Pregnancy Registries and Longitudinal Data Collection



All patients with multiple sclerosis (MS) should be offered and have access to medications that have been well studied, and these patients should receive counseling with regard to the risks and benefits of using these medications. Women with MS who are pregnant or planning a pregnancy, however, are usually at a disadvantage because of the limited data available on the safety of medications indicated for MS. Collection of post-marketing data on the effects of disease-modifying therapies (DMTs) during pregnancy can be achieved through the use of pregnancy exposure and/or disease registries that collect information on MS treatments. However, there is a need for a specific pregnancy registry for MS that would encompass a large multicenter prospective observational study, designed to collect longitudinal data on medication exposure and outcomes in exposed and unexposed MS pregnancies and provide relevant information and counseling to women with MS who are pregnant or of childbearing age.


Multiple Sclerosis Multiple Sclerosis Patient Pregnancy Outcome Spontaneous Abortion Adverse Pregnancy Outcome 


  1. 1.
    Orton SM, et al. Sex ratio of multiple sclerosis in Canada: a longitudinal study. Lancet Neurol. 2006;5(11):932–6.CrossRefPubMedGoogle Scholar
  2. 2.
    Ramagopalan S, et al. Term pregnancies and the clinical characteristics of multiple sclerosis: a population based study. J Neurol Neurosurg Psychiatry. 2012;83(8):793–5.CrossRefPubMedGoogle Scholar
  3. 3.
    Vukusic S, et al. Pregnancy and multiple sclerosis (the PRIMS study): clinical predictors of post-partum relapse. Brain. 2004;127(Pt 6):1353–60.CrossRefPubMedGoogle Scholar
  4. 4.
    Bove R, et al. Management of multiple sclerosis during pregnancy and the reproductive years: a systematic review. Obstet Gynecol. 2014;124(6):1157–68.CrossRefPubMedGoogle Scholar
  5. 5.
    Alwan S, et al. Reproductive decision making after the diagnosis of multiple sclerosis (MS). Mult Scler. 2013;19(3):351–8.CrossRefPubMedGoogle Scholar
  6. 6.
    National Multiple Sclerosis Society (NMSS). Disease management consensus statement. 2007. Accessed 24 Apr 2011.
  7. 7.
    Naya M, Fujita T, Takahashi H, Hara T, Takahira H. Toxicology study of GKT-beta-teratogenicity study in rats administered intravenously. Kiso to Rinsho. 1988;22(1):137–45.Google Scholar
  8. 8.
    Novartis International AG. Gilenya (fingolimod) [online]. Available at: Accessed 27 Aug 2015.
  9. 9.
    Sanofi Aventis US. Aubagio (teriflunomide) [online]. Available at: Accessed 27 Aug 2015.
  10. 10.
    Gresser I, et al. Delay in growth and the development of nephritis in rats treated with interferon preparations in the neonatal period. Am J Pathol. 1979;95(2):329–46.PubMedGoogle Scholar
  11. 11.
    Cook JC, et al. Analysis of the nonsteroidal anti-inflammatory drug literature for potential developmental toxicity in rats and rabbits. Birth Defects Res B Dev Reprod Toxicol. 2003;68(1):5–26.CrossRefPubMedGoogle Scholar
  12. 12.
    McBride WB. Thalidomide and congenital abnormalities. Lancet. 1961;2:1358.CrossRefGoogle Scholar
  13. 13.
    Finer LB, Zolna MR. Shifts in intended and unintended pregnancies in the United States, 2001–2008. Am J Public Health. 2014;104 Suppl 1:S43–8.CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Metropolitan Atlanta Congenital Defects Program. Scholar
  15. 15.
    National Center for Health Statistics. Scholar
  16. 16.
    Mitchell AA. Systematic identification of drugs that cause birth defects–a new opportunity. N Engl J Med. 2003;349(26):2556–9.CrossRefPubMedGoogle Scholar
  17. 17.
    Richman S, Wallace K, Liu S, Sperling B. Final results from the AVONEX® (Intramuscular Interferon Beta-1a) pregnancy exposure registry. Neurology. 2012;78 (meeting abstracts 1). p. P06–191.Google Scholar
  18. 18.
    Coyle PK, et al. Final results from the Betaseron (interferon beta-1b) Pregnancy Registry: a prospective observational study of birth defects and pregnancy-related adverse events. BMJ Open. 2014;4(5):e004536.CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Cristiano L, Bozic C, Kooijmans M. Preliminary evaluation of pregnancy outcomes from Tysabri (nat) pregnancy registry. In: Fifth joint triennial congress of the European and the Americas Committees for Treatment and Research in multiple sclerosis. 2011. p. P1005.Google Scholar
  20. 20.
    Coyle PK, et al. Pregnancy outcomes in patients with multiple sclerosis treated with glatiramer acetate (Copaxone). J Neurol Neurosurg Psychiatry. 2003;74:443 [poster].Google Scholar
  21. 21.
    Karlsson G, et al. Pregnancy outcomes in the clinical development program of fingolimod in multiple sclerosis. Neurology. 2014;82(8):674–80.Google Scholar
