{"title":"Maternal and fetal outcomes in an Italian multicentric cohort of women with multiple sclerosis exposed to dimethyl fumarate during pregnancy.","authors":"Doriana Landi,Silvia Bartolomeo,Francesca Bovis,Maria Pia Amato,Simona Bonavita,Giovanna Borriello,Maria Buccafusca,Sebastiano Bucello,Paola Cavalla,Maria Cellerino,Diego Centonze,Eleonora Cocco,Antonella Conte,Antonio Cortese,Emanuele D'Amico,Massimiliano Di Filippo,Renato Docimo,Roberta Fantozzi,Elisabetta Ferraro,Massimo Filippi,Matteo Foschi,Antonio Gallo,Franco Granella,Antonio Ianniello,Roberta Lanzillo,Lorena Lorefice,Matteo Lucchini,Giacomo Lus,Giorgia Mataluni,Massimiliano Mirabella,Lucia Moiola,Francesca Napoli,Carolina Gabri Nicoletti,Francesco Patti,Paolo Ragonese,Sabrina Realmuto,Giuseppe Schirò,Elisabetta Signoriello,Leonardo Sinisi,Maria Laura Stromillo,Valentina Tomassini,Domizia Vecchio,Maria Pia Sormani,Girolama Alessandra Marfia","doi":"10.1177/13524585241274600","DOIUrl":null,"url":null,"abstract":"BACKGROUND\r\nEvidence on the impact of dimethyl fumarate (DMF) during pregnancy in women with multiple sclerosis (MS) is limited.\r\n\r\nOBJECTIVES\r\nTo investigate disease activity and pregnancy outcomes in a retrospective cohort of women exposed to DMF in early pregnancy.\r\n\r\nMETHODS\r\nWomen 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.\r\n\r\nRESULTS\r\nThe 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.\r\n\r\nCONCLUSION\r\nDMF discontinuation does not increase relapse risk during pregnancy. Early therapy restart prevents postpartum relapses. Early DMF exposure shows no adverse fetal outcomes.","PeriodicalId":18874,"journal":{"name":"Multiple Sclerosis Journal","volume":null,"pages":null},"PeriodicalIF":4.8000,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Multiple Sclerosis Journal","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1177/13524585241274600","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}
引用次数: 0
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.
期刊介绍:
Multiple Sclerosis Journal is a peer-reviewed international journal that focuses on all aspects of multiple sclerosis, neuromyelitis optica and other related autoimmune diseases of the central nervous system.
The journal for your research in the following areas:
* __Biologic basis:__ pathology, myelin biology, pathophysiology of the blood/brain barrier, axo-glial pathobiology, remyelination, virology and microbiome, immunology, proteomics
* __Epidemology and genetics:__ genetics epigenetics, epidemiology
* __Clinical and Neuroimaging:__ clinical neurology, biomarkers, neuroimaging and clinical outcome measures
* __Therapeutics and rehabilitation:__ therapeutics, rehabilitation, psychology, neuroplasticity, neuroprotection, and systematic management
Print ISSN: 1352-4585