Neuromyelitis optica spectrum disorders and pregnancy: therapeutic considerations

Mao-Draayer, Yang; Thiel, Sandra; Mills, Elizabeth; Chitnis, Tanuja; Fabian, Michelle; Sand, Ilana Katz; Leite, Maria Isabel; Jarius, Sven; Hellwig, Kerstin

doi:10.1038/s41582-020-0313-y

Cited by 65 publications

(111 citation statements)

References 188 publications

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“…45,47 A recently published review gives a comprehensive overview about the saftey data of immunotherapies used in NMOSD during pregnancy and lactation. 44…”

Section: Pregnancy and Postpartum Periodmentioning

confidence: 99%

Gender issues of antibody-mediated diseases in neurology: (NMOSD/autoimmune encephalitis/MG)

Altıntaş

Dargvainiene

Schneider‐Gold

et al. 2020

Ther Adv Neurol Disord

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Neuromyelitis optica spectrum disorder (NMOSD), autoimmune encephalitis (AE), myasthenia gravis (MG) and Lambert-Eaton myasthenic syndrome (LEMS) are antibody-mediated neurological diseases. They have mostly female predominance, affecting many women during childbearing age. Interactions between the underlying disease (or necessary treatment) and pregnancy can occur in every of these illnesses. Herein, we present the characteristics of NMOSD, AE, MG and LEMS in general, and review published data regarding the influence of the different diseases on fertility, pregnancy, puerperium, treatment strategy during pregnancy and post-partum period, and menopause but also male factors. We summarise key elements that should be borne in mind when confronted with such cases.

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“…45,47 A recently published review gives a comprehensive overview about the saftey data of immunotherapies used in NMOSD during pregnancy and lactation. 44…”

Section: Pregnancy and Postpartum Periodmentioning

confidence: 99%

Gender issues of antibody-mediated diseases in neurology: (NMOSD/autoimmune encephalitis/MG)

Altıntaş

Dargvainiene

Schneider‐Gold

et al. 2020

Ther Adv Neurol Disord

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“…Lactation is compatible with glucocorticoid use, as glucocorticoid levels in breast milk are typically very low and no modifications to breastfeeding are recommended with short-term use. However, in those receiving high doses, delaying breastfeeding for 4 h theoretically would decrease the dose received by the infant (49,52). • Immunosuppressive Agents: Along with corticosteroids, other immunosuppressive agents form the mainstay of treatment of initial attacks and relapses.…”

Section: Discussionmentioning

confidence: 99%

“…Initiation of prophylactic immunosuppressive treatment or increasing the dose of existing medication during pregnancy and in the early postpartum period could prevent relapses. A detailed account of therapeutic considerations with NMOSD and pregnancy has been recently published ( 49 ). A summary of various medications and their safety during pregnancy and lactation, based on most up-to-date evidence ( 49 – 53 ) is presented in Table 2 , and discussed below…”

Section: Discussionmentioning

confidence: 99%

“…Corticosteroids: Glucocorticoids are administered to patients with NMOSD both at high doses (1,000 mg/day for 5 days, administered intravenously) as a treatment for acute attacks and at lower doses (30 mg) as oral immunosuppressive therapy ( 49 ). Non-fluorinated glucocorticoids such as prednisone, prednisolone and methylprednisolone have a plasma half-life of 1–3 h and a duration of action of 12–36 h ( 49 ) Systemic corticosteroids are generally well-tolerated in pregnancy. Also, only 10% crosses into the fetal circulation due to placental metabolism and initial concerns with regard to their association with fetal orofacial clefts ( 58 ) has now been disproven ( 59 – 61 ).…”

Section: Discussionmentioning

confidence: 99%

“…Immunosuppressive Agents: Along with corticosteroids, other immunosuppressive agents form the mainstay of treatment of initial attacks and relapses. Azathioprine is a relatively safe option for use during pregnancy and lactation ( 49 , 61 ), despite indications of a slightly increased risk of adverse outcomes, and should be initiated or continued, regardless of gestational age, should the clinical condition require pharmacologic management ( 62 , 63 ). Tacrolimus has been used effectively, but is not among the first line treatments approved for NMOSD.…”

Section: Discussionmentioning

confidence: 99%

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Pregnancy and Neuromyelitis Optica Spectrum Disorder – Reciprocal Effects and Practical Recommendations: A Systematic Review

