Patient-centered pregnancy planning in multiple sclerosis: evidence for a new era

Abstract

A few decades ago, women diagnosed with multiple sclerosis were discouraged from becoming pregnant. However, with new knowledge about the disease and treatments, this recommendation has changed, and it is pregnancy after the diagnosis of the disease is no longer contraindicated, with family planning being essential in this process. This review aims to provide a comprehensive overview of the family planning process for people with multiple sclerosis.

Resumo

Até recentemente, a gravidez nas pacientes com o diagnóstico de esclerose múltipla era contraindicada. O avanço no conhecimento sobre a doença e os tratamentos alterou essa recomendação, e agora a gravidez após o diagnóstico da doença não é mais contraindicada; contudo, o planeamento familiar é essencial nesse processo. Esta revisão tem como objetivo fornecer uma visão abrangente do processo de planejamento familiar para pacientes com esclerose múltipla.

Keywords

Multiple Sclerosis - Pregnancy - Postpartum Period - Breastfeeding - Family Development Planning

Palavras-chave

Esclerose Múltipla - Gravidez - Período Pós-Parto - Aleitamento Materno - Planejamento Familiar

Authors' Contributions

EMVM: conceptualization, investigation, methodology, project administration, supervision, visualization, writing – original draft, and writing – review & editing; BCAR, FTC, LAMTV: data curation, investigation, and writing – original draft; MFM, conceptualization, methodology, supervision, and writing – review & editing.

Editor-in-Chief: Ayrton Roberto Massaro.

Associate Editor: Douglas Kazutoshi Sato.

