OBJECTIVE: To investigate pregnancy-related disease activity in a contemporary multiple sclerosis (MS) cohort. METHODS: Using data from the MSBase Registry, we included pregnancies conceived after 31 Dec 2010 from women with relapsing-remitting MS or clinically isolated syndrome. Predictors of intrapartum relapse, and postpartum relapse and disability progression were determined by clustered logistic regression or Cox regression analyses. RESULTS: We included 1998 pregnancies from 1619 women with MS. Preconception annualized relapse rate (ARR) was 0.29 (95% CI 0.27-0.32), fell to 0.19 (0.14-0.24) in third trimester, and increased to 0.59 (0.51-0.67) in early postpartum. Among women who used fingolimod or natalizumab, ARR before pregnancy was 0.37 (0.28-0.49) and 0.29 (0.22-0.37), respectively, and increased during pregnancy. Intrapartum ARR decreased with preconception dimethyl fumarate use. ARR spiked after delivery across all DMT groups. Natalizumab continuation into pregnancy reduced the odds of relapse during pregnancy (OR 0.76 per month [0.60-0.95], p=0.017). DMT re-initiation with natalizumab protected against postpartum relapse (HR 0.11 [0.04-0.32], p<0.0001). Breastfeeding women were less likely to relapse (HR 0.61 [0.41-0.91], p=0.016). 5.6% of pregnancies were followed by confirmed disability progression, predicted by higher relapse activity in pregnancy and postpartum. CONCLUSION: Intrapartum and postpartum relapse probabilities increased among women with MS after natalizumab or fingolimod cessation. In women considered to be at high relapse risk, use of natalizumab before pregnancy and continued up to 34 weeks gestation, with early re-initiation after delivery is an effective option to minimize relapse risks. Strategies of DMT use have to be balanced against potential fetal/neonatal complications.

American University of Beirut Faculty of Medicine Nehme and Therese Multiple Sclerosis Center Beirut Lebanon

Amiri Hospital Kuwait

AORN San Giuseppe Moscati Avellino Italy

Bakirkoy Education and Research Hospital for Psychiatric and Neurological Diseases Turkey

Box Hill Hospital Australia

Brain and Mind Centre University of Sydney Australia

Centre de réadaptation déficience physique Chaudière Appalache Canada

Centro Sclerosi Multipla UOC Neurologia ARNAS Garibaldi Catania Italy

CHUM Hopital Notre Dame Canada

Cliniques Universitaires Saint Luc Université Catholique de Louvain Belgium

CORe Department of Medicine University of Melbourne Australia

Department NEUROFARBA University of Florence Italy

Department of Medical and Surgical Sciences and Advanced Technologies

Department of Neurology Alfred Health Melbourne Victoria Australia

Department of Neurology and Center of Clinical Neuroscience 1st Faculty of Medicine Charles University and General University Hospital Prague Czech Republic

Department of Neurology Austin Health Heidelberg Australia

Department of Neurology Hospital Clínico San Carlos Departamento de Medicina Facultad de Medicina Universidad Complutense de Madrid

Department of Neurology Hospital Universitario Donostia San Sebastian Spain

Department of Neurology Koc University School of Medicine Turkey

Department of Neurology São João Universitary Hospital Center Porto Portugal

Department of Neuroscience Central Clinical School Monash University Melbourne Victoria Australia

Dokuz Eylul University Turkey

GF Ingrassia University of Catania AOU Policlinico San Marco University of Catania

Haydarpasa Numune Training and Research Hospital Turkey

Hospital Universitario Virgen Macarena Spain

IdISSC Madrid Spain

Institut de Neurociències Universitat de Barcelona Barcelona Spain

IRCCS Fondazione Don Carlo Gnocchi Florence Italy

IRCCS Mondino Foundation Pavia Italy

John Hunter Hospital Australia

KTU Medical Faculty Farabi Hospital Turkey

Liverpool Hospital Australia

Maaslandziekenhuis Netherlands

Mayis University Medical Faculty Turkey

Melbourne MS Centre Royal Melbourne Hospital Australia

Nemocnice Jihlava Czech Republic

Neuro Rive Sud Canada

Neurology Unit Azienda Ospedaliero Universitaria of Modena Modena Italy

Ospedale Generale Provinciale Macerata Italy

Service of Neurology Hospital Clinic Institut d'Investigacions Biomediques August Pi i Sunyer

St Andrews Place Australia and Royal Brisbane and Women's Hospital Australia

Univ G d'Annunzio Chieti Pescara Italy

University of Parma Italy

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