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Postpartum relapse risk in multiple sclerosis: a systematic review and meta-analysis
  1. Charlotte Schubert1,
  2. Lea Steinberg1,
  3. Julia Peper2,
  4. Caren Ramien1,
  5. Kerstin Hellwig3,
  6. Sascha Köpke4,
  7. Alessandra Solari5,
  8. Andrea Giordano5,
  9. Stefan M Gold1,6,
  10. Tim Friede7,
  11. Christoph Heesen1,
  12. Anne Christin Rahn2
  1. 1Institute of Neuroimmunology and Multiple Sclerosis, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
  2. 2Institute of Social Medicine and Epidemiology, University of Lübeck, Lübeck, Germany
  3. 3Department of Neurology, Ruhr University Bochum, Bochum, Germany
  4. 4Faculty of Medicine and University Hospital Cologne, University Hospital Cologne, Köln, Germany
  5. 5Unit of Neuroepidemiology, Foundation IRCCS Carlo Besta Neurological Institute, Milano, Italy
  6. 6Department of Psychiatry and Neurosciences, Charite Universitatsmedizin Berlin, Berlin, Germany
  7. 7Medical Statistics, University Medical Center Göttingen, Göttingen, Germany
  1. Correspondence to Dr Charlotte Schubert, Institute of Neuroimmunology and Multiple Sclerosis, University Medical Center Hamburg-Eppendorf, Hamburg 20246, Germany; cha.schubert{at}


The influence of pregnancy on the course of multiple sclerosis (MS) has long been controversial. While historical evidence suggests a substantial decline in relapse rates during pregnancy followed by a rebound in the postpartum period, more recent work yielded equivocal results. We performed a systematic review and meta-analysis on data from cohort studies to determine whether women with MS experience increased relapse rates after delivery. A systematic literature search was conducted in the databases MEDLINE and Epistemonikos on the topic ‘motherhood choice in MS’ in March 2022. We included cohort studies assessing the association between pregnancy and MS relapse activity defined by the annualised relapse rate after 3, 6, 9 and 12 months post partum. Furthermore, information about disease-modifying therapies (DMT) and breast feeding was considered, if available. 5369 publications were identified. Of these, 93 full-text articles on MS relapse activity during the postpartum period were screened. 11 studies including 2739 pregnancies were eligible. Women with MS showed a significantly increased relapse rate in the first 6 months post partum, compared with preconception with the incidence rate ratio (IRR) almost doubled in the first 3 months post partum (1.87, 95% CI 1.40 to 2.50). However, at 10–12 months post partum, the IRR decreased significantly (0.81, 95% CI 0.67 to 0.98). Subanalysis on influencing parameters suggested that preconceptional DMTs (IRR for highly-effective DMTs 2.76, 95% CI 1.34 to 5.69) and exclusive breast feeding (risk ratio 0.39, 95% CI 0.18 to 0.86) significantly influenced postpartum relapse risk. Increased postpartum annualised relapse rate and possible modifiers should be considered in counselling women with MS who are considering pregnancy.


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  • CS and LS contributed equally.

  • Contributors CS and LS contributed equally to this paper. CS, LS, ACR and CH conceptualised the review and meta-analysis, drafted and edited the protocol. CS, LS, JP, CR, ACR and CH performed literature screening, quality assessment and data extraction. CS, LS, JP and TF analysed the data. CS, LS, JP, KH, CR, AS, AG, SMG, SK, TF, CH and ACR reviewed, edited and approved the review before publication.

  • Funding This project was funded by the Deutsche Forschungsgemeinschaft (DFG) (RA 3296/1-1 and GO 1357/8-2, KFO 296). CR was supported by the Forschungsförderungsfond der Medizinischen Fakultät, Universitätsklinikum Hamburg-Eppendorf.

  • Competing interests AG, ACR, CR, JP and LS have nothing to declare. KH reports research support and speaker honoraria from Biogen, Bayer Healthcare, Novartis Pharma, Teva, Sanofi Genzyme, Merck Serono and Roche. SMG reports honoraria from Mylan GmbH, Almirall S.A. and Celgene and research grants from Biogen, outside the submitted work. He receives research funding from the Deutsche Forschungsgemeinschaft, Bundesministerium für Bildung und Forschung, Bundesministerium für Gesundheit, the National MS Society and the European Commission. TF reports personal fees from Novartis, Bayer, Janssen, Roche, Vifor, BiosenseWebster, CSL Behring, Fresenius Kabi, Coherex Medical, LivaNova, Minoryx, Immunic, Bristol Myers Squibb, Enanta, IQVIA; all outside the submitted work. AS reports grants from the Fondazione Italiana Sclerosi Multipla and the European Academy of Neurology, during the conduct of the study; personal fees from Almirall and Merck Serono. CH received research grants or speaker honoraries from Biogen, Bristol Myers Squibb, Merck, Novartis and Roche.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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