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Chapter 11 - Teratogenicity and Antiseizure Medications

Published online by Cambridge University Press:  19 December 2024

By
Anna Serafini
Edited by
Esther Bui  and
P. Emanuela Voinescu
Esther Bui
Affiliation:
Toronto Western Hospital
P. Emanuela Voinescu
Affiliation:
Brigham & Women's Hospital, Boston, MA
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Summary

Approximately one-half million women with epilepsy are of childbearing age in the United States, and three to five births per thousand will be to women with epilepsy. However, when considering indications for neuropathy, pain, and other neurological and psychiatric disorders, the total number of children exposed in utero to ASMs is considerably greater. The goal during pregnancy is to keep a balance between seizure control and the potential teratogenic risks of antiseizure medications (ASMs). It is always important to remind patients that over 96% of pregnancies in WWE have good outcomes. The teratogenic effects of ASMs vary based on the specific moment of exposure during pregnancy. ASMs exposures during the embryonic phase of pregnancy leads to congenital malformations. Based on the exact week and the specific drug used, different malformations affecting different organs are seen. Exposures that last throughout the entire pregnancy can affect cognitive and behavioral development. Pregnancy registries have been developed all over the world to better understand the effects of ASMs. Studies on cognitive and behavioral development are more laborious and fewer. Overall studies agree on the fact that Valproate acid (VPA) the most teratogenic ASM as it pertains to major congenital malformations and cognitive and behavioral issues as well. Those effects seem to be dose dependent. VPA should be avoided in women of childbearing age when possible. ASMs with better teratogenic profile are lamotrigine and levetiracetam. More data on newer ASMs are still needed to assess their safety in pregnancy. The use of folic acid is recommended in WWE. It reduces the risks of malformations and recent studies have confirmed its positive effect on cognitive and behavioral development.

Type
Chapter
Information
Women with Epilepsy
A Practical Management Handbook
 , pp. 191 - 214
Publisher: Cambridge University Press
Print publication year: 2025

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References

Finnell, RH. Teratology: General considerations and principles. J Allergy Clin Immunol. 1999;103(2 Pt 2):S337–42.CrossRefGoogle ScholarPubMed
Gilbert-Barness, E. Teratogenic causes of malformations. Ann Clin Lab Sci. 2010;40(2):99–114.Google ScholarPubMed
Veurink, M, Koster, M, de Jong–van den Berg, LTW. The history of DES, lessons to be learned. Pharm World Sci. 2005;27(3):139–43.CrossRefGoogle ScholarPubMed
Archives, N, Administration, R. Federal Register: 44 Fed. Reg. 37191 (June 26, 1979). Vol. 44. 1979. 37191–0.Google Scholar
Pernia, S, DeMaagd, G. The new pregnancy and lactation labeling rule. PT. 2016;41(11):713–15.Google ScholarPubMed
Carlson, B. Human embryology and developmental biology. 5th ed. Philadelphia: Elsevier; 2014.Google Scholar
Corsello, G, Giuffrè, M. Congenital malformations. J Matern Neonatal Med. 2012;25(Suppl. 1):25–9.Google ScholarPubMed
Leppig, KA, Werler, MM, Cann, CI, Cook, CA, Holmes, LB. Predictive value of minor anomalies. I. Association with major malformations. J Pediatr. 1987;110(4):531–7.CrossRefGoogle ScholarPubMed
Update on overall prevalence of major birth defects: Atlanta, Georgia, 1978–2005. MMWR Morb Mortal Wkly Rep. 2008;57(1):1–5.Google Scholar
Smulian, JC, Beres-Sochka, L, DePrince, K, et al. Birth defects surveillance. N J Med. 2002;99(12):25–31.Google ScholarPubMed
Viinikainen, K, Heinonen, S, Eriksson, K, Kälviäinen, R. Community-based, prospective, controlled study of obstetric and neonatal outcome of 179 pregnancies in women with epilepsy. Epilepsia. 2006;47(1):186–92.CrossRefGoogle ScholarPubMed
