatal factors/Biochemical abnormality
 Generalized seizures
• These involve both brain hemispheres simultaneously
• May be preceded by Aura before abrupt loss of consciousness
• Generalized tonic clonic seizures
- Loss of consciousness followed by all tonic contractions of muscles &
rigid posture
- Followed by clonic contractions of all extremities
- Followed by gradual relaxation of muscles
- Followed by gradual return of consciousness
- Patient may remain confused & disoriented for several hours
 Introduction
• Common neurological disorder
• Prevalence - 5.25% per 1000 pregnancies
• About 0.15% to 10% of women have seizures during pregnancy

Aims:
- Managing epilepsy during pregnancy is to balance maternal and fetal
risks associated with uncontrolled seizures against the potential
teratogenic effects of antiepileptic drugs.
Diagnosis of Epilepsy
• Epilepsies are a heterogenous group of brain diseases with the common feature of
seizure.
• Should be a multimodality approach, along with neurologists and medical
practitioner
• Women who have remained seizure free for at least 10 years (with the last 5 years
off AEDs) and those with a childhood epilepsy syndrome who have reached
adulthood seizure and treatment free are considered no longer to have epilepsy.
• In pregnant women presenting with seizures in second half of pregnancy which
cannot be clearly attributed to epilepsy, immediate treatment should be done in the
line of Eclampsia until definitive diagnosis is made by full neurological
assessment.
• Other cardiac , metabolic and intracranial conditions should be ruled out.
 Effect of pregnancy on Women with Epilepsy
• In 50% of women with epilepsy(WWE) there is no change in frequency
of seizure, 30% have increased chance of seizure and 20% have
decreased seizure during pregnancy.

• 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.
• The disposition of many AEDs may change during pregnancy, reflected in
declining plasma drug concentrations.
• The causes are:
- Nausea and vomiting may cause missed doses
- Gastrointestinal absorption decreases because of decreased intestinal motility
and uses of antacids.
- Increased hepatic and renal clearance of most AEDs
- Expanded intravascular volume lowers serum drug levels.
- Decreased albumin levels in pregnancy leading to lower total drug levels
- Poor compliance due to fear of teratogenicity.
Effect of Epilepsy on Mother
• Women have concerns regarding the effect of epilepsy and its
treatment on motherhood.
• It includes fear of harming the baby or not being able to fulfil the role
of mother .
• Maternal and neonatal death from drowning and mothers should be
advised to bathe themselves or their children in shallow water and
with assistance.
Risk of AEDs on Mother
• Some AEDs carry an increased risk of depression with features of low
mood, inability to plan and organize thoughts, poor concentration,
tiredness, irritability or anger.

• Additionally, psychosocial problems, low esteem and fear of having

seizures may have a negative impact on cognitive performance.
Effect of AEDs on Fetus
• WWE not exposed to AEDs, the incidence of congenital
malformations is similar to those for general population.
• A study by Finnish population reported 2.8% rate of congenital
malformations in the offspring of WWE who were not exposed to
AEDs in first trimester.
• In WWE who were on AEDs, the risk of major congenital
malformation to the fetus is dependent on type, number and dose of
AEDs.
• Among AEDs, lamotrigine and carbamazepine monotherapy at lower
doses have least risk of major congenital malformation in offspring.
 Effect of AEDs on Fetus

