 Consultants
 Epilepsy Nurse
 First fit Clinic
 Rapid review clinic
 Regular Clinic and
Ward consults
 EEG Service l...
Zoltan Kaliszky MD.
Consultant Neurologist
Cumbria Partnership NHS Trust
 Preconception planning and counselling
 Teratogenic risk of specific antiepileptic drugs/
antiepileptic drug choices
 ...
 The epilepsy itself is not a contraindication to
pregnancy even if it requires AEDs.
 Planned pregnancy- (changes 6-12 ...
D/C medication prior to pregnancy?
 Consider if: seizure free for min. 2 years
 normal neuro exam + I/Q
 single type of...
 Review hx. of congenital malformations during
prev. pregnancies
 Discuss the increased risk
 Consider genetic consulta...
STRONG INDUCERS WEAK INDUCERS:
 Phenobarbital
 Phenytoin
 Carbamazepine
 Primidone
 Oxcarbazepine
 Clobazam
 Topira...
 The overall risk of major congenital
malformation in the general population is
 1.6-3.2 %.
 In general with the AED us...
 Atrial septal defect
 Cleft palate
 Hypospadias
 Polydactyly
 Craniosynostosis
 autism
 Not only the VPA but thee Phenobarbital has
also highly increased risk – mainly cardiac
malformations.
 The VPA and PB ...
 Topiramate:
 1st. Trimester exposure – facial clefts.
 NAAEDP Registry: 1.4 % ( 10 fold increase
compare to the local ...
 UK Pregnancy Registry:
 671 first trimester exposure/ 304 monotherapy
 Only 2 major congenital malformation case:
 1....
 Lamotrigine and Carbamazepine – modest
major congenital malformation risk change in
any polytherapy combination which do...
 The risk is 35.7% if the first pregnancy ended
up with major cong. malformation.
 It is 57% if it happens with VPA.
 T...
 EURAP Study ( International Registry of AEDs
and Pregnancy )
 4 drugs studied: CBZ, LTG, Pb, VPA
 The lowest major con...
Probably the safest AEDs:
LTG,CBZ,LVT, PTH
Probably have lower risk than Valproate:
OXC, ZNS, GBP
Have significant risk gr...
 Increased frequency: 20-33%
 During labour: 3.5 % ( EURAP study )
 Causes :
 sex hormone concentration changes
 AED ...
Risk of seizure to the fetus:
GTC – maternal and fetal hypoxia and acidosis
- Fetal heart rate deceleration
- Miscarriages...
 The clearance of most AED increases during
pregnancy leading to decreased serum
concentration.
 Causes:
 1. hepatic en...
 May decrease remarkably because of the primary
elimination happens via hepatic glucoronidation.
 Needs close monitoring...
 Level in case of other AEDs:
 - before conception ( x 2 )
 At the beginning of each trimester
 In the last month
 Po...
1. Vit-K.: in case of enzyme inducing AED.
- increased risk of haemorrhagic dz. of the newborn
b/o.deficiency of vit.-K de...
 Ratios between the breast milk and the serum
level:
 VPA.: 0.1
 PTH.: 0.19
 Pb.: 0.36
 CBZ.: 0.41
 Be careful with ...
Dr Zoltan Kaliszky - Epilepsy in Pregnancy
Dr Zoltan Kaliszky - Epilepsy in Pregnancy
Dr Zoltan Kaliszky - Epilepsy in Pregnancy
Dr Zoltan Kaliszky - Epilepsy in Pregnancy
Dr Zoltan Kaliszky - Epilepsy in Pregnancy
Dr Zoltan Kaliszky - Epilepsy in Pregnancy
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Dr Zoltan Kaliszky - Epilepsy in Pregnancy

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'Epilepsy in Pregnancy' - Dr Zoltan Kaliszky (Consultant Neurologist for Cumbria Partnership NHS Foundation Trust) from the Cumbria Neuroscience Conference

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Dr Zoltan Kaliszky - Epilepsy in Pregnancy