Meadow, SR. Anticonvulsant drugs and congenital abnormalities. Lancet. 1968;2(7581):1296.CrossRefGoogle ScholarPubMed
Meador, K, Reynolds, MW, Crean, S, Fahrbach, K, Probst, C. Pregnancy outcomes in women with epilepsy: A systematic review and meta-analysis of published pregnancy registries and cohorts. Epilepsy Research. 2008;81(1):1–13.CrossRefGoogle ScholarPubMed
Tomson, T, Battino, D, Perucca, E. Teratogenicity of antiepileptic drugs. Curr Opin Neurol. 2019;32(2):246–52.CrossRefGoogle ScholarPubMed
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. 2009. www.neurology.org.CrossRefGoogle Scholar
Hernández-Díaz, S, Smith, CR, Shen, A, et al. Comparative safety of antiepileptic drugs during pregnancy. Neurology. 2012;78(21):1692–9.CrossRefGoogle ScholarPubMed
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(9):1029–34.CrossRefGoogle ScholarPubMed
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;17(6):530–8.CrossRefGoogle ScholarPubMed
Vajda, FJE, Graham, JE, Hitchcock, AA, et al. Antiepileptic drugs and foetal malformation: Analysis of 20 years of data in a pregnancy register. Seizure. 2019;65(December 2018):6–11. https://doi.org/10.1016/j.seizure.2018.12.006.CrossRefGoogle Scholar
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(2):274–81.CrossRefGoogle ScholarPubMed
Cunnington, MC, Weil, JG, Messenheimer, JA, et al. Final results from 18 years of the International Lamotrigine Pregnancy Registry. Neurology. 2011;76(21):1817–23.CrossRefGoogle ScholarPubMed
Artama, M, Auvinen, A, Raudaskoski, T, Isojärvi, I, Isojärvi, J. Antiepileptic drug use of women with epilepsy and congenital malformations in offspring. Neurology. 2005;64(11):1874–8.CrossRefGoogle ScholarPubMed
Mølgaard-Nielsen, D, Hviid, A. Newer-generation antiepileptic drugs and the risk of major birth defects. Obstet Gynecol Surv. 2011;66(9):543–4.CrossRefGoogle Scholar
Wide, K, Winbladh, B, Källén, B. Major malformations in infants exposed to antiepileptic drugs in utero, with emphasis on carbamazepine and valproic acid: A nation-wide, population-based register study. Acta Paediatr Int J Paediatr. 2004;93(2):174–6.CrossRefGoogle ScholarPubMed
Veiby, G, Daltveit, AK, Engelsen, BA, Gilhus, NE. Fetal growth restriction and birth defects with newer and older antiepileptic drugs during pregnancy. J Neurol. 2014;261(3):579–88.CrossRefGoogle ScholarPubMed
Veroniki, AA, Rios, P, Cogo, E, et al. Comparative safety of antiepileptic drugs for neurological development in children exposed during pregnancy and breast feeding: A systematic review and network meta-analysis. BMJ Open. 2017;7(7):e017248. 1–11.CrossRefGoogle ScholarPubMed
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.Google ScholarPubMed
Viale, L, Allotey, J, Cheong-See, F, et al. Epilepsy in pregnancy and reproductive outcomes: A systematic review and meta-analysis. www.thelancet.com. http://dx.doi.org/10.1016.Google Scholar
Tomson, T, Marson, A, Boon, P, et al. Valproate in the treatment of epilepsy in girls and women of childbearing potential. Epilepsia. 2015;56(7):1006–19.Google ScholarPubMed
Tomson, T, Battino, D. Teratogenic effects of antiepileptic drugs. Lancet Neurol. 2012;11(9):803–13.CrossRefGoogle ScholarPubMed
Vajda, FJE, O’Brien, TJ, Graham, J, Lander, CM, Eadie, MJ. Prediction of the hazard of foetal malformation in pregnant women with epilepsy. Epilepsy Research. 2014;108:1013–17.CrossRefGoogle ScholarPubMed
Morris, JK, Garne, E, Loane, M, et al. Prevalence of valproate syndrome in Europe from 2005 to 2014: A registry based multi-centre study. Eur J Med Genet. 2018;61(9):479–82.CrossRefGoogle ScholarPubMed
Nulman, I, Scolnik, D, Chitayat, D, Farkas, LD, Koren, G. Findings in children exposed in utero to phenytoin and carbamazepine monotherapy: Independent effects of epilepsy and medications. Am J Med Genet. 1997;68(1):18–24.3.0.CO;2-U>CrossRefGoogle ScholarPubMed
