Longer Breastfeeding May Damage Brain By Delaying DMT Use

Having at least one pregnancy may lower disability scores in women with multiple sclerosis (MS), but breastfeeding for longer than six months may worsen damage to the brain, an observational study in patients has found.

Findings support the need for careful pregnancy planning, counseling, and treatment management to ensure optimal longer-term outcomes, its researchers noted.

The study, “Effects of Pregnancy and Breastfeeding on Clinical Outcomes and MRI Measurements of Women with Multiple Sclerosis: An Exploratory Real-World Cohort Study,” was published in Neurology and Therapy.

Pregnancy is known to protect women from MS relapses, with relapse rates falling by 70% after conception. However, relapse rates increase significantly after pregnancy, especially during the first three months post-delivery.

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Higher pre-pregnancy disease activity, greater disability, and frequent relapses during pregnancy are some of the factors linked to post-pregnancy relapses.

Breastfeeding may also play a role in MS activity, but existing evidence is conflicting. Current knowledge about the impact of pregnancy and breastfeeding on MS activity largely comes from short-term studies; very few long-term studies have been done.

A team of scientists at the University of Cagliari, in Italy, investigated the short- and long-term effects of pregnancy and breastfeeding on disability and brain integrity in women with MS.

Eligible patients provided demographic and clinical data, including disease-modifying treatment (DMT) use, and pregnancy and breastfeeding history. MRI images were also collected to measure whole brain, and white and grey matter volumes.

A total of 210 women, 194 with relapsing MS, were included in the study. Their mean age was 45.5 and their mean disease duration was 14.8 years. The mean Expanded Disability Status Scale (EDSS) score was 2.2, indicating minimal disability.

A total of 129 women (61.4%) reported at least one pregnancy (212 total pregnancies), 46.5% of which occurred before MS onset and 41.9% after an MS diagnosis. Fifteen other pregnancies (11.6%) were both before and after MS onset.

The researchers focused on the 90 pregnancies that occurred after MS onset to determine its effects on short-term MS outcomes. Among this group, 45% breastfed for at least two months.

About one-third (32.2%) of these women were taking a first-line disease-modifying therapy (DMT) — such as interferon-beta, glatiramer acetate, or dimethyl fumarate — during conception, and 8.8% were on a second-line DMT, such as Tysabri (natalizumab) or fingolimod (sold as Gilenya; generic forms available) before or during conception. The remainder were not using any treatment.

A total of four women experienced a relapse during pregnancy, two after stopping Tysabri and one after discontinuing fingolimod.

In the year after pregnancy, relapse rates were higher (0.54 relapses per year) compared with the year before pregnancy (0.45 annual relapses). Disability scores remained the same.

The number of relapses in the year after childbirth was significantly associated with the severity of MS symptoms in the year before conception and with breastfeeding duration.

Women who used second-line DMTs before or during pregnancy were more likely to relapse and show brain changes; brain changes were also more likely in women who breastfed for short periods.

According to the researchers, the association between greater relapse rates and the use of second-line DMTs and a shorter time breastfeeding an infant is likely driven by a more severe disease course.

“In fact, women with higher MS activity likely had to renounce or prematurely quit breastfeeding to start DMT. Thus, breastfeeding duration seems more likely to be conditioned by MS, resulting it shorter durations among subjects with clinical or neuroradiological reactivation,” the investigators wrote.

To determine the long-term effects of pregnancy and breastfeeding on MS outcomes, the researchers then evaluated MRI brain scans over a mean follow-up of 10.7 years.

Lower disability scores were found in patients who had at least one pregnancy. And while there was no link between pregnancy and whole brain, white matter and grey matter volumes, women breastfeeding for longer than six months had lower white matter volumes, indicating greater brain damage.

This loss of brain volume with breastfeeding for longer periods is likely associated with a delay in DMT use, as most DMTs are not indicated for use during pregnancy or breastfeeding.

“These finding draws attention to the importance of the post-partum period and the choice of breastfeeding, which until very recently corresponded to the choice of postponing DMT use, exposing the woman to MS reactivation with immediate effects such as those in the post-partum period or long term,” the researchers wrote.

“These findings reinforce the importance of adequate counselling and pregnancy planning to optimise therapeutic choices … [which] could affect long-term MS outcomes even more than pregnancy and prolonged breastfeeding affect MS-related disability and brain atrophy,” they added.

Among this study’s limitations is its observational nature, with patients evaluated having “different follow-up times, MS characteristics, and DMT exposures,” the researchers noted.