Pregnancy in women who have epilepsy


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Pregnancy in women who have epilepsy

  1. 1. Pregnancy in women who have epilepsy Neurology clinics 2004
  2. 2. <ul><li>Majority of women having epilepsy have normal pregnancy with favorable outcome. </li></ul><ul><li>Compared to general population – inmaternal and fetal risk </li></ul>
  3. 3. Birth control in women on AED <ul><li>Many AEDs induce hepatic cytochrome P-450 system (which is also the primary metabolic pathway for the sex steroids hormones.) </li></ul><ul><li>Result in sub-optimal dose of oral contraception </li></ul><ul><li>Barrier contraception is the best choice. </li></ul>
  4. 4. Fetal anti-convulsant syndrome <ul><li>This term is used to include various combinations of intrauterine growth retardation, cognitive dysfunction, micro-cephaly and infant mortality which has been described with the use of virtually all AEDs used in pregnant mothers. </li></ul>
  5. 5. Minor anomalies <ul><li>Defn: Structural deviation from normal that do not constitute a threat to health. </li></ul><ul><li>6% to 20% of infants born to women who have epilepsy </li></ul><ul><li>Include digital and nail hypoplasia, midline craniofacial anomalies, Ocular hyper telorism, epicanthal folds, short upturned nose, altered lips and low hairline. </li></ul><ul><li>Most minor anomalies are outgrown by the age of 5 yrs. </li></ul>
  6. 6. Major malformations <ul><li>Defn: abnormality of an essential anatomic structure present at birth that interfere significantly with function or require major intervention. </li></ul><ul><li>4% -7% ( compared to 2% in gen population) </li></ul>
  7. 7. 1-3.8% (VPA) 0.5-1.0% (CBZ) 0.06% Neural tube defect 1.7% 0.7% Urogenital defect 1.4% 0.15% Cleft lip /palate 1.5-2.0% 0.5% Congenital heart Infants of women who have epilepsy General population
  8. 8. Neural tube defects <ul><li>Faulty neuralation or abnormal development of the neural tube </li></ul><ul><li>Usually lower defects but tend to be severe and associated with hydrocephaly and other midline defects. </li></ul><ul><li>Spina bifida aperta- commonly due to VPA & CBZ </li></ul>
  9. 9. AED poly-therapy and pregnancy <ul><li>Risk of major malformations significantly higher </li></ul><ul><li>Increased major malformation incidence to about 15% to 25% </li></ul><ul><li>Hence recommendation- monotherapy better than polytherapy </li></ul>
  10. 10. Which AED is safe? <ul><li>Non </li></ul><ul><li>All drugs studied with > 1000 cohort suggested major malformations of ~6% or more. </li></ul><ul><li>Lamotrigine was found to be relatively safer </li></ul><ul><li>Levetiracetam is yet to be studied. </li></ul>
  11. 11. 47-70 Cleft maxillary palate 36 Cleft lip Face 42 VSD Heart 28 days Neural tube defect CNS Postconceptional age malformations Tissue Timing and developmental pathology of certain malformations
  12. 12. Neuro-developmental outcome <ul><li>Exposure during the last trimester may be the most detrimental . </li></ul><ul><li>Poor cognitive outcome maybe as much as 1.4% to 6% </li></ul><ul><li>Commonest with phenobarbitone, phenytoin, valproic acid and carbamazepine </li></ul>
  13. 13. Cause of anticonvulsant embryopathy <ul><li>Anti-folate effect </li></ul><ul><li>Reactive intermediates – free radicals and oxidative metabolites </li></ul><ul><li>Polytherapy promotes epoxide production and inhibit epoxide metabolism via epoxide hydrolase. </li></ul>
  14. 14. Seizure in pregnancy <ul><li>20% to 33% increase in the seizure incidence </li></ul><ul><li>Sleep deprivation and non-compliance – most important reasons </li></ul>
  15. 15. Altered free fraction; increased availability of drug for hepatic extraction Decreased maternal alb Altered systemic absorption and hepatic elimination Altered cytochrome P 450 activity ^renal clearance of unchanged drug ^Renal blood flow and GFR ^hepatic blood flow leading to ^ elimination ^cardiac output Decreased elimination of lipid soluble drugs ^Fat stores Altered drug distribution ^total body water, extracellular fluid Consequences Parameter Physiologic changes during pregnancy; effects on drug disposition
  16. 16. In brief <ul><li>All AED have adverse effect </li></ul><ul><li>GTC more dangerous than AED </li></ul><ul><li>Monotherapy safer </li></ul><ul><li>Cognitive deficits occur in significant proportion </li></ul><ul><li>Folate supplementation important </li></ul>