Publikationsverlauf

Eingereicht: 26. Februar 2024

Angenommen: 02. Juli 2024

Artikel online veröffentlicht:
02. Oktober 2024

• References

• 1 Harbo HF, Gold R, Tintoré M. Sex and gender issues in multiple sclerosis. Ther Adv Neurol Disord 2013; 6 (04) 237-248
• 2 Marques VD, Passos GRD, Mendes MF. et al. Consenso brasileiro para o tratamento da esclerose múltipla: Academia Brasileira de Neurologia e Comitê Brasileiro de Tratamento e Pesquisa em Esclerose Múltipla. Arq Neuropsiquiatr 2018; 76 (08) 539-554 Doi: × 20180078
• 3 Maia Diniz I, Guerra Junior AA, Lovato Pires de Lemos L. et al. The long-term costs for treating multiple sclerosis in a 16-year retrospective cohort study in Brazil. PLoS One 2018; 13 (06) e0199446
• 4 Lamaita R, Melo C, Laranjeira C, Barquero P, Gomes J, Silva-Filho A. Multiple sclerosis in pregnancy and its role in female fertility: a systematic review. JBRA Assist Reprod 2021; 25 (03) 493-499
• 5 Thöne J, Kollar S, Nousome D. et al. Serum anti-Müllerian hormone levels in reproductive-age women with relapsing-remitting multiple sclerosis. Mult Scler 2015; 21 (01) 41-47
• 6 Krysko KM, Dobson R, Alroughani R. et al. Family planning considerations in people with multiple sclerosis. Lancet Neurol 2023; 22 (04) 350-366
• 7 Melo EMV, Mendes MF, Olival GSD. What is the importance of family planning in multiple sclerosis? A study in the Brazilian population. Mult Scler Relat Disord 2024; 85: 105538
• 8 López-Reyes L, Guío-Sánchez C, González-Uribe C, Cárdenas-Robledo S. Fertility preferences and unmet need for family planning in women with multiple sclerosis. Front Neurol 2022; 13: 1035596
• 9 Kelly VM, Nelson LM, Chakravarty EF. Obstetric outcomes in women with multiple sclerosis and epilepsy. Neurology 2009; 73 (22) 1831-1836
• 10 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 (03) e200106
• 11 Hellwig K. Pregnancy in multiple sclerosis. Eur Neurol 2014; 72 (Suppl. 01) 39-42
• 12 Oreja-Guevara C, Rabanal A, Rodríguez CH. et al. Assisted reproductive techniques in multiple sclerosis: recommendations from an expert panel. Neurol Ther 2023; 12 (02) 427-439
• 13 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-e3002
• 14 Confavreux C, Hutchinson M, Hours MM, Cortinovis-Tourniaire P, Moreau T. Pregnancy in Multiple Sclerosis Group. Rate of pregnancy-related relapse in multiple sclerosis. N Engl J Med 1998; 339 (05) 285-291
• 15 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 (01) 69-78
• 16 Wattjes MP, Ciccarelli O, Reich DS. et al; Magnetic Resonance Imaging in Multiple Sclerosis study group, Consortium of Multiple Sclerosis Centres, North American Imaging in Multiple Sclerosis Cooperative MRI guidelines working group. 2021 MAGNIMS-CMSC-NAIMS consensus recommendations on the use of MRI in patients with multiple sclerosis. Lancet Neurol 2021; 20 (08) 653-670
• 17 Bandoli G, Palmsten K, Forbess Smith CJ, Chambers CD. A review of systemic corticosteroid use in pregnancy and the risk of select pregnancy and birth outcomes. Rheum Dis Clin North Am 2017; 43 (03) 489-502
• 18 Houtchens MK, Kolb CM. Multiple sclerosis and pregnancy: therapeutic considerations. J Neurol 2013; 260 (05) 1202-1214
• 19 Voskuhl R, Momtazee C. Pregnancy: Effect on multiple sclerosis, treatment considerations, and breastfeeding. Neurotherapeutics 2017; 14 (04) 974-984
• 20 Fragoso YD, Adoni T, Alves-Leon SV. et al. Postpartum treatment with immunoglobulin does not prevent relapses of multiple sclerosis in the mother. Health Care Women Int 2015; 36 (10) 1072-1080
• 21 Rosa GR, O'Brien AT, Nogueira EAG, Carvalho VM, Paz SC, Fragoso YD. There is no benefit in the use of postnatal intravenous immunoglobulin for the prevention of relapses of multiple sclerosis: findings from a systematic review and meta-analysis. Arq Neuropsiquiatr 2018; 76 (06) 361-366 Doi: × 20180041
