Pregnancy outcomes in aquaporin-4–positive neuromyelitis optica spectrum disorder

Abstract

Objective: To investigate the association between neuromyelitis optica spectrum disorder (NMOSD) and pregnancy outcome.Methods: An international cohort of women with aquaporin-4 antibody-positive NMOSD and $1 pregnancy was studied retrospectively. Multivariate logistic regression was used to investigate whether pregnancy after NMOSD onset was associated with an increased risk of miscarriage (cohort of 40 women) or preeclampsia (cohort of 57 women).Results: Miscarriage rate was higher in pregnancies after NMOSD onset (42.9% [95% confidence interval 17.7%-71.1%] vs 7.04% [2.33%-15.7%]). Pregnancies conceived after, or up to 3 years before, NMOSD onset had an increased odds ratio of miscarriage (7.28 [1.03-51.6] and 11.6 [1. , respectively), independent of maternal age or history of miscarriage. Pregnancies after, or up to 1 year before, NMOSD onset ending in miscarriage were associated with increased disease activity from 9 months before conception to the end of pregnancy, compared to viable pregnancies (mean annualized relapse rate 0.707 vs 0.100). The preeclampsia rate (11.5% [6.27%-18.9%]) was significantly higher than reported in population studies. The odds of preeclampsia were greater in women with multiple other autoimmune disorders or miscarriage in the most recent previous pregnancy, but NMOSD onset was not a risk factor.Conclusions: Pregnancy after NMOSD onset is an independent risk factor for miscarriage, and pregnancies conceived at times of high disease activity may be at increased risk of miscarriage. Women who develop NMOSD and have multiple other autoimmune disorders have greater odds of preeclampsia, independent of NMOSD onset timing. Neurology ® 2016;86:79-87 GLOSSARY AQP4 5 aquaporin-4; ARR 5 annualized relapse rate; CI 5 confidence interval; IgG 5 immunoglobulin G; NMO 5 neuromyelitis optica; NMOSD 5 neuromyelitis optica spectrum disorder; ON 5 optic neuritis; OR 5 odds ratio.Neuromyelitis optica spectrum disorder (NMOSD) is a severe recurrent antibody-mediated inflammatory disorder of the CNS, mainly characterized by optic neuritis (ON) and longitudinally extensive transverse myelitis, 1 but also affecting other areas in the CNS (e.g., brainstem and hypothalamus). The presence of immunoglobulin G (IgG) that binds to aquaporin-4 (AQP4), 2,3 known to be key in the pathogenic process of this disorder, distinguishes NMOSD from other CNS inflammatory disorders.1 NMOSD is up to 8 times more prevalent in women, 4 many of whom have active disease during childbearing years. [5][6][7] Recently, experimental and clinical reports have demonstrated the presence of AQP4 in human and animal placenta, and have linked AQP4-mediated placental inflammation to fetal death. [8][9][10] It is clear that the annualized relapse rate (ARR) of NMOSD is significantly increased in the 0-to 3-month postpartum period, 11-13 but there is a lack of information on the influence of NMOSD on the course of pregnancy.We investigated the effect of NMOSD on miscarriage and preeclampsia rates using multivariate logistic regre...

Management of women with multiple sclerosis through pregnancy and after childbirth

“…The attack rate is not significantly reduced during pregnancy, but then is also elevated during the 3 months postpartum [Shimizu et al 2015]. NMOSD is also associated with higher risk for miscarriage [Nour et al 2016].…”

Review: Recent advances in the understanding of the pathophysiology of neuromyelitis optica spectrum disorder

“…conducted a retrospective study to investigate the pregnancy outcomes of patients with NMOSD and observed a higher miscarriage rate after NMOSD onset (42.9% compared to 7.04% before NMOSD onset) . The clinical information obtained from this study suggested that pregnancy after NMOSD onset is a risk factor for miscarriage . Collectively, these findings provided further evidence indicating the destructive effects of AQP4‐IgG on the placenta.…”

Plasma exchange therapy for a severe relapse of Devic’s disease in a pregnant woman: A case report and concise review

“…Nevertheless, the actual influence of pregnancy in NMO cases has been scarcely described in case reports and small retrospective studies. A very recent retrospective analysis has also linked NMO to adverse pregnancy-related outcomes (preeclampsia, miscarriage) (10). Therapy for acute pregnancy-related relapses is based generally on steroids as well.…”

“…Recent case reports and reviews on the treatment of pregnancy-related relapses(13) mostly concern preemptive immunosuppression, steroids for acute attacks during pregnancy, and only scarcely use of other agents. To the best of our knowledge there are three cases reported in the literature where plasma exchange has been used during pregnancy (Bonnet et al, 1999;Cornelio et al, 2009; 1 patient in the retrospective cohort by Nour et al, 2016) (10,14,15); only one of them provided posterior follow-up details on the patient's status. This is the first report of the successful use of plasma exchange therapy in a Hispanic patient from a developing country such as our own, where there are very few comprehensive and specialized centers in the management of these patients and their neurological diseases.…”