European Journal of Epidemiology

, Volume 28, Issue 9, pp 759–769 | Cite as

Triptan safety during pregnancy: a Norwegian population registry study

  • Kateřina Nezvalová-HenriksenEmail author
  • Olav Spigset
  • Hedvig Nordeng


Knowledge on triptan safety during pregnancy remains limited to their class effect or studies on sumatriptan. Our aim was to evaluate the individual effect of four most frequently used triptans on several pregnancy outcomes. We used the Norwegian prescription database to access information on triptans redeemed by pregnant women living in Norway between 2004 and 2007. This database was linked to the Medical Birth Registry of Norway covering every institutional delivery in Norway and providing information on pregnancy, delivery, maternal and neonatal health. Estimates of associations with pregnancy outcomes were obtained by Generalised Estimation Equations analysis. Of the 181,125 women in our study, 1,465 (0.8 %) redeemed triptans during pregnancy, and 1,095 (0.6 %) redeemed triptans before pregnancy only (disease comparison group). The population comparison group comprised the remaining 178,565 women. Using this group as reference, we found no associations between triptan redemption during pregnancy and congenital malformations. Second trimester redemption was associated with postpartum haemorrhage (adjusted OR 1.57; 95 % CI 1.19–2.07). The disease comparison group had an increased risk of major congenital malformations (adjusted OR 1.48; 95 % CI 1.11–1.97), low birth weight (adjusted OR 1.39; 95 % CI 1.08–1.81), and preterm birth (adjusted OR 1.30; 95 % CI 1.06–1.60). The association of triptans with postpartum hemorrhage could be attributable to decreased platelet agreeability occurring in severe migraine. Likewise, the increased risk of major congenital malformations and other adverse pregnancy outcomes in the disease comparison group might be attributable to migraine severity.


Triptans Migraine Pregnancy Congenital malformations Adverse pregnancy outcomes 

Supplementary material

10654_2013_9831_MOESM1_ESM.pdf (97 kb)
Supplementary material 1 (PDF 98 kb)


