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Semin Neurol 2022; 42(05): 679-692
DOI: 10.1055/s-0042-1759579
Review Article

Preventing Teratogenicity in Women with Epilepsy

Michael O. Kinney
1   Department of Neurology, Royal Victoria Hospital, Belfast Health and Social Care Trust, Belfast, United Kingdom
2   School of Medicine, Queen's University of Belfast, Belfast, United Kingdom
,
Phil E. M. Smith
3   Department of Neurology, University Hospital of Wales, Cardiff, United Kingdom
,
John J. Craig
1   Department of Neurology, Royal Victoria Hospital, Belfast Health and Social Care Trust, Belfast, United Kingdom
› Author Affiliations
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Abstract

Over the last 50 years there has been a significant increase in our understanding of the issues faced by women with epilepsy, in both planning and undertaking pregnancy. The risks of teratogenicity associated with antiseizure medications have emerged slowly. The major pregnancy registers have substantially contributed to our knowledge about teratogenic risk associated with the commonly used antiseizure medications. However, there are substantial gaps in our knowledge about the potential risks associated with many third-generation drugs. The remit of the pregnancy registers and the wider research focus has moved beyond anatomical major congenital malformations. Increasingly neurodevelopmental and behavioral abnormalities have been investigated after in utero exposure to antiseizure medications. Public health approaches can help reduce the risk of teratogenicity. However, neurologists still have a vital role in reducing the risk of teratogenicity at an individual level for women attending their clinic. They also have responsibility to ensure that women with epilepsy are aware of the rationale for the different available options.

Keywords

pregnancy - reproduction - seizures - valproate - malformation - neurodevelopment


Publication History

Article published online:
13 December 2022

© 2022. Thieme. All rights reserved.

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  • References

  • 1 Yerby M. Pregnancy and teratogenesis. In: Trimble MR. ed. Women and Epilepsy. Chichester: John Wiley & Sons Ltd.; 1991: 167-192
    Google Scholar
  • 2 Kinney MO, Craig JJ. Pregnancy and epilepsy; meeting the challenges over the last 25 years: the rise of the pregnancy registries. Seizure 2017; 44: 162-168
    CrossrefPubMedGoogle Scholar
  • 3 Kinney MO, Morrow J. Epilepsy in pregnancy. BMJ 2016; 353: i2880
    CrossrefPubMedGoogle Scholar
  • 4 Meador KJ, Pennell PB, Harden CL. et al; HOPE Work Group. Pregnancy registries in epilepsy: a consensus statement on health outcomes. Neurology 2008; 71 (14) 1109-1117
    CrossrefPubMedGoogle Scholar
  • 5 Pennell PB. Use of anti-epileptic drugs during pregnancy: evolving concepts. Neurotherapeutics 2016; 13 (04) 811-820
    CrossrefPubMedGoogle Scholar
  • 6 Holmes LB, Harvey EA, Coull BA. et al. The teratogenicity of anticonvulsant drugs. N Engl J Med 2001; 344 (15) 1132-1138
    CrossrefPubMedGoogle Scholar
  • 7 Tomson T, Battino D. Teratogenic effects of antiepileptic drugs. Lancet Neurol 2012; 11 (09) 803-813
    CrossrefPubMedGoogle Scholar
  • 8 EUROCAT Guide 1.3. Instructions for the Registration of Congenital Anomalies. EUROCAT Central Registry, University of Ulster; 2005
