First fit Clinic
Rapid review clinic
Regular Clinic and
EEG Service led by
Nurse ( or 2? )
with interest in
Preconception planning and counselling
Teratogenic risk of specific antiepileptic drugs/
antiepileptic drug choices
Management of epilepsy during pregnancy
Management after delivery
The epilepsy itself is not a contraindication to
pregnancy even if it requires AEDs.
Planned pregnancy- (changes 6-12 mo.)
Over 90 % -remarkable event free/ good
Assess seizure activity- controlled? Not?
Any changes prior to pregnancy ( on VA? ?)
Monotherapy ? / if not: lowest poss. dose
There is 1.6-3.2 % risk of major congenital
malformation in the general population !
D/C medication prior to pregnancy?
Consider if: seizure free for min. 2 years
normal neuro exam + I/Q
single type of seizure + neg. EEG
and: if the patient is willing to take the risk !
Determine a good baseline level with the lowest
- Obtain serum level 2 times wks. apart ( before
the am. dose ) – this will be the range of effective
Review hx. of congenital malformations during
Discuss the increased risk
Consider genetic consultation
Change the drug used in previous pregnancy
AND: Start Folic acid 5 mg po./ day !
The overall risk of major congenital
malformation in the general population is
In general with the AED use it is 2-3x higher.
1. Valproate: first trimester exposure : 3 x
higher risk for malformation compare to the
other AEDs; absolute risk: 6-9%.
Dose related risk: > 700 mg/d – 4%. ( = LTG
<300 mg/d or CBZ 400 mg/d.)
VPA dose 1500mg – 20%.
Not only the VPA but thee Phenobarbital has
also highly increased risk – mainly cardiac
The VPA and PB has no overlap with the other
AEDs.- the CBZ, LTG, PHT, LVT – cluster
closely around 2-2.5%.
The risk ratio for malformation compared to
VPA: 5x, PB: 3x, TPM.: 2x.
1st. Trimester exposure – facial clefts.
NAAEDP Registry: 1.4 % ( 10 fold increase
compare to the local control )
UK AED Pregnancy Register: 2.2% -facial clefts
EUROCAT ( European Surveillance of
Congenital Anomalies Antiepileptic Study (
-Spina bifida ( OR: 2.6% _ - but: it is 80 % less
than in case of VPA.
UK Pregnancy Registry:
671 first trimester exposure/ 304 monotherapy
Only 2 major congenital malformation case:
1. inguinal hernia ( dose: 4000mg/d )
2. reflux - requiring op. – ( dose; 2000mg/d )
NAAEDP Registry: risk: 2.4 % - with 450
Lamotrigine and Carbamazepine – modest
major congenital malformation risk change in
any polytherapy combination which does not
Major CM rate increase in case of Lamotrigine
and any other AED: 2.9 % but with VPA: 9.1 %
In case of Carbamazepine and other AED this
increase is 2.5 % but with VA: 15.4 %
The risk is 35.7% if the first pregnancy ended
up with major cong. malformation.
It is 57% if it happens with VPA.
The maternal genetic influence predisposes to
teratogenicity and compounds the AED risk.
EURAP Study ( International Registry of AEDs
and Pregnancy )
4 drugs studied: CBZ, LTG, Pb, VPA
The lowest major cong. malformation rate:
Lamotrigine less than 300 mg/d ( 1.7%)
Carbamazepine less than 400 mg/d ( 2.0%)
CBZ > 1000 mg/d- 7.7%
LTG > 300 mg/d – 3.6%
VPA and Pb – much higher with ALL doses.
Probably the safest AEDs:
Probably have lower risk than Valproate:
OXC, ZNS, GBP
Have significant risk greater than other AED:
Topiramate ( oral clefts)
Phenobarbital ( cardiac defects)
Valproate ( spina bifida, hypospadias )
Increased frequency: 20-33%
During labour: 3.5 % ( EURAP study )
sex hormone concentration changes
Note: Seizure during the month before
conception – 3.7x increase in the risk of seizure
in the peripartum period.
Risk of seizure to the fetus:
GTC – maternal and fetal hypoxia and acidosis
- Fetal heart rate deceleration
Non-convulsive seizures: - trauma and its
consequences ( ruptured fetal membranes, etc.)
Obstetric risk in case of AED use:
Mildly increased risk for :
pre-eclampsia ( OR: 1.8 )
Gestational HTN ( OR 1.5)
Vaginal bleeding late in pregnancy ( OR: 1.9)
Delivery before 34 wks of gestation (OR: 1.5)
The clearance of most AED increases during
pregnancy leading to decreased serum
1. hepatic enzymatic induction
2.increased volume distribution
3.increased renal blood flow
4. alterations in drug absorption
5. altered concentration of albumin and alfa-1
May decrease remarkably because of the primary
elimination happens via hepatic glucoronidation.
Needs close monitoring and correction
Check the level 2 times prior to pregnancy
Check the level every month during pregnancy
Check the level at delivery and weekly later until it
is 25% higher only than the pre-pregnancy level –
Needs fast dose decrease after delivery !
Level in case of other AEDs:
- before conception ( x 2 )
At the beginning of each trimester
In the last month
( Phenytoin + Valproate – needs free level ! )
High level U/S at 14-18 wks.
Alfa – fetoprotein at 14-16 wks ( on VPA/ or CBZ )
If abn.: amniocentesis ( AFP+ Ach-esterase – 97%
1. Vit-K.: in case of enzyme inducing AED.
- increased risk of haemorrhagic dz. of the newborn
b/o.deficiency of vit.-K dependent clotting factors.
- Suppl.: 20 mg. po./d from 36 wks of gestation +
1 mg. im to the baby at birth.
2. Folate: 5 mg from the time of the planning
- decreases the risk for cong. malformations incl.
neural tube defects
Decreases the risk of spontaneous abortion
Improves the chance for better IQ.
Ratios between the breast milk and the serum
Be careful with Pb., Primidone, benzo –
Safe breast feeding practice – sitting on the