• 22 Cox JL, Koepsell SA, Shunkwiler SM. Therapeutic plasma exchange and pregnancy: A case report and guidelines for performing plasma exchange in a pregnant patient. J Clin Apher 2017; 32 (03) 191-195
• 23 Wind M, Gaasbeek AGA, Oosten LEM. et al. Therapeutic plasma exchange in pregnancy: A literature review. Eur J Obstet Gynecol Reprod Biol 2021; 260: 29-36
• 24 Capone F, Albanese A, Quadri G. et al. Disease-modifying drugs and breastfeeding in multiple sclerosis: a narrative literature review. Front Neurol 2022; 13: 851413
• 25 Rolfes L, Pfeuffer S, Ruck T. et al. Therapeutic apheresis in acute relapsing multiple sclerosis: current evidence and unmet needs-a systematic review. J Clin Med 2019; 8 (10) 1623
• 26 Soler B, Ciampi E, Uribe-San-Martín R. et al. Pregnancy outcomes in women with Multiple Sclerosis. Mult Scler Relat Disord 2021; 48: 102682
• 27 Andersen JB, Kopp TI, Sellebjerg F, Magyari M. Pregnancy-related and perinatal outcomes in women with multiple sclerosis: a nationwide Danish cross-sectional study. Neurol Clin Pract 2021; 11 (04) 280-290
• 28 van der Kop ML, Pearce MS, Dahlgren L. et al. Neonatal and delivery outcomes in women with multiple sclerosis. Ann Neurol 2011; 70 (01) 41-50
• 29 Houtchens MK, Zapata LB, Curtis KM, Whiteman MK. Contraception for women with multiple sclerosis: Guidance for healthcare providers. Mult Scler 2017; 23 (06) 757-764
• 30 Zhu B, Nestorov I, Zhao G. et al. Evaluation of potential drug-drug interaction between delayed-release dimethyl fumarate and a commonly used oral contraceptive (norgestimate/ethinyl estradiol) in healthy women. Clin Pharmacol Drug Dev 2017; 6 (06) 604-613
• 31 Otero-Romero S, Lebrun-Frénay C, Reyes S. et al. ECTRIMS/EAN consensus on vaccination in people with multiple sclerosis: Improving immunization strategies in the era of highly active immunotherapeutic drugs. Mult Scler 2023; 29 (08) 904-925
• 32 Stefanou MI, Palaiodimou L, Theodorou A. et al. Safety of COVID-19 vaccines in multiple sclerosis: A systematic review and meta-analysis. Mult Scler 2023; 29 (4-5): 585-594
• 33 Bove R, Alwan S, Friedman JM. et al. Management of multiple sclerosis during pregnancy and the reproductive years: a systematic review. Obstet Gynecol 2014; 124 (06) 1157-1168
• 34 Varytė G, Zakarevičienė J, Ramašauskaitė D, Laužikienė D, Arlauskienė A. Pregnancy and multiple sclerosis: an update on the disease modifying treatment strategy and a review of pregnancy's impact on disease activity. Medicina (Kaunas) 2020; 56 (02) 49
• 35 Westerlind H, Ramanujam R, Uvehag D. et al. Modest familial risks for multiple sclerosis: a registry-based study of the population of Sweden. Brain 2014; 137 (Pt 3): 770-778
• 36 Gold SM, Voskuhl RR. Pregnancy and multiple sclerosis: from molecular mechanisms to clinical application. Semin Immunopathol 2016; 38 (06) 709-718
• 37 Hellwig K, Verdun di Cantogno E, Sabidó M. A systematic review of relapse rates during pregnancy and postpartum in patients with relapsing multiple sclerosis. Ther Adv Neurol Disord 2021; 14 17562864211051012
• 38 Roos I, Malpas C, Leray E. et al; MSBase and OFSEP. Disease reactivation after cessation of disease-modifying therapy in patients with relapsing-remitting multiple sclerosis. Neurology 2022; 99 (17) e1926-e1944
• 39 Rød BE, Torkildsen Ø, Myhr KM, Bø L, Wergeland S. Safety of breast feeding during rituximab treatment in multiple sclerosis. J Neurol Neurosurg Psychiatry 2022; 94 (01) 38-41
• 40 Korjagina M, Hakkarainen KM, Burkill S. et al; European Interferon Beta Pregnancy Study Group and the Nordic MS Pregnancy & Interferon Beta study group. Prevalence of adverse pregnancy outcomes after exposure to interferon beta prior to or during pregnancy in women with MS: Stratification by maternal and newborn characteristics in a register-based cohort study in Finland and Sweden. Mult Scler Relat Disord 2021; 48: 102694
• 41 Hellwig K, Geissbuehler Y, Sabidó M. et al; European Interferon-beta Pregnancy Study Group. Pregnancy outcomes in interferon-beta-exposed patients with multiple sclerosis: results from the European Interferon-beta Pregnancy Registry. J Neurol 2020; 267 (06) 1715-1723
