Women Soon After Pregnancy’s End at High Risk of NMOSD Relapse

The first trimester after giving birth or ending a pregnancy is a time of high risk for women with neuromyelitis optica spectrum disorder (NMOSD), with younger patients, those with more AQP4 antibodies, or inadequate prenatal care most at risk of an attack, a study found.

According to its researchers, this study of pregnancy-related attacks in NMOSD patients at multiple Chinese hospitals, was “the largest cohort to explicitly summarise the pregnancy-related characteristics of NMOSD with different antibody subsets in China.”

The study, “Neuromyelitis optica spectrum disorder: pregnancy-related attack and predictive risk factors,” was published in the Journal of Neurology, Neurosurgery and Psychiatry.

NMOSD is an autoimmune disease in which antibodies, produced by the immune system, mistakenly attack astrocytes and oligodendrocytes — cells that support the nervous system — causing inflammation in the optic nerve and spinal cord.

Most NMOSD patients have elevated levels of antibodies that target the protein aquaporin-4 (AQP4) in astrocytes, while some also have antibodies against myelin oligodendrocyte glycoprotein (MOG).

NMOSD primarily affects women, and relapses can be triggered by pregnancy, particularly during the early postpartum period — the three month (trimester) after giving birth or terminating a pregnancy.  Higher recurrence rates during and after pregnancy associate with higher miscarriage rates and more severe disability.

Researchers investigated the effects of pregnancy on NMOSD, and risk factors that contribute to pregnancy-related relapses. 

Retrospective data covering 136 pregnancies in 110 patients with NMOSD, all treated at Huashan Hospital in Shanghai between January 2015 to April 2019, were included in the study. To develop a pregnancy-related relapse risk prediction model, an additional 35 patients with 44 pregnancies from three other hospitals were included in the analysis.

Of the 110 study group patients, 83 had antibodies against AQP4 (anti-AQP4). These women had a total of 108 pregnancies and 126 pregnancy-related attacks, of which 51 (40.5%) occurred during the three-month postpartum period. Sixty-six pregnancies in 50 of these anti-AQP4 positive patients were recorded after NMOSD onset, with an increased average rate of relapse in the year after pregnancy compared to the year before.  

Twenty-one patients had antibodies against MOG (anti-MOG), and 21 pregnancies. A total of 28 pregnancy-related attacks were reported, of which 11 (39.3%) were within three months postpartum. 

A total of 60 patients across both groups had 76 pregnancies after disease onset, with 31 deliveries and 19 terminations.  In the delivery group, the relapse rate was significantly higher during the first three months postpartum than before pregnancy. Disability measured by Expanded Disability Status Scale (EDSS) was also significantly higher during pregnancy, and at one year postpartum than before the pregnancy.

A similar pattern in relapse rate and EDSS was observed among women who ended a pregnancy. 

In their analysis of risk factors, researchers looked at 50 pregnancies with pregnancy-related attacks, and 26 without pregnancy-related attacks.

Older age at disease onset was associated with a lower risk for pregnancy-related attacks, while younger age at delivery (20–33 years old) or termination, inadequate treatment during pregnancy and after delivery or termination, and high anti-AQP4 levels were all associated with an increased risk.

Further analysis confirmed that these factors were independently linked to an increased risk of pregnancy-related attacks. A model to predict the probability of pregnancy-related attacks found agreement between the predicted and actual probability of pregnancy-related attacks in both the primary group and the additional risk analysis group.

Within the study group, a comparison of 58 patients positive for either AQP4 (42 patients) or MOG (16 patients) antibodies found that AQP4 group patients had less inflammation of the optic nerve, more inflammation of the spinal cord, and more autoantibodies that attack the patient’s own tissues. During the remission stage of pregnancy-related attacks, their median EDSS score was significantly higher than that of patients in the MOG group.

“Our results indicated that physicians might need to pay enough attention to the risk of pregnancy-related attack in patients with higher AQP4-ab titer,” the researchers wrote.