Maternal and fetal outcomes in an Italian multicentric cohort of women with multiple sclerosis exposed to dimethyl fumarate during pregnancy

Mult Scler. 2024 Oct;30(11-12):1503-1513. doi: 10.1177/13524585241274600. Epub 2024 Sep 12.

Abstract

Background: Evidence on the impact of dimethyl fumarate (DMF) during pregnancy in women with multiple sclerosis (MS) is limited.

Objectives: To investigate disease activity and pregnancy outcomes in a retrospective cohort of women exposed to DMF in early pregnancy.

Methods: Women discontinuing DMF after pregnancy confirmation were identified from 29 Italian MS Centers. Disease activity 12 months before conception, during pregnancy, and 12 months postpartum were recorded, exploring reactivation predictors. Pregnancy and fetal outcomes were assessed.

Results: The study analyzed 137 pregnancies (12 pregnancy losses, 125 live births) from 137 women (mean age 32.9 ± 4.7 years), discontinuing DMF within a median (interquartile range (IQR)) interval of 4.9 (3.7-5.7) weeks from conception. In live birth pregnancies, annualized relapse rate (ARR) significantly decreased during pregnancy (ARR = 0.07, 95% confidence interval (CI): 0.03-0.14, p = 0.021) compared to pre-conception (ARR = 0.21 (95% CI: 0.14-0.30)) and increased postpartum ((ARR = 0.22 (95% CI: 0.15-0.32), p = 0.006). Median time to first relapse (TTFR) was 3.16 (IQR: 1:87-5.42) months. Higher pre-conception relapse number (hazard ratio (HR) = 2.33, 95% CI: 1.08-5.02) and Expanded Disability Status Scale (EDSS; HR = 1.81, 95% CI: 1.17-2.74) were associated with shorter TTFR, while treatment resumption with longer TTFR (HR = 0.29, 95% CI: 0.11-0.74). Fetal outcomes were unaffected by DMF exposure.

Conclusion: DMF discontinuation does not increase relapse risk during pregnancy. Early therapy restart prevents postpartum relapses. Early DMF exposure shows no adverse fetal outcomes.

Keywords: Multiple sclerosis; dimethyl fumarate; pregnancy.

Publication types

  • Multicenter Study

MeSH terms

  • Adult
  • Dimethyl Fumarate* / adverse effects
  • Female
  • Humans
  • Immunosuppressive Agents* / adverse effects
  • Italy
  • Multiple Sclerosis* / drug therapy
  • Pregnancy
  • Pregnancy Complications* / drug therapy
  • Pregnancy Outcome*
  • Recurrence
  • Retrospective Studies

Substances

  • Dimethyl Fumarate
  • Immunosuppressive Agents