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