  22. 22.
    Kieseier B, Benamor M, Benzerdjeb H, Stuve O. Pregnancy outcomes from teriflunomide clinical development programme: retrospective analysis of the teriflunomide clinical trial database. Mult Scler. 2012;18 Suppl 4:P737.Google Scholar
  23. 23.
    Gold R, et al. Delayed-release dimethyl fumarate and pregnancy: preclinical studies and pregnancy outcomes from clinical trials and postmarketing experience. Neurol Ther. 2015;4(2):93–104.Google Scholar
  24. 24.
    McCombe P, et al. Pregnancy outcomes in the alemtuzumab MS clinical development program. ECTRIMS Online Library. 2014 64543 (Poster).Google Scholar
  25. 25.
    Hellwig K, et al. Multiple sclerosis and pregnancy: experience from a nationwide database in Germany. Ther Adv Neurol Disord. 2012;5(5):247–53.CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Amato MP, et al. Pregnancy and fetal outcomes after interferon-beta exposure in multiple sclerosis. Neurology. 2010;75(20):1794–802.CrossRefPubMedGoogle Scholar
  27. 27.
    Giannini M, et al. Pregnancy and fetal outcomes after glatiramer acetate exposure in patients with multiple sclerosis: a prospective observational multicentric study. BMC Neurol. 2012;12:124.CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Hellwig K, Haghikia A, Gold R. Pregnancy and natalizumab: results of an observational study in 35 accidental pregnancies during natalizumab treatment. Mult Scler. 2011;17(8):958–63.CrossRefPubMedGoogle Scholar
  29. 29.
    Ebrahimi N, et al. Pregnancy and fetal outcomes following natalizumab exposure in pregnancy. A prospective, controlled observational study. Mult Scler. 2015;21(2):198–205.Google Scholar
  30. 30.
    Boskovic R, et al. The reproductive effects of beta interferon therapy in pregnancy: a longitudinal cohort. Neurology. 2005;65(6):807–11.CrossRefPubMedGoogle Scholar
  31. 31.
    Weber-Schoendorfer C, Schaefer C. Multiple sclerosis, immunomodulators, and pregnancy outcome: a prospective observational study. Mult Scler. 2009;15(9):1037–42.Google Scholar
  32. 32.
    Patti F, et al. Is in utero early exposure to interferon beta a risk factor for pregnancy outcomes in multiple sclerosis? J Neurol. 2008;255(8):1250–3.CrossRefPubMedGoogle Scholar
  33. 33.
    De Las Heras V, et al. Pregnancy in multiple sclerosis patients treated with immunomodulators prior to or during part of the pregnancy: a descriptive study in the Spanish population. Mult Scler. 2007;13(8):981–4.CrossRefPubMedGoogle Scholar
  34. 34.
    Fernandez Liguori N, et al. Epidemiological characteristics of pregnancy, delivery, and birth outcome in women with multiple sclerosis in Argentina (EMEMAR study). Mult Scler. 2009;15(5):555–62.CrossRefPubMedGoogle Scholar
  35. 35.
    Lu E, et al. Perinatal outcomes in women with multiple sclerosis exposed to disease-modifying drugs. Mult Scler. 2012;18(4):460–7.CrossRefPubMedGoogle Scholar
  36. 36.
    Agency for Health Research and Quality. Registries for evaluating patient’s outcomes: a user’s guide. 2014 [cited 2014]. Available from:
  37. 37.
    Alwan S, et al. The need for a disease-specific prospective pregnancy registry for multiple sclerosis (MS). Mult Scler Relat Disord. 2015;4(1):6–17.CrossRefPubMedGoogle Scholar
  38. 38.
    Holmes LB, Wyszynski DF, Lieberman E. The AED (antiepileptic drug) pregnancy registry: a 6-year experience. Arch Neurol. 2004;61(5):673–8.CrossRefPubMedGoogle Scholar
  39. 39.
    Coscia LA, et al. Report from the National Transplantation Pregnancy Registry (NTPR): outcomes of pregnancy after transplantation. Clin Transpl. 2010:65–85. PMID 21698831.Google Scholar
  40. 40.
    Chambers CD, et al. Postmarketing surveillance for human teratogenicity: a model approach. Teratology. 2001;64(5):252–61.CrossRefPubMedGoogle Scholar
  41. 41.
    Fragoso YD, et al. Long-term use of glatiramer acetate by 11 pregnant women with multiple sclerosis: a retrospective, multicentre case series. CNS Drugs. 2010;24(11):969–76.PubMedGoogle Scholar
  42. 42.
    Salminen HJ, Leggett H, Boggild M. Glatiramer acetate exposure in pregnancy: preliminary safety and birth outcomes. J Neurol. 2010;257(12):2020–3.CrossRefPubMedGoogle Scholar
  43. 43.
    Haghikia A, et al. Natalizumab use during the third trimester of pregnancy. JAMA Neurol. 2014;71(7):891–5.CrossRefPubMedGoogle Scholar
  44. 44.
    Sandberg-Wollheim M, et al. Pregnancy outcomes in multiple sclerosis following subcutaneous interferon beta-1a therapy. Mult Scler. 2011;17(4):423–30.CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag Wien 2017

Authors and Affiliations

  1. 1.Department of Medical GeneticsUniversity of British ColumbiaVancouverCanada
  2. 2.Department of NeurologySt. Josef Hospital, Ruhr University BochumBochumGermany

Personalised recommendations