During pregnancy, a woman’s physiology undergoes tremendous changes and renders the course of any chronic illnesses, especially those of an immunological nature, more unpredictable.
There have been several studies analyzing the impact of neuromyelitis optica spectrum disorder (NMOSD) on fertility and pregnancy. NMOSD is a disease mediated by antibodies against aquaporin-4 (AQP4); studies indicate that AQP4 can affect hormone levels by interfering with the hypothalamic-pituitary-gonadal axis.
This has been demonstrated most clearly in studies involving AQP4-knockout mice. Scientists discovered that AQP4-knockout mice have significantly lower estrogen and progesterone serum levels than wild-type mice. In addition, they discovered that AQP4-knockout mice had damaged oocyte development and abnormal endometrial thickness, leading to a subfertile state.
Studies investigating fertility in human patients are scarce. One study assessed fertility in 217 patients with NMOSD and found that 6% were undergoing fertility treatment, and 13% experienced delays in achieving pregnancy after more than 12 months. Nevertheless, the study did not specify the average age at which the first attempt to conceive was initiated.
Read more about NMOSD etiology
Bias is difficult to avoid when assessing fertility in patients with NMOSD. This is driven primarily by the small pool of patients of which researchers can recruit, as well as the ethical complexities of conducting studies on fertility and pregnancy.
However, because NMOSD relapses can accelerate neurological disability, it is a matter of great interest to understand whether NMOSD attacks increase during pregnancy. Studies have previously suggested that NMOSD relapses increase during pregnancy and in the months after delivery. During pregnancy, NMOSD relapses represent a significant health risk to both mother and child.
Assessing Pregnancy-Related Attacks
In JAMA Network Open, Wang and colleagues conducted a systematic review to understand the factors associated with pregnancy-related NMOSD attacks.
The research team conducted literature searches on academic search engines using relevant terms relating to pregnancy complications and NMOSD relapses. Their goal was to identify the rate of pregnancies with NMOSD attacks and pregnancy outcomes and complications in patients with NMOSD.
A total of 15 studies were included in the final analysis. In 11 studies, the rate of pregnancies that included NMOSD attacks ranged from 7.7% to 80.8%. This suggests a high level of heterogeneity when it comes to the experiences of pregnant women with NMOSD.
The research team discovered that patients continued to receive immunosuppressive treatment, both before and during pregnancy. Patients who continued to receive immunosuppressive therapy during pregnancy had a significantly lower rate of NMOSD attacks compared to patients who stopped. Thus, a negative association could be established between the rate of immunosuppressive therapy during pregnancy and the rate of pregnancies with NMOSD relapses.
Wang and colleagues also looked into the age at conception, dividing patients into 2 categories: those who conceived at 32 years of age or older and those who conceived before 32. They discovered that the rate of pregnancy-related NMOSD attacks was significantly lower in the older age group than in younger patients.
The research team also reported that the Expanded Disability Status Scale (EDSS) of patients was insignificant in terms of the likelihood of experiencing NMOSD attacks during pregnancy. However, patients who had coexisting autoimmune diseases other than NMOSD had a significantly higher chance of developing pregnancy-related NMOSD attacks.
Among 619 pregnancies, the researchers reported that 64% ended with term deliveries and 4.8% ended with premature deliveries. A total of 22.6% of pregnancies ended in abortions — 8.1% were spontaneous, and 14.5% were elective.
“The findings of this systematic review and meta-analysis suggest that receiving immunosuppressive treatment during pregnancy and older age at conception were associated with protection against pregnancy-related NMOSD attacks,” the study authors concluded.
The wealth of information provided by this systematic review is unprecedented, given the limitations of conducting studies involving pregnant patients with NMOSD mentioned earlier. It provides statistically corroborated facts regarding the likelihood of one experiencing an NMOSD attack depending on factors such as age, treatment, and existing comorbidities.
Read more about NMOSD treatment
In real-world practice, physicians usually perform a careful walkthrough of the risks of pregnancy for patients with NMOSD who want to conceive. The greatest risk is that a severe NMOSD attack occurs during pregnancy, causing the mother to be severely ill and putting the viability of the pregnancy in doubt. It is important that patients are fully aware of this before pregnancy.
Although the study conducted by Wang and colleagues characterized the continuation of immunosuppressive therapy as being possibly protective against NMOSD attacks, in reality, the evidence for this is mixed. We do know that rituximab can cross the blood-placenta barrier, especially as the pregnancy progresses; scientists have detected rituximab in the umbilical cord blood of exposed neonates. Studies suggest rituximab treatment increases the likelihood of premature births.
“Overall, careful risk-benefit analysis of stopping or continuing immunosuppressive treatment is necessary in patients planning families,” Borisow and colleagues wrote in the EPMA Journal.
Ultimately, physicians must establish a healthy rapport with their patients so that patients are free to ask any questions about pregnancy-related NMOSD attacks and the therapeutic options available to them. Physicians can only do their best in following the latest evidence-based guidelines in helping their patients prepare for any pregnancy-related decisions they choose to undertake.
Wang L, Su M, Zhou Z, et al. Analysis of pregnancy-related attacks in neuromyelitis optica spectrum disorder: a systematic review and meta-analysis. JAMA Netw Open. Published online August 4, 2022. doi:10.1001/jamanetworkopen.2022.25438
Borisow N, Hellwig K, Paul F. Neuromyelitis optica spectrum disorders and pregnancy: relapse-preventive measures and personalized treatment strategies. EPMA J. Published online August 10, 2018. doi:10.1007/s13167-018-0143-9