Epilepsy in Pregnancy

BY

Mohamed A.S. Kandeel

(M.B.B.CH., M.Sc.(Ob/Gyn), M.D.(Ob/Gyn)

Professor of Obstetrics and Gynecology

Menofyia University
Egypt
 Learning Objectives

At the end of this presentation, you should:

1-Understand the effects of pregnancy on epilepsy and the

complications that epilepsy may have on pregnancy,
lactation and neonate.

2-Be able to outline a management plan for an epileptic

pregnant woman.

3-Be aware of the different AEDs, their toxic effects and the
safest drug that can be used in pregnancy.
 Definition and Incidence

Epilepsy is recurring spontaneous seizures due to

sudden excessive and disordered electrical discharge
from the neurones of the Cerebral cortex. It is estimated
that 7% of epileptic women become pregnant and
epilepsy affects about 0.5-1% of pregnant women.

Epilepsy can be partial or generalized.

 Classification Of Epilepsy

A- Partial Seizures (Focal Seizures): This is the commonest type and

is subcategorized as :

1-Simple Partial Seizures (Jacksonian epilepsy): The affected

woman does not lose consciousness but may experience confusion,
tingling, or odd mental and emotional events. Such events may
include déjà vu phenomenon, mild hallucinations, or extreme
responses to smell and taste.

After the seizure, the patient usually has temporary weakness in

certain muscles.
 Classification Of Epilepsy

2- Complex Partial Seizures (>50% in adults):

They can result in loss of judgment, involuntary uncontrolled
behavior & loss of consciousness. Prior to the actual seizure, some
people may experience a warning aura, which can be an odd odor,
a feeling of warmth, or a visual or auditory hallucination. They then
may lose consciousness briefly and appear to others as motionless
with a vacant stare. After a few seconds, some may begin to
perform repetitive movements, such as chewing or smacking of lips.
Episodes usually last no more than two minutes.

Ocassionally a simple or complex partial seizures evolve into

secondarily generalized seizures. The progress may be so rapid
that the partial stage is not even noticed.
 Classification Of Epilepsy

B- Generalized Seizures
They occur in more diffuse areas of the brain and they have more serious
effect on the patient. They are further subcategorized as follows:

1-Tonic-Clonic (Grand Mal) Seizures:

a-The tonic phase: muscles suddenly contract, causing the patient to fall
and lie rigidly for about 10 to 30 seconds. Some people experience aura;
most, lose consciousness without warning. If the throat or larynx is affected,
stridor occurs when the patient inhales.

b-The clonic phase: Seizure is said to enter this phase when the muscles
begin to alternate between relaxation and rigidity. After this phase, the
patient may lose bowel or urinary control.

The seizure usually lasts a total of two to three minutes, after which the
patient remains unconscious for a while and then awakens to confusion and
extreme fatigue.
 Classification Of Epilepsy

2- Absence (Petit Mal) Seizures: Petit mal or absence

seizures are brief (three to 30 seconds) losses of
consciousness and may consist of only a short cessation
of physical movement and loss of attention. Such
seizures may pass unnoticed by others. About 25% of
patients with petit mal develop grand mal seizures
 Classification Of Epilepsy

C- Other Seizures:
1- Atonic (Akinetic) Seizures. A person who has an atonic (or akinetic)
seizure loses muscle tone. Sometimes it may affect only one part of
the body so that, for instance, the jaw slackens and the head drops.
At other times, the whole body may lose muscle tone, and the
person can suddenly fall.

2- Simply Tonic or Clonic Seizures. Seizures can also be simply tonic

or clonic. In tonic seizures, the muscles contract and consciousness
is altered for about 10 seconds, but the seizures do not progress to
the clonic phase. Clonic seizures, which are very rare, occur
primarily in young children, who experience spasms of the muscles
but not their tonic rigidity.

3- Myoclonic. Myoclonic seizures are a series of brief jerky

contractions of specific muscle groups, such as the face or trunk.
 Classification Of Epilepsy

4-Gestational epilepsy: Some patients experience their first seizures

during pregnancy. This can be a result of true gestational epilepsy,
a rare syndrome of seizures occurring only during pregnancy.
Patients with this syndrome have a variable presentation with single
or multiple seizures in one or more of their pregnancies. It can also
be a manifestation of epilepsy that may extend beyond the
pregnancy.

