Pregnancies Associated With Reduced Multiple Sclerosis Risk

Allison Shelley

March 09, 2012

March 9, 2012 — Women who have multiple pregnancies may have a lower risk of developing a first clinical demyelinating event, report researchers.

They found that women who were pregnant 2 or more times had a quarter of the risk of developing symptoms. Further, women who had 5 or more pregnancies had one-twentieth the risk of developing multiple sclerosis (MS) compared with those who never had a baby.

"In our study, the risk went down with each pregnancy and the benefit was permanent," lead investigator Anne-Louise Ponsonby, PhD, from Murdoch Children's Research Institute in Melbourne, Australia, said in a news release.

The article is published online in the March 7 issue of Neurology.

Using a case-control design, investigators reviewed information on 282 Australian men and women between the ages of 18 and 59 years who had a first clinical diagnosis of central nervous system demyelination, and compared these patients with 542 people without symptoms.

They then calculated the number of pregnancies in women lasting at least 20 weeks and the number of live births. For men, they recorded the number of children born.

"Elegant Approach"

In an accompanying editorial, a team led by Martin Daumer, PhD, from the Sylvia Lawry Centre for Multiple Sclerosis Research, in Munich, Germany, called this approach "elegant" in circumventing the confounding factors seen in previous studies.

"Those with less severe disease reasonably might be expected to choose to become pregnant more often than those with more severe disease due to the fear of not being able take care of a child," the editorialists pointed out. By confining their analysis to patients with a first demyelinating event, they found that the number of pregnancies was inversely associated with symptoms.

The investigators found that women who had more births experienced a reduced risk of a first clinical demyelinating event. The adjusted odds ratio was 0.51 with a 95% confidence interval of 0.36 to 0.72 per birth.

The apparent beneficial effect was also evident among women with fewer children (P < .001). No association was found between the number of children and risk of symptoms in men.

Fewer Children, More MS?

"The rate of MS cases has been increasing in women over the last few decades, and our research suggests that this may be due to mothers having children later in life and having fewer children than they have in past years," Dr. Ponsonby explained.

"Although case-control studies are prone to confounding," the editorialists pointed out, "the authors considered a number of genetic and environmental confounders, including human leukocyte antigen type and sun exposure, among others, and none seemed to explain the observations."

The findings of this study are not consistent with most previous studies, which failed to identify any association between pregnancies and MS. However, they are similar to 2 other cohort studies.

The first reported that women with MS were more likely to be childless than the general population ( Brain. 1995;118:253-261 ). The second study found that women with 3 or more children had a reduced risk of disease ( Contraception. 1993;47:161-168).

Several possible mechanisms might explain the protective effect of pregnancy on MS, the researchers note. "Short-term mechanisms include the downregulation of inflammatory genes that are abnormally upregulated in multiple sclerosis, the increased secretion of beneficial cytokines such as interleukin-10 alterations in T regulatory cell activity, and the suppression of Epstein-Barr virus-specific cytotoxic T lymphocyte activity."

Increased estrogen has also been proposed to be beneficial. In addition, the authors explain, pregnancy is a time of increased maternal-fetal cell trafficking and it is possible that fetal microchimerism, with a permanent donation of fetal cells to the maternal circulation, may play a role.

This study was funded by the National Multiple Sclerosis Society of the United States of America, the National Health and Medical Research Council of Australia, and Multiple Sclerosis Research Australia. The researchers have disclosed no other relevant financial relationships.

Editorialist Dr. Martin Daumer is the author on device patents for Trium Analysis Online GmbH and holds stock and options in the company. He also works as a consultant for the University of Oxford, Imperial College London, the University of Southampton, Charite, the University of Vienna, Greencoat Limited, Biopartners, Biogen Idec, Bayer Schering Pharma, Roche, and Novartis.

Neurology. 2012;78:867-874. Abstract


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