Pregnancy in multiple sclerosis females – current knowledge and therapeutic aspects Review article

Article Sidebar

Requires Subscription PDF Requires Subscription PDF (Język Polski)


Published: Dec 31, 2024
DOI: https://doi.org/10.24292/01.MS.134311224.1
Keywords:
multiple sclerosis, pregnancy, breastfeeding, disease-modifying therapy

Main Article Content

Magdalena Węglewska
1. Zakład Neuroimmunologii Klinicznej, Instytut Chorób Układu Nerwowego, Uniwersytet Medyczny im. Karola Marcinkowskiego w Poznaniu. 2. Szkoła Doktorska, Uniwersytet Medyczny im. Karola Marcinkowskiego w Poznaniu
Alicja Kalinowska
Zakład Neuroimmunologii Klinicznej, Instytut Chorób Układu Nerwowego, Uniwersytet Medyczny im. Karola Marcinkowskiego w Poznaniu

Abstract

Multiple sclerosis might occur at any age group in both sexes, more often in women, typically starting during their childbearing years in their twenties and thirties. Historically patients planning pregnancy were usually taken off treatment or advised against it. Today, this trend has changed, so that patients are deciding to become pregnant more often. It is important to start disease-modifying therapies, which can be adjusted based on the maternity plans, immediately. Education regarding safe pregnancy planning should be implemented in early stages of diagnosis and treatment planning.


The optimal time for pregnancy is at least 2 years without disease activity. After stabilization of the disease, it is important to maintain the wash-out period specific for the chosen treatment. In the transition period, it is allowed to use interferon β, glatiramer acetate, and dimethyl fumarate (the latter should be discontinued after pregnancy confirmation). According to the summary of product characteristics, during pregnancy it is allowed to use only interferon beta and glatiramer acetate. In cases of high disease activity, it is permitted to use natalizumab intravenously every 6 weeks until second trimester, inclusive, after carefully weighing individual risks and benefits for both mother and baby. There is a growing body of safety data regarding pregnancy and newborn outcomes in patients who had been treated with anti-CD20 therapies, which allows an even more optimistic outlook on the highly effective therapies in patients with maternity plans. During relapses, which usually become less frequent during pregnancy, starting from the second trimester it is allowed to use methylprednisolone in standard intravenous dosage. Dexamethasone on the other hand is prohibited during the entire duration of the pregnancy.


After labor, breastfeeding and quick return to disease-modifying therapies should be encouraged. Beta-interferons, glatiramer acetate, and anti-CD20 monoclonal antibodies (namely ofatumumab, ocrelizumab and ublituximab) are considered safe during breastfeeding (with a note that anti-CD20 therapy could be started no earlier than around 2 weeks after the labor).

Article Details

Issue
Vol 13 No 4(49) (2024)
Section
Articles

Copyright © by Medical Education. All rights reserved.

