Up to 75 % of people affected by MS are women, and MS often strikes during the childbearing years. Many expectant mothers ask me, “what does my MS mean for me and my baby?” and they are often understandably concerned that their symptoms might somehow impact their fertility or pregnancy. In the past, women with MS were generally advised to avoid becoming pregnant altogether, although this advice was based on mostly inconclusive and, as it turns out, erroneous data. Over the past two decades, there has been a great deal of research examining the relationship between MS and pregnancy, and in this post I will parse out some of the scientifically-supported evidence from the misconceptions surrounding pregnancy, hormones and MS.
How shifting reproductive habits have shaped the rate of MS in the population
Studies examining rates of MS in the general population (reviewed here) show us that the incidence of MS in women has increased in many countries around the world over the past several decades. The environmental factors that influence the risk for developing MS are myriad and complex, and continue to be the subject of intense research. One demographic trend that has caught the eye of researchers is the change in women’s reproductive habits: since the 1960s, women living in urban centres in developed countries have had progressively fewer children, likely due to a rise in the number of women joining the workforce coupled with an increase in oral contraceptive use.
Several studies have drawn a link between reproduction rates and the incidence of MS among women. One study from Great Britain found that women with 3 or more children bore half the risk of developing MS than women with 0 – 2 children. Similarly, an Australian study showed that there was a cumulative beneficial effect of pregnancy, since women with a greater number of children had a lower risk of a first clinical demyelinating event – an early indicator of MS – than those with fewer children. The reasons for these demographic trends are still a mystery, although recent research has gained some insight into how the course of MS is affected by pregnancy, which I’ll discuss in the following section.
How does pregnancy affect MS symptoms?
Women with MS who become pregnant experience a considerable improvement in symptoms. In fact, there is strong scientific evidence showing that women with the relapsing-remitting form of MS (RRMS) experience far fewer relapses than usual during pregnancy, particularly during the third trimester.
The first large-scale study to examine the interaction between pregnancy and MS, dubbed the Pregnancy in Multiple Sclerosis (PRIMS) study, published its results in 1998 and showed that the relapse rate in women with MS dropped by 70 % during the third trimester. This observation is not unique to MS, and several other autoimmune disorders also improve during pregnancy, including rheumatoid arthritis and thyroiditis, just to name a few. The PRIMS study also showed that MS symptoms bounced back, or “rebounded”, during the first three months post-partum before returning to pre-pregnancy rates. Many follow-up studies have reproduced those initial findings, and researchers have been trying to determine what aspect(s) of pregnancy offer protection against the symptoms of MS.
To answer this question, it is important to understand how pregnancy normally modifies the body’s immune system. It is hardly surprising that pregnancy presents a serious immune challenge to the mother’s body, since the developing fetus carries antigens inherited from the father that would normally be considered “foreign” invaders by the mother’s immune system, in turn leading to rejection of the fetus by the body. In order to prevent fetal rejection, the mother’s immune system temporarily suppresses certain immune responses (namely, the T-helper cells become anti-inflammatory). The shift in the mother’s immune response is an important step during pregnancy, since in addition to preventing fetal rejection, it also allows maternal antibodies to be transferred across the placenta, thus arming the newborn baby with protective immunity against infection before its own immune system has a chance to develop fully.
It just so happens that this response can temporarily put a damper on MS symptoms. The pro-inflammatory T cells and their related cytokines (small messenger molecules that influence the actions of immune system cells) are believed to be major players in the autoreactive immune response in MS. On the other hand, certain cytokines – which are elevated during pregnancy – reduce inflammation and lead to improvement of symptoms in people with MS. In other words, the adaptations that the mother’s immune system makes to accommodate the developing fetus also result in a physiological environment that can lead to improvements in MS.
Pregnancy is a complex, multifaceted event in which many physiological factors change quite dramatically over the course of gestation. Scientists have been attempting to figure out which of these factors is responsible for the profound reduction in relapse rate in expectant mothers with MS. Sex hormones, particularly estriol and prolactin, have been identified as likely protective factors against MS. I looked into the literature to investigate how these pregnancy-related hormones influence MS.
