How do MS drugs affect pregnancy?

One of the largest cohorts in the world

The data for the pregnancies included in the study came from the German Multiple Sclerosis and Pregnancy Registry and was collected between November 2006 and June 2023. 2,885 pregnancies were analyzed during which the mothers had received a so-called disease-modifying therapy (DMT). The substances used in the study included interferons, glatiramer actate, 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,” points out Kerstin Hellwig. “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.”

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 finding was that exposure to most DMTs during pregnancy was not associated with a statistically significant increase in the incidence of spontaneous abortions, premature births or major congenital defects. “Due to the small number of cases in pregnancies with cladribine, teriflunomide and alemtuzumab exposure, we are unable to draw any definite conclusions about rare events such as congenital defects or severe infections,” admits Hellwig.

Increased risk of lower birth weight

Overall, the entire cohort showed an increased risk of low birth weight in relation to the duration of pregnancy. 18.8 percent of babies were affected. This figure is only 10 percent in relation to all births in Germany. Children born to mothers with MS who hadn’t received any medication were also more likely to be below average in weight, namely in 17.6 percent of cases. This risk was particularly pronounced in cases of exposure to S1P modulators (27.4 percent) and anti-CD20 antibodies (24.1 percent).

Serious infections during pregnancy were rare overall. In pregnancies without medication, they occurred in around one percent of mothers. In pregnancies with fumarate or alemtuzumab exposure, they were statistically significantly more frequent (2.8 percent and 9.1 percent respectively). More severe infections – although not statistically significantly increased compared to the control group – occurred in pregnancies treated with natalizumab in the last trimester of pregnancy and with S1P modulators at three percent each and with cladribine at 4.8 percent. “It’s interesting to note that severe infections only occurred in 0.6 percent of pregnancies exposed to anti-CD20 antibodies,” stresses 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 menstruation (23.2 percent) were more likely to receive antibiotics during pregnancy than women who hadn’t received DMT (12.1 percent).

Individual risk-benefit assessment

“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,” says Kerstin Hellwig. While most DMTs don’t 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 neonatal death as well as for numerous diseases in later life, including type 2 diabetes mellitus and cardiovascular diseases. There are plans for further evaluations in the registry, for example whether and when the children will make up for the growth disadvantage. “The results highlight the importance of an individual risk-benefit assessment and close medical supervision during pregnancy,” concludes Kerstin Hellwig.