• Congenital malformation in fetus due to AEDs – risk is doubled that of

general population
• Most of AEDs belong to Category C.
• With the four widely used AEDs (Carbamazepine, Lamotrigine, Phenytoin
and Levetiracetam), the risk of congenital malformation is around 2-
2.5%
• Polytherapy with AEDs is associated with increased risk of congenital
malformations than monotherapy.
• Several AEDs cause fetal antiepileptic drug syndrome characterised by
craniofacial anomalies( dysmorphic face and fingers with stubby distal
phalanges), finger nail hypoplasia, developmental delay, cardiac defects and
facial clefts.
• Specific teratogenesis of various antiepileptic drugs are:
• Sodium valproate: the absolute risk of major congenital malformation is 6-9%
and is three fold greater than other AEDs.
• The risk of anomalies is dose related and the risk increases to 20% when the
dose is 1500mg/day or more.
• It is also associated with cognitive abnormalities and increased risk of autism in
the offspring.
• Phenobarbitone : should be avoided as it is associated with cardiac
anomalies.
• Carbamazepine :associated with risk of spina bifida although the risk is
80% lower than valproate. Doses at or below 400mg/day are associated
with low risk of congenital malformation of around 2% as compared to
7.7% with dose exceeding 1000mg/day.
• Levetiracetam : recent studies shows low risk of teratogenesis in
pregnancy with this drug , around 2.4%. The effect is dose related, with
normal doses showing favorable outcome and high doses being
associated with reflux and inguinal hernia.
• Topiramate: its use is associated with increased incidence of facial
clefts. Thus US FDA in 2011 changed this drug from Category C to
Category D.
Longterm neurodevelopmental outcomes of exposure to
AEDs and maternal seizure in infants born to WWE
• Based on the evidence, in utero exposure to sodium valproate can
have possible adverse impact on longterm neurodevelopment of
newborn.
• In utero exposure to carbamazepine and lamotrigine does not appear
to adversely affect neurodevelopment of the offspring.
• Little evidence for levetiracetam and phenytoin.
Antiepileptics drugs
Older Antiepileptic drugs Newer Antiepileptics drugs

Phenobarbital Vigabatrin

Phenytoin Gabapentin

Primidone Lamotrigine

Ethosuximide Topiramate

Carbamazepine Tiagabine

Valproate Levetiracetam

Oxcarbazepine
Enzyme inducing AEDs Non enzyme inducing AEDs
• Carbamazepine • Sodium valproate
• Phenytoin • Levetiracetam
• Phenobarbital • Gabapentin
• Primidone • Vigabatrin
• Oxcarbazepine • Tiagabine
• Topiramate • Pregabalin
• Eslicarbazepine
 Management
• Should managed together with neurologist and physician.
• Women who have been seizure free for more than 2 years can be
considered for withdrawal of AEDs.
• In women where the drug cannot be withdrawn the treatment strategy is
to use the appropriate AED as monotherapy in the lowest effective
dosage throughout pregnancy which controls seizures and minimized the
risk to the fetus, the newborn and the breast fed infant.
 Pre pregnancy
• Any major change in the treatment of women with epilepsy should be
done before conception.
• Folic acid supplementation 5mg/day should be started 3 months prior to
conception. It is associated with significant reduction of congenital
anomalies of around 50% in the offspring.
• ACOG endorses daily folic acid supplementation of 4mg/day in women on
AEDs both during pre conception and throughout the pregnancy.
• Couple should be made to understand the importance of compliance
regarding AEDs for seizure control and the associated risk of fetal
congenital malformation.
• Regular intake of drug needs to be emphasized in the antenatal period to
achieve optimal drug levels.
• Nausea and vomiting needs to be treated in first trimester.
• Stress on adequate diet, sleep and refraining from activity that can
provoke seizures should be given during each antenatal visit.
• High levels of estrogen and progesterone in pregnancy causes induction
of antiepileptic drug metabolism in the liver which results in decreased
levels of the drug.
• There is induction of glucuronidation of lamotrigine and oxcarbazepine in
pregnancy which results in the formation of inactive metabolites of these
drugs. This is the reason for increase in frequency of seizures seen in
pregnant women taking these two drugs.
• Thus frequent monitoring and dose adjustments are required when
women are taking lamotrigine and oxcarbazepine.
• Monitoring of fetal malformation begins towards the end of the first trimester.
• Maternal serum AFP levels are elevated in open neural tube defects. The level
should be carefully interpreted according to the gestational age and
considering other factors that might result in high values like twins, placental
hemorrhage.
• Detailed USG should be integral part of antenatal check up in women with
epilepsy at 18 -21WOG(RCOG)
• Fetal echocardiography -Not required by RCOG
• Amniocentesis and cord blood sampling may be required in selected cases
where fetal karyotype is needed.
• Role of administering vitamin K during last month of pregnancy is
controversial as it is not clear that Vitamin K crosses placenta or not.

• Enzyme inducing AEDs are considered to competitively inhibit the

precursor of clotting factors (II,VII,IX and X) and affect fetal microsomal
enzymes that degrade Vitamin K, thereby increasing the risk of
hemorrhagic disease of newborn. Thus all babies born to WWE taking
enzyme inducing AEDs should be offered 1mg of intramuscular vitamin
K.
Management of Patients at Risk of Preterm Delivery

• Steroid metabolism is potentiated by enzyme-inducing anticonvulsants.

