Influences of pregnancy on neuromyelitis optica spectrum disorders and multiple sclerosis

Tong, Yanping; Liu, Jie; Yang, Tao; Kang, Youngnam; Wang, Jingwen; Zhao, Tianyou; Cheng, Chu; Fan, Yongping

doi:10.1016/j.msard.2018.07.006

Cited by 24 publications

(22 citation statements)

References 21 publications

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“…Although AQP4-IgG has been shown to cause placental inflammation and lead to negative pregnancy outcomes in animal studies, a recent study of the placentae of patients with NMOSD showed no clear decrease in placental AQP4 expression, no obvious placental inflammation or signs of damage in placental AQP4-IgG seropositive NMOSD patients, and no negative effects in term-born infants (46). It is possible that the increased disease activity and adverse pregnancy outcomes in patients with NMOSD is due to a multitude of factors, including the effect of pregnancy hormones such as estrogen, progesterone and glucocorticoids (11,45). In fact, this review indicates that pregnancy and the postpartum period appears to be a high-risk time for disease activity and relapses.…”

Section: Discussionmentioning

confidence: 98%

“…This would imply that the disease activity of NMOSD (a Th2-mediated disease) should be considerably higher than that of multiple sclerosis, which many believe is primarily a Th1mediated disease. However, a recent study has shown this not to be the case, suggesting that Th1/Th2 cytokine imbalance is not the primary pathophysiological pathway of NMOSD activity during pregnancy (11). It has also been suggested that the higher estrogen levels in pregnancy can lead to development of self-reactive peripheral B cells, which can increase antibody production in NMOSD (vs. multiple sclerosis which is not an antibody-mediated disease) (45).…”

Section: Discussionmentioning

confidence: 99%

“…Following the first round of screening, 1,520 were found not to be relevant to pregnancy and NMOSD. We sourced the remaining 62 full-texts and excluded a further 33 were excluded for reasons identified in seven publications summarized data on all pregnancies managed at one or more centres (6)(7)(8)(9)(10)(11)14).…”

Section: Included Publications and Pregnanciesmentioning

confidence: 99%

“…With regard to the antepartum period, it is unclear whether relapses occur with greater frequency during any particular trimester. Tong et al reported no increase in relapses during pregnancy in 234 pregnancies (11). Fragoso et al reported that relapses were most common in the first trimester (7), while Bourre reported it to be highest in the third trimester (10).…”

Section: Relapsesmentioning

confidence: 99%

“…Women are more likely to be affected by seropositive (AQP4+) NMOSD than men, and in some series the ratio of women-to-men affected was as high as 9:1 (5). This gender disparity, the humoral basis of the condition, and the fact that NMOSD can affect those in the reproductive age group (median age of onset 32-41 years) (2), has generated much interest in NMOSD and pregnancy over the past decade, with a number of publications suggesting increased risk of relapse and greater disability during and immediately after pregnancy (6)(7)(8)(9)(10)(11)(12)(13). Some others have also suggested an increased association between NMOSD and adverse pregnancy outcomes such as miscarriage and preeclampsia, especially in the presence of other autoimmune conditions (14).…”

Section: Introductionmentioning

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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Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

Section: Included Publications and Pregnanciesmentioning

confidence: 99%

Section: Relapsesmentioning

confidence: 99%

Section: Introductionmentioning

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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Effects of pregnancy on neuromyelitis optica spectrum disorder and predictors of related attacks

Shi

Chen

et al. 2022

Ann Clin Transl Neurol

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Objective: Our study aimed to investigate the influence of pregnancy on the course of neuromyelitis optica spectrum disorders (NMOSD) and to explore the independent predictors of pregnancy-related attacks. Methods: We performed a retrospective study of patients with NMOSD based on the Wingerchuk 2006 or the revised Wingerchuk 2015 criteria. Demographic, clinical, and pregnancy data were recorded. We compared the annualized relapse rate (ARR) before, during, and after pregnancy. The Expanded Disability Status Scale (EDSS) score was used to assess the degree of disability. Multivariate Cox proportional hazards models were used to identify the independent risk factors that predict pregnancy-related attacks. Results: There were 202 informative pregnancies following symptom onset in 112 women with NMOSD. The ARR in the first-trimester postpartum period (1.44 AE 2.04) was higher than that before pregnancy (0.23 AE 0.48; p < 0.001) and during pregnancy. The EDSS score increased from 1.40 AE 1.38 before pregnancy to 1.99 AE 1.78 postpartum (p = 0.004). Multivariate Cox proportional hazards models indicated that increased disease activity 1 year before conception (HR = 1.79, 95% CI 1.09-2.92, p = 0.021) and lack of immunotherapy during pregnancy and the postpartum period (HR = 5.25, 95% CI 1.91-14.42, p = 0.001) were independent risk factors that predicted pregnancy-related attacks. Interpretation: The postpartum period is a particularly high-risk time for the onset and relapse of NMOSD. Pregnancy exerted detrimental effects on the disease courses of NMOSD. Immunotherapy during pregnancy and the postpartum period might be recommended to decrease the risk of pregnancy-related attacks. Larger-scale prospective studies are warranted to confirm our findings.

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Contemporary management challenges in seropositive NMOSD

Costello

Burton

2022

J Neurol

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Neuromyelitis optica spectrum disorders (NMOSD) is an inflammatory disorder of the central nervous system that presents unique management challenges. Neurologic disability in NMOSD is directly linked to acute attacks, therefore, relapse prevention is an overarching goal of care. To this end, identifying effective biomarkers that predict relapse onset and severity is of critical importance. As treatment becomes more precision-based and patient-centred, clinicians will need to be familiar with managing circumstances of particular vulnerability for patients with NMOSD, including infection, pregnancy, and the post-partum phase. The discovery of the pathogenic aquaporin-4 Immunoglobulin G (AQP4 IgG) autoantibody almost 20 years ago ultimately distinguished NMOSD as an autoimmune astrocytopathy and helped spearhead recent therapeutic advancements. Targeted therapies, including eculizumab, satralizumab, and inebilizumab, approved for use in aquaporin-4 immunoglobulin G (AQP4 IgG) seropositive patients with NMOSD will likely improve outcomes, but there are formidable costs involved. Importantly, seronegative patients continue to have limited therapeutic options. Moving forward, areas of research exploration should include relapse prevention, restorative therapies, and initiatives that promote equitable access to approved therapies for all people living with NMOSD.

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Influences of pregnancy on neuromyelitis optica spectrum disorders and multiple sclerosis

Cited by 24 publications

References 21 publications

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

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

Effects of pregnancy on neuromyelitis optica spectrum disorder and predictors of related attacks

Contemporary management challenges in seropositive NMOSD

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