Epilepsy in Pregnancy
Sherifia Heron, M.D
October 20, 2009 Ob Rotation
Dept. of Family and Social Medicine
Case
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36yo G1P0000 at 35wks and 2 days with history of
epilepsy sent from clinic for elevated BPs to rule out
preeclampsia. She had no complaints. No LOF, No
VB, and +FM. No HA, Visual Changes, or epigastric
pain.
Initial BP 110/60, Range (100-125/60-80), Total of 9
visits. Initial weight 128160 = 32lbs gained.
PNI: Hx of Seizure disorder
PNL: O+, ab-, H/H 11.6/34.5, Syphilis NR, Rubella
Immune, GC Neg/Chlamydia Neg, HBSag Neg, HIV
neg, GBS neg, GTT Neg (109)
Ob Hx: None
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Past Medical Hx: Seizure D/o
 PSHx: None
 SHx: Employed, married to FOB they live together. Denies
Tob/etoh/Drugs/DV. Planned pregnancy – good support
system
 Medications: Lamotrigine (Lamictal)
 Allergies: NKDA
 PE: No epigastric pain, No edema, BP 136/67, Range
(115-142/60-92)
– FHT 140s, moderate variability, +accels, -Decels
– SVE: Ft/L/High
– EFW 3400
– Vertex by Sono
Assessment and Plan
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36yo G1P0 at 35 and 2 days with h/o seizure d/o admit to
L&D to rule out PEC
Admit to L&D, PEC labs,
PEC: BP in normal to mild range 136/67, Range (115142/60-92) No S/Sx of PEC,Will continue to monitor
FEN/GI: NPO, Except ice chips, IVF @125 cc/hr
Labor
– Expectant management
Fetus: reassuring overall, Category 1 tracing
PEC Labs
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UA: Neg for protein
 AST/ALT: 16/11
 LDH: 170
 Creatinine: 0.5
 Platelets: 199
AED
1.
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5.
6.
Are antiepileptic drugs necessary
What effect do antiepileptic drugs have on the
fetus?
What effect does maternal epilepsy have on the
fetus?
What effect does pregnancy have on seizures?
How should the patient be managed during
pregnancy and delivery?
How should the patient be managed during the
postpartum period?
Case
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At 2:10am, emergency alarm went off, two ob residents myself and
nursing staff rushed to PACU
On arrival to the PACU, approximately 12hrs after Ms. X was
admitted to monitor for PEC she was having a seizure
The seizure went on for approximately 30sec where Ms. X upper
extremities was flexed and jerking. Head neck and shoulders was also
jerking uncontrollably
Pts. Eyes were closed and rolled back in her heard. Pt. Grunted and
responded to questions by blinking once for yes and twice for no.
Vitals were taken during the attack: BP 110/60, RR 26, HR 138
After the seizure ended the pts. Reports feeling tired and drowsy and
was allowed to rest until fully awake – at which time she was
consented for a C-section
Vital Signs remained stable
Case continue
FHT: 140s  120s
 During seizure episode
 Returned to baseline 140s after seizure
 Toco: Q15-20mins
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Questions
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What Happened?
 Eclampsia vs. Epilepsy?
 Could this have been prevented by
appropriately managing her epilepsy
 Labs was drawn again and decision made to
perform a c-section
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History of seizure since age 17
– Says EEG in D.R. was “abnormal” but
subsequent EEGs in the US was negative
 No family history of seizure
 Last seizure was 2.5 years ago
 No triggers but mostly occurs at night
 No history postictal confusion,
incontinence
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Cryptogenic seizure
Epilepsy Pathophysiology
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Seizures happen when there are sudden
changes in the way normal brain cells
interact electrically.
 Consciousness, movement, sensation,
speech, mood, memory, and emotions can
all be affected during the one or two
minutes that the seizure lasts.
Seizure Medications
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*Glossary of generic to name brand drugs
Generic Name Brand
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lamotrigine ....................Lamictal
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carbemazepine ..............Tegretol, Carbatrol
gabapentin ....................Neurontin
levetiracetam..................Keppra
oxcarbazepine................Trileptal
phenytoin ......................Dilantin
tiagabine ........................Gabitril
topiramate......................Topamax
zonisamide ....................Zonegran
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Drug Monitoring
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Lamotrigine
– Several studies suggest that lamotrigine clearance increase by
about 65 to 94% and therefore should be monitored more
frequently during the second and third trimesters, to reduce the
possibility of increased seizures, as well as in the early postpartum
period, to avert toxicity
Levetiracetam
– Among 14 women monitored on levetiracetam therapy during
pregnancy, plasma concentrations were observed to decline during
pregnancy to 40% of baseline concentrations in the third trimester.