The workup of these patients should involve a neurologic

examination, consultation with a neurologist, CBC count, chemistry
panel (particularly for electrolytes), head MRI versus CT scan, and
EEG. The differential diagnosis should include eclampsia and any
possible etiology considered in the nonpregnant patient, including
stroke, electrolyte abnormalities, tumor, trauma, drugs/withdrawal,
and epilepsy
 Effects Of Pregnancy On Epilepsy
Unpredictable

1-Seizure frequency may increase: due to:

-Enhanced metabolism & increased drug clearance associated with
pregnancy can result in decreased serum drug concentration.
-Increased volume of distribution of the AED.
-Increased serum binding proteins.
-Decreased or non-compliance with medication.
-Sleep deprivation, hormonal changes of pregnancy (high E), and
associated psychological and emotional stress of pregnancy: all lower
threshold for seizures.
-Nausea and vomiting.
 Effects Of Pregnancy On Epilepsy (Cont.)

2-Seizure frequency may decrease:

Due to improved compliance with drug regimen in some patients.

3-Seizure frequency may remain unchanged.

 Effect Of Epilepsy On Pregnancy

• Data on 1st trimester losses, PROM, ante-partum

hemorrhage, operative vaginal delivery and CS are
inconclusive.

• Increased incidence of IUGR, cognitive

dysfunction, microcephaly and perinatal
mortality (1.2 - 3 times normal).

• Increased incidence of congenital malformations.

 Effect Of Epilepsy On Lactation

• No studies on the effects of AED on either quantity or quality of

breast milk.

• Breast feeding should be stopped if obvious sedation develops in an

infant and is likely to relate to the presence of AED in breast milk.
 Effects Of Epilepsy On Fetus And Neonate

1-There is increased risk for infants of epileptic mothers to have

epilepsy. The risk of neonatal susceptibility depends on:

• Nature of the mother’s seizure disorder.

• Genetic factors.
• Seizures arises during pregnancy.
• Metabolic & toxic consequences of seizures and AEDs.

2-Increase perinatal morbidity.

 Table 1. Antiepileptic Drug Exposure Through Breast Milk
Pennell PB, 2004

___________________________________
AED Breast milk/maternal conc Adult half-life NN half-life
______________________________________________________________________
Carbamazepine 0.4–0.6 8–25 8–28
Phenytoin 0.18–0.4 12–50 15–105
Phenobarbital 0.36–0.6 75–126 45–500
Ethosuximide 0.8–0.9 32–60 32–40
Primidone 0.7–0.9 4–12 7–60
Valproic acid 0.01–0.10 6–18 30–60
Lamotrigine 0.6 —— ___
Topiramate 0.69–0.86 —— ___
Zonisamide 0.41–0.93 63 61–109
Levetiracetam 3.09 —— ___
 Management

I-Preconceptional Care:

A-Re-assessment: may show that the patient does not have epilepsy
or may reveal a treatable cause before pregnancy (e.g. blood vessel
abnormality in the brain).

B-Counseling: explain to the patient that:

• There is a chance of 90% of having normal child.
• Increased chance of having epileptic child (2-5%).
• Increased pregnancy complications.
• Increased unfortunate outcome if seizures arises during pregnancy.
• Increased risk of congenital malformations.
 Management

I-Preconceptional Care:

C-Measurement of the free unbound anti-epileptic drug level in

maternal serum.

D- Preconceptional folate supplementation: 5 mg daily.

E- No trial to stop AED unless the patient is seizure free at least for 2
years. The AED dose should be tapered till stopped completely at
least 6 months prior to any planned pregnancy to provide some
reassurance that seizures are not going to recur.
 II-Antenatal Care
A-Investigations:
• Metabolic: serum glucose, urea, electrolytes, Ca & Mg
• EEK
• MRI/CT scan of the head.

B-Drugs:
Monotherapy at the lowest effective dose should be employed. If large daily
doses are needed, use frequent smaller doses or extended-release formula
to avoid high peak levels. Monitoring of serum AEDs level is mandatory.

Usually, women don't suspect they are pregnant until their fourth to sixth
week of pregnancy. By that time, if there are any harmful effects from their
AEDs, most of these effects would have already occurred.
 II-Antenatal Care

C-Selenium supplementation: in a dose of 200 µ/day may be

important to minimize the free radical mediated damage.

D-Folic acid supplements.

