Epilepsy and pregnancy

Aims of Treatment

• Seizure control• Prevent Obstetric complication• Ensure adequate Neonatal outcome

Neonatal outcome

• Risk of seizure

(3 times > normal population)

• developmental outcome

• congenital anomalies 4-8%

(2-3 times > normal population)

The most common malformation

• Congenital heart disease

• orofacial cleft

• neural tube defect

• intestinal atresia

• urogenital defects

Neural tube defect

Fetal antiepileptic drug syndrome (minor anomalies)

• Facial dysmorphism

• Distal digital hypoplasia

• Developmental delay

• Mental deficiency

Factors affecting neonatal outcome

• AED

• genetics

• folic acid

• socioeconomic

• maternal health

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.

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.

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)

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 Valproate & Carbamazepine

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

Which AED is safe?

• None• All drugs studied with > 1000 patients cohort

suggested major malformations of ~6% or more.

AED Exposure during the last trimester may also be detrimental.

• Poor cognitive outcome maybe as much as 1.4% to 6%

• Commonest with phenobarbitone, phenytoin, valproic acid and carbamazepine

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.

Seizure in pregnancy

• 20% to 33% increase in the seizure incidence• Sleep deprivation and non-compliance – most

important reasons

Physiologic changes during pregnancy; effects on drug dispositionParameter Consequences

^total body water, extracellular fluid Altered drug distribution

^cardiac output ^hepatic blood flow leading to ^ elimination

^Renal blood flow and GFR ^renal clearance of unchanged drug

Altered cytochrome P 450 activity Altered systemic absorption and hepatic elimination

Decreased maternal alb Altered free fraction; increased availability of drug for hepatic extraction

In brief

• All AED have adverse effect• GTC more dangerous than AED• Monotherapy safer• Cognitive deficits occur in significant proportion• Folate supplementation important

Effect of Pregnancy on Epilepsy

• An observational study encompassing over 300 countries has indicated that the majority of women with epilepsy who normally have a good degree of seizure control maintained this control throughout the pregnancy (63.6%), while 5.9% actually experienced improved control and only 17.9% experienced an increase in seizure frequency

Tomson T, Battino D, Bonizzoni E et al. Collaborative EURAP Study Group 2004. EURAP: an international registry of antiepileptic drugs & pregnancy.  Epilepsia45(11), 1463-1464 (2004).

1. Optimise AED before conception

2. Monotherapy as far as possible

3. Discuss Teratogenic potential of AED & risk of major & minor birth defects

4. Pre- pregnancy & Pregnancy Folic acid (0.5 mg. daily) supplementation

5. Vit. K supplementation (10mg. Daily) or

Inj. Vit. K as soon as after onset of labor

Antiepileptic drugs (AED) in pregnancy

Assess Risk of No drug with seizure vs

AED with its possible risks----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------

Congenital abnormalities if mothers taking AED : * hare lip or cleft palate, * malformation of the limbs , heart, face, eyes and ears * neural tube defects .

The risk of neural tube defects is 0.2 - 0.5 %. in the general population 1 % risk with carbamazepine 1 - 2 % with sodium valproate

For Pts. On Carbamazepine & Valproate

* Alfa Feto Protein (AFP) level - at 14 - 16 Wks.

* USG - at 16 - 20 Wks.

* Amniocentesis for AFP & Acetylcholinesterase

levels

Antiepileptic drugs (AED) in pregnancy

Women With Epilepsy

Before Conception

• Educate the family regarding risks

• Review classification of epilepsy

• Determine most appropriate medicine for seizure control

• Determine need for continued medication

- may discontinue if seizure-free for 2 or more years

- do not discontinue medication if epilepsy syndrome

suggests continued need for treatment

• Reduce medicines to monotherapy, lowest dose possible

• Start folic acid 1 mg/day

• Eliminate other risk factors – smoking, drugs, alcohol

After conception

• Do not change antiepileptic medication • Refer for prenatal care • Prescribe vitamins, including folic acid • Check ‘free’ drug levels every trimester and change doses as

needed • Evaluate for neural tube defects at 12 to 16 weeks (ultrasound,

alpha-fetoprotein, amniocentesis)

• Consider vitamin K predelivery • Check antiepileptic drug levels prior to delivery and

increase doses if needed

After Delivery

• Check drug levels in mother

Take Home Message

Thanks