    Google Scholar
  • 9 Taruscio D, Arriola L, Baldi F. et al. European recommendations for primary prevention of congenital anomalies: a joined effort of EUROCAT and EUROPLAN projects to facilitate inclusion of this topic in the National Rare Disease Plans. Public Health Genomics 2014; 17 (02) 115-123
    CrossrefPubMedGoogle Scholar
  • 10 Meador KJ, Loring DW. Developmental effects of antiepileptic drugs and the need for improved regulations. Neurology 2016; 86 (03) 297-306
    CrossrefPubMedGoogle Scholar
  • 11 Food and Drug Administration. Tegretol and Tegretol-XR. Prescribing information. March 2018. Accessed May 19, 2020 at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/016608s115_018281_ s058_018927s055_020234_s047.pdf
    PubMed
  • 12 Food and Drug Administration. Lamictal. Prescribing information. July 2018. Accessed May 19, 2020 at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/020241s056,020764s049,022251s020lbl.pdf
    PubMed
  • 13 Food and Drug Administration. KEPPRA. Prescribing information. October 2017. Accessed May 19, 2020 at: https://www.accessdata.fda.gov/drugs atfda_docs/label/2017/021035s100,021505s040lbl.pdf
    PubMed
  • 14 Walker BE, Patterson A. Induction of cleft palate in mice by tranquilizers and barbiturates. Teratology 1974; 10 (02) 159-163
    CrossrefPubMedGoogle Scholar
  • 15 Food and Drug Administration. Dilantin. Prescribing information. October 2018. Accessed May 19, 2020 at: https://www.accessdata.fda.gov/drugsatfda_ docs/label/2018/084349s085lbl.pdf
    PubMed
  • 16 Food and Drug Administration. Topamax. Prescribing information. May 2019. Accessed May 19, 2020 at: https://www.accessdata.fda.gov/drugsatfda_docs/ label/2019/020505s060,020844s051lbl.pdf
    PubMed
  • 17 Food and Drug Administration. Depakene. Prescribing information. February 2019. Accessed May 19, 2020 at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/018081s069,018082s052lbl.pdf
    PubMed
  • 18 Human birth defects. In: Moore KL, Persaud TVN, Torchia M. eds. Before We Are Born. Essentials of Embryology and Birth defects. 9th ed.. Philadelphia: Saunders an Imprint of Elsevier Inc.; 2016: 303-319
    Google Scholar
  • 19 Yerby MS. Teratogenicity and antiepileptic drugs: potential mechanisms. Int Rev Neurobiol 2008; 83: 181-204
    CrossrefPubMedGoogle Scholar
  • 20 Epilepsy: a public Health Imperative. Accessed November 14, 2022 at: https://www.who.int/publications/i/item/epilepsy-a-public-health-imperative
    PubMedGoogle Scholar
  • 21 Angus-Leppan H, Liu RSN. Weighing the risks of valproate in women who could become pregnant. BMJ 2018; 361: k1596 DOI: 10.1136/bmj.k1596.
    CrossrefPubMedGoogle Scholar
  • 22 FDA. Drug safety communication: valproate anti-seizure products contraindicated for migraine prevention in pregnant women due to decreased IQ scores in exposed children. 2013. Accessed November 14, 2022 at: http://www.fda.gov/Drugs/DrugSafety/ucm350684.htm
    PubMedGoogle Scholar
  • 23 Lenz W, Knapp K. Thalidomide embryopathy. Arch Environ Health 1962; 5: 100-105
    CrossrefPubMedGoogle Scholar
  • 24 Muller-Kuppers M. Embryopathy during pregnancy caused by taking anti-convulsants. Acta Paedopsychiatr 1963; 30: 401-405
    PubMedGoogle Scholar