E-Morning sickness: If hyperemesis gravidarum, consider giving

alternative route if vomiting is severe or prolonged.

F-Antenatal diagnosis: of congenital malformations (screening should

be done by detailed ultrasound and measurement of æ fetoprotein
at 18 weeks).
 II-Antenatal Care (Cont.)

G-Vitamin K:
Oral 20mg daily is prescribed from 36 weeks until
delivery to mothers taking hepatic enzyme-inducing
drugs (phenytoin, phenobarbitone, primidone,
carbamazepine and topiramate - Not necessary with
sodium valproate).

Be aware of the nature of the AED you are using

whether it is a hepatic enzyme inducing or not. Most of
the newer AEDs are not enzyme inducers).
 III-Labor and Delivery (Cont.)

“The risk of developing a seizure during labor is 9 times

that during the rest of pregnancy”.

Management of women with epilepsy upon labor and

delivery:

• Check levels of AEDs.

• Inform all health care providers that the patient has

epilepsy.

• Consider seizure prophylaxis with intravenous

benzodiazepines or phenytoin.
 III-Labor and Delivery (Cont.)

• Manage seizures acutely with intravenous benzodiazepines (1-2 mg

of diazepam), then load phenytoin (1 g loaded over 1 h).

• Labor management should be based on routine standards of care.

• Start administration of vitamin K1 for the infant, and send the cord
blood for clotting studies.
 III-Labor and Delivery (Cont.)

Management of a pregnant patient in status epilepticus:

• Establish the ABCs, and check vital signs.

• Assess the fetal heart rate.

• Rule out eclampsia.

• Administer a bolus of lorazepam (0.1 mg/kg, ie, 5-10 mg) at no

faster than 2 mg/min.
 III-Labor and Delivery (Cont.)

• Load phenytoin (20 mg/kg, ie, 1-2 g) at no faster than 50 mg/min,

with cardiac monitoring.

• If this is not successful, load phenobarbital (20 mg/kg, ie, 1-2 g) at

no faster than 100 mg/min.

• Check laboratory findings, including electrolytes, AED levels,

glucose, and toxicology screen.

• If fetal testing results are nonreassuring, move to emergent delivery.

 III-Labor and Delivery

• The majority of women who have epilepsy have a safe vaginal

delivery without seizure occurrence; provided, the AED is taken
before and throughout labor.

• Generalized tonic clonic Seizures GTCSs needs aggressive

interference because of the high risk for the mother and fetus,
especially if they progress to status epilepticus. Oxygen should be
administered to the patient and she should be placed on her left
side to increase uterine blood flow and decrease the risk for
maternal aspiration.
 III-Labor and Delivery (Cont.)

• Emergency C.S. should be performed when repeated GTCSs cannot be

controlled during labor or when the mother is unable to cooperate.

• Any lady having a seizure during labour must be observed closely for the
next 72 hours.

• Obstetric analgesia may be used to allow for rest before delivery. Pethidine
should never be used because it is metabolised to norpethidine, which is
epileptogenic. Diamorphine is an option. Few cases of postpartum seizures
were reported following epidural analgesia.
 III-Labor and Delivery (Cont.)

• During labor, oral absorption of AEDs may be inappropriate and any

vomiting might complicate the situation. PB, PHT, and VPA can be
given IV at the same maintenance dosage. Convulsive seizures and
repeated seizures during labor should be treated promptly with
parenteral lorazepam or diazepam.

• Benzodiazepines, in large doses, can cause neonatal cardiac and

respiratory depression; therefore, close monitoring for these
neonates is mandatory.
 IV-Postnatal Care
A-Infant:
- Inspected for malformation.
-Vitamin k 0.1mg/kg IM at birth reduces risks of hemorrhagic disease.

B-Bathing: never should be performed alone, as a brief lapse in

attention can result in a fatal drowning. Wet sponge not water bath.
Changing diapers and clothes are performed best on the floor rather
than on an elevated changing table.

C-Breast Feeding: encouraged in suitable position. If excessive infant

sedation is encountered, as may be seen with phenobarbital or
primidone, the infant should be weaned slowly with monitoring for
signs and symptoms of withdrawal and infant drug levels.
 IV-Postnatal Care

D- The following safety issues must be taken into account:

• If the mother is likely to drop objects she is holding but

remain upright, then she should use a harness when
carrying the baby.