Samrén, EB, Van Duijn, CM, Koch, S, et al. Maternal use of antiepileptic drugs and the risk of major congenital malformations: A joint European prospective study of human teratogenesis associated with maternal epilepsy. Epilepsia. 1997;38(9):981–90.CrossRefGoogle ScholarPubMed
Kaaja, E, Kaaja, R, Hiilesmaa, V. Major malformations in offspring of women with epilepsy. Neurology. 2003;60(4):575–9.CrossRefGoogle ScholarPubMed
Nicolai, J, Vles, JSH, Aldenkamp, AP. Neurodevelopmental delay in children exposed to antiepileptic drugs in utero: A critical review directed at structural study-bias. J Neurol Sci. 2008;271(1–2):1–14.CrossRefGoogle ScholarPubMed
Hanson, JW, Smith, DW. The fetal hydantoin syndrome. J Pediatr. 1975;87(2):285–90.CrossRefGoogle ScholarPubMed
Correa-Villaseñor, A, Cragan, J, Kucik, J, et al. The Metropolitan Atlanta Congenital Defects Program: 35 years of birth defects surveillance at the Centers for Disease Control and Prevention. Birth Defects Res Part A – Clin Mol Teratol. 2003;67(9):617–24.CrossRefGoogle ScholarPubMed
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):872–87.CrossRefGoogle Scholar
Hernandez-Diaz, S, Huybrechts, KF, Desai, RJ, et al. Topiramate use early in pregnancy and the risk of oral clefts A pregnancy cohort study. Neurology. 2018;90(4):E342–51.CrossRefGoogle ScholarPubMed
Hunt, S, Russell, MA, Smithson, WH, et al. Levetiracetam in pregnancy: Preliminary experience from the UK Epilepsy and Pregnancy Register. Neurology. 67(10):1876–9.CrossRefGoogle Scholar
McCluskey, G, Kinney, MO, Russell, A, et al. Zonisamide safety in pregnancy: Data from the UK and Ireland epilepsy and pregnancy register. Seizure. 2021;91:311–15.CrossRefGoogle ScholarPubMed
Hernández-Díaz, S, Mittendorf, R, Smith, CR, et al. Association between topiramate and zonisamide use during pregnancy and low birth weight. Obstet Gynecol. 2014;123(1):21–8.CrossRefGoogle ScholarPubMed
Meador, KJ, Pennell, PB, May, RC, et al. Fetal loss and malformations in the MONEAD study of pregnant women with epilepsy. Neurology. 2020;94(14):E1502–11.CrossRefGoogle ScholarPubMed
Vajda, FJE, Perucca, P, O’Brien, TJ, Lander, CM, Eadie, MJ. Teratogenic effects of zonisamide. Seizure. 2021;91(July):490.CrossRefGoogle ScholarPubMed
Patorno, E, Bateman, BT, Huybrechts, KF, et al. Pregabalin use early in pregnancy and the risk of major congenital malformations. Neurology. 2017;88(21):2020–5.CrossRefGoogle ScholarPubMed
López-Escobar, B, Fernández-Torres, R, Vargas-López, V, et al. Lacosamide intake during pregnancy increases the incidence of foetal malformations and symptoms associated with schizophrenia in the offspring of mice. Sci Rep. 2020;10(1):1–14.CrossRefGoogle ScholarPubMed
Golembesky, A, Cooney, M, Craig, J, et al. Outcomes following exposure to the antiepileptic drug lacosamide during pregnancy: Results from a global safety database (P5.231). Neurology. 2017;88(16 Supplement):P5.231.CrossRefGoogle Scholar
The North American Antiepileptic Drug Pregnancy Registry. Updated data available online. 2020.Google Scholar
Harden, CL, Meador, KJ, Pennell, PB, et al. Management issues for women with epilepsy-Focus on pregnancy (an evidence-based review): II. Teratogenesis and perinatal outcomes: Report of the Quality Standards Subcommittee and Therapeutics and Technology Subcommittee of the American Academy of Neurol. Epilepsia. 2009;50(5):1237–46.Google Scholar
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):1275–81.CrossRefGoogle ScholarPubMed
Morrow, J, Russell, A, Guthrie, E, et al. Malformation risks of antiepileptic drugs in pregnancy: A prospective study from the UK Epilepsy and Pregnancy Register. J Neurol Neurosurg Psychiatry. 2006;77(2):193–8.CrossRefGoogle ScholarPubMed
Vajda, FJE, O’Brien, TJ, Graham, JE, et al. Antiepileptic drug polytherapy in pregnant women with epilepsy. Acta Neurol Scand. 2018;138(2):115–21.CrossRefGoogle ScholarPubMed