  • 25 Janz D, Fuchs U. Are antiepileptic drugs harmful when given during pregnancy?. Ger Med Mon 1964; 9: 20-22
    PubMedGoogle Scholar
  • 26 Meadow SR. Anticonvulsant drugs and congenital abnormalities. Lancet 1968; 2 (7581): 1296
    CrossrefPubMedGoogle Scholar
  • 27 Eadie MJ, Tyrer JH. Hydantoin anticonvulsants. In: Anticonvulsant Therapy. Pharmacological Basis and Practice. Edinburgh & London: Churchill Livingstone; 1974: 35-78
    Google Scholar
  • 28 Donaldson JO. Epilepsy. In: Neurology of Pregnancy. Philadelphia: W.B. Saunders Company; 1978: 190-210
    Google Scholar
  • 29 Janz D. The teratogenic risk of antiepileptic drugs. Epilepsia 1975; 16 (01) 159-169
    CrossrefPubMedGoogle Scholar
  • 30 Yerby M, Devinsky O. Epilepsy and pregnancy. In: Devinsky O, Feldmann E, Hainline B. eds. Neurological Complications of Pregnancy. Advances in Neurology. New York: Raven Press, LTD.; 1994: 45-63
    Google Scholar
  • 31 Centers for Disease Control (CDC). Valproic acid and spina bifida: a preliminary report–France. MMWR Morb Mortal Wkly Rep 1982; 31 (42) 565-566
    PubMedGoogle Scholar
  • 32 Food and Drug Administration. Trileptal®. Prescribing information. January 2019. Accessed May 19, 2020 at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/021014s043lbl.pdf
    PubMed
  • 33 Campbell E, Kennedy F, Russell A. et al. Malformation risks of antiepileptic drug monotherapies in pregnancy: updated results from the UK and Ireland Epilepsy and Pregnancy Registers. J Neurol Neurosurg Psychiatry 2014; 85 (09) 1029-1034
    CrossrefPubMedGoogle Scholar
  • 34 Mawhinney E, Craig J, Morrow J. et al. Levetiracetam in pregnancy: results from the UK and Ireland epilepsy and pregnancy registers. Neurology 2013; 80 (04) 400-405
    CrossrefPubMedGoogle Scholar
  • 35 Hunt S, Russell A, Smithson WH. et al; UK Epilepsy and Pregnancy Register. Topiramate in pregnancy: preliminary experience from the UK Epilepsy and Pregnancy Register. Neurology 2008; 71 (04) 272-276
    CrossrefPubMedGoogle Scholar
  • 36 McCluskey G, Kinney MO, Russell A. et al. Zonisamide safety in pregnancy: data from the UK and Ireland epilepsy and pregnancy register. Seizure 2021; 91: 311-315
    CrossrefPubMedGoogle Scholar
  • 37 Hernández-Díaz S, Smith CR, Shen A. et al; North American AED Pregnancy Registry, North American AED Pregnancy Registry. Comparative safety of antiepileptic drugs during pregnancy. Neurology 2012; 78 (21) 1692-1699
    CrossrefPubMedGoogle Scholar
  • 38 Tomson T, Battino D, Bonizzoni E. et al; EURAP Study Group. Comparative risk of major congenital malformations with eight different antiepileptic drugs: a prospective cohort study of the EURAP registry. Lancet Neurol 2018; 17 (06) 530-538
    CrossrefPubMedGoogle Scholar
  • 39 Vajda FJE, Graham JE, Hitchcock AA, Lander CM, O'Brien TJ, Eadie MJ. Antiepileptic drugs and foetal malformation: analysis of 20 years of data in a pregnancy register. Seizure 2019; 65: 6-11
    CrossrefPubMedGoogle Scholar
  • 40 Thomas SV, Jeemon P, Pillai R. et al. Malformation risk of new anti-epileptic drugs in women with epilepsy; observational data from the Kerala registry of epilepsy and pregnancy (KREP). Seizure 2021; 93: 127-132
    CrossrefPubMedGoogle Scholar