• If she is likely to fall, then a stroller kept at home is a

must.
 IV-Postnatal Care

E- Sleep:
If the mother is breastfeeding, sleep deprivation may be
unavoidable. The mother should make up any missed sleep during
the infant's daytime naps, whenever possible.
 IV-Postnatal Care (Cont.)

F-Anticonvulsant: Any increase in drugs during pregnancy will need

to be decreased slowly to pre-pregnancy doses over 3-4 weeks to
avoid toxicity.

G-Contraceptions: Barriers and IUDs are recommended.

Many AEDs induce the hepatic cytochrome P-450 system, which is

the primary metabolic pathway of the sex steroid hormones. This
leads to rapid clearance of steroid hormones and allow ovulation in
women taking OCPs or other hormonal forms of birth control.
 IV-Postnatal Care (Cont.)

In 1998, the American Academy of Neurology recommended the

use of an E2 dose of 50 μg or its equivalent for 21 days of each
cycle when using OCPs with the enzyme-inducing AEDs. More
recently, however, it is recognized that this still is inadequate
protection, and a backup barrier method was recommended.
Women on low dose pills or minipills and AED may get pregnant.

Patients on hormonal contraception need to be warned that

midcycle bleeding indicates possible birth control failure, but its
absence does not indicate adequate birth control efficacy. The
newer transdermal patch formulation have a higher failure rate with
these AEDs. IM medroxyprogesterone provides higher dosages of
progestin but still may require dosing at 8- to 10-week intervals
rather than 12-week intervals.
 Table 2 . Antiepileptic drug effects on hormonal contraceptives
Guberman 1999., Krauss et al 1996., Rosenfeld et al 1997

________________________________________
Lower hormone level No significant effect
_______________________________________________
Phenobarbital Ethosuximide
Phenytoin Valproate
Carbamazepine Gabapentin
Primidone Lamotrigine
Topiramate Tiagabine
Oxcarbazepine Levetiracetam
Zonisamide
 Anti-Epileptic Drugs
I-Monitoring

The ideal AED serum free level must be established for each patient
before conception, and should be the level at which seizure control
is the best possible for that patient without debilitating side effects.
Levels should be repeated at the beginning of each trimester and
again in the last 4 weeks of pregnancy. Monitoring should continue
until the 6th to 8th week postpartum. In doing so, one may be able
to avoid symptoms of toxicity that result from the changes in
pharmacokinetics postpartum.
 Anti-Epileptic Drugs
I-Monitoring

Some authors recommend monthly monitoring, given the possibility

of rapid and unpredictable decreases in AED levels in an individual
patient.

The frequency with which levels are monitored must be tailored to

each situation, including increased monitoring for worsening seizure
control, adverse effects, and compliance issues.
 Table 3: Therapeutic Levels of Anti-Epileptic Drugs (AEDs)
Dichter MA, Brodie M.1996., Brodie M, Dichter MA 1996., Johannessen SI et al 2003.,
LaRoche SM et al 2004

Drug Common dose Doses Therapeutic levels

Carbamazepine 600 mg qd-qid 6-12 μ/ml

Gabapentin 300 mg Qd 70-120 μmol/L
Lamotrigine 25-30 mg Qd 10-60 μmol/L
Levetiracetama 500–1500 mg bid 35–120 μmol/L
Oxcarbazepine 300–600 mg bid 50–140 μmol/L
Phenobarbital 120 mg qd-bid 10–40 μ/mL
Phenytoin 300 mg qd-bid 10–20 μ/mL

Primidone 500 mg qd-bid 5–15 μ/mL

Valproic acid 1000 mg qd-bid 50–100 μ/mL
 Anti-Epileptic Drugs

II-Teratogenicity

Antiepileptic drugs (AEDs) have the potential to produce both

anatomic and behavioral teratogenesis.

Mechanisms:
1-Direct drug toxicity: due to accumulation of the drug metabolites (reactive
intermediates) which are embryotoxic.

2-Antifolate effect: Phyntoins, carbamazepine & barbiturates impair folic acid

absorption. Valproic acid interferes with the production of folinic acid.

3-Genetically determined deficiency of the detoxifying enzyme epoxide

hydroxylase.

4-Possible genetic link between maternal epilepsy and malformations.

