a brief review of antiepileptic drugs and pregnancy outcome

1. Antiepileptic Drugs and Congenital
Anomalies
The risk of congenital anomalies is increased among the infants of women with seizure
disorders who are treated with antiepileptic drugs during pregnancy.
Most common anomalies include
Orofacial clefts.
Cardiac defects
Neural tube defects

2. Valproic Acid Risks
Neural Tube Defects
• Specifically spina
bifida.
• The estimated risk is
about 2% in
populations that have
a background rate of
about 1:1000.
Major Birth Defects
• Increased by 4
to 7 fold
Developmental Issues
Associated with
1. Reduced
cognitive
ability.
2. Autism
3. Attention deficit
hyperactivity
disorder

3. Valproic Acid ….
Facial Features
• Midface hypoplasia
• Epicanthal folds
• Short nose
• Broad nasal bridge
• Thin upper lip
• Thick lower lip
• Micrognathia
Limb Defects
Subtle limb defects, primarily
hyperconvex fingernails.

4. Carbamazepine Risks
Spina Bifida
1% of infants whose mothers receive
carbamazepine treatment during pregnancy.
Craniofacial Abnormalities
1. Upslanting palpebral fissures
2. A long philtrum
3. Nail hypoplasia
Growth Issues
Growth deficiency
Microcephaly

5. Lamotrigine Risks
Risk is smaller than that associated with maternal treatment with
valproic acid and some other antiepileptic agents
Greater than that expected in the general population.

6. Levetiracetam Risks
1 Newer Drug 2 Lowest Risk 3 Limited Data
Reliable comparisons of
malformation rates
among infants of women
who were treated with
levetiracetam during
pregnancy to the rates in
infants of untreated
women are not yet
available.

7. Recommendations for Antiepileptic
Drug Use in Pregnancy
1
Plan Pregnancy
At a time when their seizures are well
controlled on the lowest effective dose
of the fewest possible antiepileptic
drugs.
2 Avoid High-Risk Drugs
Avoid use of valproic acid and other
higher risk anticonvulsants.
3
Take Folic Acid
Begin taking a folic acid supplement
(4mg) before conceiving.

8. Discontinuing Antiepileptic Drugs
Before Pregnancy
The American Academy of Neurology recommends considering
discontinuation of antiepileptic drugs before pregnancy for women who
meet the following criteria:
1 Seizure Free
for 2 to 5 years.
2 Single Seizure Type
3 Normal Assessments
Normal neurological assessment and normal intelligence.
Normal electroencephalogram after treatment

9. Congenital Malformation Risks by Drug
Highest Risk
Valproate (9% risk)
Moderate Risk
Carbamazepine(3%)
phenytoin(3%)
phenobarbital(5%)
Lowest Risk(2%)
Lamotrigine(2.9),
oxcarbazepine(3),
levetiracetam(2.8)

10. Antiepileptic Drug Exposure and
Breastfeeding
For women with epilepsy who take antiepileptic drugs during pregnancy and wish to breastfeed after
delivery, it is important to consider the following:
Drug Transfer
Most antiepileptic drugs are transferred into breast milk, exposing the infant.
Infant Monitoring
Close monitoring of the infant for potential side effects or toxicity is recommended.
Benefits of Breastfeeding
The benefits of breastfeeding should be weighed against the potential risks of drug
exposure.

11. Genetic Testing for Antiepileptic Drug
Risks
Recent research has explored the potential role of genetic testing in identifying women who may be at
higher risk for having a child with congenital malformations when taking certain antiepileptic drugs during
pregnancy.
This includes testing for genetic variants that affect drug metabolism or folate metabolism.
Genetic Variant Associated Risk
ABCC2 Increased risk with valproic acid exposure
MTHFR Increased risk with carbamazepine exposure
SCN1A Increased risk with lamotrigine exposure

12. Risks of Untreated Epilepsy During
Pregnancy
Injury Cognitive
Impairment in
child
Due to lack of oxygen
during seizures
Pregnancy
Complications
Preterm birth or low
birth weight
Mortality

13. Antiepileptic Drug Registries
Several registries have been established to collect data on antiepileptic drug use during
pregnancy and associated outcomes, including:
1 North American AED
Pregnancy Registry
Collects data on major birth defects
and fetal outcomes associated with
in utero antiepileptic drug exposure.
2 EURAP
The European Registry of
Antiepileptic Drugs and Pregnancy,
which collects similar data from
countries across Europe.
3 UK Epilepsy and Pregnancy Register
Collects prospective data on antiepileptic drug exposure and pregnancy outcomes in
the United Kingdom.