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Original article

Vol. 151 No. 0102 (2021)

Use of valproate in pregnancy and in women of childbearing age between 2014 and 2018 in Switzerland: a retrospective analysis of Swiss healthcare claims data

DOI
https://doi.org/10.4414/smw.2021.20386
Cite this as:
Swiss Med Wkly. 2021;151:w20386
Published
10.01.2021

Summary

AIMS OF THE STUDY

The prevalence of the use of valproate during pregnancy and by women of childbearing age in Switzerland is not known. We aimed to study the use of antiseizure drugs by these women in Switzerland, with a particular focus on valproate.

METHODS

We conducted a retrospective descriptive study using the healthcare claims database of the Swiss health insurance Helsana (2014–18). We established two separate study populations: (1) a cohort of pregnancies leading to a delivery, and (2) all women of childbearing age (15–45 years) who were insured with Helsana for at least one year during the study period. We identified the dispensation of valproate, lamotrigine, carbamazepine, levetiracetam, topiramate, pregabalin, gabapentin, phenobarbital, and phenytoin (1) between delivery and three months prior to the estimated date of the last menstrual period, and (2) by calendar year. We quantified exposure prevalence of each antiseizure drug as the number of women with ≥1 prescription fill per 10,000 (1) pregnancies, and (2) women by calendar year. Results were weighted for the demographic distribution of the Helsana population relative to the Swiss population.

RESULTS

We identified a weighted pregnancy population of 387,418 pregnancies, with a mean maternal age at delivery of 31.9 years (standard deviation 5.1). Lamotrigine was the most frequently dispensed antiseizure drug during pregnancy (20/10,000), followed by levetiracetam (11/10,000), and pregabalin (3.8/10,000). Valproate was dispensed to 1.9/10,000 women during pregnancy and to 1.3/10,000 women within 90 days prior to the last menstrual period but not during pregnancy. The weighted study population of women aged 15–45 years consisted of 2,781,151 women, of whom 74,080 (270/10,000) were exposed to ≥1 of the evaluated antiseizure drugs. Pregabalin was the most frequently dispensed antiseizure drug (64/10,000), followed by lamotrigine (46/10,000), topiramate (32/10,000), and valproate (25/10,000). The use of valproate decreased from 28/10,000 women in 2014 to 21/10,000 women in 2018.

CONCLUSIONS

The prevalence of exposure to valproate during pregnancy was comparable to Denmark and lower than in other European countries. Despite decreasing exposure prevalence, the use of valproate in women of childbearing age in Switzerland seems higher than the actual clinical need.