  • 41 Tomson T, Battino D, Craig J. et al; ILAE Commission on Therapeutic Strategies. Pregnancy registries: differences, similarities, and possible harmonization. Epilepsia 2010; 51 (05) 909-915
    CrossrefPubMedGoogle Scholar
  • 42 Harden CL, Meador KJ, Pennell PB. et al; American Academy of Neurology, American Epilepsy Society. Practice parameter update: management issues for women with epilepsy–focus on pregnancy (an evidence-based review): teratogenesis and perinatal outcomes: report of the Quality Standards Subcommittee and Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology and American Epilepsy Society. Neurology 2009; 73 (02) 133-141
    CrossrefPubMedGoogle Scholar
  • 43 Weston J, Bromley R, Jackson CF. et al. Monotherapy treatment of epilepsy in pregnancy: congenital malformation outcomes in the child. Cochrane Database Syst Rev 2016; 11 (11) CD010224
    CrossrefPubMedGoogle Scholar
  • 44 Tomson T, Battino D, Bromley R. et al. Management of epilepsy in pregnancy: a report from the International League Against Epilepsy Task Force on Women and Pregnancy. Epileptic Disord 2019; 21 (06) 497-517
    CrossrefPubMedGoogle Scholar
  • 45 Campbell E, Devenney E, Morrow J. et al. Recurrence risk of congenital malformations in infants exposed to antiepileptic drugs in utero. Epilepsia 2013; 54 (01) 165-171
    CrossrefPubMedGoogle Scholar
  • 46 Holmes LB, Baldwin EJ, Smith CR. et al. Increased frequency of isolated cleft palate in infants exposed to lamotrigine during pregnancy. Neurology 2008; 70 (22, Pt 2): 2152-2158
    CrossrefPubMedGoogle Scholar
  • 47 Dolk H, Jentink J, Loane M, Morris J, de Jong-van den Berg LT. EUROCAT Antiepileptic Drug Working Group. Does lamotrigine use in pregnancy increase orofacial cleft risk relative to other malformations?. Neurology 2008; 71 (10) 714-722
    CrossrefPubMedGoogle Scholar
  • 48 Kinney MO, Morrow J, Patterson CC. et al. Changing antiepilepsy drug-prescribing trends in women with epilepsy in the UK and Ireland and the impact on major congenital malformations. J Neurol Neurosurg Psychiatry 2018; 89 (12) 1320-1323
    CrossrefPubMedGoogle Scholar
  • 49 Scheuerle AE, Holmes LB, Albano JD. et al. Levetiracetam Pregnancy Registry: final results and a review of the impact of registry methodology and definitions on the prevalence of major congenital malformations. Birth Defects Res 2019; 111 (13) 872-887
    CrossrefPubMedGoogle Scholar
  • 50 Tomson T, Battino D, Bonizzoni E. et al. EURAP Study Group. Dosedependent risk of malformations with antiepileptic drugs: an analysis of data fromthe EURAP epilepsy and pregnancy registry. Lancet Neurol 2011; 10 (07) 609-617
    CrossrefPubMedGoogle Scholar
  • 51 Källén AJ. Maternal carbamazepine and infant spina bifida. Reprod Toxicol 1994; 8 (03) 203-205
    CrossrefPubMedGoogle Scholar
  • 52 Jentink J, Dolk H, Loane MA. et al; EUROCAT Antiepileptic Study Working Group. Intrauterine exposure to carbamazepine and specific congenital malformations: systematic review and case-control study. BMJ 2010; 341: c6581
    CrossrefPubMedGoogle Scholar
  • 53 Tomson T, Battino D, Perucca E. Valproic acid after five decades of use in epilepsy: time to reconsider the indications of a time-honoured drug. Lancet Neurol 2016; 15 (02) 210-218
    CrossrefPubMedGoogle Scholar
  • 54 Dalens B, Raynaud EJ, Gaulme J. Teratogenicity of valproic acid. J Pediatr 1980; 97 (02) 332-333