References

1. Ahlgren C, Odén A, Lycke J. A nationwide survey of the prevalence of multiple sclerosis in immigrant populations of Sweden. Mult Scler. 2012; 18(8): 1099-107. http://doi.org/10.1177/1352458511433062.
2. Compston A, Coles A. Multiple sclerosis. Lancet. 2002; 359(9313): 1221-31. http://doi.org/10.1016/S0140-6736(02)08220-X .
3. Confavreux C, Hutchinson M, Hours MM et al. Rate of pregnancy-related relapse in multiple sclerosis. Pregnancy in Multiple Sclerosis Group. N Engl J Med. 1998; 339(5): 285-91. http://doi.org/10.1056/NEJM199807303390501.
4. Magyari M. Role of socio-economic and reproductive factors in the risk of multiple sclerosis. Acta Neurol Scand. 2015; 132: 20-3. http://doi.org/10.1111/ane.12426.
5. Ponsonby AL, Lucas RM, van der Mei IA et al. Offspring number, pregnancy, and risk of a first clinical demyelinating event: the AusImmune Study. Neurology. 2012; 78(12): 867-74. http://doi.org/10.1212/WNL.0b013e31824c4648.
6. Nguyen AL, Vodehnalova K, Kalincik T et al. Association of Pregnancy With the Onset of Clinically Isolated Syndrome. JAMA Neurol. 2020; 77(12): 1496-503. http://doi.org/10.1001/jamaneurol.2020.3324.
7. Lebrun C, Cohen M, Chaussenot A et al. A Prospective Study of Patients with Brain MRI Showing Incidental T2 Hyperintensities Addressed as Multiple Sclerosis: a Lot of Work to do Before Treating. Neurol Ther. 2014; 3(2): 123-32. http://doi.org/10.1007/s40120-014-0024-7.
8. Houtchens MK, Edwards NC, Schneider G et al. Pregnancy rates and outcomes in women with and without MS in the United States. Neurology. 2018; 91(17): e1559-69. http://doi.org/10.1212/WNL.0000000000006384.
9. Kalinowska A, Kułakowska A, Adamczyk-Sowa M et al. Recommendations for neurological, obstetrical and gynaecological care in women with multiple sclerosis: a statement by a working group convened by the Section of Multiple Sclerosis and Neuroimmunology of the Polish Neurological Society. Neurol Neurochir Pol. 2020; 54(2): 125-37. http://doi.org/10.5603/PJNNS.a2020.0015.
10. Amato MP, Bertolotto A, Brunelli R et al. Management of pregnancy-related issues in multiple sclerosis patients: the need for an interdisciplinary approach. Neurol Sci. 2017; 38(10): 1849-58. http://doi.org/10.1007/s10072-017-3081-8.
11. Dobson R, Hellwig K. Use of disease-modifying drugs during pregnancy and breastfeeding. Curr Opin Neurol. 2021; 34(3): 303-11. http://doi.org/10.1097/WCO.0000000000000922.
12. Kamm CP, Muehl S, Mircsof D et al. Role of Family Planning in Women With Multiple Sclerosis in Switzerland: Results of the Women With Multiple Sclerosis Patient Survey. Front Neurol. 2018; 9: 821. http://doi.org/10.3389/fneur.2018.00821.
13. Graham EL, Bove R, Costello K et al. Practical Considerations for Managing Pregnancy in Patients With Multiple Sclerosis: Dispelling the Myths. Neurol Clin Pract. 2024; 14(2): e200253. http://doi.org/10.1212/CPJ.0000000000200253.
14. Hellwig K, Chen LH, Stancyzk FZ et al. Oral Contraceptives and Multiple Sclerosis/Clinically Isolated Syndrome Susceptibility. PLoS ONE. 2016; 11(3): e0149094. http://doi.org/10.1371/journal.pone.0149094.
15. Pozzilli C, De Giglio L, Barletta VT et al. Oral contraceptives combined with interferon β in multiple sclerosis. Neurol Neuroimmunol Neuroinflamm. 2015; 2(4): e120. http://doi.org/10.1212/NXI.0000000000000120.
16. Zapata LB, Oduyebo T, Whiteman MK et al. Contraceptive use among women with multiple sclerosis: a systematic review. Contraception. 2016; 94(6): 612-20. http://doi.org/10.1016/j.contraception.2016.07.013.
17. Mainguy M, Tillaut H, Degremont A et al. Assessing the Risk of Relapse Requiring Corticosteroids After In Vitro Fertilization in Women With Multiple Sclerosis. Neurology. 2022; 99(17): e1916-25. http://doi.org/10.1212/WNL.0000000000201027.
