None of the disease-modifying therapies
(DMTs) are approved for use during pregnancy
or breastfeeding. The reviews by Coyle et al., (2019)
, Vaughn et al., (2018)
, Bove et al., (2014)
and Cree (2013)
provide comprehensive information for clinicians who are counseling their patients about treatment options.
Females are advised to stop their DMT for the appropriate period of time specific to that agent (Kaisey et al., 2018
). Females of child-bearing potential, females who wish to become pregnant or males who wish to father a child who do take or will take teriflunomide or cladribine should be counseled on the teratogenic effects of those medications. Refer to the prescribing information for teriflunomide
for specific guidance. The Food and Drug Administration (FDA) has retired the A, B, C D and X pregnancy categories and replaced them with more useful information about a medication’s risk. The prescribing information
for each DMT has been updated to reflect that change.
Interferon beta and glatiramer acetate have the largest amount of data on pregnancy exposure and neither have been shown to increase risk of negative pregnancy effects in humans (Coyle et al., 2019
). Rituximab has been studied in females with highly active disease who wish to become pregnant. In a retrospective cohort of 74 females who had received rituximab before conception, holding rituximab during pregnancy was not associated with increased rebound relapse or disease activity (Smith et al., 2020
). Rituximab did not increase risk of negative fetal outcomes, including in females who received rituximab infusion within 6 months of conception (n=50) and during the first trimester (n=9). Most babies in this study were breastfed (89%) or exclusively breastfed (35%) and no harm to baby was detected, including babies being breastfed when rituximab infusions were resumed.
Recent studies reported that stopping natalizumab and/or fingolimod prior to pregnancy is associated with increased risk of relapse during pregnancy, but this observation may be confounded by the possibility that females with more active disease would be more likely to use these particular medications (Alroughani, et al., 2018
). Also stopping these agents has been reported to produce “rebound” disease activity (Das et al., 2018
, Smith et al., 2020
) which may be contributing to increased relapses seen during pregnancy after stopping natalizumab or fingolimod.
Females with MS who wish to breastfeed should be encouraged to do so unless it is judged critical that they resume their DMT as soon as possible after delivery (Langer-Gould et al., 2020
). Previous studies have shown the more active a woman’s disease is during pregnancy and the year prior, the higher her risk of postpartum relapse (Coyle, 2016
; Bove et al., 2014
; Vukusic et al., 2004
; Confavreux et al., 1998).
Recent data, however, suggest no increase in relapses in the postpartum year and breastfeeding exclusively in the first 6 months was protective from relapse even in those with sub-optimally controlled disease before pregnancy (Langer-Gould et al., 2020
). In a prospective cohort study, first year infant outcomes were not negatively impacted by maternal exposure to interferon beta or glatiramer acetate during breastfeeding, though investigators were unable to rule out rare adverse events due to small sample size (Ciplea et al., 2020
The impact of a father’s DMT regimen on spermatogenesis or fetal development has received less study. Data from several population-based clinical and health administrative databases in British Columbia, Canada found no association between paternal MS, disease duration at conception and level of disability with birth outcomes (Lu E et al., 2014)