• 42 Herbstritt S, Langer-Gould A, Rockhoff M. et al. Glatiramer acetate during early pregnancy: A prospective cohort study. Mult Scler 2016; 22 (06) 810-816
• 43 Kaplan S, Zeygarnik M, Stern T. Pregnancy, fetal, and infant outcomes following maternal exposure to glatiramer acetate during pregnancy and breastfeeding. Drug Saf 2022; 45 (04) 345-357
• 44 Ciplea AI, Langer-Gould A, Stahl A. et al. Safety of potential breast milk exposure to IFN-β or glatiramer acetate: One-year infant outcomes. Neurol Neuroimmunol Neuroinflamm 2020; 7 (04) e757
• 45 Gold R, Phillips JT, Havrdova E. et al. Delayed-release dimethyl fumarate and pregnancy: preclinical studies and pregnancy outcomes from clinical trials and postmarketing experience. Neurol Ther 2015; 4 (02) 93-104
• 46 Andersen JB, Sellebjerg F, Magyari M. Pregnancy outcomes after early fetal exposure to injectable first-line treatments, dimethyl fumarate, or natalizumab in Danish women with multiple sclerosis. Eur J Neurol 2023; 30 (01) 162-171
• 47 Hellwig K, Rog D, McGuigan C. et al. Final analysis of 379 pregnancy outcomes after exposure to dimethyl fumarate in a prospective international registry. Mult Scler 2024; 30 (02) 209-215
• 48 Ciplea AI, Datta P, Rewers-Felkins K. et al. Dimethyl fumarate transfer into human milk. Ther Adv Neurol Disord 2020; 13 1756286420968414
• 49 Liguori NF, Alonso R, Pinheiro AA. et al. Consensus recommendations for family planning and pregnancy in multiple sclerosis in argentina. Mult Scler Relat Disord 2020; 43: 102147
• 50 Vukusic S, Coyle PK, Jurgensen S. et al. Pregnancy outcomes in patients with multiple sclerosis treated with teriflunomide: Clinical study data and 5 years of post-marketing experience. Mult Scler 2020; 26 (07) 829-836
• 51 Andersen JB, Wandall-Holm MF, Magyari M. Pregnancy outcomes following maternal or paternal exposure to teriflunomide in the Danish MS population. Mult Scler Relat Disord 2022; 59: 103529
• 52 Almas S, Vance J, Baker T, Hale T. Management of multiple sclerosis in the breastfeeding mother. Mult Scler Int 2016; 2016: 6527458
• 53 Novi G, Ghezzi A, Pizzorno M. et al. Dramatic rebounds of MS during pregnancy following fingolimod withdrawal. Neurol Neuroimmunol Neuroinflamm 2017; 4 (05) e377
• 54 Pauliat E, Onken M, Weber-Schoendorfer C. et al. Pregnancy outcome following first-trimester exposure to fingolimod: A collaborative ENTIS study. Mult Scler 2021; 27 (03) 475-478
• 55 Dost-Kovalsky K, Thiel S, Ciplea AI, Gold R, Hellwig K. Cladribine and pregnancy in women with multiple sclerosis: The first cohort study. Mult Scler 2023; 29 (03) 461-465
• 56 Dobson R, Dassan P, Roberts M, Giovannoni G, Nelson-Piercy C, Brex PA. UK consensus on pregnancy in multiple sclerosis: ‘Association of British Neurologists’ guidelines. Pract Neurol 2019; 19 (02) 106-114
• 57 Giovannoni G, Galazka A, Schick R. et al. Pregnancy outcomes during the clinical development program of cladribine in multiple sclerosis: An integrated analysis of safety. Drug Saf 2020; 43 (07) 635-643
• 58 Datta P, Ciplea AI, Rewers-Felkins K. et al. Cladribine transfer into human milk: A case report. Mult Scler 2021; 27 (05) 799-801
• 59 Portaccio E, Annovazzi P, Ghezzi A. et al; MS Study Group of the Italian Neurological Society. Pregnancy decision-making in women with multiple sclerosis treated with natalizumab: I: Fetal risks. Neurology 2018; 90 (10) e823-e831
• 60 Ebrahimi N, Herbstritt S, Gold R, Amezcua L, Koren G, Hellwig K. Pregnancy and fetal outcomes following natalizumab exposure in pregnancy. A prospective, controlled observational study. Mult Scler 2015; 21 (02) 198-205
• 61 Friend S, Richman S, Bloomgren G, Cristiano LM, Wenten M. Evaluation of pregnancy outcomes from the Tysabri® (natalizumab) pregnancy exposure registry: a global, observational, follow-up study. BMC Neurol 2016; 16 (01) 150
