Antiepileptic-Drugs-and-Congenital-Anomalies copy.pptx

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 Reduced cognitive ability . Autism 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.