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Pregnancy in women who have epilepsy
Pregnancy in women who have epilepsy
Pregnancy in women who have epilepsy
Pregnancy in women who have epilepsy
Pregnancy in women who have epilepsy
Pregnancy in women who have epilepsy
Pregnancy in women who have epilepsy
Pregnancy in women who have epilepsy
Pregnancy in women who have epilepsy
Pregnancy in women who have epilepsy
Pregnancy in women who have epilepsy
Pregnancy in women who have epilepsy
Pregnancy in women who have epilepsy
Pregnancy in women who have epilepsy
Pregnancy in women who have epilepsy
Pregnancy in women who have epilepsy
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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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