18. Graham EL, Bakkensen JB, Anderson A et al. Inflammatory Activity After Diverse Fertility Treatments: A Multicenter Analysis in the Modern Multiple Sclerosis Treatment Era. Neurol Neuroimmunol Neuroinflamm. 2023; 10(3): e200106. http://doi.org/10.1212/NXI.0000000000200106.
19. Bove R, Rankin K, Lin C et al. Effect of assisted reproductive technology on multiple sclerosis relapses: Case series and meta-analysis. Mult Scler. 2020; 26(11): 1410-9. http://doi.org/10.1177/1352458519865118.
20. Rashid W, Ciccarelli O, Leary SM et al.; Association Of British Neurologists Multiple Sclerosis and Neuroinflammation Advisory Group. Using disease-modifying treatments in multiple sclerosis: Association of British Neurologists (ABN) 2024 guidance. Pract Neurol. 2025; 25(1): 18-24. http://doi.org/10.1136/pn-2024-004228.
21. Villaverde-González R, Candeliere-Merlicco A et al. Discontinuation of disease-modifying treatments in multiple sclerosis to plan a pregnancy: A retrospective registry study. Mult Scler Relat Disord. 2020; 46: 102518. http://doi.org/10.1016/j.msard.2020.102518.
22. Charakterystyka Produktu Leczniczego. Aubagio.
23. Montalban X, Gold R, Thompson AJ et al. ECTRIMS/EAN Guideline on the pharmacological treatment of people with multiple sclerosis. Mult Scler. 2018; 24(2): 96-120. http://doi.org/10.1177/1352458517751049.
24. Charakterystyka Produktu Leczniczego. Ocrevus.
25. Charakterystyka Produktu Leczniczego. Briumvi.
26. Charakterystyka Produktu Leczniczego. Kesimpta.
27. Gitlin D, Boesman M. Serum alpha-fetoprotein, albumin, and gamma-G-globulin in the human conceptus. J Clin Invest. 1966; 45(11): 1826-38. http://doi.org/10.1172/JCI105486.
28. Clements T, Rice TF, Vamvakas G et al. Update on Transplacental Transfer of IgG Subclasses: Impact of Maternal and Fetal Factors. Front Immunol. 2020; 11: 1920. http://doi.org/10.3389/fimmu.2020.01920.
29. Valor L, Ovalles-Bonilla JG, Hernández-Flórez D et al. Treatment with monoclonal antibodies and pregnancy in women with systemic inflammatory diseases: A special situation. Reumatol Clin. 2016; 12(6): 359-60. http://doi.org/10.1016/j.reuma.2016.01.006.
30. Malek A, Sager R, Kuhn P et al. Evolution of maternofetal transport of immunoglobulins during human pregnancy. Am J Reprod Immunol. 1996; 36(5): 248-55. http://doi.org/10.1111/j.1600-0897.1996.tb00172.x.
31. Jalkanen A, Alanen A, Airas L; Finnish Multiple Sclerosis and Pregnancy Study Group. Pregnancy outcome in women with multiple sclerosis: results from a prospective nationwide study in Finland. Mult Scler. 2010; 16(8): 950-5. http://doi.org/10.1177/1352458510372629.
32. Benoit A, Durand-Dubief F, Amato MP et al. History of multiple sclerosis in 2 successive pregnancies: A French and Italian cohort. Neurology. 2016; 87(13): 1360-7. http://doi.org/10.1212/WNL.0000000000003036.
33. Hellwig K, Brune N, Haghikia A et al. Reproductive counselling, treatment and course of pregnancy in 73 German MS patients. Acta Neurol Scand. 2008; 118(1): 24-8. http://doi.org/10.1111/j.1600-0404.2007.00978.x.
34. Herbstritt S, Langer-Gould A, Rockhoff M et al. Glatiramer acetate during early pregnancy: A prospective cohort study. Mult Scler. 2016; 22(6): 810-6. http://doi.org/10.1177/1352458515623366.
35. Saraste M, Väisänen S, Alanen A et al. Clinical and immunologic evaluation of women with multiple sclerosis during and after pregnancy. Gender Med. 2007; 4(1): 45-55. http://doi.org/10.1016/S1550-8579(07)80008-8.
