Multiple sclerosis

Pregnancy
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By Anthony T Reder MD

Pregnancy is as potent as any available therapy for multiple sclerosis. The exacerbation rate during pregnancy at 0.14 per year is less than baseline at 0.36 per year. The severity and rate of attacks increase during the 3 to 6 months postpartum (1.00 attack per year) (Roullet et al 1993; Damek and Shuster 1997). The average exacerbation rate during the entire year (pregnancy and postpartum period) is equivalent to the baseline rate. Multiple sclerosis is unlikely to appear de novo during pregnancy. Pregnancy decreases the later risk of a progressive course (Runmarker and Andersen 1995). Each baby and each further birth reduces the risk of multiple sclerosis by 50% (Ponsonby et al 2012). The decline in family size and later age at first birth may be linked to the increasing frequency of multiple sclerosis in women.

The decline in exacerbations during pregnancy is presumably due to a shift from Th1 to Th2 type immunity and to immunosuppressive factors such as IL-10 that prevent rejection of the placenta and fetus. Treg cells decline during pregnancy, suggesting that they are of little consequence in multiple sclerosis. Estriol progressively increases during pregnancy. The progesterone/17-beta-estradiol ratio falls during the third trimester of pregnancy, when clinical activity is low. A rebound in immune function after delivery exacerbates disease activity.

Female hormones affect disease activity; 82% of women report worse symptoms before menses (Smith and Studd 1992). The progesterone/17-beta-estradiol ratio increases during the luteal phase of the menstrual cycle, and this corresponds to higher MRI activity (Pozzilli et al 1999). MRI activity increases during ovulation when estradiol is high and progesterone is low (Bansil et al 1999). Symptoms improve with aspirin, without affecting body temperature.

Fifty-four percent of women have worse symptoms during menopause, and 75% feel symptoms improve with hormone replacement therapy. Menopause and removal of ovaries cause low-grade systemic inflammation, which can be prevented with low-dose estrogen replacement (Abu-Taha et al 2009). A small clinical trial suggests that estriol decreases relapses and MRI lesions.

Fertility drugs, follicle-stimulating hormone, and gonadotrophin-releasing hormone increase proinflammatory cytokines. They increase the relapse rate 15-fold. Interferon therapy enhances fertility, perhaps by enhancing implantation.

Breastfeeding, which elevates prolactin, has no effect on the exacerbation rate in most studies (Nelson et al 1988). Some women breastfeed for several days after delivery and then stop in order to begin an immunomodulatory drug; these women are more likely to have had active disease before or during pregnancy. (Breast-pumping for 5 hours after injections to clear interferon from milk is described at the end of the interferon section.)

Mothers with multiple sclerosis in Norway had babies with slightly lower birth weights (Dahl et al 2005). They also needed more frequent induction and interventions during delivery, but had no increase in birth defects or mortality. These mothers were 2 years older than the control group. Other studies show similar data (Franklin and Tremlett 2009), with trends for adverse delivery outcomes in women with severe disability.

Studies of interferons and glatiramer have shown no greater risk of pregnancy loss. However, multiple sclerosis therapies are classified as pregnancy category B (glatiramer), C (interferons, natalizumab, fingolimod), and D (mitoxantrone).

In This Article

Introduction
Historical note and nomenclature
Clinical manifestations
Clinical vignette
Etiology
Pathogenesis and pathophysiology
Epidemiology
Prevention
Differential diagnosis
Diagnostic workup
Prognosis and complications
Management
Pregnancy
Anesthesia
References cited
Contributors