Pregnancy Outcomes in Patients with Neuromyelitis Optica Spectrum Disorders
By Jai S. Perumal, MD
Assistant Professor of Neurology, Weill Cornell Medical College
Dr. Perumal reports she receives grant research support from Genzyme Corp, and is on the speakers bureau for Biogen Idec, Genzyme Corp., Acorda Therapeutics, and Teva Pharmaceuticals.
SYNOPSIS: Based on a retrospective analysis of an international cohort of women with neuromyelitis optica spectrum disorders who had at least one pregnancy, the authors report a higher risk for miscarriage and preeclampsia in patients who were diagnosed before pregnancy.
SOURCE: Nour MM, et al. Pregnancy outcomes in aquaporin-4 positive neuromyelitis optica spectrum disorder. Neurology 2016;86:79-87.
Neuromyelitis optica spectrum disorder (NMOSD) is typically characterized by optic neuritis and/or transverse myelitis and the presence of the NMO IgG antibody. In addition to being a diagnostic test, NMO IgG antibody, which binds to aquaporin-4, is potentially pathogenic. Experimental and clinical studies have shown the presence of aquaporin-4 in animal and human placenta and have demonstrated that aquaporin-4–mediated inflammation can lead to fetal death. Given these findings, the authors analyzed pregnancy outcomes, including the risk of miscarriage and preeclampsia, in women diagnosed with an NMOSD.
Sixty women with an NMOSD diagnosis who had 126 pregnancies were included in the study. These women were enrolled from centers in Oxford, UK; Porto, Portugal; and Sendai, Japan. There were no significant differences in parity, mean age at pregnancy, and mean age at NMOSD diagnosis between Caucasian, Afro-Caribbean, and Japanese women. Mean age at disease onset was 46.4 years and immunotherapy was started after a mean of 47.2 months after disease onset. Eight pregnancies occurred while the patient was on immunotherapy, and 63.3% of the women had clinical or immunological evidence of an additional autoimmune disease (systemic lupus erythematosus, antiphospholipid antibody syndrome, Sjogren’s, thyroid disease, myasthenia gravis).
Eighty-five pregnancies in 40 women were included in the analysis of the influence of an NMOSD diagnosis on the odds ratio (OR) of miscarriage. Eleven pregnancies in six women ended in miscarriage (12.9%; 95% confidence interval [CI], 6.64%-22.0%). This miscarriage rate (12.9%) is similar to the known risk in the general population (12%-24%). However, six of 14 (42.9%; 95% CI, 17.7%-71.1%) pregnancies that occurred after NMOSD diagnosis ended in miscarriage vs five out of 71 pregnancies (7.04%; 95% CI, 2.33%-15.7%) that occurred before a diagnosis of NMOSD. The 42.9% increased rate of miscarriage after a diagnosis is significantly higher, and there was an increased OR of miscarriage in pregnancies that occurred up to or after 3 years before the diagnosis of NMOSD. Using univariate logistic regression analysis, maternal age at pregnancy, timing of pregnancy relative to an NMOSD diagnosis, most recent pregnancy ending in miscarriage, and obstetric history of all prior pregnancies resulting in miscarriages were associated with an increased OR of miscarriage. When multivariate logistic regression was used, timing of pregnancy relative to the NMOSD diagnosis was the strongest predictor of miscarriage.
One hundred thirteen pregnancies in 57 women were included in the analysis of the effect of an NMOSD diagnosis on the OR of preeclampsia. Thirteen cases of preeclampsia occurred in 11 women (11.5%; 95% CI, 6.27%-18.9%). The rate of preeclampsia before an NMOSD diagnosis was 11.2% and after diagnosis was 13.3%. The preeclampsia rate of 11.5% is higher than the rate of 3.1% reported in control populations. Univariate and multivariate logistic regression analysis showed that prior history of miscarriage in the most recent pregnancy and history of multiple other autoimmune diseases were associated with a higher risk. There was no significant risk associated with the relative timing of an NMOSD diagnosis.
This study shows that pregnancies that occurred after a diagnosis of an NMOSD were associated with an increased OR of miscarriages compared to pregnancies before the diagnosis. Women whose pregnancies ended in miscarriages after an NMOSD diagnosis had greater levels of disease activity during the preconception period and during pregnancy and had also received treatment for these acute relapses. Based on this finding, the authors speculated that aquaporin-4 antibody could have a causative role in fetal injury and consequently the miscarriages. With regard to preeclampsia, the rate seen in women with NMOSD was higher than those seen in historical control populations. In addition, they found that a history of multiple other autoimmune diseases increased the OR for preeclampsia. Given that patients with high disease activity had the highest risk of a miscarriage, and the potential causative role of the aquaporin-4 antibody, the authors reported widely accepted recommendations that patients with antibody-mediated autoimmune disorders continue immune treatment before, during, and after pregnancy. A single case of hydrocephalus was also reported in this cohort, raising concern about a role of the aquaporin-4 antibody in abnormalities in fetal brain development. Further research is needed to study this population to better understand the role of aquaporin-4 antibody and to develop better management strategies during pregnancy for women with an NMOSD diagnosis.
Based on a retrospective analysis of an international cohort of women with neuromyelitis optica spectrum disorders who had at least one pregnancy, the authors report a higher risk for miscarriage and preeclampsia in patients who were diagnosed before pregnancy.
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