1. Pregnancy monitoring - the management of pregnant women with epilepsy -
Doina Vanghelie, Ionela Codita, Cristina Panea
Elias University Emergency Hospital
Bucharest

2. Pregnancy and epilepsy
Pregnancies in women with epilepsy are considered at high risk for adverse outcomes because can be complicated by various maternal and fetal issues
careful management by both neurological and obstetrician specialist
Asses risk and benefits with individual drugs
Limited data about newest drugs

3. Pregnancy and epilepsy
Objectives
seizure control (the occurence of seizure / increasing of seizure frequency)
monitor the development of the fetus (congenital abnormalities, cognitive and development delay)
prevent birth complications for mother/child (miscarriage, premature labor, perinatal death, hemorrhage)

4. Increase in seizure frequency
Mainly last quarter due to:
lower plasma level of AEDs
increase hepatic / renal clearance
increase the volume distribution by fluid retention
reduced protein binding
an increased level of estrogen (epileptogenic by decreasing the seizure thresold)
sleep deprivation
stress, anxiety
decreased compliance in taking AEDs ( due to nausea or concerns regarding the effect on their fetus) 
Low risk for recurrence of seizures if the patient is seizure-free for 9 month prior to pregnancy (level B)
(Gjerde et al, 1988, Tomson et al, 1994)

5. Changed AEDs plasma concentration
Pregnancy cause an increase in the clearance and decrease in the concentrations of:
lamotrigine
phenitoine
lesser for carbamazepine (9% in 2nd trim and 12% in 3rd trim)
Decrease level of levetiracetam, oxicarbamazepine (active metabolite MHD)
Recommendation: monitoring of total and free level of plasma AEDs monthly

6. Acute seizures during pregnancy
As the result of:
gestational epilepsy (idiopathic onset)
symptomatic epilepsy:
vascular malformations or meningioma with receptors for estrogen (exacerbated by pregnancy)
cerebrovascular disease (cerebral thrombophlebitis, or paradoxical amniotic embolism)
Eclampsia
Hyponatremia - due to oxytocin which promotes water retention
Syncope
In response to the used anesthetic lidocaine
Psychogenic seizure (especially peripartum)

7. Seizures related risks for foetus
During pregnancy it is essential to continue the treatment to avoid the risks associated with seizures
High: tonic-clonic seizures
Injury
miscarriage
fetal bradycardia
the level of risk depends also on seizure frequency
(definitive data is lacking)
Low: focal seizure, absence and myoclonic seizure

8. Seizures related risks for mother
Discuss with those who plan to stop AED theraphy !
SUDEP
Status epilepticus

9. Status epilepticus Exclude preeclamsia and eclampsia
Check maternal vital signs
Asses the fetal heart rate and fetal status
Laboratory findings (AED levels, electrolytes, glucose, toxicology)
Benzodiazepine iv, phenitoin with cardiac monitoring
Monitor the fetus
Emergency delivery if necessary

10. Seizures control must be balanced with the teratogenic risk

11. The AEDs cross the placenta
in clinically important amounts: Phenobarbital, primidone, phenytoin , carbamazepine, levetiracetam and valproat
potentialy clinically important amounts: Gabapentin, lamotrigine, oxcarbamazepine and topiramat
inssufficient data for ethosuximide
Symptomatic effects in newborns: lethargy, excessive somnolence, fussiness

12. Teratogenic risk
Risk of major congenital malformations is 4-9% in women receiving AEDs
Specific malformations:
PHT: risk of cleft palate (class II)
CBZ: posterior cleft palate (class II)
VPA: neural tube defects, facial clefts (class I), hypospadias (class II); more than 800mg and polytherapy included VPA are associated with higher risk
PB: cardiac malformations (class II)
EURAP epilepsy and pregnancy register

13. BUT It is recommended that do not change the AED during pregnancy

14. The teratogenic risk must be evaluated before pregnancy !
CBZ probably does not substantlly increase the risk (class I evidence)
LTG – best option
Close monitoring of child development
Fetal survey by ultrasonography at week with careful attention to the face, central nervous system and heart
Possibly amniocentesis
UK Epilepsy and Pregnancy Register

15. Folic acid
Folic acid supplementation is possibly effective in preventing or reduction the rate of neural tube defects (level C)
Started before pregnancy
At least 0.4mg (0.5-4mg) per day
At least until the end of first trimester

16. Delivery
Epilepsy and antiepileptic treatment increase the risk of maternal and fetal complications:
preeclampsia
hypertension
Miscarriage
prematurity
neonatal asphyxia
Cesarean delivery: moderately increased risk is possible (level C) compared with women with no epilepsy
Insufficient evidence for preeclampsia, hypertension premature contractions or premature labor and delivery
Increased risks for the smokers pregnant women with epilepsy
Possibly an increased risk (level C) for bleeding complications and spontaneous abortion (lack of statical data)
Viinikainen et al, 2006; Richmond et al, 2004

17. Labor and delivery Preparation and close monitoring
Inform all care providers (obstreticians, neurologist, anesthesiologist, pediatricians, nurses) that the patient has epilepsy
Check AEDs plasma level at admission
Extra doses of AED if it is necessary or switch to i.v. benzodiasepine or phenytoin (seizure prophylaxis)

18. AEDs and newborns
Newborns exposed to enzyme-inducing AED received vitamin K at delivery
inadequate evidence to determine if the newborns have substantially increased risk of hemorrhagic complications.

19. AEDs and newborns Transfer into breast milk
Possibly in clinically important amounts: primididone and levetiracetam;
probably gabapentine, lamotrigine, topiramat
Not in clinically important amounts:
valproate, phenobarbital, phenitoin and carbamazepine  

20. Conclusions
Monitor total and free level of AEDs monthly, EEG monitoring
Manage acute seizure and status epilepticus
Continue  folate supplementation
Check maternal serum alpha fetoprotein levels
Fetal survey by ultrasonography at week
It is not clear prophylactic effect of bleeding by administering vitamin K prepartum
Prepare delivery
Breastfeeding