et al. 2020

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Introduction: Neuromyelitis optica spectrum disorder (NMOSD) is an inflammatory disorder of the central nervous system characterized by severe, antibody-mediated astrocyte loss with secondary demyelination and axonal damage, predominantly targeting optic nerves and the spinal cord. Recent publications have alluded to increased disease activity during pregnancy, and adverse maternal and fetal outcomes in patients with NMOSD. Our objective was to systematically review published literature to help counsel and manage women with NMOSD contemplating pregnancy. Methods: We searched five databases including MEDLINE and EMBASE, for English-language publications describing pregnancies in women with NMOSD. Article selection, data extraction, and risk-of-bias assessment using Joanna Briggs' critical appraisal tool for case reports and case series, were performed in duplicate. Pooled incidences were calculated where possible, and a narrative summary was provided. Results: Of 2,118 identified titles, 22 case reports and seven case series, representing 595 pregnancies in 389 women, were included. The mean maternal age was 28.12 ± 5.19 years. At least 20% of cases were first diagnosed during pregnancy. There were no maternal deaths. Pooled estimates for clinical outcomes could not be obtained due to inadequate reporting. NMOSD-related disability and relapses increased considerably during pregnancy and especially in the immediate postpartum period. Although a high proportion of early pregnancy losses were reported, an association with disease activity or therapeutic interventions could not be established. Apart from one publication which reported an increased risk of preeclampsia, there was no increase in adverse obstetric outcomes including preterm birth, fetal growth restriction or congenital malformations. Initial attacks and relapses were successfully managed with oral or intravenous D'Souza et al. NMOSD and Pregnancy: Systematic Review corticosteroids and immunosuppressants, and refractory cases with immunoglobulin, plasma exchange and immunoadsorption. Conclusion: Increased NMOSD-related disability and relapses during pregnancy the postpartum period may respond to aggressive management with corticosteroids and immunosuppressants such as azathioprine, which are safely administered during pregnancy and lactation. Emerging safety data on monoclonal antibodies during pregnancy, make these attractive options, while intravenous immunoglobulin, plasma exchange and immunoadsorption can be safely used to treat severe relapses. The complex interplay between NMOSD and pregnancy outcomes would be best understood through prospective analysis of data collected through an international registry. Disclosure: Dalia Rotstein has served as a consultant or speaker for Alexion and Roche. She has received research support from Roche Canada. Rohan D'Souza has served as a consultant and speaker for Ferring Canada Inc and Ferring Global Inc, on topics unrelated to this manuscript. The other authors have no relevant relationships to disclose.

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Analysis of Pregnancy-Related Attacks in Neuromyelitis Optica Spectrum Disorder

Wang

Zhou

et al. 2022

JAMA Netw Open

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IMPORTANCERisk of relapse may be increased in the postpartum period of neuromyelitis optica spectrum disorder (NMOSD). Information regarding factors associated with pregnancy-related attacks is still lacking. OBJECTIVES To identify factors associated with pregnancy-related NMOSD attacks, investigate the integrated annualized relapse rate (ARR) and Expanded Disability Status Scale (EDSS) score in each phase of pregnancy, and summarize pregnancy outcomes and complications in patients with NMOSD. DATA SOURCES An electronic search was performed in the MEDLINE, PubMed in-process and non-MEDLINE, EMBASE, Web of Science, and Cochrane databases using the OvidSP search platform, updated through December 30, 2021. STUDY SELECTION All published and unpublished studies in English were considered, covering all patients with NMOSD with an informative pregnancy. DATA EXTRACTION AND SYNTHESIS Two independent reviewers extracted the published data with a standardized procedure following MOOSE and PRISMA guidelines. The end points were calculated with the DerSimonian and Laird inverse variance (for random effects) method. MAIN OUTCOMES AND MEASURESThe primary outcome was the rate of pregnancies with pregnancy-related NMOSD attacks, measured by risk ratios (RRs). The mean differences (MDs) in ARR and EDSS scores between each phase of pregnancy, pregnancy outcomes, and complications were defined as the secondary outcomes. RESULTSA total of 15 studies were analyzed, including 443 patients with NMOSD with 639 informative pregnancies. Patients receiving immunosuppressive treatment during pregnancy (RR, 0.43; 95% CI, 0.32-0.57; P < .001) and with older age at conception (RR, 0.67; 95% CI, 0.47-0.95; P = .02) had lower rates of pregnancy with pregnancy-related attacks. The increase in the ARR was highest in the first trimester after delivery compared with before pregnancy (MD, 1.28; 95% CI, 0.94-1.62; P < .001). The EDSS scores increased significantly both during pregnancy (MD, 0.44; 95% CI, 0.20-0.69; P < .001) and in the postpartum period (MD, 0.88; 95% CI, 0.51-1.26; P < .001) compared with before pregnancy. CONCLUSIONS AND RELEVANCEThis systematic review and meta-analysis found that receiving immunosuppressive treatment during pregnancy and older age at conception were associated with (continued) Key Points Question What are the factors associated with pregnancy-related attacks in neuromyelitis optica spectrum disorder? Findings This systematic review and meta-analysis of 15 studies with 443 patients found that receiving immunosuppressive treatment during pregnancy and older age at conception were associated with lower risk of pregnancy-related attacks. Annualized relapse rate was elevated especially during the first trimester after delivery while the Expanded Disability Status Scale score worsened during pregnancy and the postpartum period. Meaning These findings suggest that receiving immunosuppressive treatment during pregnancy and older age at conception were associated with protection against pregnancy-related neuromyelitis opti...

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Neuromyelitis optica spectrum disorders and pregnancy: therapeutic considerations

Cited by 65 publications

References 188 publications

Gender issues of antibody-mediated diseases in neurology: (NMOSD/autoimmune encephalitis/MG)

Gender issues of antibody-mediated diseases in neurology: (NMOSD/autoimmune encephalitis/MG)

Pregnancy and Neuromyelitis Optica Spectrum Disorder – Reciprocal Effects and Practical Recommendations: A Systematic Review

Analysis of Pregnancy-Related Attacks in Neuromyelitis Optica Spectrum Disorder

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