Estriol
Estriol is a specific type of estrogen that is produced by the placenta and, as such, is only found in the body in appreciable quantities during pregnancy. Over the course of pregnancy, estriol levels in the blood gradually increase until they peak during the third trimester, then rapidly decline after birth. Based on the observation that estriol levels appear to coincide with the greatest remission of MS symptoms, a team of researchers led by Dr. Rhonda Voskuhl at University of California conducted a pilot clinical trial in which 10, non-pregnant women with RRMS were administered estriol. The results, published in the Annals of Neurology in 2002, showed that estriol significantly reduced the number of brain lesions that appeared on an MRI scan. Based on these promising findings, Voskuhl’s group expanded their study to 158 non-pregnant women with RRMS in 16 sites across the United States in a phase II clinical trial, where participants were given either a combination of estriol and Copaxone (glatiramer acetate), or Copaxone and a placebo. Although the results have not yet been published, the research team recently announced that the treatment group receiving combined estriol and Copaxone had a 47 % lower relapse rate after 12 months of treatment compared to Copaxone and placebo. The researchers believe that estriol works via a two-pronged approach: not only does it exert an anti-inflammatory effect to reduce the number of attacks, but it also protects the brain so that it suffers less damage during an attack.
While the results are promising, it’s still too soon to say whether people affected by MS would benefit from treatment with estriol. Relatively high doses of estriol are in widespread use in Europe and Asia as hormone replacement therapy for women with menopause, thus making this medication readily available in many countries; however, estriol treatment is not currently approved in Canada or the US. Researchers and medical experts have also noted that estriol therapy can increase the risk of certain cancers. As such, any future strategies for treating MS symptoms with estriol will need to balance the benefits against the risks.
Prolactin
Prolactin is a hormone secreted by the brain that, in addition to its well-known role in mammary gland development and lactation, is an important regulator of immune function and neurogenesis, the process by which new cells of the central nervous system are formed. Like estriol, prolactin levels in the blood are high during pregnancy when MS symptoms are suppressed, although prolactin remains high post-partum during the rebound phase, which has led to some confusion in the research community about its role in MS. A study conducted by Canadian researchers Dr. Samuel Weiss, Dr. V. Wee Yong and Dr. Luanne Metz looked at the effects of prolactin on mice with an MS-like disease and noticed some interesting results; on one hand, high doses of prolactin appear to worsen symptoms of the MS-like condition. On the other hand, low doses of prolactin have no effect on disease symptoms, while treating mice with a combination of prolactin and interferon-β – a standard MS drug – leads to improved MS symptoms compared to interferon-β alone.
Additionally, mice in which receptors for prolactin have been genetically switched off experience aggravated MS-like symptoms. These observations are difficult to reconcile with the association between elevated prolactin during the post-partum period and the rebound in MS symptoms. However, recent findings show that breastfeeding, which stimulates elevated prolactin levels, may in fact be protective, since women who breastfed for 2 months post-partum were found to be less likely to experience a relapse than women who did not. Other studies, however, suggest that breastfeeding has no protective effect on post-partum relapses. Although the data is conflicting at times, the general observation is that, at the correct dose and in the appropriate combination, prolactin may have a protective effect against MS.
One way in which prolactin is thought to protect against MS symptoms is by stimulating the production of new cells that repair damage to the myelin following an MS attack. In a 2007 study published in the Journal of Neuroscience, the research team led by Drs. Weiss and Yong found that pregnant mice exhibited an enhanced ability to repair lesions in the brain. When the researchers supplemented prolactin in non-pregnant mice, they found that they were able to promote myelin repair in a similar fashion. Whether prolactin can be used therapeutically in people affected by MS to stimulate repair of lesions while at the same time avoiding exacerbation of symptoms is still a matter of debate, and research in this area is ongoing.
I am a woman with MS: should I become pregnant?
The decision to become pregnant and start a family is a complex one and requires careful planning by any prospective mother, whether or not she is affected by MS. Many women with MS have gone on to have successful pregnancies and raise healthy children, and as I’ve discussed in this post, pregnancy can occasionally even offer a temporary reprieve from the symptoms of MS. On the other hand, having MS poses its own set of hurdles, and some of the symptoms of MS, particularly ones that involve severe functional disability and/or fatigue, can be unpredictable and add further strain on top of the usual challenges of starting a family. New questions may arise with regards to taking medications for MS while pregnant or planning to get pregnant. As well, the tendency for symptoms to rebound in the first few months following delivery coincides with the time when the newborn infant needs the most care and attention.
If you are a woman with MS and are thinking of starting a family, discuss the benefits and challenges with your neurologist along with your partner and loved ones. Some questions to consider include: how will MS affect my pregnancy? Is it safe to take MS medications during pregnancy? How should I plan to prepare for the post-partum period? By addressing these and other questions head-on, you’ll be far better equipped to decide about whether to embark on the intimidating but remarkable journey that is starting a family.
Are you a mother who is affected by MS? Were your symptoms influenced by your pregnancy? Share your story with us in the comments below.