epilepsy in pregnancy

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					Epilepsy in Pregnancy


          Mohamed A.S. Kandeel
  (M.B.B.CH., M.Sc.(Ob/Gyn), M.D.(Ob/Gyn)

  Professor of Obstetrics and Gynecology
            Menofyia University
                 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

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

• 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                     ——          ___

                 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.

                  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
• Metabolic: serum glucose, urea, electrolytes, Ca & Mg
• MRI/CT scan of the head.

   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

• Check levels of AEDs.

• Inform all health care providers that the patient has

• 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
                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
 - 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
                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
                  Anti-Epileptic Drugs

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

Some authors recommend monthly monitoring, given the possibility
of rapid and unpredictable decreases in AED levels in an individual

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


   Antiepileptic drugs (AEDs) have the potential to produce both
   anatomic and behavioral teratogenesis.

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

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
    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-
             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 <
  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 =        vs. 8.5%; OR 2.8; 95% CI 1.1 to
              223) and AED polytherapy    9.7). The frequency was also
              (n = 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
  Table 5: Comparison of Malformation Rates During
 Pregnancy Monotherapy Versus Polytherapy (Cont.)

              Study design                     Findings
Lindhout   et Influences of changes in         Mean no. of drugs used
al. 1992      prescribing practices analyzed   during          pregnancy
              by comparing 2 cohorts,          decreased from 2.2 in the
              1972–1979 and 1980–1985, in      70s to 1.7 in the 80s.
              the Netherlands                  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
             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
•   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
              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

8-Metabolic: Hypoglycemia or hyponatremia.

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

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

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