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January 05, 2016; 86 (1) Article

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

Matthew M. Nour, Ichiro Nakashima, Ester Coutinho, Mark Woodhall, Filipa Sousa, Jon Revis, Yoshiki Takai, Jithin George, Joanna Kitley, Maria Ernestina Santos, Joseph M. Nour, Fan Cheng, Hiroshi Kuroda, Tatsuro Misu, Ana Martins-da-Silva, Gabriele C. DeLuca, Angela Vincent, Jacqueline Palace, Patrick Waters, Kazuo Fujihara, Maria Isabel Leite
First published November 18, 2015, DOI: https://doi.org/10.1212/WNL.0000000000002208
Matthew M. Nour
From the Nuffield Department of Clinical Neurosciences (M.M.N., E.C., M.W., J.R., J.G., J.K., J.M.N., F.C., G.C.D., A.V., J.P., P.W., M.I.L.), John Radcliffe Hospital, University of Oxford, UK; Departments of Neurology (I.N., Y.T., H.K.) and Multiple Sclerosis Therapeutics (T.M., K.F.), Tohoku University Graduate School of Medicine, Sendai, Japan; Department of Clinical Neurology (F.S.), Hospital de São Marcos, Braga; and Department of Clinical Neurology (A.M.-d.-S., M.E.S.), Hospital Geral Santo Antonio, Porto, Portugal.
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Ichiro Nakashima
From the Nuffield Department of Clinical Neurosciences (M.M.N., E.C., M.W., J.R., J.G., J.K., J.M.N., F.C., G.C.D., A.V., J.P., P.W., M.I.L.), John Radcliffe Hospital, University of Oxford, UK; Departments of Neurology (I.N., Y.T., H.K.) and Multiple Sclerosis Therapeutics (T.M., K.F.), Tohoku University Graduate School of Medicine, Sendai, Japan; Department of Clinical Neurology (F.S.), Hospital de São Marcos, Braga; and Department of Clinical Neurology (A.M.-d.-S., M.E.S.), Hospital Geral Santo Antonio, Porto, Portugal.
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Ester Coutinho
From the Nuffield Department of Clinical Neurosciences (M.M.N., E.C., M.W., J.R., J.G., J.K., J.M.N., F.C., G.C.D., A.V., J.P., P.W., M.I.L.), John Radcliffe Hospital, University of Oxford, UK; Departments of Neurology (I.N., Y.T., H.K.) and Multiple Sclerosis Therapeutics (T.M., K.F.), Tohoku University Graduate School of Medicine, Sendai, Japan; Department of Clinical Neurology (F.S.), Hospital de São Marcos, Braga; and Department of Clinical Neurology (A.M.-d.-S., M.E.S.), Hospital Geral Santo Antonio, Porto, Portugal.
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Mark Woodhall
From the Nuffield Department of Clinical Neurosciences (M.M.N., E.C., M.W., J.R., J.G., J.K., J.M.N., F.C., G.C.D., A.V., J.P., P.W., M.I.L.), John Radcliffe Hospital, University of Oxford, UK; Departments of Neurology (I.N., Y.T., H.K.) and Multiple Sclerosis Therapeutics (T.M., K.F.), Tohoku University Graduate School of Medicine, Sendai, Japan; Department of Clinical Neurology (F.S.), Hospital de São Marcos, Braga; and Department of Clinical Neurology (A.M.-d.-S., M.E.S.), Hospital Geral Santo Antonio, Porto, Portugal.
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Filipa Sousa
From the Nuffield Department of Clinical Neurosciences (M.M.N., E.C., M.W., J.R., J.G., J.K., J.M.N., F.C., G.C.D., A.V., J.P., P.W., M.I.L.), John Radcliffe Hospital, University of Oxford, UK; Departments of Neurology (I.N., Y.T., H.K.) and Multiple Sclerosis Therapeutics (T.M., K.F.), Tohoku University Graduate School of Medicine, Sendai, Japan; Department of Clinical Neurology (F.S.), Hospital de São Marcos, Braga; and Department of Clinical Neurology (A.M.-d.-S., M.E.S.), Hospital Geral Santo Antonio, Porto, Portugal.
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Jon Revis