References

  1. Heilmittelinstitut SS. Product Information Depakine (R) [Internet]. 2020 [cited 2020 Jan 13]. Available from: https://www.dopps.org/dpm/DPMSlideBrowser.aspx?type=ComGrp&id=1
  2. Robert E, Guibaud P. Maternal valproic acid and congenital neural tube defects. Lancet. 1982;2(8304):937. doi:.https://doi.org/10.1016/S0140-6736(82)90908-4
  3. Holmes LB, Harvey EA, Coull BA, Huntington KB, Khoshbin S, Hayes AM, et al. The teratogenicity of anticonvulsant drugs. N Engl J Med. 2001;344(15):1132–8. doi:.https://doi.org/10.1056/NEJM200104123441504
  4. Jentink J, Loane MA, Dolk H, Barisic I, Garne E, Morris JK, et al.; EUROCAT Antiepileptic Study Working Group. Valproic acid monotherapy in pregnancy and major congenital malformations. N Engl J Med. 2010;362(23):2185–93. doi:.https://doi.org/10.1056/NEJMoa0907328
  5. Hernández-Díaz S, Smith CR, Shen A, Mittendorf R, Hauser WA, Yerby M, et al.; North American AED Pregnancy Registry; North American AED Pregnancy Registry. Comparative safety of antiepileptic drugs during pregnancy. Neurology. 2012;78(21):1692–9. doi:.https://doi.org/10.1212/WNL.0b013e3182574f39
  6. Diav-Citrin O, Shechtman S, Bar-Oz B, Cantrell D, Arnon J, Ornoy A. Pregnancy outcome after in utero exposure to valproate : evidence of dose relationship in teratogenic effect. CNS Drugs. 2008;22(4):325–34. doi:.https://doi.org/10.2165/00023210-200822040-00004
  7. Adab N, Kini U, Vinten J, Ayres J, Baker G, Clayton-Smith J, et al. The longer term outcome of children born to mothers with epilepsy. J Neurol Neurosurg Psychiatry. 2004;75(11):1575–83. doi:.https://doi.org/10.1136/jnnp.2003.029132
  8. Adab N, Jacoby A, Smith D, Chadwick D. Additional educational needs in children born to mothers with epilepsy. J Neurol Neurosurg Psychiatry. 2001;70(1):15–21. doi:.https://doi.org/10.1136/jnnp.70.1.15
  9. Gaily E, Kantola-Sorsa E, Hiilesmaa V, Isoaho M, Matila R, Kotila M, et al. Normal intelligence in children with prenatal exposure to carbamazepine. Neurology. 2004;62(1):28–32. doi:.https://doi.org/10.1212/WNL.62.1.28
  10. Meador K, Baker G, Browning N, Clayton-Smith J, Combs-Cantrell D, Cohen M, et al. Cognitive Function at 3 Years of Age after Fetal Exposure to Antiepileptic Drugs. N Engl J Med. 2008;359(16):1543–54.
  11. Bromley R, Weston J, Adab N, Greenhalgh J, Sanniti A, McKay AJ, et al. Treatment for epilepsy in pregnancy: neurodevelopmental outcomes in the child. Cochrane Database Syst Rev. 2014;2014(10):CD010236. doi:.https://doi.org/10.1002/14651858.CD010236.pub2
  12. Gerard E, Meador K. An Update on Maternal Use of Antiepileptic Medications in Pregnancy and Neurodevelopment Outcomes. J Pediatr Genet. 2015;04(02):094–110.
  13. Baker GA, Bromley RL, Briggs M, Cheyne CP, Cohen MJ, García-Fiñana M, et al.; Liverpool and Manchester Neurodevelopment Group. IQ at 6 years after in utero exposure to antiepileptic drugs: a controlled cohort study. Neurology. 2015;84(4):382–90. doi:.https://doi.org/10.1212/WNL.0000000000001182
  14. Christensen J, Pedersen L, Sun Y, Dreier JW, Brikell I, Dalsgaard S. Association of Prenatal Exposure to Valproate and Other Antiepileptic Drugs With Risk for Attention-Deficit/Hyperactivity Disorder in Offspring. JAMA Netw Open. 2019;2(1):e186606. doi:.https://doi.org/10.1001/jamanetworkopen.2018.6606
  15. Meador KJ, Baker GA, Browning N, Cohen MJ, Clayton-Smith J, Kalayjian LA, et al.; NEAD Study Group. Foetal antiepileptic drug exposure and verbal versus non-verbal abilities at three years of age. Brain. 2011;134(Pt 2):396–404. doi:.https://doi.org/10.1093/brain/awq352
  16. Christensen J, Grønborg TK, Sørensen MJ, Schendel D, Parner ET, Pedersen LH, et al. Prenatal valproate exposure and risk of autism spectrum disorders and childhood autism. JAMA. 2013;309(16):1696–703. doi:.https://doi.org/10.1001/jama.2013.2270
