{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T04:13:46Z","timestamp":1793160826086,"version":"4.5.0"},"reference-count":37,"publisher":"American Medical Association (AMA)","issue":"9","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Netw Open"],"abstract":"<jats:sec id=\"ab-zoi250899-4\"><jats:title>Importance<\/jats:title><jats:p>Understanding the association between pregnancy and clinical outcomes in women with moderate to severe multiple sclerosis (MS) disability is crucial for guiding family planning and management strategies.<\/jats:p><\/jats:sec><jats:sec id=\"ab-zoi250899-5\"><jats:title>Objective<\/jats:title><jats:p>To assess peripregnancy relapse activity and disability progression in women with a preconception Expanded Disability Status Scale (EDSS) score of 3 or higher.<\/jats:p><\/jats:sec><jats:sec id=\"ab-zoi250899-6\"><jats:title>Design, Setting, and Participants<\/jats:title><jats:p>This multicenter retrospective cohort study used data from the MSBase Registry, with clinical observations spanning 1984 through 2024. Study cohorts included pregnant women with MS with a preconception EDSS score of 3 or higher (range: 3-10, with higher scores indicating more severe MS-related disability) and propensity score\u2013matched nonpregnant women with MS (controls).<\/jats:p><\/jats:sec><jats:sec id=\"ab-zoi250899-7\"><jats:title>Main Outcomes and Measures<\/jats:title><jats:p>The main outcomes were peripregnancy annualized relapse rates (ARRs) and time to 6-month confirmed disability worsening (CDW).<\/jats:p><\/jats:sec><jats:sec id=\"ab-zoi250899-8\"><jats:title>Results<\/jats:title><jats:p>A total of 1631 women with MS were included, of whom 575 were in the pregnant cohort (median [IQR] age at pregnancy, 32.5 [29.1-36.1] years) and 1056 were in the nonpregnant cohort (median [IQR] age, 32.6 [27.5-37.2] years). The median (range) preconception EDSS score was 3.5 (3.0-7.5). Relapse activity decreased during pregnancy, with a 75% reduction in ARR during the first trimester (rate ratio [RR], 0.25; 95% CI, 0.15-0.43), and increased to 36% above preconception levels in the first 3 months post partum (RR, 1.36; 95% CI, 1.06-1.75). Relapse during pregnancy was associated with a higher preconception ARR (odds ratio [OR], 1.56; 95% CI, 1.10-2.20) and preconception use of natalizumab (OR, 4.42; 95% CI, 1.24-23.57) or fingolimod (OR, 14.07; 95% CI, 2.81-91.30). Older age (OR, 0.92; 95% CI, 0.85-0.99) and continuation of disease-modifying therapy into pregnancy (OR, 0.42; 95% CI, 0.19-1.00) were associated with reduced risk. Disease-modifying therapy reinitiation within 1 month post partum was associated with lower odds of early postpartum relapse (OR, 0.45; 95% CI, 0.23-0.86). There was no significant difference in time to CDW between the pregnant and nonpregnant groups (hazard ratio [HR], 1.15; 95% CI, 0.96-1.38). However, ARR during pregnancy (HR, 1.37; 95% CI, 1.13-1.65) and postpartum EDSS score higher than 4 (HR, 2.69; 95% CI, 1.80-4.03) were associated with shorter time to CDW.<\/jats:p><\/jats:sec><jats:sec id=\"ab-zoi250899-9\"><jats:title>Conclusions and Relevance<\/jats:title><jats:p>In this cohort study, women with moderate to severe MS disability exhibited a pattern of peripregnancy relapse activity similar to that reported in women with less disability. Pregnancy was not associated with worse long-term disability outcomes, although optimizing disease control in the peripregnancy period remained critical.<\/jats:p><\/jats:sec>","DOI":"10.1001\/jamanetworkopen.2025.31581","type":"journal-article","created":{"date-parts":[[2025,9,15]],"date-time":"2025-09-15T15:00:28Z","timestamp":1757948428000},"page":"e2531581","source":"Crossref","is-referenced-by-count":7,"title":["Pregnancy-Related Disease Outcomes in Women With Moderate to Severe Multiple Sclerosis Disability"],"prefix":"10.1001","volume":"8","author":[{"given":"Jessica","family":"Shipley","sequence":"first","affiliation":[{"name":"Department of Neuroscience, School of Translational Medicine, Monash University, Melbourne, Victoria, Australia"},{"name":"Department of Neurology, Alfred Health, Melbourne, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heidi N.","family":"Beadnall","sequence":"additional","affiliation":[{"name":"Brain and Mind Centre, The University of Sydney, Sydney, New South Wales, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul G.","family":"Sanfilippo","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, School of Translational Medicine, Monash University, Melbourne, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei Zhen","family":"Yeh","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, School of Translational Medicine, Monash University, Melbourne, Victoria, Australia"},{"name":"Department of Neurology, Alfred Health, Melbourne, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dana","family":"Horakova","sequence":"additional","affiliation":[{"name":"Department of Neurology and Center of Clinical Neuroscience, First Faculty of Medicine, Charles University and General University Hospital, Prague, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva Kubala","family":"Havrdova","sequence":"additional","affiliation":[{"name":"Department of Neurology and Center of Clinical Neuroscience, First Faculty of Medicine, Charles University and General University Hospital, Prague, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pavel","family":"Hradilek","sequence":"additional","affiliation":[{"name":"Department of Neurology, Faculty of Medicine, University of Ostrava, Ostrava, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomas","family":"Kalincik","sequence":"additional","affiliation":[{"name":"Neuroimmunology Centre, Department of Neurology, Royal Melbourne Hospital, Melbourne, Victoria, Australia"},{"name":"Clinical Outcomes Research (CORe) Unit, Department of Medicine, University of Melbourne, Melbourne, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Izanne","family":"Roos","sequence":"additional","affiliation":[{"name":"Neuroimmunology Centre, Department of Neurology, Royal Melbourne Hospital, Melbourne, Victoria, Australia"},{"name":"Clinical Outcomes Research (CORe) Unit, Department of Medicine, University of Melbourne, Melbourne, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandre","family":"Prat","sequence":"additional","affiliation":[{"name":"Centre Hospitalier de l\u2019Universit\u00e9 de Montr\u00e9al (CHUM) and Universite de Montreal, Montreal, Quebec, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc","family":"Girard","sequence":"additional","affiliation":[{"name":"Centre Hospitalier de l\u2019Universit\u00e9 de Montr\u00e9al (CHUM) and Universite de Montreal, Montreal, Quebec, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zuzana","family":"Rous","sequence":"additional","affiliation":[{"name":"Department of Neurology, Faculty of Medicine, Palack\u00fd University and University Hospital Olomouc, Olomouc, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zbysek","family":"Pavelek","sequence":"additional","affiliation":[{"name":"Department of Neurology, Faculty of Medicine and University Hospital Hradec Kr\u00e1lov\u00e9, Charles University, Prague, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oliver H. 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