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Pregnancy in women who have epilepsy

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  • 1. Pregnancy in women who have epilepsy Neurology clinics 2004
  • 2.
    • Majority of women having epilepsy have normal pregnancy with favorable outcome.
    • Compared to general population – inmaternal and fetal risk
  • 3. Birth control in women on AED
    • Many AEDs induce hepatic cytochrome P-450 system (which is also the primary metabolic pathway for the sex steroids hormones.)
    • Result in sub-optimal dose of oral contraception
    • Barrier contraception is the best choice.
  • 4. Fetal anti-convulsant syndrome
    • 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.
  • 5. Minor anomalies
    • Defn: Structural deviation from normal that do not constitute a threat to health.
    • 6% to 20% of infants born to women who have epilepsy
    • Include digital and nail hypoplasia, midline craniofacial anomalies, Ocular hyper telorism, epicanthal folds, short upturned nose, altered lips and low hairline.
    • Most minor anomalies are outgrown by the age of 5 yrs.
  • 6. Major malformations
    • Defn: abnormality of an essential anatomic structure present at birth that interfere significantly with function or require major intervention.
    • 4% -7% ( compared to 2% in gen population)
  • 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. Neural tube defects
    • Faulty neuralation or abnormal development of the neural tube
    • Usually lower defects but tend to be severe and associated with hydrocephaly and other midline defects.
    • Spina bifida aperta- commonly due to VPA & CBZ
  • 9. AED poly-therapy and pregnancy
    • Risk of major malformations significantly higher
    • Increased major malformation incidence to about 15% to 25%
    • Hence recommendation- monotherapy better than polytherapy
  • 10. Which AED is safe?
    • Non
    • All drugs studied with > 1000 cohort suggested major malformations of ~6% or more.
    • Lamotrigine was found to be relatively safer
    • Levetiracetam is yet to be studied.
  • 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. Neuro-developmental outcome
    • Exposure during the last trimester may be the most detrimental .
    • Poor cognitive outcome maybe as much as 1.4% to 6%
    • Commonest with phenobarbitone, phenytoin, valproic acid and carbamazepine
  • 13. Cause of anticonvulsant embryopathy
    • Anti-folate effect
    • Reactive intermediates – free radicals and oxidative metabolites
    • Polytherapy promotes epoxide production and inhibit epoxide metabolism via epoxide hydrolase.
  • 14. Seizure in pregnancy
    • 20% to 33% increase in the seizure incidence
    • Sleep deprivation and non-compliance – most important reasons
  • 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. In brief
    • All AED have adverse effect
    • GTC more dangerous than AED
    • Monotherapy safer
    • Cognitive deficits occur in significant proportion
    • Folate supplementation important

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