Epilepsy in pregnancy

Based On GTG

1. Epilepsy in Pregnancy Dr. Kavinda Hewawitharana

2. Introduction Prevalence 0.5%-1% & 0.5% expose to AEDs in pregnancy 33% of epileptic females in reproductive age Risk of death significantly increase in pregnancy (10 Fold) Use of anti-epileptics increase fetal anomalies & affect CNS development Discontinuation or reduction of doses increase seizures

3. Diagnosis

4. Value of classifying seizure type & epilepsy syndromes

5. SUDEP Sudden , unexpected , witnessed or unwitnessed , nontraumatic & nondrowning deaths in epileptic patients There may be evidence for seizures & but no documented status epilepticus Postmortem does not reveal anatomical or toxicological causes for death Uncontrolled GTCS is the strongest risk factor for this

6. Differential diagnosis If a woman present with fits in 2 nd half of pregnancy which can not be described with epilepsy , immediately assess & manage as Eclampsia until definitive diagnosis is made with full neurological assessment Cardiac, metabolic & Intracranial conditions should be considered together with Neuropsychiatric conditions

7. Pre-pregnancy counselling. 1. Educate on risk of congenital anomalies when women is on AED or not on AED Most will have normal healthy babies Risk is low if not exposed to AED in periconceptional period Risk depend on type , number & dose of AED If not exposed to AED, risk resembles to background risk of general population (3%) If exposed 2-3 times increase major malformations compare to general population

8. Least risk of anomalies were observed in Levitracetam (0.7%) Lamotrigine (2%) , CBZ (4%) monotherapy with low doses Risk is highest with Valproate (10%) and AED polytherapy (17%) Risk of anomaly recurrence is high as (16%) if previous child was affected No significant association observed between epilepsy type & GTCS in first trimester with regard to anomalies

9. 2.Long tern neurodevelopmental outcome Obvious with in utero exposure to valproate (Intelligence Quotient ) Non verbal , verbal abilities , memory , executive function are declined with high doses of valproate In utero valproate use increases Autism Limited evidence of safety with Lamotrigine , CBZ & Phenytoin use when compared with no AED use (2014 Cochrane) Very limited data available on Levetiracetam and those are reassuring

10. 3. Can we reduce cong.anomalies Folic acid 5mg daily from pre conceptional period up to T1 completion This reduces incidence of major malformations & AED related cognitive defects Select the most safe agents & avoid poly therapy as much as possible

11. 4.How pregnancy affects seizures? There is no test to predict the risk of seizure deterioration in pregnancy 2/3 rd will not have deterioration in pregnancy If last seizure is within a year from conception, need to have a close look Women who are seizure free for 9-12 months before conception, 75%-90% of them will be seizure free in pregnancy. This is the most important factor. 75% of generalized epilepsy pts remain seizure free in pregnancy in contrast to focal epilepsy pts. (60%)

12. 5.Other factors to be considered Educate on safety precautions Advise to continue medicines as physician recommend & avoid discontinuation Prenatal screening & implications Effects of seizures & AED on pregnancy , fetus , lactation & contraception Both written & oral communication are vital Counselling sessions

13. Antepartum management 1.Recommended models of ANC & benefits of joint Obs /Neuro clinics regular ANC visits + Epilepsy clinic visits Never recommend to stop or change AED abruptly without neuro op. Local clinic registration & midwife visits

14. 2.Optimum time & method of anomaly detection

15. 3.Monitoring to avoid worsening of seizures

16. 4.Advesre effects of AED on mother & how to reduce those?

17. 5. Risk of obstetric complications Increased spontaneous miscarriage , APH , Hypertensive dx , Labour Induction , LSCS , PTL , FGR , PPH in WWE compare to no epilepsy . No difference in GDM or Perinatal deaths found. (metanalysis conducted in 2015) Those who are on AEDs are even at high risk of Induction of Labour , FGR , PPH , Neonatal ICU requirement When on Polytherapy LSCS rate is higher than mono therapy group

18. 6. Monitoring of WWE in pregnancy Routine assessment for provoking factors like lack of sleep , stress , compliance to medication , seizure types/frequency AED side effects assessment Arrange caregivers or arrange accommodations in an environment where continuous observation is there. Joint clinic assessments to avoid /address provoking factors

19. 7.Antepartum fetal surveillance Serial growth scans to find FGR No role of routine CTGs Fetal HR changes such as bradycardia & reduce variability has been reported due to possible hypoxia with seizures CTG heart rate patterns are generally not differ from non epileptics.so no evidence for routine CTG as ApFS .

20. 8.Role of Vit K Enzyme inducing AED ( CBZ,Phenytoin,Barbiturates ) competitively inhibit precursors of clotting factors & affect fetal microsomal enzyme that destroy Vit K . Thus Increase risk of bleeding. All babies born to WWE taking enzyme inducing AEDs should have IM Vit K 1mg to overcome Hemorrhagic Dx of newborn There is insufficient data of routine oral vit K for this purpose There is insufficient data for maternal Vit k therapy to lower PPH

21. 9.Optimal TOD/MOD There is no such Most will have uncomplicated labour & delivery Diagnosis of epilepsy per se is not an indication for CS or IOL Provided no other obstetric risk factors , if seizure were well controlled –no need to early induce Recurrent , prolonged seizures with risk of status epilepticus, EL/CS may be considered.