    CrossrefPubMedGoogle Scholar
  • 55 Robert E, Guibaud P. Maternal valproic acid and congenital neural tube defects. Lancet 1982; 2 (8304): 937
    CrossrefPubMedGoogle Scholar
  • 56 Lindhout D, Meinardi H. Spina bifida and in-utero exposure to valproate. Lancet 1984; 2 (8399): 396
    CrossrefPubMedGoogle Scholar
  • 57 Lindhout D, Schmidt D. In-utero exposure to valproate and neural tube defects. Lancet 1986; 1 (8494): 1392-1393
    CrossrefPubMedGoogle Scholar
  • 58 DiLiberti JH, Farndon PA, Dennis NR, Curry CJ. The fetal valproate syndrome. Am J Med Genet 1984; 19 (03) 473-481
    CrossrefPubMedGoogle Scholar
  • 59 Hanson JW, Smith DW. Fetal hydantoin syndrome. Lancet 1976; 1 (7961): 692
    CrossrefPubMedGoogle Scholar
  • 60 Jones KL, Lacro RV, Johnson KA, Adams J. Pattern of malformations in the children of women treated with carbamazepine during pregnancy. N Engl J Med 1989; 320 (25) 1661-1666
    CrossrefPubMedGoogle Scholar
  • 61 Mawhinney E, Campbell J, Craig J. et al. Valproate and the risk for congenital malformations: Is formulation and dosage regime important?. Seizure 2012; 21 (03) 215-218
    CrossrefPubMedGoogle Scholar
  • 62 Margulis AV, Mitchell AA, Gilboa SM. et al; National Birth Defects Prevention Study. Use of topiramate in pregnancy and risk of oral clefts. Am J Obstet Gynecol 2012; 207 (05) 405.e1-405.e7
    CrossrefPubMedGoogle Scholar
  • 63 Vajda FJ, O'Brien TJ, Lander CM, Graham J, Eadie MJ. Antiepileptic drug combinations not involving valproate and the risk of fetal malformations. Epilepsia 2016; 57 (07) 1048-1052
    CrossrefPubMedGoogle Scholar
  • 64 Hernández-Díaz S, Mittendorf R, Smith CR, Hauser WA, Yerby M, Holmes LB. North American Antiepileptic Drug Pregnancy Registry. Association between topiramate and zonisamide use during pregnancy and low birth weight. Obstet Gynecol 2014; 123 (01) 21-28
    CrossrefPubMedGoogle Scholar
  • 65 Kondo T, Kaneko S, Amano Y, Egawa I. Preliminary report on teratogenic effects of zonisamide in the offspring of treated women with epilepsy. Epilepsia 1996; 37 (12) 1242-1244
    CrossrefPubMedGoogle Scholar
  • 66 Thomas SV, Jose M, Divakaran S, Sankara Sarma P. Malformation risk of antiepileptic drug exposure during pregnancy in women with epilepsy: results from a pregnancy registry in South India. Epilepsia 2017; 58 (02) 274-281
    CrossrefPubMedGoogle Scholar
  • 67 Keni RR, Jose M, Sarma PS, Thomas SV. Kerala Registry of Epilepsy and Pregnancy Study Group. Teratogenicity of antiepileptic dual therapy: Dose-dependent, drug-specific, or both?. Neurology 2018; 90 (09) e790-e796
    CrossrefPubMedGoogle Scholar
  • 68 Blotière PO, Raguideau F, Weill A. et al. Risks of 23 specific malformations associated with prenatal exposure to 10 antiepileptic drugs. Neurology 2019; 93 (02) e167-e180
    CrossrefPubMedGoogle Scholar
  • 69 Vazquez B, Tomson T, Dobrinsky C, Schuck E, O'Brien TJ. Perampanel and pregnancy. Epilepsia 2021; 62 (03) 698-708
    CrossrefPubMedGoogle Scholar
  • 70 Ritchie HE, Oakes D, Farrell E, Ababneh D, Howe A. Fetal hypoxia and hyperglycemia in the formation of phenytoin-induced cleft lip and maxillary hypoplasia. Epilepsia Open 2019; 4 (03) 443-451
    CrossrefPubMedGoogle Scholar