• 62 Kapoor R, Ho PR, Campbell N. et al; ASCEND investigators. Effect of natalizumab on disease progression in secondary progressive multiple sclerosis (ASCEND): a phase 3, randomised, double-blind, placebo-controlled trial with an open-label extension. Lancet Neurol 2018; 17 (05) 405-415
• 63 Valero-López G, Millán-Pascual J, Iniesta-Martínez F. et al. Treatment with natalizumab during pregnancy in multiple sclerosis: The experience of implementing a clinical practice protocol (NAP-30). Mult Scler Relat Disord 2022; 66: 104038
• 64 Hellwig K, Tokic M, Thiel S. et al. Multiple sclerosis disease activity and disability following discontinuation of natalizumab for pregnancy. JAMA Netw Open 2022; 5 (01) e2144750
• 65 Haghikia A, Langer-Gould A, Rellensmann G. et al. Natalizumab use during the third trimester of pregnancy. JAMA Neurol 2014; 71 (07) 891-895
• 66 Proschmann U, Haase R, Inojosa H, Akgün K, Ziemssen T. Drug and neurofilament levels in serum and breastmilk of women with multiple sclerosis exposed to natalizumab during pregnancy and lactation. Front Immunol 2021; 12: 715195
• 67 Hurley WL, Theil PK. Perspectives on immunoglobulins in colostrum and milk. Nutrients 2011; 3 (04) 442-474
• 68 Hellwig K, Oreja-Guevara C, Vukusic C. et al. Pregnancy and Infant Outcomes in Women Receiving Ocrelizumab for the Treatment of Multiple Sclerosis: Analysis of the Largest Available Outcomes Database. Presented at the 9th Joint European Committee for Treatment and Research in MS - Americas Committee for Treatment and Research in MS Meeting in Milan, Italy; October 11–13,. 2023 . ECTRIMS-ACTRIMS Poster #P061
• 69 Gklinos P, Dobson R. Monoclonal antibodies in pregnancy and breastfeeding in patients with multiple sclerosis: a review and an updated clinical guide. Pharmaceuticals (Basel) 2023; 16 (05) 770
• 70 Kümpfel T, Thiel S, Meinl I. et al. Anti-CD20 therapies and pregnancy in neuroimmunologic disorders: A cohort study from Germany. Neurol Neuroimmunol Neuroinflamm 2020; 8 (01) e913
• 71 Anderson A, Rowles W, Poole S. et al. Anti-CD20 monoclonal antibody therapy in postpartum women with neurological conditions. Ann Clin Transl Neurol 2023; 10 (11) 2053-2064
• 72 Anderson A, Poole S, Rowles W. et al. Anti-CD20 monoclonal antibody therapy after 59 pregnancies in women with neurological conditions: low breastmilk transfer and normal infant development in a multicenter cohort. Mult Scler 2022; 28 (03) , suppl l ) 30
• 73 Bove R, Hellwig K, Pasquarelli N. et al. Ocrelizumab during pregnancy and lactation: Rationale and design of the MINORE and SOPRANINO studies in women with MS and their infants. Mult Scler Relat Disord 2022; 64: 103963
• 74 Hellwig K, Yamout B, Bove R. et al. Pregnancy outcomes in ofatumumab-treated patients with multiple sclerosis. In: Proceedings of the Consortium of Multiple Sclerosis Centers Annual Meeting,. National Harbor, MD, USA. 2022
• 75 Bellot M, Luetjens CM, Bagger M. et al. Effect of ofatumumab on pregnancy, parturition, and lactation in cynomolgus monkeys. Reprod Toxicol 2022; 108: 28-34
• 76 Witt L, Thiel S, Hellwig K. Schwangerschaft und Stillzeit bei Frauen mit Multipler Sklerose. [Pregnancy and breastfeeding in women with multiple sclerosis] Nervenarzt 2024; 95 (04) 329-334
• 77 Coles AJ, Cohen JA, Fox EJ. et al; CARE-MS II and CAMMS03409 Investigators. Alemtuzumab CARE-MS II 5-year follow-up: Efficacy and safety findings. Neurology 2017; 89 (11) 1117-1126
• 78 Oh J, Achiron A, Celius EG. et al; CAMMS223, CARE-MS I, CARE-MS II, CAMMS03409, and TOPAZ Investigators. Pregnancy outcomes and postpartum relapse rates in women with RRMS treated with alemtuzumab in the phase 2 and 3 clinical development program over 16 years. Mult Scler Relat Disord 2020; 43: 102146
• 79 Iyer P, Dobson R. Multiple sclerosis in pregnancy: a commentary on disease modification and symptomatic drug therapies. Neurol Ther 2023; 12 (01) 1-10