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O&G TopicsAntenatal care — neurological disorders

O&G · Antenatal care — neurological disorders

Epilepsy in pregnancy

Also known as Seizure disorder in pregnancy · Antiepileptic drugs in pregnancy · Antiseizure medication in pregnancy · Lamotrigine in pregnancy · Valproate teratogenicity · Fetal anticonvulsant syndrome

Exam-exhaustive FRANZCOG fellowship reference on epilepsy in pregnancy — preconception counselling, antiepileptic drug teratogenicity with the EURAP registry data (valproate worst at 10.3 percent, lamotrigine and levetiracetam lowest), lamotrigine clearance increase, folic acid 5 mg, vitamin K for neonates of women on enzyme-inducing AEDs, breastfeeding on AEDs, and the trade-off of seizure control vs AED risk. AAN/AES/SMFM 2024 guideline, Harden 2009, EURAP registry anchored; globally tagged to MRCOG and ABOG.

high15 referencesUpdated 26 July 202612 min readVerification in progress

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Target exams

FRANZCOGMRCOGABOGFRCSCMRCPI

Red flags

  • Status epilepticus in pregnancy — airway, left lateral, IV lorazepam, loading anticonvulsant, exclude eclampsia, prepare for caesarean if viable
  • Valproate in women of childbearing potential — Pregnancy Prevention Programme; avoid in pregnancy unless no alternative
  • Lamotrigine breakthrough seizures in pregnancy — check serum level, increase dose as clearance rises markedly
  • Stopping AEDs abruptly in pregnancy to avoid teratogenicity — the harm of uncontrolled seizures exceeds the marginal benefit of stopping
  • Eclampsia mislabelled as epilepsy — check blood pressure and urinalysis in any seizure after 20 weeks
  • Enzyme-inducing AEDs and the combined oral contraceptive pill — failure of contraception
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Your progress

Saved on this device.

Practise this topic8 MCQs with explanations

Target exams

FRANZCOGMRCOGABOGFRCSCMRCPI

Red flags

  • Status epilepticus in pregnancy — airway, left lateral, IV lorazepam, loading anticonvulsant, exclude eclampsia, prepare for caesarean if viable
  • Valproate in women of childbearing potential — Pregnancy Prevention Programme; avoid in pregnancy unless no alternative
  • Lamotrigine breakthrough seizures in pregnancy — check serum level, increase dose as clearance rises markedly
  • Stopping AEDs abruptly in pregnancy to avoid teratogenicity — the harm of uncontrolled seizures exceeds the marginal benefit of stopping
  • Eclampsia mislabelled as epilepsy — check blood pressure and urinalysis in any seizure after 20 weeks
  • Enzyme-inducing AEDs and the combined oral contraceptive pill — failure of contraception
One-line fellowship answer

Epilepsy in pregnancy is a balancing act: preconception folic acid 5 mg daily, monotherapy at the lowest effective dose with lamotrigine or levetiracetam preferred and valproate avoided, lamotrigine dose increases as clearance rises markedly in pregnancy, vitamin K for the neonate of an enzyme-inducing-AED mother, breastfeeding encouraged — and never stop AEDs abruptly, because the harm of uncontrolled seizures exceeds the marginal benefit of stopping.[1][4][5]

It is Tuesday morning and a 26-year-old with focal epilepsy on lamotrigine walks in eight weeks pregnant. Her seizures have been well-controlled on 200 mg daily for three years. If you do nothing, her lamotrigine clearance will rise by the end of the second trimester and she may seize. If you switch her to levetiracetam, you expose the fetus to a second drug. The fellowship question on epilepsy in pregnancy is almost always about this trade-off — seizure control against AED teratogenicity, with valproate as the worst offender and lamotrigine clearance as the classic exam trap.[1][4]

Overview and definition

Epilepsy in pregnancy is pre-existing seizure disorder managed on antiepileptic drugs (AEDs) or, less commonly, unmedicated. Around 0.3 to 0.7 percent of pregnancies occur in women with epilepsy, and over 90 percent have an uncomplicated pregnancy on appropriate management.[4][9]

The framework is simple and exam-examined:[1][4]

  • Preconception: optimise the drug, start folic acid 5 mg, switch off valproate if possible.
  • Pregnancy: keep the drug, increase lamotrigine as clearance rises, monitor levels, screen the fetus.
  • Peripartum: continue AEDs, avoid pethidine, regional anaesthesia preferred, vitamin K for the neonate.
  • Postpartum: reduce lamotrigine rapidly, encourage breastfeeding, address sleep deprivation.[4]