From the Nuffield Department of Clinical Neurosciences (M.M.N., E.C., M.W., J.R., J.G., J.K., J.M.N., F.C., G.C.D., A.V., J.P., P.W., M.I.L.), John Radcliffe Hospital, University of Oxford, UK; Departments of Neurology (I.N., Y.T., H.K.) and Multiple Sclerosis Therapeutics (T.M., K.F.), Tohoku University Graduate School of Medicine, Sendai, Japan; Department of Clinical Neurology (F.S.), Hospital de São Marcos, Braga; and Department of Clinical Neurology (A.M.-d.-S., M.E.S.), Hospital Geral Santo Antonio, Porto, Portugal.
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Yoshiki Takai
From the Nuffield Department of Clinical Neurosciences (M.M.N., E.C., M.W., J.R., J.G., J.K., J.M.N., F.C., G.C.D., A.V., J.P., P.W., M.I.L.), John Radcliffe Hospital, University of Oxford, UK; Departments of Neurology (I.N., Y.T., H.K.) and Multiple Sclerosis Therapeutics (T.M., K.F.), Tohoku University Graduate School of Medicine, Sendai, Japan; Department of Clinical Neurology (F.S.), Hospital de São Marcos, Braga; and Department of Clinical Neurology (A.M.-d.-S., M.E.S.), Hospital Geral Santo Antonio, Porto, Portugal.
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Jithin George
From the Nuffield Department of Clinical Neurosciences (M.M.N., E.C., M.W., J.R., J.G., J.K., J.M.N., F.C., G.C.D., A.V., J.P., P.W., M.I.L.), John Radcliffe Hospital, University of Oxford, UK; Departments of Neurology (I.N., Y.T., H.K.) and Multiple Sclerosis Therapeutics (T.M., K.F.), Tohoku University Graduate School of Medicine, Sendai, Japan; Department of Clinical Neurology (F.S.), Hospital de São Marcos, Braga; and Department of Clinical Neurology (A.M.-d.-S., M.E.S.), Hospital Geral Santo Antonio, Porto, Portugal.
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Joanna Kitley
From the Nuffield Department of Clinical Neurosciences (M.M.N., E.C., M.W., J.R., J.G., J.K., J.M.N., F.C., G.C.D., A.V., J.P., P.W., M.I.L.), John Radcliffe Hospital, University of Oxford, UK; Departments of Neurology (I.N., Y.T., H.K.) and Multiple Sclerosis Therapeutics (T.M., K.F.), Tohoku University Graduate School of Medicine, Sendai, Japan; Department of Clinical Neurology (F.S.), Hospital de São Marcos, Braga; and Department of Clinical Neurology (A.M.-d.-S., M.E.S.), Hospital Geral Santo Antonio, Porto, Portugal.
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Maria Ernestina Santos
From the Nuffield Department of Clinical Neurosciences (M.M.N., E.C., M.W., J.R., J.G., J.K., J.M.N., F.C., G.C.D., A.V., J.P., P.W., M.I.L.), John Radcliffe Hospital, University of Oxford, UK; Departments of Neurology (I.N., Y.T., H.K.) and Multiple Sclerosis Therapeutics (T.M., K.F.), Tohoku University Graduate School of Medicine, Sendai, Japan; Department of Clinical Neurology (F.S.), Hospital de São Marcos, Braga; and Department of Clinical Neurology (A.M.-d.-S., M.E.S.), Hospital Geral Santo Antonio, Porto, Portugal.
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Joseph M. Nour
From the Nuffield Department of Clinical Neurosciences (M.M.N., E.C., M.W., J.R., J.G., J.K., J.M.N., F.C., G.C.D., A.V., J.P., P.W., M.I.L.), John Radcliffe Hospital, University of Oxford, UK; Departments of Neurology (I.N., Y.T., H.K.) and Multiple Sclerosis Therapeutics (T.M., K.F.), Tohoku University Graduate School of Medicine, Sendai, Japan; Department of Clinical Neurology (F.S.), Hospital de São Marcos, Braga; and Department of Clinical Neurology (A.M.-d.-S., M.E.S.), Hospital Geral Santo Antonio, Porto, Portugal.
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Fan Cheng