• However no studies have assessed the effectiveness of higher and
frequent doses of corticosteroids on neonatal outcomes in WWE
exposed to enzyme inducing AEDs and the risk of preterm delivery.
• So higher doses of steroids not recommended.
 Labour and Delivery

• Reassured that most will have a normal vaginal delivery.

• Epilepsy is not an indication of Cesarean section
• Anti-epileptic regimen should be continued during labour.
• Adequate analgesia should be provided
• Insomnia, stress and dehydration should be avoided.
• Continuous CTG monitoring
• Tonic-clonic seizures can occur in up to 5% of patients with epilepsy
during labour.
 Pain relief during labour
• Patients with epilepsy should be offered the same range of methods of
pain relief in labour, but excluding pethidine, as it is metabolised to
Norpethidine which is an epileptogenic. In this situation morphine
would be the drug of choice.

• To limit the risk of precipitating a seizure due to pain and anxiety, early
epidural analgesia should be considered.
• If general anesthesia is necessary, it is better to avoid anaesthetic agents
like pethidine, ketamine and sevoflurane.
• The first two are known to lower seizure threshold and third may have
epileptogenic potential.
• Seizures in labour may lead to maternal hypoxia (due to apnoea during
seizure) and fetal hypoxia and acidosis secondary to uterine
hypertonus.

• Any seizure lasting for 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.
Status Epilepticus
• Left lateral tilt with maintaining airway and oxygenation.
• Benzodiazepines are the drug of choice
• Lorezepam IV 0.1mg/kg (usually 4mg bolus, with further dose after 10-
20 minutes )
• Diazepam 5-10mg slowly intravenous
• If no IV access , diazepam 10-20mg rectally and repeated after 15
minutes or midazolam 10mg buccally/Intramuscularly.(Buccal
preparation not available in Nepal)
• If seizures are not controlled , administer phenytoin or fosphenytoin at
the loading dose of 10-15mg/kg by intravenous route.
• If persistent uterine hypertonus, consider tocolytics and once mother
is stabilized , continuous fetal heart rate monitoring should be started.
If fetal heart rate does not recover within 5 minutes or seizures is
recurrent , plan for delivery.
• Neonatal team should be informed as there is risk of neonatal
withdrawl syndrome with maternal use of benzodiazepines and AEDs.
• If general anesthesia is necessary, it is better to avoid anaesthetic
agents like pethidine, ketamine and sevoflurane.
• The first two are known to lower seizure threshold and third may have
epileptogenic potential.
Postpartum
• If the women is stable and the dose has been increased during pregnancy,
decrease the AED dose within the first 10 days after delivery to a dose slightly
above pre pregnancy maintenance dose.

• In postpartum period ,the physiological changes like renal and hepatic

clearance and hemodilution are reversed and these women become at risk of
toxicity from AEDs.(drowsiness, diplopia, unsteadiness)

• Encourage Breastfeeding

• Counsel the lady regarding adequate sleep

Breast feeding

• Anti-epileptic drugs in newborn who are breastfed are probably lower

than in utero, provided the infant is healthy and born close to term.

• In the neonate as mechanisms for drug elimination are not fully

developed at birth.
Contraception
• Counseling should be offered to all women with epilepsy.
• IUCDs, Levonorgestrel releasing IUS and Depot are reliable methods
• Women should be explained that Oral contraceptive failure may occur
with phenobarbitone, primadone, Phenytoin and carbamazepine (enzyme
inducing AEDs) because of induction of hepatic microsomal enzymes.
• ACOG has recommended OCP`S with 50mcg of estrogen to be used in
women with epilepsy who take AEDs.
• Women taking Non enzyme inducing AEDs, all method of contraception
can be offered.
Conclusion
• Management of WWE requires an understanding of optimal dose of AEDs
for seizure control and their associated risk of fetal congenital
malformation.
• Seizure control before pregnancy is an important factor.
• Pre pregnancy counseling regarding the congenital abnormalities
associated with AEDs, Folic acid supplementation and fetal evaluation with
USG.
• Polytherapy is associated with congenital abnormalities so monotherapy
with least dose should be used to control the seizure.
• Lorazepam or diazepam are the drugs of choice in woman with seizures
during labor or if the woman goes in status epilepticus.