  17. Meador KJ, Baker GA, Browning N, Cohen MJ, Bromley RL, Clayton-Smith J, 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(3):244–52. doi:.https://doi.org/10.1016/S1474-4422(12)70323-X
  18. Cummings C, Stewart M, Stevenson M, Morrow J, Nelson J. Neurodevelopment of children exposed in utero to lamotrigine, sodium valproate and carbamazepine. Arch Dis Child. 2011;96(7):643–7. doi:.https://doi.org/10.1136/adc.2009.176990
  19. FDA Drug Safety Communication. Children born to mothers who took Valproate products while pregnant may have impaired cognitive development [Internet]. 2011 [cited 2020 Jan 14]. Available from: https://www.fda.gov/drugs/drug-safety-and-availability/fda-drug-safety-communication-children-born-mothers-who-took-valproate-products-while-pregnant-may
  20. Agency EM. CMDh agrees to strengthen warnings on the use of valproate medicines in women and girls [Internet]. 2014 [cited 2020 Jan 14]. Available from: https://www.ema.europa.eu/en/news/cmdh-agrees-strengthen-warnings-use-valproate-medicines-women-girls
  21. Eidgenossenschaft S. Depakine-Skandal. Untersuchung der Situation in der Schweiz. Bericht des Bundesrates in Erfüllung des Postulates 18.3092, Sänderätin Maury Pasquier Liliane, 7- März 2018. Bern; 2019.
  22. World Health Organization. International Statistical Classification of Diseases and Related Health Problems, 10th Revision. [Internet]. 2016 [cited 2018 Aug 14]. Available from: http://apps.who.int/classifications/icd10/browse/2016/en#/.
  23. MacDonald SC, Cohen JM, Panchaud A, McElrath TF, Huybrechts KF, Hernández-Díaz S. Identifying pregnancies in insurance claims data: Methods and application to retinoid teratogenic surveillance. Pharmacoepidemiol Drug Saf. 2019;28(9):1211–21. doi:.https://doi.org/10.1002/pds.4794
  24. Bundesamt für Statistik. Entbindungen und Gesundheit der Mütter im Jahr 2017 - Medizinische Statistik der Krankenhäuser | Publikation [Internet]. Medizinische Statistik der Krankenhäuser. 2019. Available from: https://www.bfs.admin.ch/bfs/de/home/statistiken/gesundheit/gesundheitszustand/reproduktive.html
  25. Daugaard CA, Sun Y, Dreier JW, Christensen J. Use of antiepileptic drugs in women of fertile age. Dan Med J. 2019;66(8):1–5.
  26. Hurault-Delarue C, Morris JK, Charlton R, Gini R, Loane M, Pierini A, et al.; EUROmediSAFE consortium. Prescription of antiepileptic medicines including valproate in pregnant women: A study in three European countries. Pharmacoepidemiol Drug Saf. 2019;28(11):1510–8. doi:.https://doi.org/10.1002/pds.4897
  27. Sante AN de securite du medicament et des produis de. Etude observationnelle ANSM-CNAMTS de l ’ exposition à l ’ acide valproïque et ses dérivés au cours de la grossesse en France. 2016.
  28. Agence national de sécurité du médicament et des produits de santé. Valproate et dérivés : l’exposition des femmes enceintes a fortement diminué mais persiste - Point d’information [Internet]. 2020 [cited 2020 Feb 5]. Available from: https://www.ansm.sante.fr/S-informer/Points-d-information-Points-d-information/Valproate-et-derives-l-exposition-des-femmes-enceintes-a-fortement-diminue-mais-persiste-Point-d-information
  29. Organisation world health. European Health INformation Gateway, Abortions per 1000 live births [Internet]. [cited 2020 Feb 4]. Available from: https://gateway.euro.who.int/en/indicators/hfa_586-7010-abortions-per-1000-live-births/visualizations/#id=19681
  30. Tomson T, Battino D, Bonizzoni E, Craig JJ, Lindhout D, Perucca E, et al.; EURAP Study Group. Antiepileptic drugs and intrauterine death: A prospective observational study from EURAP. Neurology. 2015;85(7):580–8. doi:.https://doi.org/10.1212/WNL.0000000000001840
  31. Wentzell N, Haug U, Schink T, Engel S, Liebentraut J, Linder R, et al. Prescribing valproate to girls and women of childbearing age in Germany: Analysis of trends based on claims data. Bundesgesundheitsblatt - Gesundheitsforsch - Gesundheitsschutz. 2018;61(8):1022–9.