  1. 1.
    Ertresvåg J, Zwart J-A, Helde G, Johnsen H-J, Bovim G. Headache and transient focal neurological symptoms during pregnancy, a prospective cohort. Acta Neurol Scand. 2005;111:233–7.PubMedCrossRefGoogle Scholar
  2. 2.
    Sances G, Granella F, Nappi RE, Fignon A, Ghiotto N, Polatti F, et al. Course of migraine during pregnancy and postpartum: a prospective study. Cephalalgia. 2003;23(3):197–205.PubMedCrossRefGoogle Scholar
  3. 3.
    Melhado E, Maciel JA Jr, Guerreiro CA. Headaches during pregnancy in women with a prior history of menstrual headaches. Arq Neuropsiquiatr. 2005;63(4):934–40. doi: /S0004-282x2005000600006.PubMedCrossRefGoogle Scholar
  4. 4.
    Marcus D, Scharff L, Turk D. Longitudinal prospective study of headache during pregnancy and postpartum. Headache. 1999;39(9):625–32.PubMedCrossRefGoogle Scholar
  5. 5.
    Scharff L, Marcus DA, Turk DC. Headache during pregnancy and in the postpartum: a prospective study. Headache. 1997;37(4):203–10.PubMedCrossRefGoogle Scholar
  6. 6.
    Mattsson P, Svardsudd K, Lundberg PO, Westerberg CE. The prevalence of migraine in women aged 40–74 years: a population-based study. Cephalalgia. 2000;20(10):893–9.PubMedCrossRefGoogle Scholar
  7. 7.
    Granella F, Sances G, Pucci E, Nappi R, Chiotto N, Nappi G. Migraine with aura and reproductive life events: a case control study. Cephalalgia. 2000;20(8):701–7.PubMedGoogle Scholar
  8. 8.
    Maggioni F, Alessi C, Maggino T, Zanchin G. Headache during pregnancy. Cephalalgia. 1997;17(7):765–9.PubMedCrossRefGoogle Scholar
  9. 9.
    Facchinetti F, Allais G, Nappi RE, D’Amico R, Marozio L, Bertozzi L, et al. Migraine is a risk factor for hypertensive disorders in pregnancy: a prospective cohort study. Cephalalgia. 2009;29(3):286–92. doi: 10.1111/j.1468-2982.2008.01704.x.PubMedCrossRefGoogle Scholar
  10. 10.
    Cripe SM, Frederick IO, Qiu C, Williams MA. Risk of preterm delivery and hypertensive disorders of pregnancy in relation to maternal co-morbid mood and migraine disorders during pregnancy. Paediatr Perinat Epidemiol. 2011;25(2):116–23. doi: 10.1111/j.1365-3016.2010.01182.x.PubMedCrossRefGoogle Scholar
  11. 11.
    Bushnell CD, Jamison M, James AH. Migraines during pregnancy linked to stroke and vascular diseases: US population based case-control study. BMJ. 2009;338:1–8. doi: 10.1136/bmj.b664.CrossRefGoogle Scholar
  12. 12.
    Chen HM, Chen SF, Chen YH, Lin HC. Increased risk of adverse pregnancy outcomes for women with migraines: a nationwide population-based study. Cephalalgia. 2010;30(4):433–8. doi: 10.1111/j.1468-2982.2009.01935.x.PubMedGoogle Scholar
  13. 13.
    Facchinetti F, Allais G, D’Amico R, Benedetto C, Volpe A. The relationship between headache and preeclampsia: a case-control study. Eur J Obstet Gynecol Reprod Biol. 2005;121(2):143–8. doi: 10.1016/j.ejogrb.2004.12.020.PubMedCrossRefGoogle Scholar
  14. 14.
    Adeney KL, Williams MA, Miller RS, Frederick IO, Sorensen TK, Luthy DA. Risk of preeclampsia in relation to maternal history of migraine headaches. J Matern Fetal Neonatal Med. 2005;18(3):167–72. doi: 10.1080/14767050500260566.PubMedCrossRefGoogle Scholar
  15. 15.
    Leveno KJ, Cunningham FG, Alexander JM, Bloom SL, Casey BM, Dashe JS, et al. Williams manual of obstetrics pregnancy complications. 22nd ed. New York: McGraw-Hill; 2007.Google Scholar
  16. 16.
    Nezvalová-Henriksen K, Spigset O, Nordeng H. Maternal characteristics and migraine pharmacotherapy during pregnancy: cross sectional analysis of data from a large cohort study. Cephalalgia. 2009;29:1267–76.PubMedCrossRefGoogle Scholar
  17. 17.
    Nezvalová-Henriksen K, Spigset O, Nordeng H. Triptan exposure during pregnancy and the risk of major congenital malformations and adverse pregnancy outcomes: results from the Norwegian mother and child cohort study. Headache. 2010;50:563–75.PubMedCrossRefGoogle Scholar
  18. 18.
    Nezvalova-Henriksen K, Spigset O, Nordeng HM. Errata in “Triptan exposure during pregnancy and the risk of major congenital malformations and adverse pregnancy outcomes: results from the norwegian mother and child cohort study”. Headache. 2012;52(8):1319–20. doi: 10.1111/j.1526-4610.2012.02207.x.PubMedCrossRefGoogle Scholar
  19. 19.
    Chu MK, Buse DC, Bigal ME, Serrano D, Lipton RB. Factors associated with triptan use in episodic migraine: results from the American migraine prevalence and prevention study. Headache. 2012;52(2):213–23.PubMedCrossRefGoogle Scholar
  20. 20.
    Kαllen B, Nilsson E, Otterblad Olausson P. Delivery outcome after maternal use of drugs for migraine: a register study in Sweden. Drug Saf. 2011;34(8):691–703. doi: 10.2165/11590370-000000000-00000.CrossRefGoogle Scholar
  21. 21.
    Kallen B, Lygner PE. Delivery outcome in women who used drugs for migraine during pregnancy with special reference to sumatriptan. Headache. 2001;41(4):351–6.PubMedCrossRefGoogle Scholar
  22. 22.
    Olesen C, Steffensen FH, Sorensen HT, Nielsen GL, Olsen J. Pregnancy outcome following prescription for sumatriptan. Headache. 2000;40(1):20–4.PubMedCrossRefGoogle Scholar
  23. 23.
    GlaxoSmithKline. The Sumatriptan/Naratriptan/Treximet Pregnancy. 2012.Google Scholar
  24. 24.
    Norwegian Institute of Public Health. The Medical Birth Registry of Norway. Oslo, Norway. (2013).