Vajda, FJE, O’Brien, TJ, Lander, CM, et al. Teratogenesis in repeated pregnancies in antiepileptic drug-treated women. Epilepsia. 2013;54(1):181–6.CrossRefGoogle ScholarPubMed
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;10(7):609–17.CrossRefGoogle ScholarPubMed
Perucca, P, Anderson, A, Jazayeri, D, et al. Antiepileptic drug teratogenicity and de novo genetic variation load. Ann Neurol. 2020;87(6):897–906.CrossRefGoogle ScholarPubMed
Bromley, R, Weston, J, Adab, N, et al. Treatment for epilepsy in pregnancy: Neurodevelopmental outcomes in the child. Cochrane Database of Systematic Reviews. 2014;10:CD010236.Google Scholar
Meador, KJ, Baker, GA, Browning, N, et al. Cognitive function at 3 years of age after fetal exposure to antiepileptic drugs. N Engl J Med. 2009;360(16):1597–1605.CrossRefGoogle Scholar
Cohen, MJ, Meador, KJ, Browning, N, et al. Fetal antiepileptic drug exposure: Adaptive and emotional/behavioral functioning at age 6 years. Epilepsy Behav. 2013;29(2):308–15. http://dx.doi.org/10.1016/j.yebeh.2013.08.001.CrossRefGoogle Scholar
Nadebaum, C, Anderson, V, Vajda, F, Reutens, D, Wood, A. Neurobehavioral consequences of prenatal antiepileptic drug exposure. Dev Neuropsychol. 2012;37(1):1–29. www.ncbi.nlm.nih.gov/pubmed/22292829.CrossRefGoogle ScholarPubMed
Meador, KJ, Baker, GA, Browning, N, et al. Fetal antiepileptic drug exposure and cognitive outcomes at age 6 years (NEAD study): A prospective observational study. Lancet Neurol. 2013;12(3):244–52. http://dx.doi.org/10.1016/S1474-4422(12)70323-X.CrossRefGoogle ScholarPubMed
Baker, GA, Bromley, RL, Briggs, M, et al. IQ at 6 years after in utero exposure to antiepileptic drugs: A controlled cohort study. Neurology. 2015;84(4):382–90.CrossRefGoogle ScholarPubMed
Bromley, RL, Calderbank, R, Cheyne, CP, et al. Cognition in school-age children exposed to levetiracetam, topiramate, or sodium valproate. Neurology. 2016;87(18):1943–53.CrossRefGoogle ScholarPubMed
Daugaard, CA, Pedersen, L, Sun, Y, Dreier, JW, Christensen, J. Association of prenatal exposure to valproate and other antiepileptic drugs with intellectual disability and delayed childhood milestones. JAMA Netw Open. 2020;3(11):e2025570.CrossRefGoogle ScholarPubMed
Reinisch, JM, Sanders, SA, Mortensen, EL, Rubin, DB. In utero exposure to phenobarbital and intelligence deficits in adult men. JAMA. 1995;274(19):1518–25.CrossRefGoogle ScholarPubMed
Wide, K, Henning, E, Tomson, T, Winbladh, B. Psychomotor development in preschool children exposed to antiepileptic drugs in utero. Acta Paediatr. 2002;91(4):409–14.CrossRefGoogle ScholarPubMed
Bromley, RL, Mawer, G, Love, J, et al. Early cognitive development in children born to women with epilepsy: A prospective report. Epilepsia. 2010;51(10):2058–65.CrossRefGoogle ScholarPubMed
Shallcross, R, Bromley, RL, Cheyne, CP, et al. In utero exposure to levetiracetam vs. valproate: Development and language at 3 years of age. Neurology. 2014;82(3):213–21.CrossRefGoogle ScholarPubMed
Shallcross, R, Bromley, BRL, Irwin, B, et al. Child development following in utero exposure: Levetiracetam vs sodium valproate. 2011. www.epilepsyandpregnancy.co.uk.CrossRefGoogle Scholar
Bromley, RL, Baker, GA. Fetal antiepileptic drug exposure and cognitive outcomes. Seizure. 2017;44:225–31.CrossRefGoogle ScholarPubMed
Rihtman, T, Parush, S, Ornoy, A. Preliminary findings of the developmental effects of in utero exposure to topiramate. Reprod Toxicol. 2012;34(3):308–11.CrossRefGoogle ScholarPubMed
Vinten, J, Bromley, RL, Taylor, J, et al. The behavioral consequences of exposure to antiepileptic drugs in utero. Epilepsy Behav. 2009;14(1):197–201.CrossRefGoogle ScholarPubMed
Bromley, RL, Mawer, G, Clayton-Smith, J, Baker, GA. Autism spectrum disorders following in utero exposure to antiepileptic drugs. Neurology. 2008;71(23):1923–4.CrossRefGoogle ScholarPubMed