From the Nuffield Department of Clinical Neurosciences (M.M.N., E.C., M.W., J.R., J.G., J.K., J.M.N., F.C., G.C.D., A.V., J.P., P.W., M.I.L.), John Radcliffe Hospital, University of Oxford, UK; Departments of Neurology (I.N., Y.T., H.K.) and Multiple Sclerosis Therapeutics (T.M., K.F.), Tohoku University Graduate School of Medicine, Sendai, Japan; Department of Clinical Neurology (F.S.), Hospital de São Marcos, Braga; and Department of Clinical Neurology (A.M.-d.-S., M.E.S.), Hospital Geral Santo Antonio, Porto, Portugal.
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Hiroshi Kuroda
From the Nuffield Department of Clinical Neurosciences (M.M.N., E.C., M.W., J.R., J.G., J.K., J.M.N., F.C., G.C.D., A.V., J.P., P.W., M.I.L.), John Radcliffe Hospital, University of Oxford, UK; Departments of Neurology (I.N., Y.T., H.K.) and Multiple Sclerosis Therapeutics (T.M., K.F.), Tohoku University Graduate School of Medicine, Sendai, Japan; Department of Clinical Neurology (F.S.), Hospital de São Marcos, Braga; and Department of Clinical Neurology (A.M.-d.-S., M.E.S.), Hospital Geral Santo Antonio, Porto, Portugal.
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Tatsuro Misu
From the Nuffield Department of Clinical Neurosciences (M.M.N., E.C., M.W., J.R., J.G., J.K., J.M.N., F.C., G.C.D., A.V., J.P., P.W., M.I.L.), John Radcliffe Hospital, University of Oxford, UK; Departments of Neurology (I.N., Y.T., H.K.) and Multiple Sclerosis Therapeutics (T.M., K.F.), Tohoku University Graduate School of Medicine, Sendai, Japan; Department of Clinical Neurology (F.S.), Hospital de São Marcos, Braga; and Department of Clinical Neurology (A.M.-d.-S., M.E.S.), Hospital Geral Santo Antonio, Porto, Portugal.
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Ana Martins-da-Silva
From the Nuffield Department of Clinical Neurosciences (M.M.N., E.C., M.W., J.R., J.G., J.K., J.M.N., F.C., G.C.D., A.V., J.P., P.W., M.I.L.), John Radcliffe Hospital, University of Oxford, UK; Departments of Neurology (I.N., Y.T., H.K.) and Multiple Sclerosis Therapeutics (T.M., K.F.), Tohoku University Graduate School of Medicine, Sendai, Japan; Department of Clinical Neurology (F.S.), Hospital de São Marcos, Braga; and Department of Clinical Neurology (A.M.-d.-S., M.E.S.), Hospital Geral Santo Antonio, Porto, Portugal.
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Gabriele C. DeLuca
From the Nuffield Department of Clinical Neurosciences (M.M.N., E.C., M.W., J.R., J.G., J.K., J.M.N., F.C., G.C.D., A.V., J.P., P.W., M.I.L.), John Radcliffe Hospital, University of Oxford, UK; Departments of Neurology (I.N., Y.T., H.K.) and Multiple Sclerosis Therapeutics (T.M., K.F.), Tohoku University Graduate School of Medicine, Sendai, Japan; Department of Clinical Neurology (F.S.), Hospital de São Marcos, Braga; and Department of Clinical Neurology (A.M.-d.-S., M.E.S.), Hospital Geral Santo Antonio, Porto, Portugal.
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Angela Vincent
From the Nuffield Department of Clinical Neurosciences (M.M.N., E.C., M.W., J.R., J.G., J.K., J.M.N., F.C., G.C.D., A.V., J.P., P.W., M.I.L.), John Radcliffe Hospital, University of Oxford, UK; Departments of Neurology (I.N., Y.T., H.K.) and Multiple Sclerosis Therapeutics (T.M., K.F.), Tohoku University Graduate School of Medicine, Sendai, Japan; Department of Clinical Neurology (F.S.), Hospital de São Marcos, Braga; and Department of Clinical Neurology (A.M.-d.-S., M.E.S.), Hospital Geral Santo Antonio, Porto, Portugal.
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Jacqueline Palace