 Table 4: Timing Of Embryonic Organogenesis
(Pennell PB 2003)

Organ system Defect Postconception age

CNS NTD 28 days

Face Cleft lip & palate 36 and 70 days

CVS VSD 42 days

Urogenital Hypospadius 56 days

system
 Prenatal Screening for Fetal Malformations

• Transvaginal U/S can be performed at 18-20 weeks to diagnose the

most severe defets (face - heart). However, sensitivity is better, for
cleft palate and lips, if U/S is repeated between 24-28 weeks.

• Screening for NTD: by combination of Maternal serum α –

fetoprotein at 15-22 weeks and Level II,structural Ultrasound, at 16-
20 weeks.

• If results are equivocal, proceed with amniocentesis with

measurements of amniotic fluid α -fetoprotein and acetylcholine-
esterase.
 Anti-Epileptic Drugs (Cont.)

Specific Syndromes Of Malformations

1-Fetal Hydantoin Syndrome:

• 11% of infants exposed will have the syndrome.
• There is pre and postnatal growth deficiency, dysmorphic facies and
mental retardation.
 Anti-Epileptic Drugs (Cont.)

Specific Syndromes Of Malformations

2-Facial Valproate Syndrome:

• Brachycephaly with high forehead, shallow orbits, small nose, small
mouth & low posterior ears.
• Long overlapping fingers & toes & hyperconvex nails.
• Cleft palate & congenital heart diseases.

3-Barbiturates Withdrawal Symptoms

Starts 1 week after birth & includes restlessness, constant crying,
irritability, difficult sleeping & vasomotor instability.
 Anti-Epileptic Drugs (Cont.)

Behavioral Teratogenesis

In utero AED exposure can produce long-term behavioral changes:

• In a retrospective Danish study, babies exposed in utero to phenobarbital

had a 7-point decline in verbal IQ.

• A prospective Finnish study found the mean verbal IQ score following in

utero exposure to valproate was 82 compared with 96 for carbamazepine
and 95 for healthy controls.

• In a retrospective UK study of school-aged children exposed to in utero

AEDs, 30% of children exposed to valproate monotherapy had additional
educational needs compared with 3.2% of children exposed to
carbamazepine monotherapy and 6.5% for other ani-epileptics.
 Anti-Epileptic Drugs

III-Mono Versus Polytherapy

• It is better to prescribe the lowest possible dose of a single drug to

prevent and control fits.

• Studies have shown higher incidence of malformations with

polytherapy compared to montherapy.

• If large daily doses are needed, then frequent smaller doses or

extended-release formula may be helpful to avoid high peak levels.
Dose should be divided into 3-4 doses/day. This is because high
peak plasma levels of the drug is more teratogenic.
 Table 5: Comparison of Malformation Rates During
Pregnancy Monotherapy Versus Polytherapy

Study design Findings

Kaneko et al. 1988 Prospective Malformation rates were 6.5%
study &15.6% for monotherapy &
polytherapy (p = 0.01)

Oguni et al. 1992 Comparison of 2 Major malformations decreased

prospectively from 24.1% to 8.8% (p < 0.01),
followed cohorts paralleling an increased no. of
patients receiving monotherapy.
Dravet et al. 1992 Prospective study Malformations was higher in
of effects of AEDs infants exposed to poly (15%)
compared to monoth. (5%) (p <
0.01)
 Table 5: Comparison of Malformation Rates During
Pregnancy Monotherapy Versus Polytherapy (Cont.)

Study design Findings

Holmes et Frequency of embryopathy Frequency of embryopathy
al. 2001 in control infants not was higher in infants exposed
exposed to AEDs (n = 508) to AED monotherapy vs.
and in infants exposed to nonexposed controls (20.6%
AED monotherapy (n = 223) vs. 8.5%; OR 2.8; 95% CI 1.1 to
and AED polytherapy (n = 9.7). The frequency was also
93) were compared higher in infants exposed to
AED polytherapy vs.
nonexposed controls (28.0%
vs. 8.5%: OR 4.2; 95% CI 1.1 to
5.1)
 Table 5: Comparison of Malformation Rates During
Pregnancy Monotherapy Versus Polytherapy (Cont.)

