Pregnancy Delays Likely MS Onset by About 3 Years, Large Study Finds

After a pregnancy or childbirth, most women who went on to develop clinically isolated syndrome (CIS) did so about three years later than those who were never pregnant, a large and multicenter study reported.

Multiple pregnancies or births, however, were not seen to further affect CIS onset.

More research is needed to understand the reasons pregnancy appears to have protective effects regarding the possible start of  multiple sclerosis (MS).

CIS, a neurologic episode that lasts at least 24 hours, is often the first clinical presentation of this neurologic disease.

“At present, we don’t know exactly how pregnancy slows the development of MS, but we believe that it has to do with alterations made to a woman’s DNA,” Vilija Jokubaitis, PhD, the study’s senior author and a neuroscientist at the Monash University, in Australia, said in a university press release.

“We are now seeking funding opportunities to explore this exciting possibility,” Jokubaitis added.

The study, “Association of Pregnancy With the Onset of Clinically Isolated Syndrome,” was published in the journal JAMA Neurology.

More than 2.5 million people worldwide are estimated to have MS, and women are three times more likely than men to be among them. Since MS occurs frequently among women of childbearing age, an increasing number of studies have focused on whether pregnancy affects disease onset and its course.

However, there is still no consensus on the association of pregnancy with MS or CIS onset.

Researchers in Australia, Czech Republic, and Italy evaluated whether pregnancy and childbirth can delay a first appearance of CIS — which often precedes MS — and whether a higher number of pregnancies or births further affected CIS onset.

They chose CIS onset, rather than MS, as their focus to minimize the influence of other factors that may precede an MS diagnosis, such as pregnancy avoidance due to early symptoms or to fertility problems due to subclinical disease.

Data analyzed covered 2,557 women with CIS who were part of MSBase, a registry run by Monash University that includes data on more than 70,000 MS patients in 35 countries. Women in this study were followed at four MS clinics in Australia and the Czech Republic.

All pregnancies, including those ending in a miscarriage or abortion, were considered for the analysis. Childbirth was recognized as any birth with a gestational age of more than 20 weeks, including a stillbirth.

The women’s mean age was 23.3 years at first pregnancy, 23.8 years at first childbirth, and 31.5 years at CIS onset. Almost half had at least one pregnancy (1,188 or 46%) or childbirth (1,100 or 43%) before CIS onset.

A total of 71 (3%) women were pregnant at the time of CIS onset, and 66 (93%) of them gave birth, three (4%) had spontaneous miscarriages, and two (3%) had induced abortions.

Results showed that CIS onset was significantly later in women with a history of pregnancy or childbirth compared with those without this history. CIS symptom onset was a median of 3.3 years later in women with a pregnancy, and 3.4 years in those with childbirth.

The researchers noted that these findings were consistent with those reported in one previous study that explored time to CIS or MS onset. That study, involving 770 women with MS living in Sweden, found an eight year delay in CIS onset.

Notably, a higher number of pregnancies or childbirths was not associated with a further delay in CIS onset. This lack of “cumulative response” may be due to epigenetic changes potentially occurring during pregnancy and persisting for several years, the team suggested.

Epigenetic mechanisms influence genes’ activities without altering their underlying DNA sequence through the addition or removal of chemical tags.

An exploratory analysis using time to MS onset as the main outcome also showed a trend toward delayed MS onset in women with previous pregnancies and childbirths, compared with those without these events.

However, “this association was not as strong as the association for CIS,” the researchers wrote, noting that it highlights “the importance of using CIS as the outcome.”

Overall, the “findings support the notion that pregnancy is associated with a delay in CIS onset,” the team wrote, “but having more pregnancies or childbirths did not appear to be associated with a later CIS onset.”

Increases seen in the frequency of MS among women of childbearing age may also be associated with the current and global trend delayed family planning and lower pregnancy rates.

Future studies are needed to confirm these associations between pregnancy and the timing of CIS onset, and to better understand the molecular mechanisms behind them.