Christensen, J, Grønborg, TK, Merete, M, et al. Prenatal valproate exposure and risk of autism spectrum disorders and childhood autism. JAMA. 2013;309(16):1696–1703.CrossRefGoogle ScholarPubMed
Wieck, A, Jones, S. Dangers of valproate in pregnancy. BMJ (Clinical research ed.). 2018;361:k1609.CrossRefGoogle ScholarPubMed
Huber-Mollema, Y, Oort, FJ, Lindhout, D, Rodenburg, R. Behavioral problems in children of mothers with epilepsy prenatally exposed to valproate, carbamazepine, lamotrigine, or levetiracetam monotherapy. Epilepsia. 2019;60(6):1069–82.CrossRefGoogle ScholarPubMed
Bromley, RL, Mawer, GE, Briggs, M, et al. NIH Public Access. 2014;84(6):637–43.Google Scholar
Veiby, G, Daltveit, AK, Schjolberg, S, et al. Exposure to antiepileptic drugs in utero and child development. NIH. 2013;54(8):1462–72.Google ScholarPubMed
Ritter, AC, Wagner, AK, Fabio, A, et al. Incidence and risk factors of posttraumatic seizures following traumatic brain injury: A traumatic brain injury model systems study. Epilepsia. 2016;57(12):1968–77.CrossRefGoogle ScholarPubMed
Shannon, GD, Alberg, C, Nacul, L, Pashayan, N. Preconception health care and congenital disorders: Mathematical modelling of the impact of a preconception care programme on congenital disorders. BJOG. 2013;120(5):555–66.CrossRefGoogle ScholarPubMed
Czeizel, AE, Dudás, I, Métneki, J. Pregnancy outcomes in a randomised controlled trial of periconceptional multivitamin supplementation: Final report. Arch Gynecol Obstet. 1994;255(3):131–9.CrossRefGoogle Scholar
Mills, JL, Molloy, AM, Reynolds, EH. Do the benefits of folic acid fortification outweigh the risk of masking vitamin B(12) deficiency? BMJ. 2018;360:k724.CrossRefGoogle ScholarPubMed
Dansky, LV, Rosenblatt, DS, Andermann, E. Mechanisms of teratogenesis: Folic acid and antiepileptic therapy. Neurology. 1992;42(4 Suppl 5):32–42.Google ScholarPubMed
Spiegelstein, O, Merriweather, MY, Wicker, NJ, Finnell, RH. Valproate-induced neural tube defects in folate-binding protein-2 (Folbp2) knockout mice. Birth Defects Res A Clin Mol Teratol. 2003;67(12):974–8.CrossRefGoogle ScholarPubMed
Ogawa, Y, Kaneko, S, Otani, K, Fukushima, Y. Serum folic acid levels in epileptic mothers and their relationship to congenital malformations. Epilepsy Res. 1991;8(1):75–8.CrossRefGoogle ScholarPubMed
Reynolds, EH, Green, R. Valproate and folate: Congenital and developmental risks. Epilepsy Behav. 2020;108:107068. https://doi.org/10.1016/j.yebeh.2020.107068.CrossRefGoogle ScholarPubMed
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(5):506–11.CrossRefGoogle ScholarPubMed
Surén, P, Roth, C, Bresnahan, M, et al. Association between maternal use of folic acid supplements and risk of autism spectrum disorders in children. JAMA. 2013;309(6):570–7. https://doi.org/10.1001/jama.2012.155925.Google ScholarPubMed
Husebye, ESN, Gilhus, NE, Riedel, B, et al. Verbal abilities in children of mothers with epilepsy: Association to maternal folate status. Neurology. 2018;91(9):e811–21.CrossRefGoogle ScholarPubMed
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(2):160–8.CrossRefGoogle ScholarPubMed
Roth, C, Magnus, P, Schjølberg, S, et al. Folic acid supplements in pregnancy and severe language delay in children. JAMA. 2011;306(14):1566–73. https://doi.org/10.1001/jama.2011.1433.CrossRefGoogle ScholarPubMed
Schmidt, RJ, Iosif, A-M, Guerrero Angel, E, Ozonoff, S. Association of maternal prenatal vitamin use with risk for autism spectrum disorder recurrence in young siblings. JAMA Psychiatry. 2019;76(4):391–8. https://doi.org/10.1001/jamapsychiatry.2018.3901.CrossRefGoogle ScholarPubMed
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;93:127–32. https://doi.org/10.1016/j.seizure.2021.10.015.CrossRefGoogle ScholarPubMed
Duncan, S, Mercho, S, Lopes-Cendes, I, et al. Repeated neural tube defects and valproate monotherapy suggest a pharmacogenetic abnormality. Epilepsia. 2001;42:750–3.CrossRefGoogle ScholarPubMed

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