  32. Murphy S, Bennett K, Doherty CP. Prescribing trends for sodium valproate in Ireland. Seizure. 2016;36:44–8. doi:.https://doi.org/10.1016/j.seizure.2016.01.019
  33. Virta LJ, Kälviäinen R, Villikka K, Keränen T. Declining trend in valproate use in Finland among females of childbearing age in 2012-2016 - a nationwide registry-based outpatient study. Eur J Neurol. 2018;25(6):869–74. doi:.https://doi.org/10.1111/ene.13610
  34. Démographiques institut national d’études. Population par sexe et âge au 1er janvier [Internet]. [cited 2020 Feb 5]. Available from: https://www.ined.fr/fr/tout-savoir-population/chiffres/france/structure-population/population-sexe-ages/
  35. Marson AG, Al-Kharusi AM, Alwaidh M, Appleton R, Baker GA, Chadwick DW, et al.; SANAD Study group. The SANAD study of effectiveness of carbamazepine, gabapentin, lamotrigine, oxcarbazepine, or topiramate for treatment of partial epilepsy: an unblinded randomised controlled trial. Lancet. 2007;369(9566):1000–15. doi:.https://doi.org/10.1016/S0140-6736(07)60460-7
  36. Jallon P, Latour P. Epidemiology of idiopathic generalized epilepsies. Epilepsia. 2005;46(s9, Suppl 9):10–4. doi:.https://doi.org/10.1111/j.1528-1167.2005.00309.x
  37. Herzog A. HB M, MacEachern D. Association of Unintended Pregnancy With Spontaneous Fetal Loss in Women With Epilepsy Findings of the Epilepsy Birth Control Registry. JAMA Neurol. 2019;76(1):50–5. doi:.https://doi.org/10.1001/jamaneurol.2018.3089
  38. Tomson T, Battino D, Bromley R, Kochen S, Meador K, Pennell P, et al. Executive Summary: Management of epilepsy in pregnancy: A report from the International League Against Epilepsy Task Force on Women and Pregnancy. Epilepsia. 2019;60(12):2343–5. doi:.https://doi.org/10.1111/epi.16395
  39. Goldman SA. Limitations and strengths of spontaneous reports data. Clin Ther. 1998;20(Suppl C):C40–4. doi:.https://doi.org/10.1016/S0149-2918(98)80007-6
  40. Frank AS, Lupattelli A, Nordeng H. Risk factors for discontinuation of thyroid hormone replacement therapy in early pregnancy: a study from the Norwegian Mother and Child Cohort Study and the Medical Birth Registry of Norway. Acta Obstet Gynecol Scand. 2018;97(7):852–60. doi:.https://doi.org/10.1111/aogs.13339
  41. Benevent J, Hurault-Delarue C, Araujo M, Montastruc JL, Lacroix I, Damase-Michel C. POMME: The New Cohort to Evaluate Long-Term Effects After Prenatal Medicine Exposure. Drug Saf. 2019;42(1):45–54. doi:.https://doi.org/10.1007/s40264-018-0712-9
  42. Innovationasausschuss GB. AMTS in utero - Untersuchung zur Arzneimitteltherapiesicherheit in der Schwangerschaft basierend auf Routinedaten in Deutschland [Internet]. 2020. Available from: https://innovationsfonds.g-ba.de/projekte/versorgungsforschung/amts-untersuchungen-zur-arzneimitteltherapiesicherheit-in-der-schwangerschaft-basierend-auf-routinedaten-in-deutschland.10
  43. Platt R, Brown JS, Robb M, McClellan M, Ball R, Nguyen MD, et al. The FDA Sentinel Initiative - An Evolving National Resource. N Engl J Med. 2018;379(22):2091–3. doi:.https://doi.org/10.1056/NEJMp1809643
  44. Bundesrat D. Die gesundheitspolitische Strategie des Bundesrates 2020-2030 [Internet]. 2020. Available from: https://www.fda.gov/safety/fdas-sentinel-initiative/fdas-sentinel-initiative-background
  45. Swissmedic. Wichtige Sicherheitsinformationen - Valproat: Risiko kongenitaler Missbildungen und Entwicklungsstörungen bei der Exposition während der Schwangerschaft [Internet]. 2011. Available from: https://webcache.googleusercontent.com/search?q=cache:N377P9_J-5wJ:https://www.swissmedic.ch/dam/swissmedic/de/dokumente/marktueberwachung/dhpc_hpc/dhpc_-_valproat.pdf.download.pdf/dhpc_-_valproat.pdf+&cd=1&hl=de&ct=clnk&gl=ch

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