22. 10.Do we need to double the Dexa dose? Even with enzyme inducing AEDs, it is not recommended. But they may enhance drug catabolism & reduce efficacy Currently no studies to address this . Better to attach same doses.

23. Intrapartum care 1.what are the risks & risk factors for seizures during labour? Risk of seizure during labour is low (3.5%) GTCS 1-2% during labour& 1-2% In immediate postpartum 24hrs may occur Fits in labour can cause maternal hypoxia due to apnea during seizure Uterine hypertonus associated with seizure can cause fetal hypoxia & acidosis Fits are provoked by pain,fatigue,stress,dehydration,lack of sleep,avoidance of AEDs

24. How to minimize? AED should continue during labour (even as IV agents if need) Hydrate well Pain relief with epidural Overcome avoidable delays related to decision of Early IOL /ELCS Long acting Benzodiazepine (Clobazam) can consider around peripartum period Clobazam may cause neonatal respiratory depression-Alert Neonatal team Prophylactic clobazam use if recent convulsions, fits provoked by above factors , previous history exists

25. 2.What to do if a seizure developed in LR? Any seizure lasing >5min is unusual & represent high risk of status epilepticus (1% of pregnancies in WWE) Immediately control/terminate seizure using Benzodiazepines before status occurs & treatment resistance develops Continuous CTG monitoring of fetus Left lateral tilt with airway + O 2 supply doses- IV Lorazepam 4mg stat + further dose after 20min IV Diazepam 5-10mg slow infusion PR Diazepam 10-20mg stat + further dose after 15 min Buccal Midazolam 10mg stat

26. Cont. If seizures not settling , IV Phenytoin 10-15mg/Kg loading dose (1000mg stat) infuse Meantime get the help of VP / Anesthetist & Neurologist If evidence of persistent uterine hypertonia exists, Tocolysis need & if FHS fails to recover in 5 min or seizures continues/recurrent expedite delivery by AVD or CS Keep inform neonatal team to attend as there is a risk of neonatal withdrawal syndromes with AEDs

27. 3.What are the suitable analgesia methods in labour? TENS , Entonox & Regional analgesia suitable & safe Epidural is better Diamorphine is better than Pethidine (since its norpethidine metabolite is epileptogenic) If GA requires avoid Pethidine & ketamine as they reduce seizure threshold and also Sevoflurane which is epileptogenic

28. 4.Will AEDs affect Induction Agents? Methods? No contraindication for any induction agents No evidence that AEDs affect induction agents Anyhow WWE are at high risk of inductions than normal pts.

29. 5.Ideal setting for delivery Consultant lead units with 1 to 1 care Maternal + neonatal resuscitation teams should be available Water birth offer if seizure free for long period + not on AEDs For high risk of seizure pts-CTG monitoring need So In SL-Tertiary care center

30. Postpartum period (PPP) 1.what is the risk of seizure deterioration in PPP & how to minimize? Overall chance is low but relatively higher than APP Risk is highest on PP 3 rd day and when last seizure occurred 1 month prior to delivery Continue AED Avoid provoking factors Supportive staff ( aid feeding with expressed milk during night )

31. 2.Is it necessary to modify AED doses? Yes if doses increased during APP , it should be R/V within 10days of delivery to avoid drug toxicity

32. 3. Impact to fetus by AED Rate of AED transfer via placenta & BF vary Many AED cross placenta freely Fetal accumulation is slightly high with Gabapentin, valproate & levetiracetam . Babies may shows toxicity & withdrawal symptoms Magnitude of AED transfer in Breast milk unknown But pts should encouraged to continue Breast feeding Valproate , CBZ , phenytoin are the least transferring agents via milk BF has not affected cognitive functions in studies

33. 4.Safety precautions in PPP Nursing baby on the floor Shallow baby baths Keep baby down if warning symptoms appear Bath baby with help of a someone Avoid sleep deprivation , alcohol Identification tags First aid & emergency contact details display Keep a companion as much as possible

34. contraception

35. Promote Cu-IUD / LNG-IUS / IM DMPA as reliable methods which are not affected by enzyme inducers Efficacy of COCP & Progesterone implants affected by enzyme inducers (COCP failure rate is 3 times higher) All methods of contraceptive can offer for non enzyme inducers When emergency contraception requires , Cu-IUD is the choice for enzyme inducers Lamotrigine & COCP cross react to reduce Lamotrigine level thus seizures may increase

36. Cont. If a women on enzyme inducing AEDs request COCP , contraceptive efficacy may improved by High dose estradiol pills , reduce pill free interval to 4 days & Tricycling by taking 3 back to back packs But there are no data for success rates They should be on backup methods- barrier methods on top of COCP

37. References Green-top No 68 TOG 2006- 10.1576/toag.8.1.020.27204 TOG 2017 -10.1111/tog.12413