Poorer Pregnancy Outcomes, Increased Risk of Miscarriage Observed With NMOSD

Adel Hassanein Gad

In a recently published study of Egyptian female patients with neuromyelitis optica spectrum disorder (NMOSD), results showed that having NMOSD increased the risk of miscarriage and cesarean delivery as well as decreased the likelihood of successful breastfeeding. In addition, pregnancy was linked to a higher rate of NMOSD relapse and potential disability, which may be attributed to the upregulation of aquaporin-4 (AQP4) during pregnancy and the postpartum period.¹

Led by Adel Hassanein Gad, a professor in the department of neurology at Cairo University, the retrospective study included 66 married female patients with NMOSD, with a total of 277 pregnancies. Of these, 211 pregnancies occurred before the onset of the disease, while 66 occurred after. When comparing pregnancies before and after NMOSD onset, most were still planned after diagnosis, with 86.4% being intentional; however, there was a higher incidence of complications during pregnancy, occurring in 42.4% of cases.

These complications, while not statistically significant between groups, included bleeding, premature labor, anemia, hyperemesis gravidarum, preeclampsia, and gestational diabetes. Out of the 66 post-NMOSD pregnancies, 19 (28.7%) ended in abortion, 7 (10.6%) had fetal complications, and 40 (60.6%) resulted in normal, healthy babies. Notably, the rate of abortions was higher among those who became pregnant after the onset of NMOSD. Additionally, more than half of the post-NMOSD pregnancies resulted in cesarean section deliveries and the babies were artificially fed, in contrast to those who became pregnant and delivered before the onset of the disease.

Of the 66 post-NMOSD pregnancies, 59 (89.3%) were complicated by peripartum relapses. Of these, 15 out of 66 (22.7%) experienced relapses during pregnancy, with more than half (53.3%) occurring in the first trimester. Among these relapses, 6 (40%) were not treated. Furthermore, when looking at all the post-NMOSD pregnancies, 44 (66.7%) resulted in postpartum relapses, with the majority (88.7%) occurring within the first 3 months after delivery.

After giving birth, all patients resumed their use of immunotherapy within an average of 3.09 (±0.58) months. Because of this, investigators concluded that the majority of postpartum relapses occurred before the patients resumed their immunotherapy treatment.

"Previous studies have shown that patients who continued taking high doses of immunosuppressive drugs, such as prednisolone and azathioprine, were able to remain free of relapses," Gad et al wrote.¹ "This suggests that adequate and relatively safe immunosuppression can prevent pregnancy-related attacks. Azathioprine can be transferred through the placenta to the fetus. However, due to the fetus lacking the enzyme necessary for producing active metabolites, the concentrations of these metabolites are typically lower in the fetus compared to the mother."

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In the study, patients had an average age of 36.5 (±7.2) years, with a median Expanded Disability Status Scale (EDSS) of 5 at the time of completing their pregnancy questionnaire. Overall, the mean annualized relapse rate of the cohort was 2.3 (±1.9), and most patients were prescribed rituximab (31.8%) and azathioprine (25.4%).

The upregulation of AQP4 may also play a role in patient outcomes as well, the data suggested. When comparing patients with positive and negative aquaporin status who had pregnancies after the onset of NMOSD, EDSS scores were significantly higher in aquaporin-negative patients (5.59 [±1.96]) compared with aquaporin-positive patients (4.59 [±1.78]), with a P value of .03). Despite this, there were no between-group differences in terms of pregnancy-related complications, attack rate, or abortions.

Among those who had pregnancies occur before the onset of NMOSD, results revealed significantly higher odds of complications during delivery (38.4%) in aquaporin-positive patients vs those who were negative (21.9%). Additionally, cesarean deliveries were significantly higher in aquaporin-negative patients (31.5%) compared with aquaporin-positive patients (12.3%) with a P value of .01 and 0.0007, respectively. Similar to the previously reported group, there were no significant differences in terms of delivery-related complications, lactation, or abortions regardless of AQP4-status in those who delivered before the onset of NMSOD.

The study authors concluded that, "More prospective studies are needed to examine the impact of changing or stopping immunosuppressant treatment during pregnancy on both the pregnancy and the disease. Additionally, further research is necessary to understand the connection between sex hormones, anti-mullerian hormone (AMH), and fetal aquaporin 4 antibody levels and pregnancy complications and outcomes."

REFERENCE
1. Gad AH, Kishk N, Shalaby NM, et al. Pregnancy characteristics in Egyptian female patients with NMOSD. Mult Scler J. Published online August 11, 2024. doi:10.1177/20552173241271878