36. Vukusic S, Hutchinson M, Hours M et al.; Pregnancy In Multiple Sclerosis Group. Pregnancy and multiple sclerosis (the PRIMS study): clinical predictors of post-partum relapse. Brain. 2004; 127(Pt 6): 1353-60. http://doi.org/10.1093/brain/awh152.
37. Thiel S, Langer-Gould A, Rockhoff M et al. Interferon-beta exposure during first trimester is safe in women with multiple sclerosis – A prospective cohort study from the German Multiple Sclerosis and Pregnancy Registry. Mult Scler. 2016; 22(6): 801-9. http://doi.org/10.1177/1352458516634872.
38. Yeh WZ, Widyastuti PA, Van der Walt A et al.; MSBase Study Group. Natalizumab, Fingolimod and Dimethyl Fumarate Use and Pregnancy-Related Relapse and Disability in Women With Multiple Sclerosis. Neurology. 2021; 96(24): e2989-3002. http://doi.org/10.1212/WNL.0000000000012084.
39. Alroughani R, Akhtar S, Zeineddine M et al. Risk of relapses during pregnancy among multiple sclerosis patients. Mult Scler Relat Disord. 2019; 34: 9-13. http://doi.org/10.1016/j.msard.2019.06.007.
40. Roullet E, Verdier-Taillefer MH, Amarenco P et al. Pregnancy and multiple sclerosis: a longitudinal study of 125 remittent patients. J Neurol Neurosurg Psychiatry. 1993; 56(10): 1062-65.
41. Worthington J, Jones R, Crawford M, Forti A. Pregnancy and multiple sclerosis–a 3-year prospective study. J Neurol. 1994; 241 (4): 228-33. http;//doi.org/10.1007/BF00863773.
42. Pastò L, Portaccio E, Ghezzi A et al. Epidural analgesia and cesarean delivery in multiple sclerosis post-partum relapses: theItalian cohort study. BMC Neurol. 2012; 12: 165. http;//doi.org/10.1186/ 1471-2377-12-165.
43. Portaccio E, Ghezzi A, Hakiki B et al. Breastfeeding is not related to postpartum relapses in multiple sclerosis. Neurology. 2011; 77(2): 145–150. http://doi.org/10.1212/WNL.0b013e318224afc9.
44. Bsteh G, Algrang L, Hegen H et al. Pregnancy and multiple sclerosis in the DMT era: A cohort study in Western Austria. Mult Scler. 2020; 26(1): 69-78. http://doi.org/10.1177/1352458518816614.
45. Dobson R, Jokubaitis VG, Giovannoni G. Change in pregnancy-associated multiple sclerosis relapse rates over time: a meta-analysis. Mult Scler Relat Dis. 2020; 44: 102241. http://doi.org/10.1016/j.msard.2020.102241.
46. Lehmann H, Zveik O, Levin N et al. Brain MRI activity during the year before pregnancy can predict post-partum clinical relapses. Mult Scler. 2021; 27(14): 2232-9. http://doi.org/10.1177/13524585211002719.
47. Lorefice L, Fronza M, Fenu G et al. Effects of Pregnancy and Breastfeeding on Clinical Outcomes and MRI Measurements of Women with Multiple Sclerosis: An Exploratory Real-World Cohort Study. Neurol Ther. 2022; 11(1): 39-49. http://doi.org/10.1007/s40120-021-00297-6.
48. Anderson A, Krysko KM, Rutatangwa A et al. Clinical and Radiologic Disease Activity in Pregnancy and Postpartum in MS. Neurol Neuroimmunol Neuroinflamm. 2021; 8(2): e959. http://doi.org/10.1212/NXI.0000000000000959.
49. Houtchens M, Bove R, Healy B et al. MRI activity in MS and completed pregnancy: Data from a tertiary academic center. Neurol Neuroimmunol Neuroinflamm. 2020; 7(6): e890. http://doi.org/10.1212/NXI.0000000000000890.
50. Krysko KM, Rutatangwa A, Graves J et al. Association Between Breastfeeding and Postpartum Multiple Sclerosis Relapses: A Systematic Review and Meta-analysis. JAMA Neurol. 2020; 77(3): 327. http://doi.org/10.1001/jamaneurol.2019.4173.
51. Hellwig K, Rockhoff M, Herbstritt S et al. Exclusive Breastfeeding and the Effect on Postpartum Multiple Sclerosis Relapses. JAMA Neurol. 2015; 72(10): 1132-8. http://doi.org/10.1001/jamaneurol.2015.1806.
52. Krysko KM, Dobson R, Alroughani R et al. Family planning considerations in people with multiple sclerosis. Lancet Neurol. 2023; 22(4): 350-66. http://doi.org/10.1016/S1474-4422(22)00426-4.