Sonia Khan , MD , FRCP

Fertility& the issue of polycystic ovaries.

Oral contraceptive interaction.
Pregnancy & Teratogenicity.
Ubdate on international epilepsy & pregnancy
registries .
Breast feeding & Perpurium.

Oral contraceptive interactions

Topiramate &Oral Contraceptives

Pregnancy&Teratogenicity

Pregnancy&Teratogenicity

Pregnancy&Teratogenicity

Category D

Category C

Pregnancy&Teratogenicity

EPILEPSY IN WOMEN

Pregnancy & Teratogenicity

EPILEPSY IN WOMEN

Pregnancy & Teratogenicity

EPILEPSY IN WOMEN

Pregnancy & Teratogenicity

EPILEPSY IN WOMEN

Pregnancy & Teratogenicity

Holmes et al AES ,Boston 4-8 ,12,2009

Topiramate 4.2%
Phenytoin 2.9%
Levetiracetam 2.4%

9.3%
5.5%
3%

2%

EPILEPSY IN WOMEN

UK Register Update, AES 4-8, December 2009

5.4

LEV (163 pts) 2.3

TPX (81 pts) 1.9

EPILEPSY IN WOMEN

Levetiracetam in pregnancy: results from the UK

and Ireland epilepsy and pregnancy registers.
Report on first-trimester exposures to levetiracetam from 10/2000
to 8/ 2011, for 671 pregnancies. 304 had been exposed to
levetiracetam in monotherapy, and 367 had been exposed to
levetiracetam polytherapy.
2 MCM in the monotherapy group (0.70%) &19 in the polytherapy
group (5.56%) .
MCM rate in the polytherapy group varied by AED regimen, with
lower rates with levetiracetam with lamotrigine (1.77%)&with
valproate (6.90%)or carbamazepine (9.38%)
With respect to MCM, levetiracetam taken in monotherapy can be considered a
safer alternative to valproate for women with epilepsy of childbearing age.

EPILEPSY IN WOMEN

EPILEPSY IN WOMEN

EPILEPSY IN WOMEN

Results from 18 Years of the International

Lamotrigine Pregnancy Registry
Of 1,558 first trimester exposures to lamotrigine, 35 infants with
MCMs were observed. 2.2% & is similar to general population.
Infants with MCMs among 150 lamotrigine & valproic acid
combination therapy 10.7%
No consistent type of malformation that occurred.
No appreciable increase in malformation frequency after the use of
first trimester lamotrigine.
The proportion of infants with malformations who take
lamotrigine &valproic acid was high but is similar to what has been
reported with valproic acid alone. Ongoing research is still needed
Long term use of lamotrigine is relatively safe compared to other agents; valproic
acid should likely be avoided in women who are of childbearing years or who plan
to become pregnant.

EPILEPSY IN WOMEN

223

Pregnancy&Teratogenicity

Effects of Maternal Epilepsy and Antiepileptic Drug Use

during Pregnancy on Perinatal Health in Offspring:
Nationwide, Retrospective Cohort Study in Finland.

EPILEPSY IN WOMEN

Pregnancy & Teratogenicity

EPILEPSY IN WOMEN

Pregnancy & Teratogenicity

A total of 305 mothers & 311 children (six twin pairs) in the
primary analysis. 224 children completed 6 years of follow-up .
Multivariate analysis of all children showed that age-6 IQ was
lower after exposure to valproate than to carbamazepine ,lamotrigine
or phenytoin .
Children exposed to valproate did poorly on measures of verbal &
memory abilities compared with those exposed to the other AEDs &
on non-verbal & executive functions compared with lamotrigine (but
not carbamazepine or phenytoin).
High dose valproate was -vely associated with IQ ,verbal &nonverbal ability memories & executive function, but not other AEDs
Age-6 IQ correlated with IQs at younger ages & IQ improved with
age for infants exposed to any AED. .

Compared with a normative sample right-handedness was less

frequent in children in this study & in lamotrigine & valproate gps.
Verbal abilities were worse than non-verbal abilities in children in
this study overall & in the lamotrigine & valproate groups.
Mean IQs were higher in children exposed to periconceptional
folate
Fetal valproate exposure has dose-dependent associations with
reduced cognitive abilities across a range of domains at 6 years of
age. Reduced right-handedness & verbal (vs non-verbal) abilities
might be attributable to changes in cerebral lateralisation induced by
exposure to AEDs. The positive association of periconceptional folate
with IQ is consistent with other recent studies

Na Valproate in pregnancy tied to

autism risk

polytherapy was correlated with an enhanced risk for SGA delivery. Re-evaluating
PMID:
22955634
[PubMed - in process]

Generalized tonic-clonic seizures & AEDs

during pregnancy

129 singleton pregnancies with live births from 9/1999 to 10/ 2010 in 106
women with epilepsy on AED therapy, recorded within the framework of the
EURAP inAustria were studied.
Occurrence of 1 GTCS during pregnancy was associated with a shorter GA
with 5 times higher preterm risk & reduced birth weight more in boys.
In primipara, when compared to multipara, GTCS 1 significantly reduced the
GA & raised the incidence of low birth weight (LBW) in neonates.
AEDs polytherapy significantly increased the risk for small-for-gestational-age
regarding weight and/or length (SGA(W/L)
Re-evaluating the need for drug therapy (in particular polytherapy), maintaining
seizure control for a given period before pregnancy and counseling about the
importance of preventing GTCS might improve pregnancy outcome in women with
epilepsy.

Predictors of seizures
during pregnancy in
women with epilepsy

Pregnancy&Teratogenicity

Pregnancy&Teratogenicity

Pregnancy&Teratogenicity

Breast feeding & Perpurium

Breast feeding & Perpurium

AED

Milk c. /Plasma c . (%)

Milk to plasma ratio

Valproate

3%

0.01-0.1

Benzodiazipine

15%

0.3-0.4

Phenobarbitone

40%

0.4-0.6

Carbamazipine

45%

0.4-0.6

Oxcarbamazipine

50%

0.5

Primidone

80%

0.7-0.9

Phenytoin

20%

0.1-0.5

Ethosuximide

90%

0.8-1

Topiramate

10-20%

0.86

Breast feeding & Perpurium