The sentence that anchors every station: the harm of uncontrolled seizures exceeds the marginal benefit of stopping AEDs in pregnancy.[4][9]

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References15ShowHide
  1. [1]Tomson T, Battino D, Bonizzoni E, et al. Comparative risk of major congenital malformations with eight different antiepileptic drugs: a prospective cohort study of the EURAP registry Lancet Neurol, 2018.PMID 29680205
  2. [2]Tomson T, Battino D, Bonizzoni E, et al. Dose-dependent teratogenicity of valproate in mono- and polytherapy: an observational study Neurology, 2015.PMID 26085607
  3. [3]Tomson T, Battino D, Bonizzoni E, et al. Dose-dependent risk of malformations with antiepileptic drugs: an analysis of data from the EURAP epilepsy and pregnancy registry Lancet Neurol, 2011.PMID 21652013
  4. [4]Pack AM, Oskoui M, Williams Roberson S, Donley DK, French J, Gerard EE, Gloss D, Miller WR, Munger Clary HM, Osmundson SS, McFadden B, Parratt K, Pennell PB, Saade G, Smith DB, Sullivan K, Thomas SV, Tomson T, Dolan O'Brien M, Botchway-Doe K, Silsbee HM, Keezer MR Teratogenesis, Perinatal, and Neurodevelopmental Outcomes After In Utero Exposure to Antiseizure Medication: Practice Guideline From the AAN, AES, and SMFM Neurology, 2024.PMID 38748979
  5. [5]Harden CL, Pennell PB, Koppel BS, et al. Practice parameter update: management issues for women with epilepsy--focus on pregnancy (an evidence-based review): vitamin K, folic acid, blood levels, and breastfeeding: report of the Quality Standards Subcommittee and Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology and American Epilepsy Society Neurology, 2009.PMID 19398680
  6. [6]Battino D, Tomson T, Bonizzoni E, et al. Seizure control and treatment changes in pregnancy: observations from the EURAP epilepsy pregnancy registry Epilepsia, 2013.PMID 23848605
  7. [7]Tomson T, Battino D, Bonizzoni E, et al. Withdrawal of valproic acid treatment during pregnancy and seizure outcome: Observations from EURAP Epilepsia, 2016.PMID 27319360
  8. [8]Reisinger TL, Newman M, Loring DW, Pennell PB, Meador KJ Antiepileptic drug clearance and seizure frequency during pregnancy in women with epilepsy Epilepsy Behav, 2013.PMID 23911354
  9. [9]Razaz N, Tomson T, Wikström AK, Cnattingius S Association Between Pregnancy and Perinatal Outcomes Among Women With Epilepsy JAMA Neurol, 2017.PMID 28672292
  10. [10]Meador KJ, Baker GA, Browning N, et al. Breastfeeding in children of women taking antiepileptic drugs: cognitive outcomes at age 6 years JAMA Pediatr, 2014.PMID 24934501
  11. [11]Ban L, Fleming KM, Doyle P, Smeeth L, Hubbard RB, Fiaschi L, Tata LJ Congenital Anomalies in Children of Mothers Taking Antiepileptic Drugs with and without Periconceptional High Dose Folic Acid Use: A Population-Based Cohort Study PLoS One, 2015.PMID 26147467
  12. [12]Bromley R, Weston J, Adab N, Greenhalgh J, Sanniti A, McKay AJ, Tudur Smith C, Marson AG Treatment for epilepsy in pregnancy: neurodevelopmental outcomes in the child Cochrane Database Syst Rev, 2014.PMID 25354543
  13. [13]Mawer G, Briggs M, Baker GA, et al. Pregnancy with epilepsy: obstetric and neonatal outcome of a controlled study Seizure, 2010.PMID 20036166
  14. [14]Vajda FJ, O'Brien TJ, Graham JE, Lander CM, Eadie MJ Dose dependence of fetal malformations associated with valproate Neurology, 2013.PMID 23911758
  15. [15]Battino D, Tomson T, Bonizzoni E, et al. Risk of Major Congenital Malformations and Exposure to Antiseizure Medication Monotherapy JAMA Neurol, 2024.PMID 38497990

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