Study design Findings

Lindhout et Influences of changes in
al. 1992 prescribing practices analyzed
by comparing 2 cohorts,
1972–1979 and 1980–1985, in
the Netherlands
Mean no. of drugs used
during pregnancy
decreased from 2.2 in the
70s to 1.7 in the 80s.
Rates of anomalies were
9.9% & 7.6% in 70s and
80s cohorts, respectively.
The difference did not
reach stat significance

Samrén et al. Pooled data from 5 For the AED-exposed

1997 prospective European studies children, the RR for a
major malformation was
2.3 (95% CI 1.2 to 4.7) vs
controls
 Anti-Epileptic Drugs (Cont.)

VI-Clinical Or Subclinical Coagulopathy

• Factors II,VII,IX & X are decreased.

• Factors V, VIII & fibrinogen are normal.

• PT & PTT should be determined at delivery.

• If values are low or clinical coagulopathy develops in the neonatal

period, TTT is by the infusion of FFP or concentrates of deficient
factors in addition to the routine administration of vitamin K1.
 Anti-Epileptic Drugs (Cont.)

IV-Failure of AEDs

An AED's failure to reduce seizures can be

attributed to factors such as:
1-Wrong dosing.
2-Improper timing.
3-Rapid administration of the drug.
4-Ignoring conditions that precipitated the seizure.
 Anti-Epileptic Drugs (AEDs) (Cont.)

IV-Failure of AEDs

5-Instability of the drugs. Many drugs disintegrate easily with moisture.

AEDs should be stored in a dry place and kept away from heat.

6-Toxicity. 40% of patients experience toxic effects from older AEDs

which often causes them to withdraw. Among the most distressing
are sleepiness, problems in coordination and weight gain.
 Anti-Epileptic Drugs (Cont.)

IV-Failure of AEDs

7-About a quarter of patients who do not respond to AEDs actually

have nonepileptic seizures that in many cases are caused by
psychiatric conditions (e.g., panic attack, personality disorders).
 Differential Diagnosis
1-Eclamptic Seizures:
• HTN & Ptnuria are always present.
• Urine output is diminished & anuria may develop. Hemoglobinuria is
common.
• Fever of 39º C or more indicates impending CNS hemorrhage.

2-Migraine headaches, particularly migraine with auras, may

sometimes be confused with epilepsy. With epileptic seizure, the
preceding aura is often seen as multiple, brightly colored, circular
spots, while migraine sufferers tend to see black, white, or colorless
lined or zigzag flickering patterns. Typically the migraine pain
expands gradually over minutes toward one side.
 Differential Diagnosis (Cont.)

3-Panic Attacks: One study reported on patients with

partial seizures that resembled panic disorder.
Symptoms of panic disorder include palpitations,
sweating, trembling, sensation of breathlessness, chest
pain, feeling of choking, nausea, faintness, chills or
flushes, and fear of losing control and fear of dying.

4-Narcolepsy: a sleep disorder that causes a sudden loss of muscle

tone & excessive daytime sleepiness, can be confused with
epilepsy.
 Differential Diagnosis (Cont.)

5-Local Anesthetic Toxicity: Occurs due to either injection of the local

agent into a bl. vessel or the administration of excessive amounts.
Manifestations of systemic toxicity are those of C.N.S. & C.V.S.

6-Pheochromocytoma: Clinically, there is hypertensive crisis, seizure

disorder or anxiety attacks. Diagnosis is by 24 hrs VMA,
metanephrines or unconjugated catecholamines. Adrenal
localization is usually successful with CT or MRI.
 Differential Diagnosis (Cont.)

7-Tetany: Occurs as a part of maternal hypo-parathyroidism.

Diagnosis is confirmed by low ionized calcium & parathormone
levels & by measurement of urinary AMP excretion after
administration of parathormone.

8-Metabolic: Hypoglycemia or hyponatremia.

9-Fulminant hepatic failure: Due to acute fatty liver of pregnancy or

acute viral hepatitis.
 Conclusions

1 -Epileptic woman can get pregnant. They are not

different than other women population.

2-Epilepsy and its medications increases the incidence

of malformations 2-3 times normal. However; there is
90% chance of having a normal child.

3-The most common malformations are cleft lip, left

palate and congenital heart diseases.
 Conclusions (Cont.)

4-A woman should not stop AED unless she has not
had seizures for 2 years; gradual discontinuation
can then be attempted.

5-A pregnant should not stops her AED Since most

malformations develop during the 1st trimester.

6-Current AEDs are considered to be a necessary evil

until newer drugs become available. However, the
safest are: Phenobarbital and phenytoins.
Thank you