  • 71 Vajda FJE, Hitchcock AA, Graham J, O'Brien TJ, Lander CM, Eadie MJ. The teratogenic risk of antiepileptic drug polytherapy. Epilepsia 2010; 51 (05) 805-810
    CrossrefPubMedGoogle Scholar
  • 72 Tomson T, Battino D, Bonizzoni E. et al; EURAP Study Group. Dose-dependent teratogenicity of valproate in mono- and polytherapy: an observational study. Neurology 2015; 85 (10) 866-872
    CrossrefPubMedGoogle Scholar
  • 73 Holmes LB, Mittendorf R, Shen A, Smith CR, Hernandez-Diaz S. Fetal effects of anticonvulsant polytherapies: different risks from different drug combinations. Arch Neurol 2011; 68 (10) 1275-1281
    CrossrefPubMedGoogle Scholar
  • 74 Marson A, Burnside G, Appleton R. et al; SANAD II collaborators. The SANAD II study of the effectiveness and cost-effectiveness of valproate versus levetiracetam for newly diagnosed generalised and unclassifiable epilepsy: an open-label, non-inferiority, multicentre, phase 4, randomised controlled trial. Lancet 2021; 397 (10282): 1375-1386
    CrossrefPubMedGoogle Scholar
  • 75 Vajda FJE, O'Brien TJ, Graham JE, Hitchcock AA, Lander CM, Eadie MJ. The contribution of non-drug factors to fetal malformation in anti-seizure-medication-treated pregnancy. Epilepsy Behav 2021; 118: 107941
    CrossrefPubMedGoogle Scholar
  • 76 Medicines and Healthcare products Regulatory Agency. Public Assessment Report of antiepileptic drugs: review of safety of use in pregnancy. Published 7 January 2021. Accessed February 1, 2022 at: https://www.gov.uk/government/publications/public-assessment-report-of-antiepileptic-drugs-review-of-safety-of-use-during-pregnancy
    PubMedGoogle Scholar
  • 77 Meador KJ, Baker GA, Browning N. et al; NEAD Study Group. Fetal antiepileptic drug exposure and cognitive outcomes at age 6 years (NEAD study): a prospective observational study. Lancet Neurol 2013; 12 (03) 244-252
    CrossrefPubMedGoogle Scholar
  • 78 Christensen J, Grønborg TK, Sørensen MJ. et al. Prenatal valproate exposure and risk of autism spectrum disorders and childhood autism. JAMA 2013; 309 (16) 1696-1703
    CrossrefPubMedGoogle Scholar
  • 79 Cohen MJ, Meador KJ, Browning N. et al. Fetal antiepileptic drug exposure: motor, adaptive, and emotional/behavioral functioning at age 3 years. Epilepsy Behav 2011; 22 (02) 240-246
    CrossrefPubMedGoogle Scholar
  • 80 Bromley RL, Calderbank R, Cheyne CP. et al; UK Epilepsy and Pregnancy Register. Cognition in school-age children exposed to levetiracetam, topiramate, or sodium valproate. Neurology 2016; 87 (18) 1943-1953
    CrossrefPubMedGoogle Scholar
  • 81 Vajda FJ, O'Brien TJ, Lander CM, Graham J, Roten A, Eadie MJ. Teratogenesis in repeated pregnancies in antiepileptic drug-treated women. Epilepsia 2013; 54 (01) 181-186
    CrossrefPubMedGoogle Scholar
  • 82 Perucca P, Anderson A, Jazayeri D. et al; EpiPGX and EPIGEN Consortia. Antiepileptic drug teratogenicity and de novo genetic variation load. Ann Neurol 2020; 87 (06) 897-906
    CrossrefPubMedGoogle Scholar
  • 83 Morrow JI, Hunt SJ, Russell AJ. et al. Folic acid use and major congenital malformations in offspring of women with epilepsy: a prospective study from the UK Epilepsy and Pregnancy Register. J Neurol Neurosurg Psychiatry 2009; 80 (05) 506-511
    CrossrefPubMedGoogle Scholar
