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Neuromyelitis optica spectrum disorders and pregnancy: therapeutic considerations

Nature Reviews Neurology volume 16, pages 154–170 (2020)Cite this article

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Abstract

Neuromyelitis optica spectrum disorders (NMOSD) are a type of neurological autoimmune disease characterized by attacks of CNS inflammation that are often severe and predominantly affect the spinal cord and optic nerve. The majority of individuals with NMOSD are women, many of whom are of childbearing age. Although NMOSD are rare, several small retrospective studies and case reports have indicated that pregnancy can worsen disease activity and might contribute to disease onset. NMOSD disease activity seems to negatively affect pregnancy outcomes. Moreover, some of the current NMOSD treatments are known to pose risks to the developing fetus and only limited safety data are available for others. Here, we review published studies regarding the relationship between pregnancy outcomes and NMOSD disease activity. We also assess the risks associated with using disease-modifying therapies for NMOSD during the course of pregnancy and breastfeeding. On the basis of the available evidence, we offer recommendations regarding the use of these therapies in the course of pregnancy planning in individuals with NMOSD.

Key points

  • Several studies have shown that women with neuromyelitis optica spectrum disorders (NMOSD) have an increased risk of relapse postpartum; the available data are insufficient to accurately define the relapse risk during pregnancy.

  • Aquaporin 4 (AQP4), which is the main target antigen in NMOSD, is expressed at high levels in the placenta, and women with active NMOSD have a high risk of miscarriage.

  • AQP4 antibodies cross the placenta and are found in the blood of newborn infants without causing symptoms; however, other autoantibodies or comorbid autoimmune conditions can cause symptoms in the newborn infant.

  • Azathioprine, rituximab, eculizumab and glucocorticoids seem to be relatively safe in pregnancy and are the treatments of choice; tocilizumab can be considered in women with very severe NMOSD.

  • Given the risk of obstetric complications and postpartum NMOSD relapse, patients should be informed about the advantages and risks of the use of NMOSD treatments at the time of conception or during pregnancy, and should be monitored in a multidisciplinary manner.

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Fig. 1: AQP4 and MOG autoimmunity during pregnancy and NMOSD treatments.

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Acknowledgements

K.H. is an investigator of the NEMOS cohort/NationNMO supported by the German Ministry for Education and Research (BMBF) as part of the ‘German Competence Network Multiple Sclerosis’ (KKNMS; FKZ 01GI1602). She is also a member of the international Guthy-Jackson Charitable Foundation (GJCF) and coordinator of the GJCF International Clinical Consortium Sex & Gender Specificity Working Group, and receives grant support from the Innovation Fund of the Federal Joint Committee. I.K.S. has received research funding from the National Multiple Sclerosis Society, the US Department of Defense and the Guthy-Jackson Charitable Foundation. S.J. thanks the Dietmar Hopp Foundation and Merck Serono for funding research on AQP4-IgG-positive NMOSD and on MOG encephalomyelitis. Y.M.-D. is currently supported by grants from the NIH National Institute of Allergy and Infectious Diseases Autoimmune Center of Excellence (UM1-AI110557; NIH NINDS R01-NS080821). E.M. was supported by a Kirschstein-NRSA (2T32HD007505–21) grant. T.C. is currently supported by grants from the Department of Defense, the Guthy-Jackson Charitable Foundation and the National MS Society. S.T. is currently supported by the Innovation Fund of the Federal Joint Committee. M.I.L. receives support from the National Health Service National Specialized Commissioning Group for Neuromyelitis Optica UK and the National Institute for Health Research Oxford Biomedical Research Centre. The authors thank C. Fisher for her assistance in designing the figures for this Review.

Author information

Author notes

  1. These authors contributed equally: Yang Mao-Draayer, Sandra Thiel.

Authors and Affiliations

  1. Department of Neurology, University of Michigan Medical School, Ann Arbor, MI, USA

    Yang Mao-Draayer & Elizabeth A. Mills

  2. Graduate Program in Immunology, Program in Biomedical Sciences, University of Michigan Medical School, Ann Arbor, MI, USA

    Yang Mao-Draayer

  3. Department of Neurology, St. Josef-Hospital, Ruhr-University Bochum, Bochum, Germany

    Sandra Thiel & Kerstin Hellwig

  4. Department of Neurology, Brigham and Women’s Hospital and Massachusetts General Hospital, Boston, MA, USA

    Tanuja Chitnis

  5. Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY, USA

    Michelle Fabian & Ilana Katz Sand

  6. Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK

    M. Isabel Leite

  7. Molecular Neuroimmunology Group, Department of Neurology, University of Heidelberg, Heidelberg, Germany

    Sven Jarius

Authors
  1. Yang Mao-Draayer
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  2. Sandra Thiel
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  3. Elizabeth A. Mills
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  4. Tanuja Chitnis
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  5. Michelle Fabian
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  6. Ilana Katz Sand
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  7. M. Isabel Leite
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  8. Sven Jarius
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  9. Kerstin Hellwig
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Contributions

The authors contributed equally to all aspects of the article.

Corresponding author

Correspondence to Kerstin Hellwig.

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Competing interests

Y.M.-D. has served as a consultant, speaker and/or received grant support from Acorda, Bayer Pharmaceutical, Biogen Idec, Celgene, Chugai, EMD Serono, Novartis, Questor, Roche-Genentech, Sanofi-Genzyme and Teva Neuroscience. T.C. has served as a one-time consultant for Alexion. M.F. has received speaker honoraria from Biogen Idec. M.I.L. received travel funding and speaker honoraria from Biogen Idec and received a travel grant from Novartis. The work of S.J. was indirectly supported by grants from Dietmar Hopp Stiftung, Germany, and from Merck Serono, Germany (to B. Wildemann, Department of Neurology, University Hospital Heidelberg). K.H. received research support and speaker honoraria from Bayer, Biogen Idec, Genzyme, Merck Serono, Novartis, Roche and Teva. E.M., I.K.S. and S.T. declare no competing interests.

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Nature Reviews Neurology thanks J. de Seze, H. J. Kim and M. Levy for their contribution to the peer review of this work.

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Mycophenolate Risk Evaluation and Mitigation Strategy: https://www.mycophenolaterems.com/

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Mao-Draayer, Y., Thiel, S., Mills, E.A. et al. Neuromyelitis optica spectrum disorders and pregnancy: therapeutic considerations. Nat Rev Neurol 16, 154–170 (2020). https://doi.org/10.1038/s41582-020-0313-y

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