Limited information on seizure control was provided, but the
possibility of increased seizures during this time suggests the need
for closer monitoring
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Oxcarbazepine
– In one large pregnancy registry oxcarbazepine
monotherapy increased the risk of seizure, suggesting
the possibility that it, too, is associated with
pharmacokinetic changes in pregnancy, and requires
more frequent monitoring.
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Topiramate
– A study describing 12 women on topiramate therapy
during pregnancy reported that serum concentrations
declined by about 30%. Increased seizure frequency in
pregnancy was also observed in this series
Types of Seizures
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Generalized Seizures
– Absence seizures
– Myoclonic seizures
– Atonic seizures
– Tonic seizures
– Clonic seizures
– Tonic-clonic seizures
Partial Seizures
– Simple partial seizures (awareness retained)
 Motor, autonomic, sensory or psychological
– Complex partial seizures (awareness lost)
Secondary generalized seizures
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Status Epilepticus
Status epilepticus is prolonged, repetitive seizure activity that lasts more than 20 to 30 minutes,
during time which the patient is unconscious. Status epilepticus is a medical emergency with a
significantly poor outcome; it can result in death if not treated aggressively. Its causes include
improper use of certain medications, stroke, infection, trauma, cardiac arrest, drug overdose,
and brain tumor
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Simple Partial Seizures
– Awareness preserved
– Memory preserved
– Consciousness preserved
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Complex Partial Seizures
Awareness preserved
Memory preserved
Consciousness preserved
Epilepsy Statistics
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90% of women with epilepsy have normal
pregnancy
 Nonetheless, there are a number of fetal and
obstetrical complications associated with
women with epilepsy.
Preconception Management
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This should include information regarding
risks associated with epilepsy and
pregnancy,
– potential interactions with oral contraceptive
therapy, and
– recommended folate supplementation
Contraception
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inducers of the hepatic cytochrome P-450
system
– hormonal contraceptive failure
Folic acid supplementation
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Animal studies have shown that valproate
and phenytoin decrease the concentration of
certain forms of folate and are associated
with neural tube defects
Folic acid supplementation
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It has not yet been conclusively determined
if folic acid supplementation prevents
neural tube defects in women receiving
AEDs.
Continued folic acid
supplementation
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Once a woman with epilepsy who is taking
AEDs becomes pregnant, serum and red cell
folate levels can be monitored (goal is
concentration about 4 mg/ml).
Obstetrical Complications
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Low birth weight
Lower apgar scores
Preeclampsia
Bleeding
Placental abruption
Prematurity
The rates of stillbirth, neonatal death, and perinatal death vary widely and have
been reported to be as high as two to three times greater in infants born to
women with epilepsy
The mechanism of risk is not well understood. In one study, the
investigators found an increased risk of spontaneous abortion for both
fathers and mothers with epilepsy
Necessity for antiepileptic
drugs
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Is the diagnosis of epilepsy well
established? In some patients, routine EEG
recordings or continuous video/EEG
monitoring may be warranted to confirm the
diagnosis
 Does the patient require AEDs and if so, is
she on the most appropriate medications
and the minimum dose to maintain seizure
control
Are Antiepileptic Drugs
Necessary
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Many physicians will consider withdrawal of
AEDs after a period of two years without seizures.
The frequency of seizure recurrence within six and
twelve months of discontinuing therapy is 12 and
32 percent, respectively.
 Thus, if a woman has been seizure-free for a
satisfactory period, a taper and withdrawal of
AEDs at least six months prior to becoming
pregnant is suggested
Choice of antiepileptic drug
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If it is felt that medications cannot be
withdrawn, the patient should take the most
suitable medication for the seizure type.
 The optimal treatment of women with
epilepsy who are of childbearing age is
unclear because of a lack of conclusive data
on the comparative teratogenicity of
different AEDs.
