High Risk of NMOSD Recurrence Identified in First Trimester Post-Partum


The largest cohort to explicitly summarize the pregnancy-related characteristics of NMOSD with different antibody subsets demonstrated higher rates of annualized relapse during first trimester after delivery or abortion.

A study that evaluated women with neuromyelitis optica spectrum disorder (NMOSD) during stages of pregnancy and post-pregnancy revealed that the first trimester post-partum is a high-risk period for relapse recurrence.

Lead author Liang Wang, PhD, department of neurology, Shanghai Medical College, Fudan University, and colleagues also found that patients with younger age, higher aquaporin-4 antibody (AQP4-ab)-positive titer and inadequate treatment are at higher risk for pregnancy-related attack as well. Annualized relapse rate (ARR) was compared 12 months before pregnancy with every trimester of pregnancy and after delivery/abortion. There were significant increases during the first trimester after delivery (P <.001) or abortion (P = .0019) compared with that before pregnancy.

The investigators used multivariate analyses to explore the independent risk factors involved while a nomogram was used to generate the prediction of pregnancy-related attacks. Overall, independent risk factors predicting pregnancy-related attack included age at delivery (20–26.5 years; P = .018) or abortion (26.5–33 years; P = .001), AQP4-ab titer (≥1:100; P = .049) and inadequate treatment during pregnancy and postpartum period (P = .004).

There was no association between counts of pregnancy-related attacks and time interval from disease onset to pregnancy, time interval from last attack to pregnancy, relapse within 1 year before pregnancy, ARR before pregnancy, Expanded Disability Status Scale (EDSS) score before pregnancy or counts (≥1, ≥2) of concomitant autoimmune antibodies.

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There were 110 female patients with NMOSD with 136 informative pregnancies included in the study. Among them, 83 were AQP4-ab-positive, 21 were myelin oligodendrocyte glycoprotein-antibody-positive (MOG-ab), and none were positive for both. Pregnancy-related attacks were defined as an attack that occurred during pregnancy or within 1 year after delivery/abortion. Among the 83 AQP4-ab-positive patients who experienced 108 informative pregnancies, 51 counts (40.5%) of the 126 pregnancy-related attacks occurred during the 0–3 months after delivery/abortion, the most of any period.

Of the 50 AQP4-ab-positive patients who underwent 66 pregnancies after disease onset, the mean adjusted ARR was 0.33 (95% CI, 0.26–0.41) during 12–0 months before pregnancy and 0.69 (95% CI, 0.61–0.78) during 0–12 months after pregnancy.

There were 21 MOG-ab-positive patients who experienced 21 informative pregnancies with 28 pregnancy-related attacks. Wang and colleagues noted that attacks during the first trimester post-partum were the most common, with 11 counts (39.3%) total.

Researchers created a predictive model for pregnancy-related attacks using a nomogram according to whether pregnancy-related attacks occurred. In the primary cohort, the C-index of this nomogram was 0.86 (95% CI, 0.77–0.95) and 0.87 with bootstrap resampling, with the mean overoptimism value as 0.0570. Furthermore, the C-index in the external validation cohort was 0.77 (95% CI, 0.63–0.92) and 0.77 with bootstrap resampling, and the mean overoptimism value was –0.0093.

A sub-analysis of patients with NMOSD who underwent pregnancies after disease onset (31 deliveries, 19 abortions) demonstrated that EDSS score increased significantly during pregnancy and within 1 year after abortion compared with that before pregnancy (P = .016 and P <.001, respectively). Similarly, ARRs also increased significantly during pregnancy and the first trimester after abortion compared with that before pregnancy (P = .008 and P = .019, respectively).

"The primary limitation of our study included its retrospective nature, small number of MOG subset. Besides AQP4-ab titers were not detected at fixed time points after NMOSD onset. Future prospective studies with larger sample size and protocol defined timing of antibody detection are therefore warranted to confirm and extend our findings,” Wang et al concluded.

Wang L, Zhou L, ZhangBao J, et al. Neuromyelitis optica spectrum disorder: pregnancy-related attack and predictive risk factors. J Neurol Neurosurg Psychiatry. Published online November 20, 2020. doi: 10.1136/jnnp-2020-323982
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