The Short and Long-Term Effects of Pregnancy on Multiple Sclerosis and Experimental Autoimmune Encephalomyelitis

Abstract

The role of pregnancy in multiple sclerosis (MS) is of importance because many patients with MS are young women in the childbearing age who require information to inform their reproductive decisions. Pregnancy is now well-known to be associated with fewer relapses of MS and reduced activity of autoimmune encephalomyelitis (EAE). However, in women with multiple sclerosis, this benefit is not always sufficient to protect against a rebound of disease activity if disease-modulating therapy is ceased for pregnancy. There is concern that use of assisted reproductive therapies can be associated with relapses of MS, but more data are required. It is thought that the beneficial effects of pregnancy are due to the pregnancy-associated changes in the maternal immune system. There is some evidence of this in human studies and studies of EAE. There is also evidence that having been pregnant leads to better long-term outcome of MS. The mechanism for this is not fully understood but it could result from epigenetic changes resulting from pregnancy or parenthood. Further studies of the mechanisms of the beneficial effects of pregnancy could provide information that might be used to produce new therapies.

Modulation of cytokine patterns and microbiome during pregnancy in IBD

“…Interestingly, some autoimmune diseases, including rheumatoid arthritis and multiple sclerosis, show improvement during pregnancy, while risk of flares increases postpartum 14–16. This suggests that pregnancy-induced physiological changes affect immune processes at peripheral sites, and it has been suggested that increased levels of Tregs and a shift towards Th2 cytokine patterns contribute to amelioration of Th1-driven diseases41 42 and conversely also play a role in exacerbation of Th2-driven inflammatory diseases such as systemic lupus erythematosus during pregnancy 43 44. CD is generally thought to constitute a Th1/Th17 disease, while UC is more Th2/Th17 driven, which may explain differences in disease patterns during pregnancy observed between these types of IBD 10.…”

Pregnancy does not modify the risk of MS in genetically susceptible women

“…Although we considered pregnancy as a single environmental exposure, pregnancy is a complex and heterogeneous combination of physiologic changes that result in weight gain, increases in lipid levels, and changes in basal metabolic rate, among others. 5 These physiologic changes are the product of pregnancy-induced modifications in hormones, such as estriol, progesterone, prolactin, early pregnancy growth factor, alpha-fetoprotein, and leptin as well as elevated levels of other growth factors. There are increases in circulated regulatory T cells and B cells, increased Th2 responses, and decreased Th-1 and Th-17 immune responses.…”

“…There are increases in circulated regulatory T cells and B cells, increased Th2 responses, and decreased Th-1 and Th-17 immune responses. 5 These immune changes are important for fetal tolerance, as the maternal immune system and endocrine pathways respond to fetal antigens that circulate in the mother. 34 Following pregnancy, hormone levels and immune adaptions quickly return to prepregnancy states.…”

“…36 Little is known about how physiologic changes during pregnancy affect the risk of developing MS, but it is hypothesized that the pregnancy-induced changes in endocrine pathways and immune system have protective effects. 5 Epidemiologic studies investigating the effect of pregnancy on MS risk have reported conflicting results. 1 Five studies reported a protective association between parity and risk of MS; however, 2 of these studies attributed their protective associations to reverse causality from reduced fertility and increased likelihood of miscarriage among women with latent MS. 7,8,10,11,15 Five additional studies reported no association between pregnancy and risk of MS. 9,[12][13][14]16 A recent study investigating breastfeeding, ovulatory years, and risk of MS found evidence that cumulative duration of breastfeeding is associated with a decreased risk of MS. 37 The authors suggest that breastfeeding duration confounds the association between parity/pregnancy and risk of MS and may explain previously reported conflicting findings.…”

“…2 MS is more prevalent among females than males, and symptoms typically emerge during child-bearing ages, often soon after pregnancy. 2,3 This has led many to hypothesize that female-specific exposures, such as those related to reproduction, pregnancy, and lactation, have a role in MS. Pregnancy appears to have short-term beneficial effects on existing MS symptoms, 4 but there is no agreement in the scientific literature about the effect of pregnancy on MS risk in general or among women with genetic susceptibility to MS. 1,5 Gene-environment (G × E) interactions, for which the effect of an environmental exposure is modified by specific genotype(s), are believed to contribute substantially to complex disease risk, and discovery of these interactions can identify subgroups with higher risk of disease. 6 Studies of pregnancy and MS risk have yielded conflicting results; however, no studies, to date, have investigated interaction between pregnancy and genetic susceptibility for risk of MS. [7][8][9][10][11][12][13][14][15][16] We used case-only G × E methods to evaluate interaction between pregnancy before symptom onset and known genetic risk factors for MS, including HLA-DRB1*15:01.…”