After Pregnancy, Women Show More Brain Lesions, Volume Loss

Women with relapsing-remitting multiple sclerosis (RRMS) have more brain lesions and accelerated brain volume loss (BVL) after pregnancy compared with pre-pregnancy measurements, recent data showed.

Brain lesions in the early postpartum period — the first months following childbirth — were associated with a higher risk of worsened disability and relapse later on.

“An occurrence of active lesions and accelerated BVL is associated with brain tissue damage and long-term disability, therefore, a better understanding of the dynamics of brain changes in MS during pregnancy is of importance,” the researchers wrote.

These results are described in the study, “Pregnancy-induced brain MRI changes in women with multiple sclerosis,” which was published in the European Journal of Neurology. 

Brain changes, including volume loss, known as BVL, have been reported in healthy women during pregnancy. These changes are usually restored to pre-pregnancy levels in the months after delivery.

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Women of reproductive age make up the largest proportion of people with multiple sclerosis (MS), but relatively little is known about how pregnancy might influence brain changes like BVL in women with MS.

“Given that previous studies were conducted on healthy women, there is little clarity of the dynamics of pregnancy-induced BVL changes in women with neurological disorders such as MS,” wrote the research team from Charles University, in Prague.

To learn more, the scientists conducted an observational study of 1,839 women at the MS Center at the General University Hospital, in Prague, between 2000 and 2015. Included in the final report were data from 62 women with RRMS for whom MRI data were available before and after pregnancy.

Most of the women had a mild disability status with an average disease duration of 5.5 years, and a median age of 32.

Among the 62 women, 18 (29%) had a relapse in the year before pregnancy, nine (14.5%) during pregnancy, and 20 (32.3%) in the year after delivery. This is consistent with other studies that showed a reduced risk of relapse during pregnancy, the team noted.

Researchers observed that the average T2 lesion volume (T2-LV) — a measure of disease activity on MRI — increased between pre-pregnancy, or less than six months before pregnancy, and the early postpartum period, or within three months after childbirth. Specifically, the median was 1.18 ml versus 0.94 ml in pre-pregnancy.

This increase was more pronounced in women who had higher T2-LV before pregnancy, as well as in women who experienced relapse during pregnancy, the results showed.

Increased T2-LV persisted in follow-up scans conducted 12-24 months, or one to two years after pregnancy, with 70.7% of the women (29 of 41) still showing higher levels than they did before pregnancy.

According to the researchers, since the measurements were taken before and after, but not during pregnancy, the results cannot pinpoint exactly when the changes in MRI activity happened.

“However, based on previous studies showing a decrease in MRI and relapse activity during the second half of pregnancy, it is likely that an outbreak of lesion MRI activity occurred during the early postpartum period,” they wrote.

The researchers also emphasized that the observed brain changes come with clinical implications.

On average, most women did not experience a change in disability status up to one year after pregnancy. However, seven of the women (11.3%) experienced a confirmed disability worsening or CDW. A trend toward elevated risk for CDW with higher T2-LV increases in the early postpartum period was observed.

Similarly, 38 women (62.3%) experienced new relapse activity after the postpartum period, which was associated with higher T2-LV increases after childbirth.

“The outbreak of MRI lesion activity following pregnancy was clinically relevant because the postpartum increase of T2-LV was associated with greater risk of new relapse activity. There was also a trend for greater risk of future disability worsening,” the researchers wrote.

Based on the results, the team suggested that T2-LV measurements may help identify women at high risk for relapse after pregnancy, and could inform how and when clinicians decide to make changes to disease-modifying therapies (DMT) for these women.

The study also tested whether pregnancy induced any changes in brain volume. Between pre- and post- pregnancy measurements, a reduction in the brain parenchymal fraction (BPF) and an accelerated rate of brain volume loss were observed. This loss of brain volume was still not recovered by the time of the follow-up scans at least one year later.

Higher T2-LV levels before pregnancy also could predict an increased BVL rate between pre-pregnancy and follow-up scans, the researchers noted.

Also, when compared with a control group of 38 women with RRMS who had not been pregnant for at least two years, pregnant women had a higher BVL rate, although this was not statistically significant.

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While MS itself could contribute to the accelerated BVL over time, it cannot be the only factor, since BVL seems to speed up after conception, the researchers noted.

“In our study, we hypothesize that pregnancy-induced BVL with subsequent incomplete brain volume recovery was primarily driven by physiological hormone changes, and only to a lesser extent also by concurrent MS pathology,” they wrote.

Exclusion criteria for clinical trials do not usually include recent pregnancy, so these findings may have implications for trial enrollment.

“Our findings need to be taken into account especially when enrolling women into clinical trials in which BVL is an outcome measure,” the scientists wrote.

Overall, the results did not show any differences in brain changes between women who were on DMTs before pregnancy and those who weren’t. The researchers noted, however, that many women are weaned off DMTs during pregnancy, which could complicate the results of the study.

“It is unknown whether pregnancy itself or rather the prolonged time without DMT during and after pregnancy, or combination thereof played a bigger role,” the team wrote.

As their overall conclusion, the researchers wrote that “the postpartum period was associated with an increase in T2 lesion volume and accelerated brain volume loss in a considerable proportion of women. This should be considered in treatment decision-making and designing clinical trials.”

One limitation to the study is the short disease duration and mild disability status of most of the women analyzed, the team noted. “Assessment of pregnancy-induced brain changes at different disease stages … is needed to establish generalizability of the results to the general MS population,” they wrote.

According to the team, future studies should address these limitations in addition to including a healthy control population and more measurements of disease activity.