Research shows that MS medications do not increase the risk of pregnancy

Research shows that MS medications do not increase the risk of pregnancy

An analysis of over 3,700 pregnancies of women with multiple sclerosis shows that the therapy does not lead to an increased risk of miscarriages, premature births or serious birth defects.

Many women are diagnosed with multiple sclerosis (MS) at an age when they are thinking about starting a family. What does the disease and its medication mean for the child? To answer this question, a team of researchers led by Professor Kerstin Hellwig from the Department of Neurology at the Ruhr University Bochum analyzed over 3,700 pregnancies of women with MS. More than 2,800 of them were treated with various immunomodulating agents before or during pregnancy. “We found that most therapies were not associated with an increased risk of miscarriages, premature births or serious birth defects,” says Kerstin Hellwig. The researchers published their results on December 2, 2024 in The Lancet Regional Health Europe.

One of the largest cohorts in the world

The data from the pregnancies included in the study come from the German Multiple Sclerosis and Pregnancy Register and were collected between November 2006 and June 2023. 2,885 pregnancies were analyzed in which the mothers had received so-called disease-modifying therapy (DMT). The substances used in the study included interferons, glatirameractate, dimethyl fumarate, teriflunomide, S1P modulators (fingolimod, ponesimod), alemtuzumab, natalizumab, anti-CD20 antibodies (rituximab, ocrelizumab, ofatumumab) and cladribine. 837 pregnant women had not received any medication for MS. “This cohort is one of the largest in the world,” emphasizes Kerstin Hellwig. "There is a high variability in exposure to the different immunotherapies. Most women had only received medication in the first trimester of pregnancy."

The researchers compared the frequency of spontaneous abortions, infections during pregnancy, premature births and birth defects and recorded the children's weight at birth. The primary outcome was that exposure to most DMTs during pregnancy was not associated with a statistically significant increase in the incidence of spontaneous abortion, preterm birth, or major congenital defects.

Due to the small number of cases in pregnancies exposed to cladribine, teriflunomide and alemtuzumab, we cannot draw clear conclusions about rare events such as congenital defects or serious infections.”

Professor Kerstin Hellwig, Department of Neurology at the Ruhr University Bochum, Germany

Increased risk of lower birth weight

Overall, the entire cohort showed an increased risk of low birth weight relative to the length of pregnancy. 18.8 percent of babies were affected. Based on all births in Germany, this value is only 10 percent. Children of mothers with MS who had not received any medication were also more likely to have below average weight, in 17.6 percent of cases. This risk was particularly pronounced when exposed to S1P modulators (27.4 percent) and anti-CD20 antibodies (24.1 percent).

Overall, serious infections during pregnancy were rare. In pregnancies without medication, they occurred in about one percent of mothers. They were statistically significantly more common in pregnancies exposed to fumarate or alemtuzumab (2.8 percent and 9.1 percent, respectively). More serious infections - although not statistically significantly increased compared to the control group - occurred in pregnancies treated in the last trimester with natalizumab and with S1P modulators at three percent each and with cladribine at 4.8 percent. “It is interesting that only 0.6 percent of pregnancies exposed to anti-CD20 antibodies resulted in serious infections,” emphasizes Kerstin Hellwig. Women who received natalizumab in the second (26.7 percent) or third (20.7 percent) trimester of pregnancy or were treated with anti-CD20 antibodies up to six months before their last menstrual period (23.2 percent) were more likely to receive antibiotics during pregnancy than women who did not receive DMT (12.1 percent).

Individual benefit-risk assessment

“When interpreting the results, it should be noted that the risk of serious birth defects triples in around 300 pregnancies and doubles in around 1,000,” says Kerstin Hellwig. While most DMTs do not increase the risk of critical pregnancy complications, exposure to S1P modulators, natalizumab, and anti-CD20 antibodies increases the likelihood of low birth weight and slowed intrauterine growth. This is a risk factor for both fetal and newborn death and numerous diseases later in life, including type 2 diabetes mellitus and cardiovascular disease. Further evaluations in the register are planned, for example whether and when the children compensate for the stunted growth. “The results illustrate how important an individual benefit-risk assessment and close medical monitoring are during pregnancy,” concludes Kerstin Hellwig.

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