Pregnancy-related issues in women with multiple sclerosis: an evidence-based review with practical recommendations

Abstract

Objective: To review the current evidence regarding pregnancy-related issues in multiple sclerosis (MS) and to provide recommendations specific for each of them. Research design and methods: A systematic review was performed based on a comprehensive literature search. Results: MS has no effect on fertility, pregnancy or fetal outcomes, and pregnancies do not affect the long-term disease course and accumulation of disability. There is a potential risk for relapse after use of gonadotropin-releasing hormone agonists during assisted reproduction techniques. At short-term, pregnancy leads to a reduction of relapses during the third trimester, followed by an increased risk of relapses during the first three months postpartum. Pregnancies in MS are not per se high risk pregnancies, and MS does not influence the mode of delivery or anesthesia unless in the presence of significant disability. MRI is not contraindicated during pregnancy; however, gadolinium contrast media should be avoided whenever possible. It is safe to use pulse dose methylprednisolone infusions to manage acute disabling relapses during pregnancy and breastfeeding. However, its use during the first trimester of pregnancy is still controversial. Women with MS should be encouraged to breastfeed with a possible favorable effect of exclusive breastfeeding. Disease-modifying drugs can be classified according to their potential for pregnancy-associated risk and impact on fetal outcome. Interferon beta (IFNb) and glatiramer acetate (GA) may be continued until pregnancy is confirmed and, after consideration of the individual risk-benefit if continued, during pregnancy. The benefit of continuing natalizumab during the entire pregnancy may outweigh the risk of recurring disease activity, particularly in women with highly active MS. GA and IFNb are considered safe during breastfeeding. The use of natalizumab during pregnancy or lactation requires monitoring of the newborn. Conclusions: This review provides current evidence and recommendations for counseling and management of women with MS preconception, during pregnancy and postpartum.

Early Aggressive Treatment Approaches for Multiple Sclerosis

“…Natalizumab treatment is typically not recommended during pregnancy and a 2-month washout period is suggested prior to pregnancy. Although, some MS patients with highly active disease have continued on natalizumab throughout pregnancy and in those continuing this therapy through the third trimester have observed reversible hematological abnormalities in the majority of their newborns [ 78 ]. Fingolimod may cause fetal harm (two-fold increased risk of congenital malformations) and is not recommended for continuation during pregnancy, with a recommended washout period of at least 2 months [ 78 ].…”

“…Although, some MS patients with highly active disease have continued on natalizumab throughout pregnancy and in those continuing this therapy through the third trimester have observed reversible hematological abnormalities in the majority of their newborns [ 78 ]. Fingolimod may cause fetal harm (two-fold increased risk of congenital malformations) and is not recommended for continuation during pregnancy, with a recommended washout period of at least 2 months [ 78 ]. Given the risk of rebound disease activity with natalizumab and fingolimod after a prolonged washout period [ 77 ], some clinicians recommend transitioning patients to a different therapy (without such rebound potential) for a couple months prior to attempting to conceive.…”

Family Planning Decision Making in People With Multiple Sclerosis

“…In wMS that are contemplating pregnancy, it is necessary to evaluate the impact that treatment cessation may have on the course of their disease. For the majority of DMTs, it is generally recommended that wMS stop treatment before becoming pregnant, and do not re-start until after they have stopped breastfeeding ( 4 ). However, this puts the patient at risk of recurrence or rebound of disease activity.…”

Rituximab in Multiple Sclerosis: Are We Ready for Regulatory Approval?

“…Moreover, in the suspended rituximab women, only one maternal relapse occurred during pregnancy and only one of four patients who relapsed in the first quarter after delivery experienced new GAD+ lesions. These results suggest a prolonged protective effect on MS disease activity of rituximab, which can encompass pregnancy and postpartum period, without the high risk of disease reactivation or rebound described with natalizumab withdrawal before pregnancy ( 111 ). In line with these data, a German cohort study ( 112 ), analyzing 88 pregnancies from 81 women with neuroimmune diseases (including MS and NMOSDs) treated with anti-CD20 mAbs in the year before conception, showed a good control of disease activity during pregnancy and postpartum, with no major safety concerns (with the exception of two congenital abnormalities reported in women exposed to ocrelizumab during pregnancy) and with pregnancy outcomes within the range expected for the general population.…”