Multiple sclerosis (MS) is a demyelinating disorder of the central nervous system that typically begins in young adults and affects women twice as often as men.^1,2 As MS is more prevalent in women of childbearing age than in other populations, it is important that neurologists be aware of the effect of pregnancy on the course of MS and have the most current information on the management of MS during pregnancy.³ This information is essential in order to work in concert with the patient and her obstetrician-gynecologist to make clinical decisions. It is also necessary for accurate counseling of patients who are considering becoming pregnant.

Before the 1950s it was generally believed that pregnancy had an adverse effect on the course of MS. In some cases termination of pregnancy was even recommended.⁴ Subsequent studies found no difference in overall disease course between women with MS who became pregnant and those who did not.⁴ However, both retrospective and prospective studies have shown a reduction in relapse rate during pregnancy, followed by an increase in relapse rate during the postpartum period.⁵

Changes in maternal immunity may help to explain the alteration in relapse rate seen during and after pregnancy. Symptoms associated with autoimmune disorders may change for the better or worse during pregnancy. Symptoms improve during pregnancy for women with cell-mediated autoimmune disorders, such as rheumatoid arthritis, and worsen during pregnancy for women with antibody-mediated autoimmune disorders, such as systemic lupus erythematosus.⁸

During pregnancy there appears to be a shift from a predominance of T_H1 cells to T_H2 cells.⁸ This shift appears to revert back during the postpartum period to the prepregnancy state. These shifts may well contribute to the changes in MS relapse rate seen during pregnancy and the postpartum period, as MS is believed to involve myelin-sensitized T_H1 cells that secrete proinflammatory cytokines.⁹ The shifts may be advantageous from an evolutionary standpoint, because they reduce the risk of T_H1-mediated rejection of the fetus as a foreign body.¹⁰

Because of the improvement in MS relapse rate seen during pregnancy, researchers have investigated the therapeutic use of pregnancy hormones to mimic the pregnant state in MS. For example, estriol, an estrogen produced by the fetal placental unit that is not present in the nonpregnant state, has been studied in both murine models of MS and humans. In mice with experimental autoimmune encephalomyelitis, estriol was found to significantly reduce the severity of disease compared with placebo (Figure 1).¹¹ In a small pilot study in nonpregnant women with MS, estriol was found to decrease gadolinium-enhancing lesions on magnetic resonance imaging (MRI).¹² When estriol treatment was stopped the lesions increased to pretreatment levels, but upon reinstatement of therapy they again decreased significantly. Additional research is needed with larger human studies, but these preliminary results suggest that mimicking the pregnant state offers a potential therapeutic intervention for patients with MS and other T_H1-mediated autoimmune disorders.