  25. 25.
    Norwegian Institute of Public Health. The Norwegian Prescription Database. Oslo, Norway. (2013).
  26. 26.
    Al-Zirqi I, Stray-Pedersen B, Forsen L, Daltveit AK, Vangen S. Validation study of uterine rupture registration in the Medical Birth Registry of Norway. Acta Obstet Gynecol Scand. 2013;. doi: 10.1111/aogs.12148.PubMedGoogle Scholar
  27. 27.
    Vikanes A, Magnus P, Vangen S, Lomsdal S, Grjibovski AM. Hyperemesis gravidarum in the Medical Birth Registry of Norway—a validity study. BMC Pregnancy Childbirth. 2012;12:115. doi: 10.1186/1471-2393-12-115.PubMedCrossRefGoogle Scholar
  28. 28.
    Engeland A, Bjorge T, Daltveit AK, Vollset SE, Furu K. Validation of disease registration in pregnant women in the Medical Birth Registry of Norway. Acta Obstet Gynecol Scand. 2009;88(10):1083–9. doi: 10.1080/00016340903128454.PubMedCrossRefGoogle Scholar
  29. 29.
    Melve KK, Lie RT, Skjaerven R, Van Der Hagen CB, Gradek GA, Jonsrud C, et al. Registration of down syndrome in the Medical Birth Registry of Norway: validity and time trends. Acta Obstet Gynecol Scand. 2008;87(8):824–30. doi: 10.1080/00016340802217184.PubMedCrossRefGoogle Scholar
  30. 30.
    Baghestan E, Bordahl PE, Rasmussen SA, Sande AK, Lyslo I, Solvang I. A validation of the diagnosis of obstetric sphincter tears in two Norwegian databases, the Medical Birth Registry and the Patient Administration System. Acta Obstet Gynecol Scand. 2007;86(2):205–9. doi: 10.1080/00016340601111364.PubMedCrossRefGoogle Scholar
  31. 31.
    Irgens LM. The Medical Birth Registry of Norway. Epidemiological research and surveillance throughout 30 years. Acta Obstet Gynecol Scand. 2000;79(6):435–9.PubMedCrossRefGoogle Scholar
  32. 32.
    ATC/DDD Index 2008 [database on the Internet]. Available from: <> (2009). Accessed 3 June 2009.
  33. 33.
    World Health Organization. International Classification of Diseases. 2013.
  34. 34.
    Fiore M, Shields KE, Santanello N, Goldberg MR. Exposure to rizatriptan during pregnancy: post-marketing experience up to 30 June 2004. Cephalalgia. 2005;25(9):685–8. doi: 10.1111/j.1468-2982.2004.00929.x.PubMedCrossRefGoogle Scholar
  35. 35.
    Banhidy F, Acs N, Horvath-Puho E, Czeizel AE. Maternal severe migraine and risk of congenital limb deficiencies. Birth Defects Res A. 2006;76(8):592–601. doi: 10.1002/bdra.20288.CrossRefGoogle Scholar
  36. 36.
    Williams MA, Peterlin BL, Gelaye B, Enquobahrie DA, Miller RS, Aurora SK. Trimester-specific blood pressure levels and hypertensive disorders among pregnant migraineurs. Headache. 2011;51(10):1468–82. doi: 10.1111/j.1526-4610.2011.01961.x.PubMedCrossRefGoogle Scholar
  37. 37.
    Nappi G, Sandrini G, Sances G. Tolerability of the triptans: clinical implications. Drug Saf. 2003;26(2):93–107.PubMedCrossRefGoogle Scholar
  38. 38.
    Gupta S, Hanff LM, Visser W, Steegers EA, Saxena PR, Vulto AG, et al. Functional reactivity of 5-HT receptors in human umbilical cord and maternal subcutaneous fat arteries after normotensive or pre-eclamptic pregnancy. J Hypertens. 2006;24(7):1345–53. doi: 10.1097/01.hjh.0000234115.40648.88.PubMedCrossRefGoogle Scholar
  39. 39.
    Blair EM, Nelson KB. Migraine and preterm birth. J perinatol. 2011;31(6):434–9. doi: 10.1038/jp.2010.148.PubMedCrossRefGoogle Scholar
  40. 40.
    Marozio L, Facchinetti F, Allais G, Nappi RE, Enrietti M, Neri I, et al. Headache and adverse pregnancy outcomes: a prospective study. Eur J Obstet Gynecol Reprod Biol. 2012;161(2):140–3. doi: 10.1016/j.ejogrb.2011.12.030.PubMedCrossRefGoogle Scholar
  41. 41.
    Cripe SM, Sanchez S, Lam N, Sanchez E, Ojeda N, Tacuri S, et al. Depressive symptoms and migraine comorbidity among pregnant Peruvian women. J Affect Disord. 2010;122(1–2):149–53. doi: 10.1016/j.jad.2009.07.014.PubMedCrossRefGoogle Scholar
  42. 42.
    Rossi C, Pini LA, Cupini ML, Calabresi P, Sarchielli P. Endocannabinoids in platelets of chronic migraine patients and medication-overuse headache patients: relation with serotonin levels. Eur J Clin Pharmacol. 2008;64(1):1–8. doi: 10.1007/s00228-007-0391-4.PubMedCrossRefGoogle Scholar
  43. 43.
    Melve K, Lie R, Skjærven R, Van Der Hagen C, Gradek G, Jonsrud C, et al. Registration of down syndrome in the Medical Birth Registry of Norway: validity and time trends. Acta Obstet Gynecol Scand. 2008;87:824–30.PubMedCrossRefGoogle Scholar
  44. 44.
    Kubon C, Sivertsen A, Vindenes HA, Abyholm F, Wilcox A, Lie RT. Completeness of registration of oral clefts in a medical birth registry: a population-based study. Acta Obstet Gynecol Scand. 2007;86(12):1453–7. doi: 10.1080/08037050701645090.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2013

Authors and Affiliations

  • Kateřina Nezvalová-Henriksen
    • 1
    Email author
  • Olav Spigset
    • 2
    • 3
  • Hedvig Nordeng
    • 1
    • 4
  1. 1.Department of Pharmacy, School of Pharmacy, Faculty of Mathematics and Natural SciencesUniversity of OsloOsloNorway
  2. 2.Department of Clinical PharmacologySt Olav’s University HospitalTrondheimNorway
  3. 3.Department of Laboratory Medicine, Children’s and Women’s HealthNorwegian University of Science and TechnologyTrondheimNorway
  4. 4.Division of Mental HealthThe Norwegian Institute of Public HealthOsloNorway

Personalised recommendations