  • 84 Meador KJ, Pennell PB, May RC. et al; NEAD Investigator Group. Effects of periconceptional folate on cognition in children of women with epilepsy: NEAD study. Neurology 2020; 94 (07) e729-e740
    CrossrefPubMedGoogle Scholar
  • 85 Bjørk M, Riedel B, Spigset O. et al. Association of folic acid supplementation during pregnancy with the risk of autistic traits in children exposed to antiepileptic drugs in utero. JAMA Neurol 2018; 75 (02) 160-168
    CrossrefPubMedGoogle Scholar
  • 86 National Institute for Health and Care Excellence. Epilepsies: diagnosis and management. Clinical guideline [CG137] 2012, updated 2020. Accessed January 3, 2022 at: https://www.nice.org.uk/guidance/cg137
    PubMedGoogle Scholar
  • 87 Scottish Intercollegiate Guidelines Network (SIGN). Diagnosis and management of epilepsy in adults. Edinburgh: SIGN; 2015. (SIGN publication no. 143). [May 2015]. Accessed December 15, 2021 at: https://www.sign.ac.uk/our-guidelines/epilepsies-in-children-and-young-people-investigative-procedures-and-management/
    PubMed
  • 88 Royal College of Obstetricians and Gynaecologists. Epilepsy in pregnancy. Green top guideline 68 2016. Accessed March 13, 2022 at: https://www.rcog.uk/en/guidelines-research-services/guidelines/gtg68/
    PubMed
  • 89 Herzog AG, MacEachern DB, Mandle HB. et al. Folic acid use by women with epilepsy: findings of the Epilepsy Birth Control Registry. Epilepsy Behav 2017; 72: 156-160
    CrossrefPubMedGoogle Scholar
  • 90 Campbell E, Hunt S, Kinney MO. et al. The effect of socioeconomic status on treatment and pregnancy outcomes in women with epilepsy in Scotland. Epilepsy Behav 2013; 28 (03) 354-357
    CrossrefPubMedGoogle Scholar
  • 91 Medicines and Healthcare Products Regulatory Agency. Valproate use by women and girls. 2021. Accessed December 12, 2021 at: https://www.gov.uk/guidance/valproate-use-by-women-and-girls
    PubMed
  • 92 Shakespeare J, Sisodiya S. Guidance Document on Valproate Use in Women and Girls of Childbearing Years. Accessed January 3, 2022 at: www.theabn.org/news/542727/Updated-Guidance-Document-on-Valproate.htm
    PubMed
  • 93 Tomson T, Battino D, Bonizzoni E. et al; EURAP Study Group. Withdrawal of valproic acid treatment during pregnancy and seizure outcome: observations from EURAP. Epilepsia 2016; 57 (08) e173-e177
    CrossrefPubMedGoogle Scholar
  • 94 Saving Lives MBRRACE. Improving Mothers' Care: Lessons learned to inform maternity care from the UK and Ireland Confidential Enquiries into Maternal Deaths and Morbidity 2018-18. Accessed November 13, 2022 at: https//www.npeu.ox.ac.uk/assets/downloads/mbrrce-uk/reports/maternal-report-2020/MBRRACEUK_Maternal_Report_Dec_2020_v10.pdf
    PubMed
  • 95 Tomson T, Battino D, Bonizzoni E. et al; EURAP Study Group. Declining malformation rates with changed antiepileptic drug prescribing: an observational study. Neurology 2019; 93 (09) e831-e840
    CrossrefPubMedGoogle Scholar
  • 96 Pennell PB, French JA, May RC. et al; MONEAD Study Group. Changes in seizure frequency and antiepileptic therapy during pregnancy. N Engl J Med 2020; 383 (26) 2547-2556
    CrossrefPubMedGoogle Scholar
  • 97 Seshachala BB, Jose M, Lathikakumari AM, Murali S, Kumar AS, Thomas SV. Valproate usage in pregnancy: an audit from the Kerala Registry of Epilepsy and Pregnancy. Epilepsia 2021; 62 (05) 1141-1147
    CrossrefPubMedGoogle Scholar