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Original article| Volume 44, 102241, September 2020

Change in pregnancy-associated multiple sclerosis relapse rates over time: a meta-analysis

  • Ruth Dobson
    Correspondence
    Corresponding author: Dr. Ruth Dobson, Preventive Neurology Unit, Wolfson Institute of Preventive Medicine, Charterhouse Square, Queen Mary University London. Tel: 020 7882 6463. @drruthdobson.
    Affiliations
    Preventive Neurology Unit, Wolfson Institute of Preventive Medicine, Queen Mary University London

    Department of Neurology, Royal London Hospital, BartsHealth NHS Trust
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  • Vilija G. Jokubaitis
    Affiliations
    Department of Neuroscience, Central Clinical School, Monash University, Melbourne
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  • Gavin Giovannoni
    Affiliations
    Preventive Neurology Unit, Wolfson Institute of Preventive Medicine, Queen Mary University London

    Department of Neurology, Royal London Hospital, BartsHealth NHS Trust

    Blizard Institute, QMUL
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      Highlights

      • The historic assumption that MS relapse rate reduces during pregnancy and increases again post-partum remains true, despite significant changes in the MS treatment landscape, and increasing rates of treatment with DMT.
      • MS relapse rate appears to be decreasing over time in women both prior to pregnancy and in the post-partum period.
      • Neither diagnostic criteria, DMT exposure, nor proportion of women breastfeeding appears to associate with the change in relapse rate at a population level.

      Abstract

      Background

      Women with MS are advised that relapse rates fall during pregnancy and rebound post-partum. This advice originates from 1998; smaller, more recent, studies have not been previously pooled.

      Methods

      All studies published since 1998 providing raw relapse data were considered for inclusion. Single arm meta-analysis was performed using a restricted maximum likelihood random effects model with inverse variance; secondary subgroup analysis and meta regression were then performed. Annualised relapse rates (ARR), or relapse numbers/rates suitable for conversion into ARR during pregnancy and the post-partum period were included. Secondary subgroup analysis examined year of data collection, DMT exposure, breastfeeding and data source.

      Results

      7034 pregnancies from 6430 women were included. ARR fell from 0.57 (95%CI 0.45-0.70) pre-pregnancy to 0.36 (0.28-0.44), 0.29 (0.21-0.36) and 0.16 (0.11-0.21) during trimesters 1,2, and 3, with a post-partum rebound (ARR 0.85, 95%CI 0.70-1.00). ARR reduced pre-pregnancy and post-partum over time (p<0.001). Relapse rates were lower in claims databases than elsewhere.

      Conclusions

      Despite high heterogeneity, we confirm the historic assumption that ARR reduces during pregnancy, and demonstrate an overall reduction in ARR over time. Studies using data originating from claims databases demonstrated a lower relapse rate at all time points, which has not previously been demonstrated.

      Keywords

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      References

        • Tao C
        • Simpson Jr., S
        • van der Mei I
        • Blizzard L
        • Havrdova E
        • Horakova D
        • et al.
        Higher latitude is significantly associated with an earlier age of disease onset in multiple sclerosis.
        J Neurol Neurosurg Psychiatry. 2016; 87: 1343-1349
        • Confavreux C
        • Hutchinson M
        • Hours MM
        • Cortinovis-Tourniaire P
        • Moreau T
        Rate of pregnancy-related relapse in multiple sclerosis.
        Pregnancy in Multiple Sclerosis Group. N Engl J Med. 1998; 339: 285-291
        • De Angelis F
        • Brownlee WJ
        • Chard DT
        • Trip SA
        New MS diagnostic criteria in practice.
        Pract Neurol. 2019; 19: 64-67
        • Hobart J
        • Bowen A
        • Pepper G
        • Crofts H
        • Eberhard L
        • Berger T
        • et al.
        International consensus on quality standards for brain health-focused care in multiple sclerosis.
        Mult Scler. 2018; (1352458518809326)
        • Van Der Walt A
        • Nguyen A-L
        • Jokubaitis V
        Family planning, antenatal and post partum care in multiple sclerosis: a review and update.
        Med J Aust. 2019; 211: 230-236
        • Bove R
        • Alwan S
        • Friedman JM
        • Hellwig K
        • Houtchens M
        • Koren G
        • et al.
        Management of multiple sclerosis during pregnancy and the reproductive years: a systematic review.
        Obstet Gynecol. 2014; 124: 1157-1168
        • Finkelsztejn A
        • Brooks JBB
        • Jr Paschoal FM
        • Fragoso YD
        What can we really tell women with multiple sclerosis regarding pregnancy? A systematic review and meta-analysis of the literature.
        BJOG. 2011; 118: 790-797
      1. Ottawa Hospital Research Institute [Internet]. [cited 13 Aug 2019]. Available: http://www.ohri.ca/programs/clinical_epidemiology/oxford.asp.

        • Benoit A
        • Durand-Dubief F
        • Amato M-P
        • Portaccio E
        • Casey R
        • Roggerone S
        • et al.
        History of multiple sclerosis in 2 successive pregnancies: A French and Italian cohort.
        Neurology. 2016; 87: 1360-1367
        • Howie PW
        • McNeilly AS
        • Houston MJ
        • Cook A
        • Boyle H
        Fertility after childbirth: infant feeding patterns, basal PRL levels and post-partum ovulation.
        Clin Endocrinol. 1982; 17: 315-322
        • Portaccio E
        • Amato MP
        Breastfeeding and post-partum relapses in multiple sclerosis patients.
        Mult Scler. 2019; 25: 1211-1216
      2. Results: Breastfeeding Rates | Breastfeeding | CDC [Internet]. 1 Aug 2019 [cited 6 Aug 2019]. Available: https://www.cdc.gov/breastfeeding/data/nis_data/results.html.

        • GBD 2016 Multiple Sclerosis Collaborators
        Global, regional, and national burden of multiple sclerosis 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016.
        Lancet Neurol. 2019; 18: 269-285
        • Gaetani L
        • Prosperini L
        • Mancini A
        • Eusebi P
        • Cerri MC
        • Pozzilli C
        • et al.
        2017 revisions of McDonald criteria shorten the time to diagnosis of multiple sclerosis in clinically isolated syndromes.
        J Neurol. 2018; 265: 2684-2687
        • Krysko KM
        • Rutatangwa A
        • Jraves J
        • Lazar A
        • Waubant E
        Association between breastfeeding and postpartum multiple sclerosis relapses: a systematic review and meta-analysis.
        JAMA Neurol. 2019; (Dec 9 [epub ahead of print])