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 [1.05-128], 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.

Figure 1. Relationships between adverse pregnancy outcome, NMOSD onset, and maternal age

(A) Distribution of pregnancies ending in miscarriage, plotted against maternal age and pregnancy timing with respect to NMOSD onset. Blue squares denote viable pregnancies at time of delivery. Red triangles denote pregnancies ending in miscarriage, at time of miscarriage. Black vertical line marks onset of NMOSD. (B) Distribution of pregnancies complicated by preeclampsia, plotted against maternal age and pregnancy timing with respect to NMOSD onset. Blue squares denote viable pregnancies without preeclampsia, at time of delivery. Red triangles denote viable pregnancies complicated by preeclampsia, at time of delivery. Black vertical line marks onset of NMOSD. NMOSD = neuromyelitis optica spectrum disorder.

Figure 2. NMOSD ARR in pregnancies after NMOSD or within 1 year of NMOSD onset

ARR is shown for the 9 months before conception, intrapregnancy period, and the 9 months postpregnancy. Shaded gray region represents the intrapregnancy period (9 months in viable pregnancies, 1–4 months for miscarriages). Blue squares represent viable pregnancies (n = 20). Red triangles represent pregnancies ending in miscarriage (n = 7). All data points show the ARR derived from the relapse rate per 3-month period (with the exception of the intrapregnancy period for pregnancies ending in miscarriage, where the single data point represents the ARR calculated from the number of relapses during the truncated pregnancy-specific duration). Error bars are +1 SEM. ARR = annualized relapse rate; NMOSD = neuromyelitis optica spectrum disorder.