  1. 1.  Consultants  Epilepsy Nurse  First fit Clinic  Rapid review clinic  Regular Clinic and Ward consults  EEG Service led by Neurophysiologist Consultant  The future:  Another Epilepsy Nurse ( or 2? )  Video Telemetry Unit?  Another Consultant with interest in epilepsy
  2. 2. Zoltan Kaliszky MD. Consultant Neurologist Cumbria Partnership NHS Trust
  3. 3.  Preconception planning and counselling  Teratogenic risk of specific antiepileptic drugs/ antiepileptic drug choices  Management of epilepsy during pregnancy  Management after delivery
  4. 4.  The epilepsy itself is not a contraindication to pregnancy even if it requires AEDs.  Planned pregnancy- (changes 6-12 mo.)  Over 90 % -remarkable event free/ good outcome  Assess seizure activity- controlled? Not?  Any changes prior to pregnancy ( on VA? ?)  Monotherapy ? / if not: lowest poss. dose  There is 1.6-3.2 % risk of major congenital malformation in the general population !
  5. 5. D/C medication prior to pregnancy?  Consider if: seizure free for min. 2 years  normal neuro exam + I/Q  single type of seizure + neg. EEG  and: if the patient is willing to take the risk ! Determine a good baseline level with the lowest effective dose: - Obtain serum level 2 times wks. apart ( before the am. dose ) – this will be the range of effective level.
  6. 6.  Review hx. of congenital malformations during prev. pregnancies  Discuss the increased risk  Consider genetic consultation  Change the drug used in previous pregnancy  AND: Start Folic acid 5 mg po./ day !
  7. 7. STRONG INDUCERS WEAK INDUCERS:  Phenobarbital  Phenytoin  Carbamazepine  Primidone  Oxcarbazepine  Clobazam  Topiramate  Lamotrigine  Felbamate NON INDUCERS: Valproate, Levetiracetam, Ethosuximide, Gabapentin, Clonazepam,Zonisamide
  8. 8.  The overall risk of major congenital malformation in the general population is  1.6-3.2 %.  In general with the AED use it is 2-3x higher.  1. Valproate: first trimester exposure : 3 x higher risk for malformation compare to the other AEDs; absolute risk: 6-9%.  Dose related risk: > 700 mg/d – 4%. ( = LTG <300 mg/d or CBZ 400 mg/d.)  VPA dose 1500mg – 20%.
  9. 9.  Atrial septal defect  Cleft palate  Hypospadias  Polydactyly  Craniosynostosis  autism
  10. 10.  Not only the VPA but thee Phenobarbital has also highly increased risk – mainly cardiac malformations.  The VPA and PB has no overlap with the other AEDs.- the CBZ, LTG, PHT, LVT – cluster closely around 2-2.5%.  The risk ratio for malformation compared to Lamotrigine:  VPA: 5x, PB: 3x, TPM.: 2x.
  11. 11.  Topiramate:  1st. Trimester exposure – facial clefts.  NAAEDP Registry: 1.4 % ( 10 fold increase compare to the local control )  UK AED Pregnancy Register: 2.2% -facial clefts  Carbamazepine:  EUROCAT ( European Surveillance of Congenital Anomalies Antiepileptic Study (  -Spina bifida ( OR: 2.6% _ - but: it is 80 % less than in case of VPA.
  12. 12.  UK Pregnancy Registry:  671 first trimester exposure/ 304 monotherapy  Only 2 major congenital malformation case:  1. inguinal hernia ( dose: 4000mg/d )  2. reflux - requiring op. – ( dose; 2000mg/d )  NAAEDP Registry: risk: 2.4 % - with 450 exposures.
  13. 13.  Lamotrigine and Carbamazepine – modest major congenital malformation risk change in any polytherapy combination which does not contain VPA.  Major CM rate increase in case of Lamotrigine and any other AED: 2.9 % but with VPA: 9.1 %  Also:  In case of Carbamazepine and other AED this increase is 2.5 % but with VA: 15.4 %
  14. 14.  The risk is 35.7% if the first pregnancy ended up with major cong. malformation.  It is 57% if it happens with VPA.  The maternal genetic influence predisposes to teratogenicity and compounds the AED risk.
  15. 15.  EURAP Study ( International Registry of AEDs and Pregnancy )  4 drugs studied: CBZ, LTG, Pb, VPA  The lowest major cong. malformation rate:  Lamotrigine less than 300 mg/d ( 1.7%)  Carbamazepine less than 400 mg/d ( 2.0%)  CBZ > 1000 mg/d- 7.7%  LTG > 300 mg/d – 3.6%  VPA and Pb – much higher with ALL doses.
  16. 16. Probably the safest AEDs: LTG,CBZ,LVT, PTH Probably have lower risk than Valproate: OXC, ZNS, GBP Have significant risk greater than other AED: Topiramate ( oral clefts) Phenobarbital ( cardiac defects) Valproate ( spina bifida, hypospadias )
  17. 17.  Increased frequency: 20-33%  During labour: 3.5 % ( EURAP study )  Causes :  sex hormone concentration changes  AED metabolism  Sleep deprivation  New stresses  Non-compliance  Note: Seizure during the month before conception – 3.7x increase in the risk of seizure in the peripartum period.
  18. 18. Risk of seizure to the fetus: GTC – maternal and fetal hypoxia and acidosis - Fetal heart rate deceleration - Miscarriages - stillbirth Non-convulsive seizures: - trauma and its consequences ( ruptured fetal membranes, etc.) Obstetric risk in case of AED use: Mildly increased risk for : pre-eclampsia ( OR: 1.8 ) Gestational HTN ( OR 1.5) Vaginal bleeding late in pregnancy ( OR: 1.9) Delivery before 34 wks of gestation (OR: 1.5)
  19. 19.  The clearance of most AED increases during pregnancy leading to decreased serum concentration.  Causes:  1. hepatic enzymatic induction  2.increased volume distribution  3.increased renal blood flow  4. alterations in drug absorption  5. altered concentration of albumin and alfa-1 glycoproteins
  20. 20.  May decrease remarkably because of the primary elimination happens via hepatic glucoronidation.  Needs close monitoring and correction  Recommendation:  Check the level 2 times prior to pregnancy  Check the level every month during pregnancy  Check the level at delivery and weekly later until it is 25% higher only than the pre-pregnancy level – TOXICITY !!!  Needs fast dose decrease after delivery !
  21. 21.  Level in case of other AEDs:  - before conception ( x 2 )  At the beginning of each trimester  In the last month  Post delivery  ( Phenytoin + Valproate – needs free level ! )  High level U/S at 14-18 wks.  Alfa – fetoprotein at 14-16 wks ( on VPA/ or CBZ )  If abn.: amniocentesis ( AFP+ Ach-esterase – 97% sensitivity)
  22. 22. 1. Vit-K.: in case of enzyme inducing AED. - increased risk of haemorrhagic dz. of the newborn b/o.deficiency of vit.-K dependent clotting factors. - Suppl.: 20 mg. po./d from 36 wks of gestation + 1 mg. im to the baby at birth. 2. Folate: 5 mg from the time of the planning  - decreases the risk for cong. malformations incl. neural tube defects  Decreases the risk of spontaneous abortion  Improves the chance for better IQ.
  23. 23.  Ratios between the breast milk and the serum level:  VPA.: 0.1  PTH.: 0.19  Pb.: 0.36  CBZ.: 0.41  Be careful with Pb., Primidone, benzo – sedation  Safe breast feeding practice – sitting on the floor, etc.

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