MS treatments don’t raise miscarriage, birth defect risk: Study
Some treatments may be linked to low birth weight
Most treatments for multiple sclerosis (MS) don’t increase the risk of major problems when used during pregnancy, an analysis showed.
“We found that most therapies were not associated with an increased risk of miscarriage, premature birth or major birth defects,” Kerstin Hellwig, MD, study co-author and MS specialist at Ruhr University Bochum in Germany, said in a university press release.
However, some MS treatments may increase the likelihood of low birth weight or serious infections during pregnancy, the analysis found. Small size for gestational age is associated with a higher risk of infant death, as well as higher risk of later-in-life issues such as heart disease, the scientists noted.
“The results highlight the importance of an individual risk-benefit assessment and close medical supervision during pregnancy,” Hellwig said.
The study, “Impact of disease-modifying therapies on pregnancy outcomes in multiple sclerosis: a prospective cohort study from the German multiple sclerosis and pregnancy registry,” was published in The Lancet Regional Health Europe.
Little data on MS treatments and pregnancy
Disease-modifying therapies (DMTs) are anti-inflammatory medicines that can slow the progression of MS. Although MS primarily affects women, there’s minimal data on the use of DMTs during pregnancy.
The researchers investigated the impact of DMT exposure on pregnancy outcomes using data collected from 2006 to 2023 as part of the German Multiple Sclerosis and Pregnancy Registry. They looked at data on more than 3,000 pregnancies. In 2,885 of those, the pregnant person had a DMT in their system at some point during the pregnancy, and 837 had no DMT exposure.
“This cohort is one of the largest in the world,” Hellwig said. “It has a high variability of exposure to the different immunotherapies. Most of the women had only received medication in the first trimester of pregnancy.”
Overall, the results showed that DMT use was not associated with major birth defects or miscarriage. More granular analyses looking at individual medications showed generally consistent results, though the researchers noted that, for a few specific DMTs, there weren’t enough people exposed to the medicine to draw statistically reliable conclusions.
“Due to the small number of cases in pregnancies with cladribine [Mavenclad], teriflunomide [Aubagio] and alemtuzumab [Lemtrada] exposure, we are unable to draw any definite conclusions about rare events such as congenital defects or severe infections,” Hellwig said.
Although different medications have different specific mechanisms of action, all DMTs work to suppress the immune system, tamping down the inflammation that drives MS. Since the immune system is normally responsible for defending the body against infections, one of the biggest safety risks with many DMTs is infection.
Serious infections were uncommon irrespective of DMT exposure, the analysis found. Compared with patients who were not exposed to DMTs, certain medicines — namely Lemtrada or fumarate therapies, which include Bafiertam (monomethyl fumarate), Tecfidera (dimethyl fumarate), and Vumerity (diroximel fumarate) — were associated with a statistically significant increase in the risk of severe infections, but still, fewer than one in 10 patients exposed to these therapies actually experienced a severe infection during pregnancy.
In the general German population, about 10% of babies are born small for their gestational age. Rates were notably higher among the MS patients, but were overall similar in the entire study group (18.8%) and in patients not exposed to DMTs (17.6%).
Further analyses showed the risk of low weight for gestational age was particularly elevated for patients who were exposed to S1P modulators — such as Gilenya (fingolimod), Mayzent (siponimod), Ponvory (ponesimod), or Zeposia (ozanimod) — or to anti-CD20 antibodies such as Ocrevus (ocrelizumab), Kesimpta (ofatumumab), or Briumvi (ublituximab). Exposure to Tysabri (natalizumab) during the third trimester was also linked with an increased risk of a baby’s being small for gestational age, although the difference compared with the control group was not statistically significant.
“A novel finding is that growth restriction was associated with second line DMTs, especially S1P-modulators, anti-CD20 antibodies, and [Tysabri] during third trimester, but also MS itself,” the researchers wrote.
The scientists said the data may help inform discussions about the risks and benefits of using DMTs during pregnancy for people with MS. But they stressed that the results cannot be considered definitive, since there wasn’t a large amount of data for each individual DMT.
“When interpreting the results, one limitation to bear in mind is that it takes approximately 300 pregnancies to show a tripling of the risk of major birth defects and approximately 1,000 to show a doubling,” Hellwig said.
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