Pregnancy has long been a controversial topic. It was not that long ago that neurologists recommended to patients to avoid getting pregnant for fear of worsening the disease course. Much has since been learned. We can now confidently affirm that:
Multiple sclerosis does not affect pregnancy or the fetus. Patients with MS can have a normal pregnancy receive epidural analgesia and breastfeed.
The risk of developing MS in the offspring is proportional to the genetic loading.
Pregnancy affects the course of the disease. The annual relapse rate (ARR) tends to diminish during pregnancy, reaching the lowest point during the third trimester. The ARR then increases during the first three months post-partum. In the PRIMS study, 28% of patients experienced a relapse in the post-partum period. Overall, for the 12 months of pregnancy and the postpartum period, the effect is, however, neutral. The AAR in the year prior to the pregnancy is predictive of the risk of relapse during the pregnancy and in the postpartum period. Second pregnancies have the same impact on disease course. Treatment with disease modifying therapy prior to pregnancy has been shown to reduce the risk of post-partum relapses. Therapy should thus, whenever possible and safe, be maintained until conception.
Breastfeeding does not increase the risk of relapse but whether it has a protective effect remains unproven. Many contradictory studies exits which are confounded by a well-established inverse relationship between disease severity and incidence of breastfeeding. The decision to breastfeed has to be weighed against the need to restart disease-modifying therapy on case-by-case basis. Ultimately the mother’s decision has to be respected.
Hormonal manipulation to induce ovulation have shown to significantly increase the risk of relapse. The latter however was not seen in woman who received gonadotropin releasing hormone antagonist instead of agonists and those that became pregnant. Patients who plan to receive such reproduction assistance should be forewarned and their disease modifying therapy maintained until conception. The use GnRH antagonists rather than agonists should be encouraged.
Initiation of any disease modifying therapy to a woman with MS of child bearing age should include a discussion about planning for possible future pregnancy.
All disease modifying therapies in MS have a potential risk to the fetus. We have to keep in mind, however, that all pregnancies have a 1-2% risk of ending with a birth defect. We should thus not systematically recommend therapeutic abortions to all pregnancies exposed to a therapy.1)
1 lists all the accepted therapies with some off label therapies with their FDA classification and instructions in case of pregnancy. Ideally disease modifying therapies in order to reduce the risk of relapse in the mother should be continued up until conception is confirmed. As of recent only glatiramer, beta-interferons and perhaps natalizumab can used safely in this manner. Dimethyl fumarate has insufficient data to make any conclusion. All other accepted therapies have to be stopped several months before conception is attempted.
Disease-Modifying Treatments & Pregnancy
Table 1 lists all the accepted therapies, including some off-label therapies, with their FDA classification and instructions in case of pregnancy. Ideally, disease-modifying therapies, in order to reduce the risk of relapse in the mother, should be continued up until conception is confirmed. As of recently, only glatiramer, beta-interferons and perhaps natalizumab, can be used safely in this manner. Dimethyl fumarate has insufficient data to make any conclusion. All other accepted therapies have to be stopped several months before conception is attempted.
Information concerning possible therapy during pregnancy for persistent disease activity is limited. Corticosteroids have been associated with a slight increase in risk of orofacial cleft defects and thus should be reserved for treating relapses associated with functional impairment. Glatiramer acetate is the therapy with a B rating but EMA considers it contraindicated on the grounds of insufficient animal or human data. Natalizumab has been used as rescue therapy in the third trimester in a small study of 12 patients with severe disease activity. Newborns were healthy except for mild hematological abnormalities.
Prevention of post-partum relapses has been studied using IVIG with conflicting results. In another study, six monthly 1gm IV methyl prednisolone did reduce the risk of post-partum relapses, but this needs to be confirmed in a larger trial.
Therapy during breast feeding is not recommended as all drugs either have been shown to be present in breastmilk or have no data: