{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T00:18:16Z","timestamp":1792801096486,"version":"4.5.0"},"reference-count":38,"publisher":"American Medical Association (AMA)","issue":"10","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Neurol"],"published-print":{"date-parts":[[2025,10,1]]},"abstract":"Importance<\/jats:title>In women with multiple sclerosis (MS), disease-modifying therapy (DMT) management during pregnancy might impact relapse risk.<\/jats:p><\/jats:sec>Objective<\/jats:title>To estimate the effect of DMT management during pregnancy on MS relapse rate and compare different therapeutic strategies.<\/jats:p><\/jats:sec>Design, Setting, and Participants<\/jats:title>This was a multicenter retrospective cohort study using data from January 1990 to December 2023. Data were extracted in December 2023 from the French MS registry. Among 52\u202f955 women in the registry, we included pregnancies identified through childbirths in patients with relapsing-onset MS who were monitored for at least 18 months before delivery and 9 months after. Pregnancies occurring less than 18 months apart or with missing month of birth were excluded.<\/jats:p><\/jats:sec>Exposures<\/jats:title>Mediation analysis was used to estimate the total, direct, and indirect (mediated by DMT management) effects of pregnancy. Different therapeutic strategies were compared: DMT interruption, switching to or maintaining interferon \u03b2 or glatiramer acetate, switching to or maintaining natalizumab until the third trimester, and switching to or maintaining intravenous anti-CD20 and interrupting it 3 months before conception.<\/jats:p><\/jats:sec>Main Outcomes and Measures<\/jats:title>The primary outcome was the annualized relapse rate (ARR) during the preconception, gestation, and postpartum periods. Within a causal inference framework, counterfactual ARRs were estimated using longitudinal g-computation, combining a random forest algorithm for predicting DMTs, and a mixed-effects Poisson model for relapses.<\/jats:p><\/jats:sec>Results<\/jats:title>We included 6341 pregnancies occurring in 4998 women (mean [SD] age at conception, 31.5 [4.5] years). DMT management during pregnancy significantly increased ARR during gestation (causal rate ratio [cRR], 1.13; 95% CI, 1.06-1.22) and postpartum (cRR, 1.08; 95% CI, 1.01-1.16) periods. This led to a deleterious total effect of pregnancy on ARR, particularly in women receiving natalizumab before pregnancy with prolonged interruption (ie, interruption before the second trimester or resumption more than 3 months after delivery; cRR, 2.18; 95% CI, 1.76-2.69), and in women receiving fingolimod (cRR, 2.15; 95% CI, 1.60-2.93). Compared to DMT interruption, anti-CD20 strategy was the most effective (cRR, 0.38; 95% CI, 0.25-0.52), followed by the natalizumab strategy with short interruption (cRR, 0.80; 95% CI, 0.71-0.90), whereas interferon \u03b2 (cRR, 0.93; 95% CI, 0.86-0.99) and glatiramer acetate strategies (cRR, 0.91; 95% CI, 0.84-0.99) were less effective.<\/jats:p><\/jats:sec>Conclusion<\/jats:title>In this study, DMT management during pregnancy significantly increased relapse risk, particularly in patients receiving natalizumab with prolonged interruption or fingolimod. The strategy based on the use of anti-CD20 before pregnancy was the most effective to mitigate this risk.<\/jats:p><\/jats:sec>","DOI":"10.1001\/jamaneurol.2025.2550","type":"journal-article","created":{"date-parts":[[2025,8,4]],"date-time":"2025-08-04T15:00:24Z","timestamp":1754319624000},"page":"994","source":"Crossref","is-referenced-by-count":17,"title":["Therapeutic Management During Pregnancy and Relapse Risk in Women With Multiple Sclerosis"],"prefix":"10.1001","volume":"82","author":[{"given":"Antoine","family":"Gavoille","sequence":"first","affiliation":[{"name":"Hospices Civils de Lyon, Service de Neurologie, scl\u00e9rose en plaques, pathologies de la my\u00e9line et neuro-inflammation, F-69677 Bron, France"},{"name":"Universit\u00e9 de Lyon, Universit\u00e9 Lyon 1, CNRS, Laboratoire de Biom\u00e9trie et Biologie \u00c9volutive UMR 5558, F-69100 Villeurbanne, France"},{"name":"Service de Biostatistique-Bioinformatique, Hospices Civils de Lyon, F-69003 Lyon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabien","family":"Rollot","sequence":"additional","affiliation":[{"name":"Hospices Civils de Lyon, Service de Neurologie, scl\u00e9rose en plaques, pathologies de la my\u00e9line et neuro-inflammation, F-69677 Bron, France"},{"name":"Universit\u00e9 de Lyon, Universit\u00e9 Claude Bernard Lyon 1, F-69000 Lyon, France"},{"name":"Observatoire Fran\u00e7ais de la Scl\u00e9rose en Plaques, Centre de Recherche en Neurosciences de Lyon, INSERM 1028 et CNRS UMR 5292, F-69003 Lyon, France"},{"name":"Eug\u00e8ne Devic EDMUS Foundation Against Multiple Sclerosis, F-69677 Bron Cedex, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Romain","family":"Casey","sequence":"additional","affiliation":[{"name":"Hospices Civils de Lyon, Service de Neurologie, scl\u00e9rose en plaques, pathologies de la my\u00e9line et neuro-inflammation, F-69677 Bron, France"},{"name":"Universit\u00e9 de Lyon, Universit\u00e9 Claude Bernard Lyon 1, F-69000 Lyon, France"},{"name":"Observatoire Fran\u00e7ais de la Scl\u00e9rose en Plaques, Centre de Recherche en Neurosciences de Lyon, INSERM 1028 et CNRS UMR 5292, F-69003 Lyon, France"},{"name":"Eug\u00e8ne Devic EDMUS Foundation Against Multiple Sclerosis, F-69677 Bron Cedex, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guillaume","family":"Mathey","sequence":"additional","affiliation":[{"name":"Department of Neurology, Nancy University Hospital, F-54035 Nancy, France; Universit\u00e9 de Lorraine, Inserm, INSPIIRE, F-54000 Nancy, France; CHRU de Nancy, Universit\u00e9 de Lorraine, Inserm, CIC 1433 EC, F-54000 Nancy, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emmanuelle","family":"Le Page","sequence":"additional","affiliation":[{"name":"CHU Pontchaillou, Department of Neurology, CRC-SEP, CIC1414 INSERM, F-35000 Rennes, 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