Antiepilepsy Drugs
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The most common major congenital malformations associated with AED are
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neural tube,
congenital heart and urinary tract defects,
skeletal abnormalities,
and cleft palate.
Specific AEDs, combination drug therapy, a family history of birth defects,
and other risk factors appear to be associated with increased risk of these, at
least in some studies
– Particularly valporate and carbemazepine monotherapy,
– benzodiazepines in polytherapy, and caffeine in combination with
phenobarbital
 In addition to the specific AED used alone or in combination, the gestational
timing of the exposure and the dose of AED used are also likely to be
important. These have been best associated with valporate
 Many of these drugs appear to be implicated in dysmorphisms such as
hypoplasia of the nails and distal phalanges, hypertelorism, and the
“anticonvulsant face” – Broad or depressed nasal bridge, short nose with
anteverted nostrils, long upper lip, maxillary hypoplasia
Other newer AEDs
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There is limited human information on the
fetal risks of the newer antiepileptic drugs
(eg, gabapentin, felbamate, topiramate,
tiagabine, levetiracetam, pregabalin).
Management During
Pregnancy
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The AED should be administered at the lowest dose and lowest plasma level
that protects against tonic-clonic and/or complex partial seizures
The plasma drug level should be monitored regularly during pregnancy
including, if available, the physiologically important free or unbound drug
concentration
The use of multiple agents should be avoided, if possible, especially
combinations involving valproate, carbemazepine, and phenobarbital
If there is a family history of neural tube defects, both valproate and
carbemazepine should be avoided, unless a patient’s seizures cannot otherwise
be controlled
In established pregnancy, changes to alternate AED therapy should not be
undertaken solely to reduce teratogenic risk for several reasons
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Changing the AEDs may precipitate seizures
Overlapping AEDs during the change exposed the fetus to effects of an additional
aED
– There is limited advantage to changing AEDs if pregnancy has already been
established for several weeks
Vitamin K Supplementation
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Most physicians recommend administration of
prophylactic vitamin K during the last month of
pregnancy to women treated with AEDs to protect
the child against severe postnasal bleeding due to
a deficiency in vitamin K-dependent clotting
factors
 Enzyme-induced AEDs, such as phenobarbital,
phenytoin, and carbemazepine, cross the placenta
and may increase the rate of oxidative degradation
of vitamin K in the fetus, an effect that can be
overcome by large doses of vitamin K
Effects of Epilepsy on the
Fetus
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In addition to concerns about fetal exposure to antiepileptic drugs
(AEDs), there are risks to the fetus from maternal seizures and
maternal epilepsy.
 Few studies have been performed on the direct effects of maternal
seizures on the fetus.
 Fetal hypoxia
 One report of fetal heart rate monitoring during a maternal
generalized tonic-clonic seizure lasting 2.5 mins revealed
significant fetal heart rate deceleration lasting up to 30 mins after
the seizure. While nonconvulsive seizures are believed to be less
dangerous, another case report has documented significant fetal
bradycardia during a one-minute, complex partial seizure.
Effects of pregnancy on
seizures
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The frequency of seizures does not increase
during pregnancy in the majority of women
with epilepsy.
At Delivery
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Most women have a normal vaginal delivery.
 Elective cesarean section
– frequent seizures during the third trimester
– history of status epilepticus during severe stress
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A tonic-clonic seizure occurs during labor in 1 to
2% of women with epilepsy, and in another 1 to
2% 24hrs after delivery.
 It is therefore essential to maintain a plasma AED
level known to protect against seizures during the
third trimester and during delivery. Doses must
not be missed during the period of labor.
Speak
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Most women have a normal vaginal delivery. However,
elective cesarean section may be justified in women with
frequent seizures during the third trimester or a history of
status epilepticus during severe stress
A tonic-clonic seizure occurs during labor in 1 to 2% of
women with epilepsy, and in another 1 to 2% 24hrs after
delivery. It is therefore essential to maintain a plasma
AED level known to protect against seizures during the
third trimester and during delivery.
Doses must not be missed during the period of labor.
Reference
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“Risk associated with epilepsy and pregnancy” and “Management
of epilepsy and pregnancy”
– www.uptodate.com
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http://www.webmd.com/epilepsy/medications-treat-seizures
– www.webMD.com
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http://www.uptodate.com/patients/content/topic.do?topicKey=~8
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