From the Nuffield Department of Clinical Neurosciences (M.M.N., E.C., M.W., J.R., J.G., J.K., J.M.N., F.C., G.C.D., A.V., J.P., P.W., M.I.L.), John Radcliffe Hospital, University of Oxford, UK; Departments of Neurology (I.N., Y.T., H.K.) and Multiple Sclerosis Therapeutics (T.M., K.F.), Tohoku University Graduate School of Medicine, Sendai, Japan; Department of Clinical Neurology (F.S.), Hospital de São Marcos, Braga; and Department of Clinical Neurology (A.M.-d.-S., M.E.S.), Hospital Geral Santo Antonio, Porto, Portugal.
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Patrick Waters
From the Nuffield Department of Clinical Neurosciences (M.M.N., E.C., M.W., J.R., J.G., J.K., J.M.N., F.C., G.C.D., A.V., J.P., P.W., M.I.L.), John Radcliffe Hospital, University of Oxford, UK; Departments of Neurology (I.N., Y.T., H.K.) and Multiple Sclerosis Therapeutics (T.M., K.F.), Tohoku University Graduate School of Medicine, Sendai, Japan; Department of Clinical Neurology (F.S.), Hospital de São Marcos, Braga; and Department of Clinical Neurology (A.M.-d.-S., M.E.S.), Hospital Geral Santo Antonio, Porto, Portugal.
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Kazuo Fujihara
From the Nuffield Department of Clinical Neurosciences (M.M.N., E.C., M.W., J.R., J.G., J.K., J.M.N., F.C., G.C.D., A.V., J.P., P.W., M.I.L.), John Radcliffe Hospital, University of Oxford, UK; Departments of Neurology (I.N., Y.T., H.K.) and Multiple Sclerosis Therapeutics (T.M., K.F.), Tohoku University Graduate School of Medicine, Sendai, Japan; Department of Clinical Neurology (F.S.), Hospital de São Marcos, Braga; and Department of Clinical Neurology (A.M.-d.-S., M.E.S.), Hospital Geral Santo Antonio, Porto, Portugal.
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Maria Isabel Leite
From the Nuffield Department of Clinical Neurosciences (M.M.N., E.C., M.W., J.R., J.G., J.K., J.M.N., F.C., G.C.D., A.V., J.P., P.W., M.I.L.), John Radcliffe Hospital, University of Oxford, UK; Departments of Neurology (I.N., Y.T., H.K.) and Multiple Sclerosis Therapeutics (T.M., K.F.), Tohoku University Graduate School of Medicine, Sendai, Japan; Department of Clinical Neurology (F.S.), Hospital de São Marcos, Braga; and Department of Clinical Neurology (A.M.-d.-S., M.E.S.), Hospital Geral Santo Antonio, Porto, Portugal.
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Full PDF
Citation
Pregnancy outcomes in aquaporin-4–positive neuromyelitis optica spectrum disorder
Matthew M. Nour, Ichiro Nakashima, Ester Coutinho, Mark Woodhall, Filipa Sousa, Jon Revis, Yoshiki Takai, Jithin George, Joanna Kitley, Maria Ernestina Santos, Joseph M. Nour, Fan Cheng, Hiroshi Kuroda, Tatsuro Misu, Ana Martins-da-Silva, Gabriele C. DeLuca, Angela Vincent, Jacqueline Palace, Patrick Waters, Kazuo Fujihara, Maria Isabel Leite
Neurology Jan 2016, 86 (1) 79-87; DOI: 10.1212/WNL.0000000000002208

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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 [1.05–128], 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.

GLOSSARY

AQP4=
aquaporin-4;
ARR=
annualized relapse rate;
CI=
confidence interval;
IgG=
immunoglobulin G;
NMO=
neuromyelitis optica;
NMOSD=
neuromyelitis optica spectrum disorder;
ON=
optic neuritis;
OR=
odds ratio

Footnotes

  • Go to Neurology.org for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.

  • Supplemental data at Neurology.org

  • Received August 18, 2014.
  • Accepted in final form August 25, 2015.
  • © 2015 American Academy of Neurology
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