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.
Women of reproductive potential are advised to stop their DMT for the appropriate period of time specific to that agent (Kaisey et al., 2018
). Women and men of reproductive potential 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.
There are no data definitively linking interferon beta or glatiramer acetate to adverse fetal outcomes and some clinicians will allow use up until conception (Coyle, 2016
). Rituximab has been studied in women of reproductive potential with highly active disease who wish to become pregnant. In a retrospective cohort (n=74) 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 those 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.
When suspended within 6 months of conception, rituximab may exert longstanding, beneficial effects on disease activity during pregnancy and the postpartum period compared to suspended natalizumab and no treatment (Razaz et al., 2020
). 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 women of reproductive potential 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.
Rituximab, interferon beta and glatiramer acetate are considered compatible with breastfeeding by some clinicians (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
). Gastroenterologists and rheumatologists consider monoclonal antibodies to be compatible with breastfeeding (Ciplea et al., 2020
) and there have been recent efforts to improve safety data on monoclonal antibody transfer to breastmilk in mothers with MS (Krysko et al., 2020
). A small prospective cohort study of 9 mothers with MS demonstrated limited transfer of rituximab to breastmilk at levels that would likely degrade in the newborn gastrointestinal tract, though minimal newborn exposure cannot be excluded (Krysko et al., 2020
Mothers on other DMTs 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. Previous studies have shown the more active the disease during pregnancy and the year prior, the higher the risk of postpartum relapse (Coyle, 2016
; Bove et al., 2014
; Vukusic et al., 2004
; Confavreux et al., 1998).
In a recent study of 466 pregnancies over 8 years, 74% of pregnancies were not followed by relapse in the first postpartum year and there was no rebound effect (i.e., post pregnancy relapse rates where not higher than prepartum relapse rates) (Langer-Gould et al., 2020
). High relapse activity prepartum was associated with postpartum relapses throughout the first year, but not within the first 6 months, and lower relapse risk was seen in mothers who breastfed exclusively (Langer-Gould et al., 2020
). This study population is noted to have milder disease compared to university-based academic centers, which could contribute to the positive outcomes and complicate comparisons across studies (Houtchens 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)